Intracranial and Intraocular Pressure at the Lamina Cribrosa: Gradient Effects

Abstract

Purpose of Review

A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD.

Recent Findings

For normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory.

Summary

Data from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients.

https://ift.tt/2qobKR8

National Trends in Readmission Following Inpatient Surgery in the Hospital Readmissions Reduction Program Era

Objective: The aim of this study was to investigate whether the Hospital Readmissions Reduction Program, a national program that introduced financial penalties for high readmission rates for certain medical conditions, had a "spillover" effect on surgical conditions. Summary Background Data: During the past decade, there have been multiple national efforts to improve surgical care. Readmission rates are a key metric for assessing surgical quality. Whether surgical readmission rates have declined, and whether the Hospital Readmissions Reduction Program has had an influence is unclear. Methods: Using national Medicare data, we identified patients undergoing a range of procedures during the past decade. We examined whether certain procedures that would be targeted by the HRRP had a differential change in readmissions compared to other procedures. We used an interrupted time-series model to examine readmission trends in three time periods: pre-ACA, HRRP implementation, and HRRP penalty. Results: Between 2005 and 2014, 17,423,106 patients underwent the procedures of interest; risk-adjusted rates of readmission across the 8 procedures declined from 12.2% to 8.6%. Pre-ACA rates of readmission were decreasing [−0.060% per quarter (−0.072%, −0.048%), P

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135th Congress of the German Society of Surgery (DGCH)

Eur Surg Res 2018;59:1–68

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Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma

Abstract

Background

As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance.

Patients and Methods

From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were performed of imaging outcomes.

Results

170 patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56% - 83%. Negative scans had predictive values of 89% - 96% for true non-recurrence (negative predictive values (NPV)) until the next scan. A negative PET at 18 months had NPVs of 80% - 84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median).

Conclusions

Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

https://ift.tt/2HjjPAg

Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer

Abstract

Background

PD-L1 immunohistochemistry (IHC) testing is usually performed on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay.

Methods

A total of 1419 consecutive cases of non-small cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as < 1%, 1-49% and ≥ 50% tumor cells. A total of 100 viable tumor cells were required for adequacy.

Results

Of the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥ 50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (P=0.04), and 29% of surgical resections (P=0.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P= 0.001).

Conclusion

Our results show that when the TPS ≥50% is used as the endpoint, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.

https://ift.tt/2v7uf0D

In upcoming issues...

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Endoscopic submucosal dissection for early Barrett’s esophagus neoplasia

We read with interest the article by Yang et al1 evaluating endoscopic submucosal dissection (ESD) for early Barrett's esophagus (BE) neoplasia. The authors found that ESD for early BE neoplasia is a reasonable choice for the management of BE neoplasia. Because their findings are important to current practice, several questions deserve attention.

https://ift.tt/2v56Ehp

Response:

I thank Dr Thomson for his helpful comments on our recent publication, which exposed the poor state of credentialing for ERCP in the United States.1 He kindly clarified the role of the Conjoint Committee in Australia, which we highlighted because of its pioneering work in enhancing and confirming the quality of their endoscopic practice.

https://ift.tt/2JCrE24

Too loose to lose: an investigation into endoscopic anastomotic reduction to reestablish weight loss

Failure of weight loss, regain of weight, or both after laparoscopic Roux-en-Y gastric bypass (RYGB) resulting from lack of restriction has been reported in long-term follow-up studies. Shulman et al1 in this study determine the safety and effectiveness of reestablishing the restrictive component of the operation by reducing the outlet of the gastrojejunal anastomosis using an endoscopic approach.

https://ift.tt/2v8tlRB

Focus on...

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Blood urea nitrogen increase is an expected finding in nonvariceal upper GI bleeding patients with underlying moderate or severe renal disease

In a recent article, Kumar et al1 studied the association between increased blood urea nitrogen (BUN) at 24 hours and outcomes in nonvariceal upper GI bleeding in a retrospective study design. The authors speculated that a BUN increase within 24 hours of admission could be a risk factor for worse outcomes, as observed in acute pancreatitis by Wu et al.2 Their study cohort included 357 patients. Of those, 320 (90%) experienced a decrease or no change in BUN, whereas 37 patients (10%) had an increase in BUN at 24 hours after admission.

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Continuing Medical Education Exam: May 2018

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Thoughts of the safety and efficacy of EUS-guided cyst ablation with the use of lauromacrogol

We read with interest the clinical trial by Linghu et al1 investigating the safety and effectiveness of lauromacrogol for EUS-guided ablation of pancreatic cystic neoplasms. The authors reported an adverse event (AE) rate of 8.3% and an overall complete response rate of 37%. They concluded that this approach as safe and efficient. We have a few thoughts, which may be helpful.

https://ift.tt/2EFnS4n

ERCP credentialing approaches in Australia and throughout the world

The recent article about credentialing practitioners of ERCP in United States healthcare facilities states the following: "Other countries have national authorities charged with establishing and also policing the quality of endoscopy."1

https://ift.tt/2JFZF1k

Improving quality of care in patients with Barrett’s esophagus by measuring and improving neoplasia detection rates

The goal of screening and surveillance endoscopy in patients with Barrett's esophagus (BE) is to reduce the rising incidence of esophageal adenocarcinoma (EAC) and ultimately mortality from this lethal cancer.1 However, despite all advances in the field of screening, surveillance, and treatment of BE, we have not made a significant dent in the incidence of this cancer. One potential explanation is the quality gap in the care of patients with BE and dysplasia. Unlike for the management of colonoscopy and colorectal cancer, there are no uniformly agreed-upon quality metrics for the care of BE patients.

https://ift.tt/2EFnOl9

ASGE update

https://ift.tt/2JzHsCR

Contents

https://ift.tt/2JDoYBj

Response

We thank Drs Gaballa and Moyer1 for their interest in our recently published article.2 Their recommendation to use a standardized lexicon for adverse events (AEs) is of great value. The AE rate in our study was 8.3% (3/36). It was revealed that EUS-guided ablation with ethanol with or without paclitaxel injection was fairly safe, with an AE rate of 10% to 15%.3 The advantage of lauromacrogol seemed to be weak compared with ethanol in treatment safety. In our opinion, lauromacrogol may have an advantage over ethanol for its anesthetic effect of relieving pain during and after surgery.

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Editors

https://ift.tt/2JEsj39

Information for readers

https://ift.tt/2v5i2cV

Endoscopic removal of obstructing food bolus: Can a cap do the trick?

Foreign body ingestion and food bolus (FB) impaction are commonly encountered indications for emergency endoscopy in clinical practice.1 Foreign body ingestion is commonly seen in children because of accidental swallowing, whereas FB impaction is more frequent in adults.1 FB impaction in the esophagus is mostly seen in edentulous, psychiatric, or intoxicated patients; the majority have an underlying esophageal motility disorder or a luminal pathologic condition like web, ring, stricture, diverticula, external compression, anastomosis, or eosinophilic esophagitis.

https://ift.tt/2JF6DDN

Response:

We thank Li et al1 for their letter to the editor, insightful comments, and interest in our article "Endoscopic submucosal dissection for early Barrett's neoplasia: a meta-analysis."2 In recent years, there has been an increasing interest in endoscopic submucosal dissection (ESD) for the management of superficial GI neoplasms, given its superiority to EMR in terms of en bloc, curative resection, and recurrence.3 Recent systematic reviews and meta-analyses support a role for ESD in the treatment of esophageal neoplasms.

https://ift.tt/2EEN8Yo

Response:

We thank Dr Köker for his interest in our study, "Association between an increase in blood urea nitrogen at 24 hours and worse outcomes in acute nonvariceal upper GI bleeding."1 In his letter to the editor, the author notes that renal disease is an independent risk factor for upper GI bleeding (UGIB). Given that blood urea nitrogen (BUN) elevations are more likely to be seen in patients with renal disease, the author expresses concern that the findings of our study were driven by the patients with moderate or severe renal disease in our study sample.

https://ift.tt/2JEw0pB

Table of Contents

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Editorial Board

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FDA Expands Indication for Nilotinib [News in Brief]

Tyrosine kinase inhibitor approved for children with chronic myeloid leukemia.

https://ift.tt/2HijzkT

A survey on data reproducibility and the effect of publication process on the ethical reporting of laboratory research

Purpose: The successful translation of laboratory research into effective therapies is dependent upon the validity of peer-reviewed publications. However, several publications in recent years suggested that published scientific findings could only be reproduced 11-45% of the time. Multiple surveys attempted to elucidate the fundamental causes of data irreproducibility and underscored potential solutions; more robust experimental designs, better statistics, and better mentorship. However, no prior survey has addressed the role of the review and publication process on honest reporting. Experimental Design: We developed an anonymous online survey intended for trainees involved in bench research. The survey included questions related to mentoring/career development, research practice, integrity and transparency, and how the pressure to publish, and the publication process itself influence their reporting practices. Results: Responses to questions related to mentoring and training practices were largely positive, although an average of ~25% didn't seem to receive optimal mentoring. 39.2% revealed having been pressured by a principle investigator or collaborator to produce "positive" data. 62.8% admitted that the pressure to publish influences the way they report data. The majority of respondents did not believe that extensive revisions significantly improved the manuscript while adding to the cost and time invested. Conclusions: This survey indicates that trainees believe that the pressure to publish impacts honest reporting, mostly emanating from our system of rewards and advancement. The publication process itself impacts faculty and trainees and appears to influence a shift in their ethics from honest reporting ("negative data") to selective reporting, data falsification, or even fabrication.

https://ift.tt/2INsCrf

Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma

Purpose: Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a Phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. Experimental Design: Patients were given prexasertib 105 mg/m2 as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed. Results: Prexasertib was given to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and neck (SCCHN), and 16 with squamous cell non-small cell lung cancer (sqNSCLC). Patients were heavily pretreated (49% ≥3 prior regimens). The most common treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients had febrile neutropenia. Median progression-free survival was 2.8 months (90% CI 1.9, 4.2) for SCC of the anus, 1.6 months (1.4, 2.8) for SCCHN, and 3.0 months (1.4, 3.9) for sqNSCLC. The clinical benefit rate at 3 months (complete response+partial response+stable disease) across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four patients with SCC of the anus had partial or complete response (overall response rate [ORR]=15%), and three patients with SCCHN had partial response (ORR=5%). Biomarker analyses focused on genes that altered DNA damage response or increased replication stress. Conclusions: Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m² was confirmed as the recommended Phase II dose.

https://ift.tt/2qomBKu

Natural killer cells target and differentiate cancer stem-like cells/undifferentiated tumors: strategies to optimize their growth and expansion for effective cancer immunotherapy

Kawaljit Kaur | Milica Perišic Nanut | Meng-Wei Ko | Tahmineh Safaie | Janko Kos | Anahid Jewett

https://ift.tt/2HuVPb0

FDA Puts New Restrictions on Contraceptive Implant Essure

WEDNESDAY, April 11, 2018 -- To help curb complications tied to the permanent contraceptive implant Essure, the U.S. Food and Drug Administration has placed new restrictions on the sale of the device. A minority of patients receiving the implant...

https://ift.tt/2HfCooU

ZIKV RNA Often ID'd in Semen of Men With Symptomatic Infection

WEDNESDAY, April 11, 2018 -- Zika virus (ZIKV) RNA is frequently present in the semen of men with symptomatic ZIKV infection and can persist for over six months, according to a study published in the April 12 issue of the New England Journal of...

https://ift.tt/2v9cBd6

FDA Approves First Auto-Darken Contact Lenses

WEDNESDAY, April 11, 2018 -- The U.S. Food and Drug Administration has approved the first contact lenses that automatically darken in bright light, the agency said Tuesday in a news release. The technology, used for years in eyeglasses, stems from...

