Food Science &Nutrition, EarlyView.
https://ift.tt/2MnNI0y
Τρίτη 11 Σεπτεμβρίου 2018
Physicochemical characterization and antioxidant activity of Palestinian honey samples
Inhibition of vection by grasping an object
Abstract
The present study investigated whether vection could be modified by an object grasping movement. Twenty-five university students were asked to do one of the following four types of left-hand movements while they were viewing a radial optic flow: (1) grasping the hand-gripper strongly; (2) holding the hand-gripper; (3) clenching fist strongly; and (4) open hand without having anything in their left hands (normal hand condition). The participants' tasks were to keep pressing a button with their right hands while they were perceiving vection. After each trial, they estimated the subjective strength of vection on a 101-point scale. The result showed that the vection was inhibited by strongly grasping the hand-gripper task more than by the other hand movements. Vection could be weakened by the object grasping movement. It might be suggested that vection could be inhibited by the presence of an object being grasped and also by the grasping movement itself. We speculated that the mechanism underlying this inhibition might be related to cognitive pressure, attentional load, power and muscle tonus, and multisensory and proprioception interactions.
https://ift.tt/2x5TVZj
Risk‐based breast cancer follow‐up stratified by age
Cancer Medicine, EarlyView.
https://ift.tt/2CLQFZc
Effects of whole-body electromyostimulation combined with individualized nutritional support on body composition in patients with advanced cancer: a controlled pilot trial
Abstract
Background
Physical exercise and nutritional treatment are promising measures to prevent muscle wasting that is frequently observed in advanced-stage cancer patients. However, conventional exercise is not always suitable for these patients due to physical weakness and therapeutic side effects. In this pilot study, we examined the effect of a combined approach of the novel training method whole-body electromyostimulation (WB-EMS) and individualized nutritional support on body composition with primary focus on skeletal muscle mass in advanced cancer patients under oncological treatment.
Methods
In a non-randomized controlled trial design patients (56.5% male; 59.9 ± 12.7 years) with advanced solid tumors (UICC III/IV, N = 131) undergoing anti-cancer therapy were allocated to a usual care control group (n = 35) receiving individualized nutritional support or to an intervention group (n = 96) that additionally performed a supervised physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz) 2×/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary outcomes of body composition, body weight and hand grip strength were measured at baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary outcomes of physical function, hematological and blood chemistry parameters, quality of life and fatigue were assessed at baseline and week 12. Changes were analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests.
Results
Twenty-four patients of the control and 58 of the WB-EMS group completed the 12-week trial. Patients of the WB-EMS group had a significantly higher skeletal muscle mass (0.53 kg [0.08, 0.98]; p = 0.022) and body weight (1.02 kg [0.05, 1.98]; p = 0.039) compared to controls at the end of intervention. WB-EMS also significantly improved physical function and performance status (p < 0.05). No significant differences of changes in quality of life, fatigue and blood parameters were detected between the study groups after 12 weeks.
Conclusions
Supervised WB-EMS training is a safe strength training method and combined with nutritional support it shows promising effects against muscle wasting and on physical function in advanced-stage cancer patients undergoing treatment.
Trial registration
ClinicalTrials.gov NCT02293239 (Date: November 18, 2014).