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Later Natural Menopause Can Benefit Future Verbal Memory

WEDNESDAY, April 11, 2018 -- Women who have a later natural menopause maintain a small benefit in verbal memory compared with women with earlier menopause, according to a study published online April 11 in Neurology. Diana Kuh, Ph.D., from...

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Declines Seen in Cardiovascular Risk Factors From 1990 to 2010

WEDNESDAY, April 11, 2018 -- Among adults aged 40 years and older, cardiovascular risk decreased in men from 1990 to 2010 and increased followed by a decrease in women over the same time period, according to a study published online March 22 in...

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Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

Horm Metab Res
DOI: 10.1055/a-0594-2404

In this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Bone Morphogenetic Proteins 2/4 Are Upregulated during the Early Development of Vascular Calcification in Chronic Kidney Disease

Vascular calcification is a main cause of increased cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study aimed to investigate the role of the bone morphogenetic protein (BMP) signaling pathway in the early development of vascular calcification in CKD. A CKD vascular calcification rat model was established by providing rats with a 1.8% high-phosphorus diet and an intragastric administration of 2.5% adenine suspension. The kidney and aortic pathologies were analyzed. Blood biochemical indicators, serum BMP-2 and BMP-4 levels, and aortic calcium content were determined. The expression levels of BMP-2, BMP-4, bone morphogenetic protein receptor-IA (BMPR-IA), and matrix Gla protein (MGP) in aorta were examined by quantitative real-time polymerase chain reaction and immunohistochemistry. Compared with the normal control (Nor) rats, the CKD rats exhibited a significantly decreased body weight and an increased kidney weight as well as abnormal renal function and calcium-phosphorus metabolism. Aortic von Kossa and Alizarin red staining showed massive granular deposition and formation of calcified nodules in aorta at 8 weeks. The aortic calcium content was significantly increased, which was positively correlated with the serum BMP-2 (; ) and serum BMP-4 (; ) levels in CKD rats. The rat aortic BMP-2 mRNA level in the CKD rats was persistently increased, and the BMP-4 mRNA level was prominently increased at the 4th week, declining thereafter. Strong staining of BMP-2, BMP-4, BMPR-IA, and MGP proteins was observed in the tunica media of the aorta from the 4th week after model induction. In conclusion, activation of the BMP signaling pathway is involved in the early development of vascular calcification in CKD. Therefore, elevated serum BMP-2 and BMP-4 levels may serve as serum markers for CKD vascular calcification.

https://ift.tt/2GU7Vt5

Jejunal ectopic pancreas

https://ift.tt/2HtxiD5

Antibody Concentrations Decrease 14-fold in Children With Celiac Disease on a Gluten-free Diet but Remain High at 3 Months

Celiac disease can be identified by a serologic test, for immunoglobulin A (IgA) against tissue transglutaminase (IgA-TTG), in a large proportion of children. However, the increased concentrations of antibody rarely normalize within the months after children are placed on a gluten-free diet (GFD). Early serological predictors of sufficient adherence to gluten-free diet are required for optimal treatment.

https://ift.tt/2GXbU8k

A Rare Cause of Dysphagia – Metastatic Cervical Cancer Causing Esophageal Compression

https://ift.tt/2Htd4t2

Factors Associated With Response to Placebo in Patients With Irritable Bowel Syndrome and Constipation

A high proportion of patients with irritable bowel syndrome (IBS) respond to placebo in clinical trials (estimated at about 40%). We aimed to identify factors that contribute to the high placebo response rate using data from a placebo-controlled trials of patients with IBS.

https://ift.tt/2GU5F54

Reduced Unplanned Care and Disease Activity and Increased Quality of Life After Patient Enrollment in an Inflammatory Bowel Disease Medical Home

Specialty medical homes (SMHs) are a new healthcare model in which a multidisciplinary team and specialists manage patients with chronic diseases. As part of a large integrated payer–provider network, we formed an inflammatory bowel diseases (IBD) SMH and investigated its effects on healthcare use, disease activity, and quality of life (QoL).

https://ift.tt/2HuQ7G6

Lifestyle Factors in Late Adolescence Associate With Later Development of Diverticular Disease Requiring Hospitalization

The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life.

https://ift.tt/2GXbIpC

Efficacy of MaZiRenWan, a Chinese Herbal Medicine, in Patients With Functional Constipation in a Randomized Controlled Trial

The Chinese herbal medicine, MaZiRenWan (MZRW), has been used for more than 2000 years to treat constipation, but it has not been tested in a randomized controlled trial. We performed a trial to evaluate the efficacy and safety of MZRW, compared with the stimulant laxative senna or placebo, for patients with functional constipation (FC).

https://ift.tt/2HrIuA1

Endoscopic management of octopus food bolus lodged within the esophagus

https://ift.tt/2GVmfS5

Fifty years of ERCP: a personal review

https://ift.tt/2v9etCC

Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms

Abstract

Purpose of Review

To review the epidemiology, diagnostic challenges, pathogenesis, and treatment strategies for patients with myeloproliferative neoplasm-associated splanchnic vein thrombosis.

Recent Findings

The epidemiology of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT) has been well characterized. While typical MPN-associated thrombosis affects older patients and involves the arterial circulation, MPN-SVT mostly impacts younger women. An association with JAK2 V617F is well-known; recent studies have demonstrated only a weak association with CALR mutations. JAK inhibition may represent a novel treatment strategy, complementing anticoagulation, and management of portal hypertension.

Summary

While the epidemiology has been well characterized, more work is needed to identify novel contributors to disease pathogenesis, beyond the JAK2 V617F mutation itself, and endothelial compromise. Testing for MPN mutations in the setting of non-cirrhotic SVT is commonplace; JAK2 V617F is the most likely to be identified. Testing for CALR or MPL mutations requires clinical judgement, though not unreasonable. The mainstay of therapy is indefinite anticoagulation; the role of direct oral anticoagulants is unclear. JAK inhibition may play a role in addressing associated splenomegaly and portal hypertension.

https://ift.tt/2qqOQro

The Effect of Targeted Therapies on Prognostic Factors, Patterns of Care and Survival in Patients with Renal Cell Carcinoma and Brain Metastases

Brain metastases are common in renal cell carcinoma. In the era of targeted therapies, outcomes in patients with renal cell carcinoma (RCC) have improved but it is unknown whether outcomes or prognostic factors for RCC patients with brain metastases have changed. This multi-institutional retrospective review refines prognostic factors for these patients and confirms outcomes for RCC patients with brain metastases have improved. These data will be helpful in clinical decision-making and stratification of clinical trials.

https://ift.tt/2GQCILf

Clinical and Dosimetric Factors Predicting Grade ≥2 Radiation Pneumonitis after Postoperative Radiotherapy for Patients with Non-Small Cell Lung Carcinoma

Because no standard dose-volume criteria have been established for predicting radiation pneumonitis after postoperative radiotherapy for patients with non-small cell lung cancer, we retrospectively analyzed clinical and dosimetric factors from 199 such patients and identified V10 >30% and V20 >20% as cutoff points for that risk.

https://ift.tt/2quI443

Longitudinal evaluation of lung function in patients with advanced Non-small cell lung cancer treated with concurrent chemo-radiotherapy

This study prospectively evaluated how concurrent radiotherapy (CCRT), a common therapeutic course for lung cancer, affects pulmonary function tests (PFT) initially, throughout and after treatment. The longitudinal evaluation with PFT efficiently detected early changes in lung function after CCRT-induced damage; these changes are independent of the presence of symptoms. We document the longitudinal evaluation of lung function through PFTs and detected CCRT-induced damage before the appearance of clinical symptoms associated with CCRT lung toxicity.

https://ift.tt/2qqYuu9

Acute epithelial toxicity is prognostic for improved prostate cancer response to radiotherapy: a retrospective multi-centre cohort study

We hypothesised that increased early radiation toxicity, measured using specific subdomains, is associated with improved local control following prostate radiotherapy. We used a discovery cohort to select the specific subdomains of acute GU and GI toxicity most likely to represent epithelial damage, and subsequently confirmed in patients from 2 other institutions that acute toxicity significantly reduces late biochemical failure. This confirms there is a potential genetic link between acute radiation toxicity and cancer outcomes.

https://ift.tt/2qslIzM

Baseline albumin-bilirubin (ALBI) in Western patients with hepatocellular carcinoma treated with stereotactic body radiotherapy (SBRT)

In a prospective series of 102 Western patients with Child Pugh A hepatocellular carcinoma (HCC) managed with stereotactic body radiotherapy (SBRT), the baseline albumin-bilirubin (ALBI) score was evaluated as a predictor of survival and hepatic toxicity. ALBI was an independent significant predictor of toxicity and survival, and was more discriminating than Child Pugh score. Thus, ALBI warrants further investigation and should be included as a factor for stratification in future clinical trials.

https://ift.tt/2GQqna6

A Randomized Phase II Trial of Consolidation Chemotherapy after Preoperative Chemoradiation versus Chemoradiation alone for Locally Advanced Rectal Cancer: KCSG CO 14-03

Preoperative chemoradiation followed by 6-8 weeks of rest until total mesorectal excision is the standard of care in locally advanced rectal cancer. This randomized phase II study suggested pathologic downstaging could be marginally improved with consolidation chemotherapy after preoperative chemoradiation before total mesorectal excision.