https://ift.tt/2O8Mc43
The role of RIP3 in cardiomyocyte necrosis induced by mitochondrial damage of myocardial ischemia–reperfusion
Abstract
Myocardial damage caused by myocardial ischemia–reperfusion injury (MIRI) is difficult to be alleviated because cardiomyocyte necrosis is an irreversible and unregulated death form. Recently, necroptosis, a necrosis form caused by tumor necrosis factor-α (TNF-α) and Fas ligand (FasL), was found to be regulated by receptor interacting protein 3 (RIP3) and RIP3-receptor interacting protein 1 (RIP1)-mixed lineage kinase domain like protein (MLKL) pathway. But it is unclear whether they also play a regulatory role in MIRI-induced necroptosis. Our previous results showed that in rat MIRI, RIP3 could translocate and express highly in mitochondria. Therefore, it is important to explore proteins that interact with RIP3 which was translocated to mitochondria. The aim of this study was to explore the role of RIP3 in cardiomyocyte necrosis induced by mitochondrial damage of hypoxia/reoxygenation (H/R). Our results showed that H/R could cause RIP3-depended mitochondrial fragmentation and necrosis-based death; and RIP3-promoted H/R-induced necroptosis in H9c2 cells through increasing lactate dehydrogenase release and inhibiting cell viability. This process did not require RIP1 or MLKL but dynamin-related protein 1 (Drp1), which was related to Drp1 activation, reactive oxygen species elevation, and ΔΨm decline. This study provides novel insights into the role of RIP3 in cardiomyocyte injury during H/R. RIP3 may serve as a potential target for the treatment of MIRI.https://ift.tt/2OaPq7h
Safety and Efficacy of Cabozantinib for Metastatic Nonclear Renal Cell Carcinoma: Real-world Data From an Italian Managed Access Program
Objective: The activity of cabozantinib in nonclear cell histologies has not been evaluated. Materials and Methods: Data were collected across 24 Italian hospitals. Patients were aged 18 years and older with advanced nonclear cell renal cell carcinoma (RCC), with an Eastern Cooperative Oncology Group Performance Status 0 to 2, who had relapsed after previous systemic treatments for metastatic disease. Cabozantinib was administered orally at 60 mg once a day in 28 days cycles. Dose reductions to 40 or 20 mg were made due to toxicity. Adverse events (AEs) were monitored using CTCAE version 4.0. Results: Seventeen patients were enrolled. Three (18%) patients were diagnosed type I papillary RCC, 9 (53%) type II papillary, 3 (18%) chromophobe, and 2 (11%) with Bellini duct carcinoma. In total, 11 patients started with 60 mg. Six patients started a lower dose of 40 mg. Median progression-free survival was 7.83 months (0.4 to 13.4 mo), while median overall survival was not reached but 1-year overall survival was about 60%. Six patients (35%) experienced a partial response to treatment and 6 patients (35%) showed a stable disease. In the remaining 5 (30%), we observed a progressive disease. Grade 3 and 4 AEs were observed in 41% of patients. Among 20 patients, only 1 (6%) discontinued treatment due to AEs. Asthenia (41%), diarrhea (35%), aminotransferase increasing (35%), mucosal inflammation (35%), hand and foot syndrome (24%), and hypothyroidism (24%) were the most frequently AEs. Conclusions: Our data showed that, cabozantinib is a active and feasible treatment in patient with nonclear cell RCC. G.P. reports receiving fees for serving on advisory boards from Astellas, Bayer, Bristol-Myers Squibb, Ipsen, Janssen, Novartis and Pfizer. R.I. reports receiving fees for serving on advisory boards from Novartis, Pfizer, Bristol-Myers Squibb, and Ipsen. U.D.G. reports receiving fees for serving on advisory boards from Janssen, Astellas, Sanofi, Bristol-Myers Squibb, Pfizer, Novartis and Ipsen. E.V. reports receiving fees for serving on advisory boards from Ipsen, Janssen, Novartis and Pfizer. The remaining authors declare no conflicts of interest. Reprints: Michele Prisciandaro, MD, Department of Medical Oncology, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Giacomo Venezian 1, Milan 20133, Italy. E-mail: michele.prisciandaro@istitutotumori.mi.it. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2N6rPYU
https://ift.tt/2N6rPYU
Nuclear Medicine Therapy With 223Radium-dichloride for Osseous Metastases in Prostate Carcinoma
Painful osseous metastasis resulting from castration-resistant prostate carcinoma is a common clinical problem. Historically, nuclear medicine offered several palliative beta-emitting radiopharmaceuticals targeting the skeleton with the goal of decreasing pain. However, these have largely been replaced by the alpha-emitting agent 223radium (Ra). 223Ra received Food and Drug Administration approval in 2013 for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases without visceral metastases. 223Ra offers an improved therapeutic profile due to its alpha-particle emissions resulting in a relatively higher linear energy transfer and lower particle range compared with beta-emitters. 223Ra also has demonstrated to increase overall survival in patients and to delay adverse skeletal events. Running a successful clinical nuclear therapy program with 223Ra requires a multidisciplinary team approach and this article suggests an implementation strategy from the authors' institution. Potential new nuclear radiopharmaceuticals still under investigation offering the future possibility of radioligand therapy are also discussed briefly. The authors declare no conflicts of interest. Reprints: Domenico Rubello, MD, Department of Nuclear Medicine and PET/CT center, Via Tre Martiri 89, 45100 Rovigo, Italy. E-mail: domenico.rubello@libero.it. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2OifUUc
https://ift.tt/2OifUUc
Effects of High-Intensity Interval Training Under Normobaric Hypoxia on Cardiometabolic Risk Markers in Overweight/Obese Women
High Altitude Medicine &Biology, Ahead of Print.