https://ift.tt/2GQCN1v

Radiotherapy Quality Assurance (RTQA) of Concurrent Chemoradiotherapy for Locally Advanced Non–Small Cell Lung Cancer in the PROCLAIM Phase 3 Trial

Results from PROCLAIM study, the largest global randomized study using RTQA in Stage III NSCLC, showed poorer outcomes at centers with multiple major violations. Those findings are hypothesis-generating and support the importance of real-time RTQA in future randomized trials. Real-time RTQA can play an important role in improving overall RT quality for patients entered and treated on studies.

https://ift.tt/2GSGCn7

Genetic Testing in Clinical Settings

Genetic testing is used for screening, diagnosis, and prognosis of diseases consistent with a genetic cause and to guide drug therapy to improve drug efficacy and avoid adverse effects (pharmacogenomics). This In Practice review aims to inform about DNA-related genetic test availability, interpretation, and recommended clinical actions based on results using evidence from clinical guidelines, when available. We discuss challenges that limit the widespread use of genetic information in the clinical care setting, including a small number of actionable genetic variants with strong evidence of clinical validity and utility, and the need for improving the health literacy of health care providers and the public, including for direct-to-consumer tests.

https://ift.tt/2v25q6m

Dietary Management of Hyperphosphatemia

In their article, St. Peter et al1 provide an excellent analysis of the high cost of phosphate binders in patients with chronic kidney disease despite the lack of conclusive evidence supporting improvement in important clinical end points. Exceeding $1.5 billion in 2015 for Medicare Part D, the high cost of phosphate binders reinforces the need to explore alternate cost-effective ways to reduce serum phosphate levels. As alluded to by the authors, this is especially relevant because many patients are nonadherent to phosphate-binder treatment, with a systematic review suggesting that 52.5% of hemodialysis patients were nonadherent to phosphate-binder treatment, with those with larger pill burdens having higher rates of nonadherence.

https://ift.tt/2qqyQGs

Influence of Percutaneous Endoscopic Gastrostomy on Gastroesophageal Reflux Disease in Children

To determine if gastroesophageal reflux disease (GERD) is present at long-term follow-up after percutaneous endoscopic gastrostomy (PEG), and to identify factors associated with the occurrence or aggravation of GERD after PEG placement.

https://ift.tt/2v5WYD9

Non-Nutritive Sweeteners and Metabolic Health Outcomes in Children: A Systematic Review and Meta-Analysis

To systematically assess and quantitatively synthesize the literature regarding the association of consumption of non-nutritive sweeteners (NNS) during childhood with negative metabolic health outcomes.

https://ift.tt/2qnNPAW

Applicability of the Curaçao Criteria for the Diagnosis of Hereditary Hemorrhagic Telangiectasia in the Pediatric Population

To evaluate the accuracy of the clinical Curaçao criteria in the diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and adolescents.

https://ift.tt/2v5WVar

Comparison of the Severity of Respiratory Disease in Children Testing Positive for Enterovirus D68 and Human Rhinovirus

To compare the characteristics and severity of respiratory disease in children testing positive for enterovirus D68 (EV-D68) and for human rhinovirus (RhV).

https://ift.tt/2H9tSYz

More Thoughts on Standards and Reproducibility

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 85-86, April 2018.


https://ift.tt/2v3cGz6

Effects of Repeated Aurora-A siRNA Transfection on Cilia Generation and Proliferation of SK-MES-1 or A549 Cells

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 110-117, April 2018.


https://ift.tt/2HijVbm

CLR 125 Auger Electrons for the Targeted Radiotherapy of Triple-Negative Breast Cancer

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 87-95, April 2018.


https://ift.tt/2EE2k80

MiR-17 Regulates Prostate Cancer Cell Proliferation and Apoptosis Through Inhibiting JAK-STAT3 Signaling Pathway

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 103-109, April 2018.


https://ift.tt/2qoHSEa

Constructing a Novel Hypoxia-Inducible Bidirectional shRNA Expression Vector for Simultaneous Gene Silencing in Colorectal Cancer Gene Therapy

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 118-123, April 2018.


https://ift.tt/2v4wHVI

An Alternative Approach to Study Primary Events in Neurodegeneration Using Ex Vivo Rat Brain Slices

We present a method which can provide further insights into the early events underlying neurodegeneration and based on the established ex-vivo brain technique, combining the advantages of in vivo and in vitro experiments. Moreover, it represents a unique opportunity for direct comparison of treated and untreated group in the same anatomical plane.

https://ift.tt/2JFTmLw

Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study

Here we describe a method to generate three-dimensional spheroid cultures of human nasal epithelial cells. Spheroids are then stimulated to drive Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-dependent ion and fluid secretion, quantifying the change in the spheroid luminal size as a proxy for CFTR function.

https://ift.tt/2JBiNh6

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

Radiation therapy is a highly complex cancer treatment that requires multiple specialists to create a treatment plan and provide quality assurance (QA) prior to delivery to a patient. This protocol describes the use of a fully automated system, the Radiation Planning Assistant (RPA), to create high-quality radiation treatment plans.

https://ift.tt/2HcBtW3

A Protocol for Laboratory Housing of Turquoise Killifish (Nothobranchius furzeri)

Laboratory housing of turquoise killifish can be scaled up to house and efficiently raise thousands of individual fish in a centralized water filtration system, employing the same infrastructure used for standard zebrafish facilities. Here we detail a list of standardized procedures that allow efficient killifish maintenance.

https://ift.tt/2vbjsmo

Sleep Deficiency Leads to Higher Number of Motor Vehicle Crashes

WEDNESDAY, April 11, 2018 -- Sleep deficiency due to sleep apnea or sleep duration less than seven hours is associated with motor vehicle crashes independent of self-reported excessive sleepiness, according to a study published online March 20 in...

https://ift.tt/2v1BHui

Smoke Exposure Tied to Higher CV, Cerebrovascular ER Visits

WEDNESDAY, April 11, 2018 -- For all adults, and especially for those older than 65 years, smoke exposure is associated with cardiovascular and cerebrovascular emergency department visits, according to a study published online April 11 in the...

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Civilian Prehospital Tourniquets Linked to Reduction in Mortality

WEDNESDAY, April 11, 2018 -- Civilian prehospital tourniquet application is associated with a six-fold mortality reduction in patients with peripheral vascular injuries, according to a study published in the Journal of the American College of...

https://ift.tt/2ECNq2b

Guidance Offered for Improving Mental Health in Workplace

WEDNESDAY, April 11, 2018 -- Four recommendations for action have been developed for improving mental health in the workplace; the guidance forms the basis for an article published online in the April issue of the Journal of Occupational and...

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Odds of Prescribing Drugs Up With Doc Receipt of Payments

WEDNESDAY, April 11, 2018 -- Physicians receiving general payments from pharmaceutical companies are more likely to prescribe their drugs, according to a research letter published online April 9 in JAMA Internal Medicine. Aaron P. Mitchell, M.D.,...

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About Half of Pregnant Women With HIV Have C-Sections

WEDNESDAY, April 11, 2018 -- About half of pregnant women with HIV infection underwent cesarean delivery between 1998 and 2013, according to a study published online April 6 in Obstetrics & Gynecology. Kartik K. Venkatesh, M.D., Ph.D., from the...

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Caffeine Therapy for Apnea of Prematurity Safe Over Long Term

WEDNESDAY, April 11, 2018 -- Neonatal caffeine therapy for apnea of prematurity has no detrimental long-term effects and even improves some neurologic measures, according to a study published online April 11 in Pediatrics. Ines M. Mrner-Lavanchy,...

https://ift.tt/2vbGdX4

No Reduced CVD Risk for SBP <120 mm Hg in Type 2 Diabetes

WEDNESDAY, April 11, 2018 -- For patients with type 2 diabetes mellitus (T2DM), there is no reduction in cardiovascular disease (CVD) risk with achieved systolic blood pressure (SBP) of <120 mm Hg versus <130 or <140 mm Hg, according to a...

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Chemo, Immunotherapy Feasible in Metastatic Bladder Cancer

WEDNESDAY, April 11, 2018 -- Gemcitabine and cisplatin (GC) plus ipilimumab is associated with a 69 percent objective response rate and 61 percent one-year overall survival for patients with metastatic urothelial cancer, according to a study...

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TBI Associated With Increased Risk of Subsequent Dementia

WEDNESDAY, April 11, 2018 -- Traumatic brain injury (TBI) is associated with increased risk of dementia, according to a study published online April 10 in The Lancet Psychiatry. Jesse R. Fann, M.D., from the University of Washington in Seattle, and...

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Regulation of Nociceptive Glutamatergic Signaling by Presynaptic Kv3.4 Channels in the Rat Spinal Dorsal Horn

Presynaptic voltage-gated K⁺ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. Furthermore, Kv3.4 dysfunction is implicated in the pathophysiology of neuropathic pain in multiple pain models. We hypothesized that, through their ability to modulate AP repolarization, Kv3.4 channels in DRG nociceptors help to regulate nociceptive synaptic transmission. To test this hypothesis, we investigated Kv3.4 immunoreactivity (IR) in the rat cervical superficial dorsal horn (sDH) in both sexes and implemented an intact spinal cord preparation to investigate glutamatergic synaptic currents from second order neurons in the sDH under conditions that selectively inhibit the Kv3.4 current. We found presynaptic Kv3.4 IR in peptidergic and nonpeptidergic nociceptive fibers of the sDH. The Kv3.4 channel is hypersensitive to 4-aminopyridine and tetraethylammonium (TEA). Accordingly, 50 μm 4-aminopyridine and 500 μm TEA significantly prolong the AP, slow the maximum rate of repolarization in small-diameter DRG neurons, and potentiate monosynaptic excitatory postsynaptic currents (EPSCs) in dorsal horn laminae I and II through a presynaptic mechanism. In contrast, highly specific inhibitors of BK, Kv7, and Kv1 channels are less effective modulators of the AP and have little to no effect on EPSCs. The results strongly suggest that presynaptic Kv3.4 channels are major regulators of nociceptive synaptic transmission in the spinal cord.

SIGNIFICANCE STATEMENT Intractable neuropathic pain can result from disease or traumatic injury and many studies have been conducted to determine the underlying pathophysiological changes. Voltage-gated ion channels, including the K⁺ channel Kv3.4, are dysregulated in multiple pain models. Kv3.4 channels are ubiquitously expressed in the dorsal root ganglion (DRG), where they are major regulators of DRG excitability. However, little is known about the ionic mechanisms that regulate nociceptive synaptic transmission at the level of the first synapse in the spinal cord, which is critical to pain transmission in both intact and pathological states. Here, we show that Kv3.4 channels have a significant impact on glutamatergic synaptic transmission in the dorsal horn, further illuminating its potential as a molecular pain therapeutic target.

https://ift.tt/2Hsn1Ha

The Role of the Mechanotransduction Ion Channel Candidate Nanchung-Inactive in Auditory Transduction in an Insect Ear

Insect auditory receivers provide an excellent comparative resource to understand general principles of auditory transduction, but analysis of the electrophysiological properties of the auditory neurons has been hampered by their tiny size and inaccessibility. Here we pioneer patch-clamp recordings from the auditory neurons of Müller's organ of the desert locust Schistocerca gregaria to characterize dendritic spikes, axonal spikes, and the transduction current. We demonstrate that dendritic spikes, elicited by sound stimuli, trigger axonal spikes, and that both types are sodium and voltage dependent and blocked by TTX. Spontaneous discrete depolarizations summate upon acoustic stimulation to produce a graded transduction potential that in turn elicits the dendritic spikes. The transduction current of Group III neurons of Müller's organ, which are broadly tuned to 3 kHz, is blocked by three ion channel blockers (FM1-43, streptomycin, and 2-APB) that are known to block mechanotransduction channels. We investigated the contribution of the candidate mechanotransduction ion channel Nanchung-Inactive—which is expressed in Müller's organ—to the transduction current. A specific agonist of Nanchung-Inactive, pymetrozine, eliminates the sound-evoked transduction current while inducing a tonic depolarizing current of comparable amplitude. The Nanchung-Inactive ion channels, therefore, have the required conductance to carry the entire transduction current, and sound stimulation appears not to open any additional channels. The application of three mechanotransduction ion channel blockers prevented the pymetrozine-induced depolarizing current. This implies that either Nanchung-Inactive is, or forms part of, the mechanotransduction ion channel or it amplifies a relatively small current (<30 pA) produced by another mechanotransduction ion channel such as NompC.

SIGNIFICANCE STATEMENT The mechanically activated ion channel underpinning hearing is not known. We have pioneered intracellular patch-clamp recordings from locust auditory neurons to unravel the role of the candidate mechanotransduction ion channel Nanchung-Inactive in auditory transduction in insects.

https://ift.tt/2INjXVz

JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JNK-interacting protein 1 (JIP1) scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDAR currents, increased NMDAR-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDAR-mediated synaptic plasticity and learning.

SIGNIFICANCE STATEMENT The results of this study demonstrate that c-Jun N-terminal kinase (JNK) activation induced by the JNK-interacting protein 1 (JIP1) scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study identifies JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDAR-dependent synaptic plasticity and memory.

https://ift.tt/2ILIBpC

Odynophagia and neck pain after exercise

Description

A previously healthy, non-asthmatic, non-smoker, 16-year-old male came for medical attention because of odynophagia and pain located at anterior cervical area and upper retrosternal area, increasing with swallowing and deep breathing, that begun after physical exercise at gymnastic class. The adolescent also mentioned a felling of air bubbles running up and down that area. There was no history of local trauma. He referred stuffed nose and mild cough but no other respiratory complaints or fever. Physical examination was unremarkable, with normal auscultation and no alterations on cervical and thoracic examination. Lateral soft tissue neck X-ray revealed free air in retropharyngeal space (figure 1, arrows). Chest X-ray showed a small amount of air in the upper mediastinum. Blood count was normal, and C reactive protein was negative. Mycoplasma pneumoniae IgM was negative. The patient was treated with high concentration oxygen and oral analgesia. The next day, he...

https://ift.tt/2JCb0j9

Food-dependent exercise-induced anaphylaxis

Food-dependent exercise-induced anaphylaxis (FDEIAn), first reported in 1979, is a condition defined by the consumption of a trigger food with temporally related exercise that results in an immediate hypersensitivity (type 1) reaction in the setting of the trigger food being tolerated independent of exercise and exercise being tolerated in the absence of trigger food consumption. The most common trigger food in the west is wheat and shellfish in Asia. The exact mechanism of FDEIAn is unknown, though several hypotheses exist. Cofactors such as non-steroidal anti-inflammatory drug use, alcohol consumption and others have been associated with reported cases.

https://ift.tt/2GSFvQ1

Inadvertent inflation of Foley catheter balloon with contrast: an error that caused unnecessary apprehensions

Description 

A 30-year-old male patient underwent percutaneous nephrolithotomy (PCNL) for a 3.5 cm right renal calculus. As per our institutional protocol he underwent a check X-ray the next day. The relatives of the patient immediately came to us asking whether some residual fragments of the calculus were there in the urinary bladder. When we reviewed the X-ray film, there was a radio-opaque shadow with a smooth contour in the region of urinary bladder. On careful examination this shadow was continuous with a radio-opaque line along the Foley catheter (figure 1). We immediately removed the Foley catheter and did another check X-ray. The shadow had disappeared. We then realised that the catheter's balloon was inflated with contrast solution prepared for fluoroscopy-guided puncture during PCNL. We acknowledged this error to the patient and his relatives and explained them how sorry we were for their anxiety, following which they were...

https://ift.tt/2JCaXDZ

Arthroscopic reduction and fixation of a lateral inverted osteochondral fracture of the talus ('LIFT)

Some ankle sprains hide important lesions beyond the classic lateral ligament complex injuries. The lateral inverted osteochondral fracture of the talus (LIFT) represents a rare osteochondral lesion, whose diagnosis relies on a high clinical suspicion followed by correct image study interpretation. We present a successful arthroscopic fixation of a LIFT lesion in a 45-year-old active man. At 8 months follow-up, the patient was pain free and able to return to his daily activities without limitation. The imagiological study showed osteochondral fragment consolidation with no signs of hardware failure. This midterm results reassemble the need for early diagnosis and correct treatment to achieve a good outcome in these complex and rare osteochondral lesions.

https://ift.tt/2GUqDRr

Rare and unexpected complication after a malpositioned nasogastric tube in a neonate

Description

A full-term newborn boy was admitted to the high dependency unit at the age of 4 hours with signs of respiratory distress, tachypnoea and recession with low oxygen saturation. There was no perinatal history of concerns; delivery was normal and uneventful, but the mother was colonised with Group B streptococcus.

A plan was made on admission for a chest X-ray, a nasogastric tube (NGT) insertion and antibiotics. NGT was placed by a senior neonatal nurse without incident, followed by chest X-ray primarily looking for respiratory causes of the respiratory distress. This however revealed that the NGT was malposed into the right main bronchus (figure 1). There were no signs of choking or cough at the time of insertion. NGT was then pulled out and a new one reinserted in a satisfactory position and confirmed on a repeat chest X-ray (figure 2). A right-sided small and...

https://ift.tt/2Jysmxr

Orbital metastasis from an occult breast carcinoma (T0, N1, M1)

The authors report a case of an orbital metastasis from an occult breast carcinoma. A 66-year-old woman presented with a growing left orbital tumour. Orbital CT scan was consistent with lymphoma. However, ocular pathology revealed small neoplastic cells showing an 'indian file pattern' suggestive of metastatic carcinoma and immunohistochemistry was positive for CK7, CK CAM5.2 and oestrogen receptor. A systemic evaluation was then performed with mammogram, breast ultrasound and MRI considered normal. An exhaustive systemic evaluation revealed multiple bone lesions, a right axillary lymph node lesion, which presented the same pattern on pathology and immunohistochemistry, with no evidence of a primary tumour. A diagnosis of a metastatic lobular carcinoma of the breast (T0, N1, M1) was made and the patient was started on chemotherapy and adjuvant hormonal therapy.

https://ift.tt/2GPNEVr

Treatment-refractory ALK-positive inflammatory myofibroblastic tumour of the oral cavity

We present a challenging case of a previously healthy 23-year-old man who developed an inflammatory myofibroblastic tumour of the hard palate, harbouring a rearrangement of the anaplastic lymphoma kinase (ALK) locus. Despite surgical intervention, radiotherapy and ALK-inhibition therapy, the tumour recurred locally and metastasised to regional lymph nodes, and the patient passed away roughly 9 months after diagnosis from local progression. The rapid progression of this patient's disease and its resistance to treatment demonstrate the potentially aggressive clinical course of inflammatory myofibroblastic tumours. ALK-inhibition therapy was unsuccessful in this ALK-positive tumour, highlighting the need for further investigation of markers predictive of disease progression and treatment response.

https://ift.tt/2JCaO3p

Sphingomonas paucimobilis empyema caused by remote foreign body aspiration

Empyema secondary to foreign body aspiration is rare in adults. We present a case of empyema in a 77-year-old male patient related to a remote aspiration event during a dental procedure. A CT of the chest and bronchoscopy confirmed that a metallic foreign body was located within the right lower lobe bronchus. His pleural fluid culture revealed Sphingomonas paucimobilis which is a low-virulent opportunistic gram-negative bacilli and rarely causes infection. The patient received meropenem followed by levofloxacin and recovered uneventfully. The attempt of foreign body removal was failed due to chronic inflammation, and the patient refused further surgical management.

https://ift.tt/2EEzXGZ

Peripherally inserted central catheter (PICC) placement: beware of the bends

Description 

The peripherally inserted central catheter (PICC) is used as a long-term vascular access to deliver medications and venous nutrition. The PICC tip terminates close to the heart or in one of the great vessels—the superior vena cava or the inferior vena cava. Catheter tip confirmation is usually achieved by plain radiography. We describe a case of a 9-month-old boy with complex congenital heart disease (heterotaxy syndrome, polysplenia type) who underwent pulmonary artery banding to reduce pulmonary blood flow to control heart failure symptoms. PICC was placed in the left femoral vein during the postoperative period. PICC tip confirmation was obtained by anteroposterior plain abdominal radiograph (figure 1), which demonstrated catheter tip bending at T12. The lateral radiograph of the abdomen showed that the PICC courses posteriorly into the lumbar venous plexus (figure 2). The ascending lumbar veins arises at L5–S1 from the common iliac vein and drains into...

https://ift.tt/2JBkM50

Improvement of thoracic myelopathy following bariatric surgery in an obese patient