https://ift.tt/2N6ro0I
SOX3 can promote the malignant behavior of glioblastoma cells
Abstract
Purpose
Glioblastoma is the most common and lethal adult brain tumor. Despite current therapeutic strategies, including surgery, radiation and chemotherapy, the median survival of glioblastoma patients is 15 months. The development of this tumor depends on a sub-population of glioblastoma stem cells governing tumor propagation and therapy resistance. SOX3 plays a role in both normal neural development and carcinogenesis. However, little is known about its role in glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in glioblastoma.
Methods
SOX3 expression was assessed using real-time quantitative PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT, immunocytochemistry and Transwell assays were used to evaluate the effects of exogenous SOX3 overexpression on the viability, proliferation, migration and invasion of glioblastoma cells, respectively. The expression of Hedgehog signaling pathway components and autophagy markers was assessed using RT-qPCR and Western blot analyses, respectively.
Results
Higher levels of SOX3 expression were detected in a subset of primary glioblastoma samples compared to those in non-tumoral brain tissues. Exogenous overexpression of this gene was found to increase the proliferation, viability, migration and invasion of glioblastoma cells. We also found that SOX3 up-regulation was accompanied by an enhanced activity of the Hedgehog signaling pathway and by suppression of autophagy in glioblastoma cells. Additionally, we found that SOX3 expression was elevated in patient-derived glioblastoma stem cells, as well as in oncospheres derived from glioblastoma cell lines, compared to their differentiated counterparts, implying that SOX3 expression is associated with the undifferentiated state of glioblastoma cells.
Conclusion
From our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells.
https://ift.tt/2xffFlV
Single agent efficacy of the HDAC inhibitor DATS in preclinical models of glioblastoma
Abstract
Purpose/introduction
Glioblastoma (GB) remains incurable despite aggressive chemotherapy, radiotherapy, and surgical interventions; immunotherapies remain experimental in clinical practice. Relevant preclinical models that can accurately predict tumor response to therapy are equally challenging. This study aimed to validate the effect of the naturally occurring agent diallyl trisulfide (DATS) in human GB in relevant pre-clinical models.
Methods
Ex vivo slice culture, in vivo cell line derived orthotopic xenograft and patient-derived orthotopic xenograft (PDX) animal models of GB were utilized to assess efficacy of treatment with DATS.
Results
Our results showed 72-h treatments of 25 µM DATS induced cell death in ex vivo human GB slice culture. We treated U87MG orthotopic xenograft models (U87MGOX) and patient-derived orthotopic xenograft models (PDX) with daily intraperitoneal injections of DATS for 14 days. Magnetic resonance (MR) imaging of mice treated with DATS (10 mg/kg) demonstrated reduced tumor size at 5 weeks when compared with saline-treated U87MGOX and PDX controls. Hematoxylin (H&E) staining demonstrated dose-dependent reduction in gross tumor volume with decreased proliferation and decreased angiogenesis. Western blotting showed that DATS was associated with increases in histone acetylation (Ac-Histone H3/H4) and activated caspase-3 in this novel preclinical model. Histological assessment and enzyme assays showed that even the highest dose of DATS did not negatively impact hepatic function.
Conclusions
DATS may be an effective and well-tolerated therapeutic agent in preventing tumor progression and inducing apoptosis in human GB.
https://ift.tt/2QqHAIn
Response:
We are grateful for the thoughtful letter from our colleagues1 in the United Kingdom concerning our article2 and for the opportunity to continue a dialogue on the important and evolving approach to dysplasia in patients with chronic colitis.
https://ift.tt/2NuzcsH
Response:
We thank Drs Kidambi, Terdiman, and Lee1 for their interest and their thoughtful comments related to our study.2 Our proposed adenoma and polyp management efficiency indices are not meant to supplant but rather to complement current quality metrics while also providing a platform to measure colonoscopy efficiency during fellowship training. To this point, the negative withdrawal time is not truly an efficiency metric because it sets a minimum withdrawal time threshold for an adequate quality examination.