Revision spine surgery is extremely challenging in super-super obese patients (body mass index (BMI) ≥60 kg/m²). This is the first report describing how bariatric surgery was useful for a super-super obese patient with progressing myelopathy. A 44-year-old man with a BMI of 62.9 kg/m² presented with an ambulatory disorder caused by thoracic ossification of the posterior longitudinal ligament (T7–8). Before this paraparesis, he had undergone four spinal operations, and was not considered a good candidate for a fifth spine surgery. At the time of the fourth operation, he had reached a maximum weight of 205 kg (BMI 69.3 kg/m²). Instead, he underwent a laparoscopic sleeve gastrectomy. Sixteen months later, his body weight had decreased to BMI 35.2 kg/m², and he could walk without a walker. In addition to reducing our patient's load, a 'non-operative' form of dekyphosis due to altered thoracic spinal alignment secondary to weight loss may explain the improvement in his myelopathy.

https://ift.tt/2EEzVyR

Spontaneous rectus sheath haematoma due to cough on apixaban

Description 

A 69-year-old woman on apixaban for 4 years due to her atrial fibrillation presented with severe left lower abdominal pain. She was discharged from the hospital 4 days prior after treatment for influenza and had finished a course of oseltamivir. She did not receive any heparin products and was continued on apixaban during that admission. A few hours before presentation, she reported coughing severely with sudden onset of excruciating abdominal pain. She denied trauma or injury to the abdomen. On exam, she was alert, normotensive and tachycardic, with significant left lower quadrant tenderness in the abdomen. Laboratory results were significant for decreased haemoglobin from 15.2 to 12.9 g/dL. CT of the abdomen showed acute left inferior rectus abdominis muscle haematoma (7.5 cm), along with stable and unchanged left adnexal cystic lesion (figure 1). Apixaban was discontinued, and the patient was closely monitored in the hospital with supportive care....

https://ift.tt/2JBkL0W

Pseudoaneurysm of the gastroduodenal artery: an unusual cause for hyperamylasaemia

A 79-year-old man was admitted electively for investigation of weight loss. While he was an inpatient, he developed severe epigastric pain and an initial blood test revealed an acutely raised amylase (>2000) and deranged liver function tests. A contrast CT angiography showed a large haematoma adjacent to the duodenum, spreading in the retroperitoneal space, arising from a 2 cm bleeding pseudoaneurysm in the region of the gastroduodenal artery. Due to his underlying comorbidities, he was deemed unfit for surgical repair and he had coil embolisation with successful haemostasis. The gastroduodenal artery aneurysms are rare and constitute 1.5% of all visceral artery aneurysms. They can be an incidental finding or they can present with haemorrhagic shock, abdominal pain and rarely with obstructive jaundice or hyperamylasaemia. The diagnosis is usually made with an angiography. Variable treatment options are available depending on the patient's fitness and haemodynamic stability.

https://ift.tt/2EDTvLA

Single coronary artery with bicuspid aortic valve

Description

A 45-year-old man with known history of coronary artery disease and bicuspid aortic valve (BAV) (figure 1) was admitted for worsening symptoms of angina. Coronary angiogram showed single coronary artery arising from the left cusp, trifurcating into right coronary artery, left anterior descending (LAD) and left circumflex artery (LCx) (figure 2). No course of the left main coronary artery between the aortic root and the pulmonary artery was noted. There was obstructive disease in proximal LAD (70%), first diagonal artery (80%) and proximal LCx (70%). Peak gradient of 51 mm Hg across the BAV was registered. He underwent bypass graft surgery along with an aortic valve replacement successfully.

Figure 1

Transoesophageal echocardiogram. Parasternal short axis view revealing bicuspid aortic valve (BAV). Red arrows pointing at aortic valve cusps.

Figure 2

(A) Left anterior oblique (LAO) caudal view....

https://ift.tt/2JzfS8B

Development of Recombinant Proteins to Treat Chronic Pain

In this paper we provide details for the methods of production and quality control of an IL4-10 recombinant fusion protein. We also show how to test the effectiveness of this protein to resolve pain in a mouse model of inflammatory pain.

https://ift.tt/2INI8D9

Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma

The following protocol focuses on the establishment of a primary culture of patient-derived soft tissue sarcoma (STS). This model could help us to better understand the molecular background and pharmacological profile of these rare malignancies and could represent a starting point for further research aimed at improving STS management.

https://ift.tt/2qo9Fo3

Functional MRI Responses to Passive, Active, and Observed Touch in Somatosensory and Insular Cortices of the Macaque Monkey

Neurophysiological data obtained in primates suggests that merely observing others' actions can modulate activity in the observer's motor cortices. In humans, it has been suggested that these multimodal vicarious responses extend well beyond the motor cortices, including somatosensory and insular brain regions, which seem to yield vicarious responses when witnessing others' actions, sensations, or emotions (Gazzola and Keysers, 2009). Despite the wealth of data with respect to shared action responses in the monkey motor system, whether the somatosensory and insular cortices also yield vicarious responses during observation of touch remains largely unknown. Using independent tactile and motor fMRI localizers, we first mapped the hand representations of two male monkeys' primary (SI) and secondary (SII) somatosensory cortices. In two subsequent visual experiments, we examined fMRI brain responses to (1) observing a conspecific's hand being touched or (2) observing a human hand grasping or mere touching an object or another human hand. Whereas functionally defined "tactile SI" and "tactile SII" showed little involvement in representing observed touch, vicarious responses for touch were found in parietal area PFG, consistent with recent observations in humans (Chan and Baker, 2015). Interestingly, a more anterior portion of SII, and posterior insular cortex, both of which responded when monkeys performed active grasping movements, also yielded visual responses during different instances of touch observation.

SIGNIFICANCE STATEMENT Common coding of one's own and others' actions, sensations, and emotions seems to be widespread in the brain. Although it is currently unclear to what extent human somatosensory cortices yield vicarious responses when observing touch, even less is known about the presence of similar vicarious responses in monkey somatosensory cortex. We therefore localized monkey somatosensory hand representations using fMRI and investigated whether these regions yield vicarious responses while observing various instances of touch. Whereas "tactile SI and SII" did not elicit responses during touch observation, a more anterior portion of SII, in addition to area PFG and posterior insular cortex, all of which responded during monkeys' own grasping movements, yielded vicarious responses during observed touch.

https://ift.tt/2HtWiu2

Bilateral Tactile Input Patterns Decoded at Comparable Levels But Different Time Scales in Neocortical Neurons

The presence of contralateral tactile input can profoundly affect ipsilateral tactile perception, and unilateral stroke in somatosensory areas can result in bilateral tactile deficits, suggesting that bilateral tactile integration is an important part of brain function. Although previous studies have shown that bilateral tactile inputs exist and that there are neural interactions between inputs from the two sides, no previous study explored to what extent the local neuronal circuitry processing contains detailed information about the nature of the tactile input from the two sides. To address this question, we used a recently introduced approach to deliver a set of electrical, reproducible, tactile afferent, spatiotemporal activation patterns, which permits a high-resolution analysis of the neuronal decoding capacity, to the skin of the second forepaw digits of the anesthetized male rat. Surprisingly, we found that individual neurons of the primary somatosensory can decode contralateral and ipsilateral input patterns to comparable extents. Although the contralateral input was stronger and more rapidly decoded, given sufficient poststimulus processing time, ipsilateral decoding levels essentially caught up to contralateral levels. Moreover, there was a weak but significant correlation for neurons with high decoding performance for contralateral tactile input to also perform well on decoding ipsilateral input. Our findings shed new light on the brain mechanisms underlying bimanual haptic integration.

SIGNIFICANCE STATEMENT Here we demonstrate that the spiking activity of single neocortical neurons in the somatosensory cortex of the rat can be used to decode patterned tactile stimuli delivered to the distal ventral skin of the second forepaw digits on both sides of the body. Even though comparable levels of decoding of the tactile input were achieved faster for contralateral input, given sufficient integration time each neuron was found to decode ipsilateral input with a comparable level of accuracy. Given that the neocortical neurons could decode ipsilateral inputs with such small differences between the patterns suggests that S1 cortex has access to very precise information about ipsilateral events. The findings shed new light on possible network mechanisms underlying bimanual haptic processing.

https://ift.tt/2HtWMQS

Convergence and Divergence of CRH Amacrine Cells in Mouse Retinal Circuitry

Inhibitory interneurons sculpt the outputs of excitatory circuits to expand the dynamic range of information processing. In mammalian retina, >30 types of amacrine cells provide lateral inhibition to vertical, excitatory bipolar cell circuits, but functional roles for only a few amacrine cells are well established. Here, we elucidate the function of corticotropin-releasing hormone (CRH)-expressing amacrine cells labeled in Cre-transgenic mice of either sex. CRH cells costratify with the ON alpha ganglion cell, a neuron highly sensitive to positive contrast. Electrophysiological and optogenetic analyses demonstrate that two CRH types (CRH-1 and CRH-3) make GABAergic synapses with ON alpha cells. CRH-1 cells signal via graded membrane potential changes, whereas CRH-3 cells fire action potentials. Both types show sustained ON-type responses to positive contrast over a range of stimulus conditions. Optogenetic control of transmission at CRH-1 synapses demonstrates that these synapses are tuned to low temporal frequencies, maintaining GABA release during fast hyperpolarizations during brief periods of negative contrast. CRH amacrine cell output is suppressed by prolonged negative contrast, when ON alpha ganglion cells continue to receive inhibitory input from converging OFF-pathway amacrine cells; the converging ON- and OFF-pathway inhibition balances tonic excitatory drive to ON alpha cells. Previously, it was demonstrated that CRH-1 cells inhibit firing by suppressed-by-contrast (SbC) ganglion cells during positive contrast. Therefore, divergent outputs of CRH-1 cells inhibit two ganglion cell types with opposite responses to positive contrast. The opposing responses of ON alpha and SbC ganglion cells are explained by differing excitation/inhibition balance in the two circuits.