https://ift.tt/2x8FUdD
Chromoendoscopy: adding color to duodenal polyps
Adenomatous polyposis syndromes, such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP), are well-characterized inherited conditions resulting from germline mutations in the APC and MUTYH genes, respectively. These mutations predispose an individual to colonic and extracolonic malignancies; if they are left untreated, the risk of colorectal cancer (CRC) in FAP is nearly 100%. The most common cause of extracolonic cancer mortality in affected persons is duodenal or ampullary cancer.
https://ift.tt/2x8FGmN
Negative withdrawal time: simple and efficient
We read with great interest the study from Bitar et al1 examining colonoscopy quality and efficiency according to level of training. The authors should be lauded for investigating a topic with implications for all gastroenterology training programs as they assess their endoscopy curriculum in the context of placing patient outcomes and colon cancer prevention first. Despite the potential limitations associated with a retrospective study, the primary finding of similar high-quality colonoscopies performed by second-year and third-year fellows in the absence of an attending for the duration of the procedure is noteworthy and reassuring.
https://ift.tt/2NG3ZCC
Age is not just a number: surveillance colonoscopy is low yield in individuals younger than 50
For the colonoscopist, deciding on a repeat interval after a screening or surveillance examination is among the more difficult and consequential intellectual tasks associated with colonoscopy. It is also the moment when an individual colonoscopist's decision can greatly influence the overall efficiency of a colon cancer screening program. To better prevent colon cancers while controlling the morbidity and costs of our procedures, we need to do more colonoscopies on patients who will truly benefit and fewer colonoscopies on those who will not benefit.
https://ift.tt/2NyR6ug
Borescope examination: Is there value in visual assessment of endoscope channels?
The recent recognition of duodenoscope-related multidrug-resistant infectious outbreaks has prompted the review of current endoscope reprocessing practices. Multiple society and manufacturer recommendations have outlined the importance of meticulous stepwise reprocessing, with emphasis on adequacy of precleaning and washing and on visual inspection to identify endoscope damage and verify reprocessing efficacy. However, some outbreaks have occurred despite documented adherence to all steps, which suggests that the current recommendations may be inadequate.
https://ift.tt/2NHpe7q
Removal of duodenal adenomas: the importance of proper technical application and operator expertise
The diagnosis of duodenal epithelial neoplasms in the general population is relatively uncommon, occurring in less than 1% of patients undergoing upper endoscopy.1 However, with increasing widespread use of endoscopy, the incidence of duodenal polyps is likely to rise. Approximately 30% to 85% of duodenal adenomas can progress to malignancy.1 Therefore, early detection and removal of duodenal adenomas before malignant transformation represents a key opportunity to prevent future cancer.
https://ift.tt/2x8Fns9
Reassessing colectomy in young patients with familial adenomatous polyposis
Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited syndrome caused by a germline mutation in the APC gene that accounts for approximately 1% of colorectal cancer cases in the United States. Mutations between codons 169-1393 result in classic FAP, whereas mutations closer to the 5' and 3' of the APC gene cause attenuated FAP, which has a less severe phenotype.1 FAP is characterized by the development of multiple adenomatous colorectal polyps in childhood and adolescence, which inevitably progresses to colorectal carcinoma.
https://ift.tt/2NCLnn7
Autologous esophageal mucosa transplantation to prevent esophageal stricture after endoscopic submucosal dissection: promising, but too early to draw a conclusion
We read with great interest the article by Liao et al,1 who explored the feasibility and efficacy of endoscopic transplantation of autologous esophageal mucosa to prevent esophageal stricture after circumferential endoscopic submucosal dissection (cESD). Although stricture occurred in 88.9% (8/9) of the cases, this approach nearly halved the mean number of dilation sessions needed. In addition, the authors concluded that transplantation of autologous esophageal mucosa could be a safe way of relieving the severity of esophageal stricture after cESD.
https://ift.tt/2x8FfZH
“I want a new drug…”1
The practice of endoscopy continues to evolve. New equipment, new techniques, new indications, and new anesthetics expand the field over time. As endoscopists struggle to meet the burgeoning demand of an ever-expanding endoscopic practice, there is a tendency to become complacent with a given approach to the practice of endoscopy. Discussions with the patient regarding informed consent become standardized or generalized, equipment choices narrow, and sedation becomes rote whether given by the endoscopist, nurse anesthetist, or anesthesiologist.
https://ift.tt/2NHp1Ba
Computational aeroacoustics to identify sound sources in the generation of sibilant /s/
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2x3zLjG
Cancers, Vol. 10, Pages 324: No Increase in Colon Cancer Risk Following Induction with Neu5Gc-Bearing Rabbit Anti-T Cell IgG (ATG) in Recipients of Kidney Transplants
Cancers, Vol. 10, Pages 324: No Increase in Colon Cancer Risk Following Induction with Neu5Gc-Bearing Rabbit Anti-T Cell IgG (ATG) in Recipients of Kidney Transplants
Cancers doi: 10.3390/cancers10090324
Authors: Jean-Paul Soulillou Caner Süsal Bernd Döhler Gerhard Opelz
Because of a mutation of the gene allowing the synthesis of the Neu5Gc form of neuraminidic acid, humans lack the Neu5Gc present in other mammals and develop anti-Neu5Gc. However, humans can absorb dietary Neu5Gc and normal colon epithelium displays minute amounts of Neu5Gc. The potential “physiological” formation of in situ immune complexes has been proposed as a risk factor for colon cancer and as the link between red meat-rich diet and colon carcinoma. In this article, we took advantage of evidence that polyclonal rabbit IgG (ATG) elicits an immune response against Neu5Gc and we consulted a large data base of allograft recipients treated or not with animal-derived IgG to discuss this hypothesis. Based on data from 173,960 and 38,505 patients without and with ATG induction, respectively, we found no evidence that exposure to higher levels of anti-Neu5Gc is associated with a higher incidence of colon carcinoma.
https://ift.tt/2x2IdzM
Graded Combined Aerobic Resistance Exercise (CARE) to Prevent or Treat the Persistent Post-concussion Syndrome
Abstract
Purpose of Review
To review the growing body of indirect and direct evidence that suggests that exercise can be helpful for children, adolescents, and adults with persistent symptoms following a mild traumatic brain injury (mTBI).
Recent Findings
The direct evidence shows that graded exercise assessments are safe, and that aerobic exercise interventions are associated with improvement of multiple symptoms and other benefits, including earlier return-to-sport. The indirect evidence supports this approach via studies that reveal the potential mechanisms, and show benefits for related presentations and individual symptoms, including headaches, neck pain, vestibular problems, sleep, stress, anxiety, and depression. We document the forms of exercise used for the post-acute management of mTBI, highlight the knowledge gaps, and provide future research directions.
Summary
We recommend trialing a new approach that utilizes a graduated program of individually prescribed combined aerobic resistance exercises (CARE) if mTBI symptoms persist. This program has the potential to improve patient outcomes and add to the management options for providers.
https://ift.tt/2Mk4gq9
Adaptation of myocardial twist in the remodelled athlete's heart is not related to cardiac output
Experimental Physiology, Volume 0, Issue ja, -Not available-.
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Hypothalamic DNA methylation in rats with dihydrotestosterone‐induced polycystic ovary syndrome: effects of low‐frequency electro‐acupuncture
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2CLybbj
Telomere length, telomerase reverse transcriptase promoter mutations, and melanoma risk
Genes, Chromosomes and Cancer, EarlyView.
https://ift.tt/2x7tFOs
Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A retrospective study from the French Innovative Leukemia Organization (FILO) working group
Genes, Chromosomes and Cancer, EarlyView.
https://ift.tt/2x2eGG2
Improved cytogenetic characterization and risk stratification of pediatric acute lymphoblastic leukemia using single nucleotide polymorphism array analysis: A single center experience of 296 cases
Genes, Chromosomes and Cancer, EarlyView.
https://ift.tt/2x1ZMPi
How the Public Autopsy of a Slave Joice Heth Launched P.T. Barnum's Career as the Greatest Showman on Earth
Clinical Anatomy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2x1YKmo
What the ʾell? testicle is a diminutive!
Clinical Anatomy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2oZCNkp
Disruption of Symmetry: A Quantitative Assessment of Facial Skeleton Anatomy in Children born with Unilateral Cleft Lip and Palate
Clinical Anatomy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2x4TheN
Variations in pelvic dimensions; an anatomical and computed tomography study
Clinical Anatomy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2oZLRWp
Response to Letter to Editor by D'Antoni, AV & Mtui, EP (2018)
Clinical Anatomy, EarlyView.