SIGNIFICANCE STATEMENT A goal of neuroscience research is to explain the function of neural circuits at the level of specific cell types. Here, we studied the function of specific types of inhibitory interneurons, corticotropin-releasing hormone (CRH) amacrine cells, in the mouse retina. Genetic tools were used to identify and manipulate CRH cells, which make GABAergic synapses with a well studied ganglion cell type, the ON alpha cell. CRH cells converge with other types of amacrine cells to tonically inhibit ON alpha cells and balance their high level of excitation. CRH cells diverge to different types of ganglion cell, the unique properties of which depend on their balance of excitation and inhibition.

https://ift.tt/2HwCOF6

ACC to Dorsal Medial Striatum Inputs Modulate Histaminergic Itch Sensation

Itch is an unpleasant sensation that initiates scratching behavior. The itch–scratch reaction is a complex phenomenon that implicates supraspinal structures required for regulation of sensory, emotional, cognitive, and motivational aspects. However, the central mechanisms underlying the processing of itch and the interplay of the supraspinal regions and spinal cord in regulating itch–scratch processes are poorly understood. Here, we have shown that the neural projections from anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) constitute a critical circuit element for regulating itch-related behaviors in the brains of male C57BL/6J mice. Moreover, we demonstrate that ACC-DMS projections selectively modulate histaminergic, but not nonhistaminergic, itch-related behavior. Furthermore, photoactivation of ACC-DMS projections has also no significant effects on pain behavior induced by thermal, mechanical, and chemical stimuli except for a relief on inflammatory pain evoked by formalin and complete Freund's adjuvant. We further demonstrate that the dorsal spinal cord exerts an inhibitory effect on itch signal from ACC-DMS projections through B5-I neurons, which represent a population of spinal inhibitory interneurons that mediate the inhibition of itch. Therefore, this study presents the first evidence that the ACC-DMS projections modulate histaminergic itch-related behavior and reveals an interplay between the supraspinal and spinal levels in histaminergic itch regulation.

SIGNIFICANCE STATEMENT This study reveals that the projections from anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) constitute a supraspinal circuit for modulation of histaminergic, but not nonhistaminergic, itch. Manipulation of ACC-DMS projections has no effect on acute pain sensation. Furthermore, the dorsal spinal cord exerts an inhibitory effect on itch signal from ACC-DMS projections through B5-I neurons. Understanding the supraspinal itch circuits is of great significance in the development of new therapies for chronic itch-related intractable diseases.

https://ift.tt/2Ht3MNF

Deletion of the Cold Thermoreceptor TRPM8 Increases Heat Loss and Food Intake Leading to Reduced Body Temperature and Obesity in Mice

The coupling of energy homeostasis to thermoregulation is essential to maintain homeothermy in changing external environments. We studied the role of the cold thermoreceptor TRPM8 in this interplay in mice of both sexes. We demonstrate that TRPM8 is required for a precise thermoregulation in response to cold, in fed and fasting. Trpm8^–/– mice exhibited a fall of 0.7°C in core body temperature when housed at cold temperatures, and a deep hypothermia (<30°C) during food deprivation. In both situations, TRPM8 deficiency induced an increase in tail heat loss. This, together with the presence of TRPM8-sensory fibers innervating the main tail vessels, unveils a major role of this ion channel in tail vasomotor regulation. Finally, TRPM8 deficiency had a remarkable impact on energy balance. Trpm8^–/– mice raised at mild cold temperatures developed late-onset obesity and metabolic dysfunction, with daytime hyperphagia and reduction of fat oxidation as plausible causal factors. In conclusion, TRPM8 fine-tunes eating behavior and fuel utilization during thermoregulatory adjustments to mild cold. Persistent imbalances in these responses result in obesity.

SIGNIFICANCE STATEMENT The thermosensitive ion channel TRPM8 is required for a precise thermoregulatory response to cold and fasting, playing an important role in tail vasoconstriction, and therefore heat conservation, as well as in the regulation of ingestive behavior and metabolic fuel selection upon cooling. Indeed, TRPM8-deficient mice, housed in a mild cold environment, displayed an increase in tail heat loss and lower core body temperature, associated with the development of late-onset obesity with glucose and lipid metabolic dysfunction. A persistent diurnal hyperphagia and reduced fat oxidation constitute plausible underlying mechanisms in the background of a deficient thermoregulatory adjustment to mild cold ambient temperatures.

https://ift.tt/2IMV2BJ

Imaging of urgencies and emergencies in the lung cancer patient

Abstract

Lung cancer patients often experience potentially life-threatening medical urgencies and emergencies, which may be a direct or indirect result of the underlying malignancy. This pictorial review addresses the most common thoracic, neurological and musculoskeletal medical emergencies in lung cancer patients, including superior vena cava syndrome, pulmonary embolism, spontaneous pneumothorax, cardiac tamponade, massive haemoptysis, central airway obstruction, oesophagorespiratory fistula, malignant spinal cord compression, carcinomatous meningitis, cerebral herniation and pathological fracture. Emphasis is placed on imaging findings, the role of different imaging techniques and a brief discussion of epidemiology, pathophysiology and therapeutic options. Since early diagnosis is important for adequate patient management and prognosis, radiologists have a crucial role in recognising and communicating these urgencies and emergencies.

Teaching points

• Multiplanar multidetector computed tomography is the imaging examination of choice for thoracic urgencies and emergencies.

• Magnetic resonance imaging is the imaging modality of choice for investigating central nervous system emergencies.

• Urgencies and emergencies can be the initial manifestation of lung cancer.

• Radiologists have a crucial role in recognising and in communicating these urgencies/emergencies.

https://ift.tt/2qnLpBR

Redfin R3800-H Full HD Camera Head and Cable

Compatible with

• R3800 Full HD Endoscope Camera System

Features

• Full HD Endoscope Camera Head
• 10ft Cable Included
• Waterproof Design, Fully Soakable
• Includes 22mm Universal Coupler
• Rugged Construction
• Pause and Zoom functions
• Not compatible with 3rd party consoles
  
  

For more information contact sales@fireflyglobal.com

https://ift.tt/2GSPntg

Evaluation of prognostic models developed using standardised image features from different PET automated segmentation methods

Abstract

Background

Prognosis in oesophageal cancer (OC) is poor. The 5-year overall survival (OS) rate is approximately 15%. Personalised medicine is hoped to increase the 5- and 10-year OS rates. Quantitative analysis of PET is gaining substantial interest in prognostic research but requires the accurate definition of the metabolic tumour volume. This study compares prognostic models developed in the same patient cohort using individual PET segmentation algorithms and assesses the impact on patient risk stratification.

Consecutive patients (n = 427) with biopsy-proven OC were included in final analysis. All patients were staged with PET/CT between September 2010 and July 2016. Nine automatic PET segmentation methods were studied. All tumour contours were subjectively analysed for accuracy, and segmentation methods with < 90% accuracy were excluded. Standardised image features were calculated, and a series of prognostic models were developed using identical clinical data. The proportion of patients changing risk classification group were calculated.

Results

Out of nine PET segmentation methods studied, clustering means (KM2), general clustering means (GCM3), adaptive thresholding (AT) and watershed thresholding (WT) methods were included for analysis. Known clinical prognostic factors (age, treatment and staging) were significant in all of the developed prognostic models. AT and KM2 segmentation methods developed identical prognostic models. Patient risk stratification was dependent on the segmentation method used to develop the prognostic model with up to 73 patients (17.1%) changing risk stratification group.

Conclusion

Prognostic models incorporating quantitative image features are dependent on the method used to delineate the primary tumour. This has a subsequent effect on risk stratification, with patients changing groups depending on the image segmentation method used.

https://ift.tt/2GPEts1

Subject-specific Musculoskeletal Model for Studying Bone Strain During Dynamic Motion

During landing, lower-body bones experience large mechanical loads and are deformed. It is essential to measure bone deformation to better understand the mechanisms of bone stress injuries associated with impacts. A novel approach integrating subject-specific musculoskeletal modeling and finite element analysis is used to measure tibial strain during dynamic movements.

https://ift.tt/2GPGnZY

Use of oxidized regenerated cellulose to achieve hemostasis during laparoscopic cholecystectomy: a retrospective cohort analysis

Laparoscopic cholecystectomy is the first-choice treatment for symptomatic cholelithiasis. Though generally safe, this procedure is not without complications, with bleeding the most frequent cause of conversio...

https://ift.tt/2GUVE7t

Absence of flexor carpi radialis identified during volar approach for fixation of distal radius fracture: a case report

Volar locking plate fixation of distal radius fractures is commonly performed because of its good clinical outcomes. The flexor carpi radialis (FCR) approach is one of the most popular approaches to dissecting...

https://ift.tt/2JDv4lo

Intra cavernous aneurysm of internal carotid artery masquerading as a pituitary adenoma: a case report

Pituitary dysfunction in adults are often associated with tumors of the gland and manifests with mass effects and hypopituitarism. MRI of pituitary region often provides confirmation of the diagnosis and assis...

https://ift.tt/2ILI6vQ

Tuberculous tenosynovitis of the flexor tendons of the wrist: a case report

Tuberculous tenosynovitis poses a significant public health challenge, especially in developing countries. It usually affects the flexor tendons of the wrist.

https://ift.tt/2qozm88

Histone deacetylase SIRT6 inhibits glioma cell growth through down-regulating NOTCH3 expression

Abstract

Gliomas are the most common brain tumors of the central nervous system. In this study, we investigated the molecular mechanisms and biological function of SIRT6 in human gliomas. The expression levels of SIRT6 in glioma tissues and cells were analyzed by qRT-PCR and western blot analysis. CCK8 and clonogenicity assays were performed to detect the cell proliferation. Furthermore, the migration and invasion of glioma cells were examined by transwell assays. It was found that the expression of SIRT6 was significantly lower in human glioma tissues or cell lines compared with the normal brain tissue or NHA. Up-regulated SIRT6 significantly decreased cell proliferation, migration and invasion of U87 and U251 cells. By contrast, knockdown of SIRT6 dramatically increased cell proliferation, migration and invasion of U87 and U251 cells. Moreover, over expression of NOTCH3 significantly increased the cell proliferation, migration, and invasion of U87 and U251 cells. However, these effects were abolished after overexpression of SIRT6. These results suggest that SIRT6 may suppress cell proliferation, migration, and invasion via inhibition of the NOTCH3 signaling pathway in glioma.

https://ift.tt/2GU7nTQ

MiR-31 regulates the function of diabetic endothelial progenitor cells by targeting Satb2