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The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial [Research Articles]
CDK4/6 inhibition with endocrine therapy is now a standard of care for advanced estrogen receptor positive breast cancer. Mechanisms of CDK4/6 inhibitor resistance have been described pre-clinically, with limited evidence from clinical samples. We conducted paired baseline and end of treatment circulating tumor DNA sequencing from 195 patients in the PALOMA-3 randomized phase III trial of palbociclib plus fulvestrant versus placebo plus fulvestrant. We show that clonal evolution occurs frequently during treatment, reflecting substantial sub-clonal complexity in breast cancer that has progressed after prior endocrine therapy. RB1 mutations emerged only in the palbociclib plus fulvestrant arm and in a minority of patients (6/127, 4.7%, p=0.041). New driver mutations emerged in PIK3CA (p=0.00069) and ESR1 after treatment in both arms, in particular ESR1 Y537S (p=0.0037). Evolution of driver gene mutations was uncommon in patients progressing early on palbociclib plus fulvestrant but common in patients progressing later on treatment. These findings inform future treatment strategies to address resistance to palbociclib plus fulvestrant.
https://ift.tt/2Qn5xQA
Cervical Cancer Screening Every 5 Years OK [News in Brief]
New recommendations say HPV testing—without a Pap test—sufficient for most women.
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Review of epiglottitis in the post Haemophilus influenzae type‐b vaccine era
ANZ Journal of Surgery, EarlyView.
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Ileo‐ileal knot: a rare case of acute intestinal obstruction
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2NBHChF
Role of post‐operative serum C‐reactive protein levels as a predictor of complications in upper gastrointestinal surgery
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2x9HFXO
Too frail for surgery? A frailty index in major colorectal surgery
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2Nz0bmK
Impact of an acute surgical unit on outcomes in acute cholecystitis
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2x3DCMM
Endovascular embolization of a giant hepatic artery aneurysm
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2NHau8A
Spontaneous hepaticoduodenal fistula following extended right hemihepatectomy
ANZ Journal of Surgery, EarlyView.
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Accessory spleen mimicking an intra‐abdominal tumour
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2NCTCzq
Prognostic value of retrieved lymph node counts in patients with node‐negative perihilar cholangiocarcinomas
ANZ Journal of Surgery, EarlyView.
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Diverse Functions of Macrophages in Different Tumor Microenvironments
Tumor-associated macrophages are a major constituent of malignant tumors and are known to stimulate key steps in tumor progression. In our review in this journal in 2006, we postulated that functionally distinct subsets of these cells exist in different areas within solid tumors. Here, we review the many experimental and clinical studies conducted since then to investigate the function(s), regulation, and clinical significance of macrophages in these sites. The latter include three sites of cancer cell invasion, tumor nests, the tumor stroma, and areas close to, or distant from, the tumor vasculature. A more complete understanding of macrophage diversity in tumors could lead to the development of more selective therapies to restore the formidable, anticancer functions of these cells. Cancer Res; 78(19); 1–12. ©2018 AACR.
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Precision medicine approaches when prostate cancer Akts up
Ipatasertib combined with abiraterone in PTEN null prostate cancer improved progression-free survival in a randomized phase II study of patients with mCRPC, providing clinical evidence of reciprocal activation between the Akt and AR pathways. These data revive the rationale for targeting PTEN loss in prostate cancer.
https://ift.tt/2CK4w2r
Combining Vascular Normalization with an Oncolytic Virus Enhances Immunotherapy in Advanced Stage Ovarian Cancer
Purpose: Intravenous delivery of oncolytic viruses often leads to tumor vascular shutdown, resulting in decreased tumor perfusion and elevated tumor hypoxia. We hypothesized that using 3TSR to normalize tumor vasculature prior to administration of an oncolytic Newcastle disease virus (NDV) would enhance virus delivery and trafficking of immunological cell subsets to the tumor core, resulting in systemically enhanced immunotherapy and regression of advanced stage Epithelial Ovarian Cancer (EOC). Experimental Design: Using an orthotopic, syngeneic mouse model of advanced stage EOC, mice were pre-treated with 3TSR (4mg/kg per day) alone or followed by combination with fusogenic NDV(F3aa) (1.0x10 8PFU). Results: Treatment with 3TSR normalized tumor vasculature, enhanced blood perfusion of primary EOC tumors and induced disease regression. Animals treated with combination therapy had the greatest reduction in primary tumor mass, ascites accumulation and secondary lesions (50% of mice were completely devoid of peritoneal metastases). Combining 3TSR+NDV(F3aa) led to enhanced trafficking of immunological cells into the primary tumor core. Conclusions: We have shown, for the first time that NDV, like other oncolytic viruses, is a potent mediator of acute vascular shutdown and that preventing this through vascular normalization can promote regression in a preclinical model of advanced stage ovarian cancer. This challenges the current focus on induction of intravascular thrombosis as a requisite for successful oncolytic virotherapy.
https://ift.tt/2p2CXHD
Dual PAK4-NAMPT inhibition impacts growth and survival, and increases sensitivity to DNA-damaging agents in Waldenstrom Macroglobulinemia.
Purpose: p21-activated kinase 4 (PAK4) plays a significant biological and functional role in a number of malignancies, including multiple myeloma (MM). Based on our promising findings in MM, we here characterize PAK4 expression and role in WM cells, as well effect of dual PAK4-NAMPT inhibitor (KPT-9274) against WM cell growth and viability. Experimental Design: We have analyzed mRNA and protein expression levels of PAK4 in WM cells, and used loss-of-function approach to investigate its contribution to WM cell viability. We have further tested the in vitro and in vivo effect of KPT-9274 against WM cell growth and viability. Results: We report here high-level expression and functional role of PAK4 in WM, as demonstrated by shRNA-mediated knockdown; and significant impact of KPT-9274 on WM cell growth and viability. The growth inhibitory effect of KPT-9274 was associated with decreased PAK4 expression and NAMPT activity, as well as induction of apoptosis. Interestingly, in WM cell lines treated with KPT-9274, we detected a significant impact on DNA damage and repair genes. Moreover, we observed that apart from inducing DNA damage, KPT-9274 specifically decreased RAD51 and the double strand break repair by the homologous recombination pathway. As a result, when combined with a DNA alkylating agents bendamustine and melphalan, KPT-9274 provided a synergistic inhibition of cell viability in WM cell lines and primary patient WM cells in vitro and in vivo. Conclusions: These results support the clinical investigation of KPT-9274 in combination with DNA-damaging agent for treatment of WM.
https://ift.tt/2CK4oQv
Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety and Biomarkers
Background: HER2-targeted therapy is not standard of care for human epidermal growth factor receptor 2 (HER2)-positive non-small cell lung cancer (NSCLC). This phase II study investigated efficacy and safety of the HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with previously treated advanced HER2-overexpressing NSCLC. Methods: Eligible patients had HER2-overexpressing NSCLC (centrally-tested immunohistochemistry [IHC]), and received previous platinum-based chemotherapy and targeted therapy in the case of EGFR mutation or ALK gene rearrangement. Patients were divided into cohorts based on HER2 IHC (2+, 3+). All patients received T-DM1 3.6 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was investigator-determined overall response rate (ORR) using Response Evaluation Criteria in Solid Tumors v1.1. Results: Forty-nine patients received T-DM1 (29 IHC 2+, 20 IHC 3+). No treatment responses were observed in the IHC 2+ cohort. Four partial responses were observed in the IHC 3+ cohort (ORR 20%; 95% confidence interval 5.7-43.7%). Clinical benefit rates were 7% and 30% in the IHC 2+ and 3+ cohorts, respectively. Response duration for the responders was 2.9, 7.3, 8.3, and 10.8 months. Median progression-free and overall survival were similar between cohorts. Three of four responders had HER2 gene amplification. No new safety signals were observed. Discussion T-DM1 showed a signal of activity in patients with HER2-overexpressing (IHC 3+) advanced NSCLC. Additional investigation into HER2 pathway alterations is needed to refine the target population for T-DM1 in NSCLC; however, HER2 IHC as a single parameter was an insufficient predictive biomarker.