Abstract

Endothelial malfunctions in patients with diabetes are known to result in vascular diseases, and endothelial progenitor cells (EPCs) are indispensable for the functional preservation of the vascular endothelium. MicroRNA-31 (miR-31) has been found to be able to modulate the differentiation of stem cells. However, it is still unclear how miR-31 functions in diabetic EPCs. The aim of this study was to investigate how miR-31 regulates diabetic EPC function. In the current study, miR-31 expression was compared between normal and diabetic EPCs. Satb2 was recognized as a functionally related target of miR-31 in EPCs according to computational prediction. We also explored the role of miR-31 in terms of its anti-apoptotic effects. A remarkable elevation in miR-31 expression was found in diabetic EPCs, and this elevated expression resulted in suppressed cell proliferation under high glucose. It was also found that miR-31 targets Satb2, leading to the anti-apoptotic effect and maintenance of the functions of EPCs. Furthermore, knockdown of Satb2 exhibited an inhibitory effect on proliferation and migration of EPCs in both healthy and diabetic subjects, which showed the same trend as miR-31 overexpression. Conversely, overexpression of Satb2 showed the opposite effect. Moreover, overexpression of Satb2 attenuated the miR-31-induced migration and colony-forming ability reduction and apoptosis induction of EPCs in both healthy and diabetic subjects. In diabetic EPCs, elevated glucose level was found to up-regulate miR-31 expression, which in turn enhanced the malfunction and death of EPCs. In conclusion, our results indicate that up-regulation of miR-31 may underlie endothelial dysfunction in diabetes by targeting Satb2.

https://ift.tt/2Hs6KCd

An EGF receptor-targeting amphinase recombinant protein mediates anti-tumor activity in vitro and in vivo

Abstract

Utilizing cytotoxic proteins linked to tumor targeting molecules as anti-tumor drugs is a promising approach. However, most cytotoxins derived from bacteria or plants have inherent problems such as large molecular weights and they trigger a strong immune system reaction, which leads to drug failure and serious side effects. Amphinase (Amph) is a ribonuclease with a low molecular weight that is found in northern leopard frog oocytes. It has strong cytotoxicity against tumor cell lines in vitro and weak immunogenicity in vivo, and is a promising candidate in the development of targeted drugs. Transforming growth factor-α (TGF-α) that binds to the epidermal growth factor receptor (EGFR) is being used as a targeting molecule for the treatment of EGFR high-expressing tumors. In this study, we expressed and purified a recombinant amphinase and its TGF-α fusion protein (AGT) separately from Escherichia coli. AGT exhibited more significant cytotoxicity in vitro on EGFR high-expressing tumor cell lines, and stronger anti-tumor effects in vivo. This fusion protein also exhibited unusual thermostability, low in vivo immunogenicity, and side effects. Our results provide a new entry point for the development of novel, highly efficient anti-tumor targeting biological agents with low immunogenicity.

https://ift.tt/2INbpOt

An ultrasensitive biological probe enhanced RT-IPCR assay for detecting benzo[a]pyrene in environmental samples based on the specific polyclonal antibody

Abstract

Benzo[a]pyrene (BaP), a type of polycyclic aromatic hydrocarbon, is widely distributed in the environment. In this study, BaP immunogen and coating antigen were respectively prepared by different methods, and the specific antibody targeting the BaP analyte was obtained. Moreover, gold nanoparticles modified with the specific polyclonal antibody and thiol-capped DNA were prepared as biological probes. Based on the work above, an ultrasensitive biological probe enhanced real-time immuno-polymerase chain reaction (BP-rt-iPCR) assay was developed to detect BaP in several environmental samples. Under optimal conditions, the proposed method was used to detect BaP with a linearity ranging from 5 pg/l to 50 ng/l. The limit of detection was 1.63 pg/l. The recovery rates of the spiked samples ranged from 92.12% to 109.76% and the coefficients of variation were 7.53%–11.06%. This immunoassay was successfully used to detect BaP in environmental samples, and the BaP detection results were consistent with those obtained using high performance liquid chromatography, indicating that the BP-rt-iPCR method is accurate and reliable, and has great potential to detect trace amounts of BaP.

https://ift.tt/2HuVyVa

What causes black gums?

The gums come in many natural colors, including red, pink, brown, and black. However, changes in gum color can indicate an underlying health problem. In this article, learn about what causes black gums, including smoking, gingivitis, Addison's disease, and amalgam tattoos. We also look at treatment and prevention.

https://ift.tt/2EDJcHw

Ordinary Cannulated Compression Screws or Headless Cannulated Compression Screws? A Synthetic Bone Biomechanical Research in the Internal Fixation of Vertical Femoral Neck Fracture

Purpose. The purpose of this study is to verify whether the headless cannulated compression screw (HCCS) has higher biomechanical stability than the ordinary cannulated compression screw (OCCS) in the treatment of vertical femoral neck fractures. Materials and Methods. 30 synthetic femur models were equally divided into 2 groups, with 50°, 60°, and 70° Pauwels angle of femoral neck fracture, under 3D printed guiding plates and C-arm fluoroscopic guidance. The femur molds were fixed with three parallel OCCSs as OCCS group and three parallel HCCSs as HCCS group. All specimens were tested for compressive strength and maximum load to failure with a loading rate of 2 mm/min. Results. The result showed that there was no significant difference with the compressive strength in the Pauwels angle of 50° and 60°. However, we observed that the maximum load to failure with the Pauwels angle of 50°, 60°, and 70° and the compressive strength with 70° of HCCS group showed better performance than the OCCS group. Conclusion. HCCS performs with better biomechanical stability than OCCS in the treatment of vertical femoral neck fracture, especially with the Pauwels angle of 70°.

https://ift.tt/2qo3VuF

A Skeptical Approach to the Management of Persistent Oral Ulceration in a Child

The diagnosis of oral lesions is sometimes difficult due to both the clinician's limited experience with the conditions that may cause the lesions and their similar appearances, especially in children. Correctly establishing a definitive diagnosis is of major importance to clinicians who manage patients with oral mucosal diseases. In patients with Fanconi anaemia (FA), oral ulcers occur frequently, which are quite variable, and may lead to a misdiagnosis or failure to diagnose. Here, we report the case of a 15-year-old boy who was examined for squamous cell cancer of the tongue and diagnosed as having FA without any haematological manifestations. While surgery could not be done, both radiotherapy and chemotherapy had to be decreased. He died of progressive disease 6 months after the diagnosis. Unexplained ulcers in a child with a duration longer than 2 weeks should be further evaluated, especially for FA, even without the presence of anaemia.

https://ift.tt/2HitxCZ

Treatment of Urolithiasis with Medicinal Plant Salvia miltiorrhiza: A Nationwide Cohort Study

Salvia miltiorrhiza Bunge (Danshen), a common medicinal plant in traditional Chinese medicine, has been tested effectively to prevent urolithiasis in animals; nevertheless, the clinical application for urolithiasis remains unclear. We thus investigated the clinical effect of Danshen by analyzing the database from the Taiwan National Institute of Health. The cohort "Danshen-users" was prescribed Chinese herb medicine Danshen after the initial diagnosis of calculus. The control group (non-Danshen-users) was not given Danshen after the initial diagnosis of calculus. The date of first using Danshen after new diagnosis date of calculus was considered as index date. The outcome variables were categorized into two categories: the first category included calculus surgical treatment, including extracorporeal shock wave lithotripsy, ureteroscopy, percutaneous nephrostomy with fragmentation, and ureterolithotomy; the second category included any bleeding disorders, including gastrointestinal bleeding, intracranial hemorrhage, and blood transfusions. The incidence of calculus surgical treatment in the Danshen-users was less than that in the non-Danshen-users: 1.071% in 1,000 person-years (200 people followed up for 5 years) and 3.142% in 1,000 person-years, respectively. The adjusted hazard ratio for calculus surgical treatment in the Danshen-users was 0.34 (95% confidence intervals: 0.31–0.38) as compared to the non-Danshen-users. When stratified by sex, the incidence of calculus surgical treatment in Danshen-users was 0.685% in 1,000 person-years and 1.575% in 1,000 person-years for women and men, respectively, which was lower than that in non-Danshen-users. Danshen decreased the ratio of subsequent stone treatment after the first treatment in the study population; there was no increased bleeding risk due to long-term Danshen use.

https://ift.tt/2GTgHf2

Chromatin Fiber Folding Directed by Cooperative Histone Tail Acetylation and Linker Histone Binding

In eukaryotic chromatin, islands of histone tail acetylation are found near transcription start sites and enhancers, whereas linker histones (LHs) are localized in intergenic regions with wild-type (WT) histone tails. However, the structural mechanisms by which acetylation, in combination with LH binding, modulates chromatin compaction and hence transcription regulation are unknown. To explore the folding propensity by which these features may govern gene expression, we analyze 20 kb fibers that contain regularly spaced acetylation islands of two sizes (2 or 5 kb) with various LH levels by mesoscale modeling.

https://ift.tt/2qpoiXA

Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas

Abstract

Despite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues. We performed a genomic analysis of recurrent tumors from 17 pediatric medulloblastoma patients. Whole transcriptome sequencing revealed that a subset of recurrent tumors initially diagnosed as locally recurrent medulloblastomas are secondary glioblastomas after radiotherapy, showing high similarity to the non-G-CIMP proneural subtype of glioblastoma. Further analysis, including whole exome sequencing, revealed missense mutations or complex gene fusion events in PDGFRA with augmented expression in the secondary glioblastomas after radiotherapy, implicating PDGFRA as a putative driver in the development of secondary glioblastomas after treatment exposure. This result provides insight into the possible application of PDGFRA-targeted therapy in these second malignancies. Furthermore, genomic alterations of TP53 including 17p loss or germline/somatic mutations were also found in most of the secondary glioblastomas after radiotherapy, indicating a crucial role of TP53 alteration in the process. On the other hand, analysis of recurrent medulloblastomas revealed that the most prevalent alterations are the loss of 17p region including TP53 and gain of 7q region containing EZH2 which already exist in primary tumors. The 7q gain events are frequently accompanied by high expression levels of EZH2 in both primary and recurrent medulloblastomas, which provides a clue to a new therapeutic target to prevent recurrence. Considering the fact that it is often challenging to differentiate between recurrent medulloblastomas and secondary glioblastomas after radiotherapy, our findings have major clinical implications both for correct diagnosis and for potential therapeutic interventions in these devastating diseases.

https://ift.tt/2qn7bWg

Effect of Moringa oleifera consumption on diabetic rats

Therapeutic use of leaves of M. oleifera has been evaluated in diabetes because of its possible capacity to decrease blood glucose and lipids concentration after ingestion, as result of the polyphenols content an...

https://ift.tt/2v81MYK

Evaluation of the antioxidant and endothelial protective effects of Lysimachia christinae Hance (Jin Qian Cao) extract fractions

Lysimachia christinae Hance is a traditional Chinese medicine with diuretic, detumescent, and detoxifying effects. Our aimed to optimize the extraction protocol to maximize the yield of flavonoids from Lysimachia...

https://ift.tt/2HaP4gL

Standardized Duplex Ultrasound-Based Protocol for Early Diagnosis of Transplant Renal Artery Stenosis: Results of a Single-Institution Retrospective Cohort Study

Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after kidney transplantation (KT) and has been associated with potentially reversible refractory hypertension, graft dysfunction, and reduced patient survival. The aim of the study is to describe the outcomes of a standardized Duplex Ultrasound- (DU-) based screening protocol for early diagnosis of TRAS and for selection of patients potentially requiring endovascular intervention. We retrospectively reviewed our prospectively collected database of KT from January 1998 to select patients diagnosed with TRAS. The follow-up protocol was based on a risk-adapted, dynamic subdivision of eligible KT patients in different risk categories (RC) with different protocol strategies (PS). Of 598 patients included in the study, 52 (9%) patients had hemodynamically significant TRAS and underwent percutaneous angioplasty (PTA) and stent placement. Technical and clinical success rates were 97% and 90%, respectively. 7 cases of restenosis were recorded at follow-up and treated with re-PTA plus stenting. Both DU imaging and clinical parameters improved after stent placement. Prospective high-quality studies are needed to test the efficacy and safety of our protocol in larger series. Accurate trial design and standardized reporting of patient outcomes will be key to address the current clinical needs.

https://ift.tt/2JDbntY

Successful Clarithromycin Monotherapy in a Patient with Primary Follicular Lymphoma of the Duodenum

Primary follicular lymphoma of the duodenum (FL-D) constitutes a rare subtype of extranodal follicular lymphoma with a usually indolent course. To date, no distinct treatment recommendations have been defined for those patients. We report the case of a 58-year-old male patient presenting with endoscopically assessed, symptomatic FL-D who was treated with clarithromycin monotherapy in analogy to recent data for mucosa-associated lymphoid tissue lymphoma. Each treatment cycle consisted of clarithromycin 500 mg twice daily for 3 weeks followed by a 2-week break. After four cycles of treatment, the patient showed a very good response with normal macroscopic findings confirmed by endosonographic examination and only focal minimal residual disease of lymphoma persisting in the histological assessment. The patient is currently asymptomatic and without treatment for 24+ months. As clarithromycin combines antimicrobial and direct antiproliferative effects mediated through a variety of pleiotropic mechanisms, this appears to be an interesting treatment approach for indolent lymphoma, particularly in those where a chronic infectious background cannot be completely ruled out, i.e., gastrointestinal manifestations. We suggest further investigation of this treatment approach.
Case Rep Oncol 2018;11:239–245

https://ift.tt/2qpUPN9

Subcutaneous Eikenella corrodens, Actinomyces sp., and α-Hemolytic Streptococcus Abscess of the Thigh following a Vitamin B12 Injection

This case report describes a 38-year-old female presenting with a thigh abscess caused by Eikenella corrodens, Actinomyces sp., and α-hemolytic Streptococcus following an intramuscular vitamin B12 injection administered at an outpatient clinic. After failure to improve clinically with intravenous daptomycin and after visualization of the abscess with gas bubbles on CT scan, she was taken to the operating room for three separate surgical irrigation and debridement procedures. Treatment also included intravenous ampicillin/sulbactam followed by oral amoxicillin/clavulanic acid therapy. She remained symptom free and without infection at nine months following hospitalization. It was suspected that poor hygiene played a role in the infection, but a definitive cause was not identified.

https://ift.tt/2vaZiIW

A Case of Biliary Tract Infection Caused by KPC-2-Producing Kluyvera ascorbata

Kluyvera spp. can cause various infections. However, carbapenemase-producing Kluyvera spp. has not been previously reported. We report a case of biliary tract infection caused by KPC-2-producing K. ascorbata in a 13-year-old female. To the best of our knowledge, this is the first report on infection caused by carbapenemase-producing Kluyvera spp.

https://ift.tt/2He4K2S

Lactobacillus paracasei feeding improves the control of secondary experimental meningococcal infection in flu-infected mice

The use of probiotics to improve anti-microbial defence, such as for influenza infections, is increasingly recommended. However, no data are available on the effect of probiotics on flu-associated secondary ba...

https://ift.tt/2JENpOW

The Highest Cited Papers in Brucellosis: Identification Using Two Databases and Review of the Papers’ Major Findings

Citation classics represent the highest impact work in a given field. We aim to identify and analyze the most frequently cited papers on brucellosis. We used the databases Scopus and Web of Science to determine the most frequently cited papers. The most cited fifty papers in each database were identified. We then ranked the papers according to the highest citation count recorded from any of the two databases. The most frequently cited paper received 964 citations and was by DelVecchio VG et al. reporting the complete genomic sequencing of Brucella melitensis. The papers were published in 30 journals led by the "Infection and Immunity" journal and the "Veterinary Microbiology" journal (each had 7 papers). Citation classics in brucellosis were all in English except one in French and were mostly of basic science type. In addition, we noticed that 12 articles that were identified among the highest fifty articles in one database were missed by the other database and vice versa. Therefore, we suggest that searching in more than one database would detect additional citation classics.

https://ift.tt/2Hil6HP

Evaluation of a new biphasic calcium phosphate for maxillary sinus floor elevation: Micro‐CT and histomorphometrical analyses

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2JznCHM

Bexarotene-Induced Hypertriglyceridemia: A Case Report

We present a case of a patient with cutaneous T-cell lymphoma started on bexarotene 300 mg/m² due to progressing disease. The patient experienced good clinical response, but unfortunately, she developed rapid and profound hypertriglyceridemia. Although hypertriglyceridemia occurs in high incidence with bexarotene therapy, management recommendations are scarce. Due to the rise in triglycerides, atorvastatin 10 mg daily was initiated in combination with fenofibrate 120 mg daily. Triglycerides continued to increase, so the patient was instructed to take atorvastatin 40 mg, fenofibrate 120 mg, and to hold bexarotene for 2 weeks. After the 2-week break, bexarotene was restarted at 150 mg/m².
Case Rep Oncol 2018;11:234–238

https://ift.tt/2JDJr9i

The Impact of Dose and Simultaneous Use of Acid-Reducing Agents on the Effectiveness of Vemurafenib in Metastatic BRAF V600 Mutated Melanoma: a Retrospective Cohort Study

Abstract

Background

The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown.

Objectives

To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs.

Patient and Methods

A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012–March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital. Cox regression analysis was used to estimate the risk of progression with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n = 77). Analyses were adjusted for age and sex.

Results

In total, disease progression occurred in 55% of treated patients on vemurafenib, with a median progression-free survival of 6.0 (95% confidence interval [CI] 5.0–6.9) months. Compared to patients on vemurafenib alone, there was no increased risk of progression among patients requiring vemurafenib at a reduced dose or among patients receiving simultaneous therapy with vemurafenib and ARAs. In addition, there was no increased risk of progression among patients who used reduced-dose vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole therapy. However, a tendency for progression was observed among patients who used full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted hazard ratio [HRa] 2.37; 95% CI 0.97–5.76), which became statistically significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51–13.75).

Conclusions

There was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating  full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation.

https://ift.tt/2GQrruy

Personalized cancer vaccines: adjuvants are important, too

Abstract

Therapeutic cancer vaccines have shown limited clinical efficacy so far. Nevertheless, in the meantime, our understanding of immune cell function and the interactions of immune cells with growing tumors has advanced considerably. We are now in a position to invest this knowledge into the design of more powerful vaccines and therapy combinations aimed at increasing immunogenicity and decreasing tumor-induced immunosuppression. This review focuses essentially on peptide-based human vaccines. We will discuss two aspects that are critical for increasing their intrinsic immunogenicity: the selection of the antigen(s) to be targeted, and the as yet unmet need for strong adjuvants.

https://ift.tt/2qmIFW9

Extraction of Polysaccharide from Spirulina and Evaluation of Its Activities

Background. Polysaccharide of Spirulina platensis (PSP) is a kind of water-soluble polysaccharide extracted from Spirulina platensis. It has been proved to have antitumor, antioxidation, antiaging, and antivirus properties. And it has a promising prospect for wide application. Objective. This study aims to identify an extraction process for high-purity polysaccharide in Spirulina (PSP) through a series of optimization methods and then evaluates its initial antiaging activities. Methods. Four kinds of extraction methods—hot-water extraction, alkali extraction, ultrasonic-assisted extraction, and freeze-thaw extraction—were compared to find the optimal one, which was further optimized by response surface methodology. PSP was obtained after the crude PSP was deproteinized and depigmented. The antiaging effects of PSP were preliminarily evaluated through in vitro cell experiments. Results. The alkali extraction method was determined as the optimal method, with the optimized extraction process consisting of a solid-liquid ratio of 1 : 50, a pH value of 10.25, a temperature of 89.24°C, and a time of 9.99 h. The final PSP contained 71.65% of polysaccharide and 8.54% of protein. At a concentration of 50 μg/mL, PSP exerted a significant promoting effect on the proliferation and traumatic fusion of human immortalized epidermal cells HaCaT. Conclusion. An extraction method for high-purity PSP with a high extraction rate was established, and in vitro results suggest antioxidation and antiaging activities.

https://ift.tt/2JDqT8O

Update on PARP Inhibitors in Breast Cancer

Opinion statement

The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer. The US Food and Drug Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so far to treat certain ovarian cancers, including those with gBRCAm and olaparib for treatment of gBRCAm breast cancers. Several PARPi are now under clinical development for breast cancer in the various treatment settings. Recently, two phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3-month progression-free survival improvement with PARPi compared to physician's choice single agent chemotherapy in metastatic gBRCAm breast cancer. To date, PARPi seems less efficacious in metastatic breast cancer patients than those with BRCA mutated platinum-sensitive recurrent ovarian cancer, perhaps reflecting the biologic heterogeneity and low somatic BRCA mutation rate in breast cancer. The use of PARPi is gradually evolving, including combination strategies with chemotherapy, targeted agents, radiotherapy, or immunotherapy in women with and without gBRCAm. The role of predictive biomarkers, including molecular signatures and homologous recombination repair deficiency scores based on loss of heterozygosity and other structural genomic aberrations, will be crucial to identify a subgroup of patients who may have benefit from PARPi. An improved understanding of the mechanisms underlying PARPi clinical resistance will also be important to enable the development of new approaches to increase efficacy. This is a field rich in opportunity, and the coming years should see a better understanding of which breast cancer patients we should treat with PARPi and where these agents should come in over the course of treatment.

https://ift.tt/2Hprb2s