https://ift.tt/2CK4hEz
Antibody-Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non-Small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade
Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinico-pathological features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non-small cell lung cancer (NSCLC) treated with ICI at our Institute, cases with HP were identified according to clinical and radiological criteria. Baseline histological samples from patients treated with ICI were evaluated by immunohistochemistry (IHC) for myeloid and lymphoid markers. T-cell deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDXs) belonging to specific mutational subsets, were assessed for tumor growth after treatment with antibodies against mouse and human programmed death receptor-1 (PD-1). The immune microenvironment was evaluated by flow cytometry and IHC. Results: Among 187 patients, 152 were evaluable for clinical response. We identified 4 categories: 32 cases were defined as Responders (21%), 42 patients with Stable Disease (27.7%), 39 cases defined as Progressors (25.7%) and 39 patients with HP (25.7%). Pre-treatment tissue samples from all patients with HP showed tumor-infiltration by M2-like CD163+CD33+PD-L1+ clustered epithelioid macrophages. Enrichment by tumor-associated macrophages (TAM) was observed, even in tumor nodules from immunodeficient mice injected with human lung cancer cells and with PDXs. In these models, tumor growth was enhanced by treatment with anti-PD-1, but not by anti-PD-1 F(ab)2-fragments. Conclusions: These results suggest a crucial role of TAM reprogramming, upon Fc receptor engagement by ICI, eventually inducing HP and provide clues on a distinctive immunophenotype potentially able to predict HP.
https://ift.tt/2p2CQfb
Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients
Purpose: Methotrexate chemotherapy can be associated with neurologic complications during therapy and long-term neurologic deficits. This study evaluated demographic and clinical factors associated with incidence of methotrexate neurotoxicity and described the impact of neurotoxicity on acute lymphoblastic leukemia (ALL) therapy in pediatric patients.
Experimental Design: Patients were enrolled between 2012 and 2017 from three pediatric cancer treatment centers in the United States. Medical records for suspected cases of methotrexate neurotoxicity, defined as an acute neurologic event following methotrexate therapy, were reviewed. Cox proportional hazards models were used to estimate the association between race/ethnicity and methotrexate neurotoxicity. Multivariable linear regression models compared treatment outcomes between patients with and without methotrexate neurotoxicity.
Results: Of the 280 newly diagnosed patients enrolled, 39 patients (13.9%) experienced methotrexate neurotoxicity. Compared with non-Hispanic whites, Hispanic patients experienced the greatest risk of methotrexate neurotoxicity (adjusted HR, 2.43; 95% CI, 1.06–5.58) after accounting for sex, age at diagnosis, BMI Z-score at diagnosis, and ALL risk stratification. Patients who experienced a neurotoxic event received an average of 2.25 fewer doses of intrathecal methotrexate. Six of the 39 cases of neurotoxicity (15.4%) experienced relapse during the study period, compared with 13 of the 241 (2.1%) patients without neurotoxicity (P = 0.0038).
Conclusion: Hispanic ethnicity was associated with increased risk of methotrexate neurotoxicity, which was associated with treatment modifications and relapse. Understanding the mechanism and predictors of methotrexate neurotoxicity is important to improving treatment outcomes in pediatric ALL. Clin Cancer Res; 1–6. ©2018 AACR.
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GNAS, GNAQ, and GNA11 Alterations in Patients With Diverse Cancers
Cancer, EarlyView.
https://ift.tt/2MpIy46
Cancer Survivorship and Palliative Care: Shared Progress, Challenges, and Opportunities
Cancer, EarlyView.
https://ift.tt/2MncYEa
The Use of Neoadjuvant Larotrectinib in the Management of Children With Locally Advanced TRK Fusion Sarcomas
Cancer, EarlyView.
https://ift.tt/2x5JmpX
Lifestyle Factors and Health‐Related Quality of Life in Adult Survivors of Childhood Cancer: A Report From the St. Jude Lifetime Cohort Study
Cancer, EarlyView.
https://ift.tt/2MjOKKV
Photonic Capsule Sensors with Built‐In Colloidal Crystallites
Advanced Materials, EarlyView.
https://ift.tt/2x6uGq5
Advanced Multimaterial Electronic and Optoelectronic Fibers and Textiles
Advanced Materials, EarlyView.
https://ift.tt/2NCYB3o
Bioresponsive Nanoparticles Targeted to Infectious Microenvironments for Sepsis Management
Advanced Materials, EarlyView.
https://ift.tt/2xaydUm
Reply to ‘Comment on ‘Circulating Neutrophils in patients with hepatocellular carcinoma”
Reply to 'Comment on 'Circulating Neutrophils in patients with hepatocellular carcinoma"
Reply to 'Comment on 'Circulating Neutrophils in patients with hepatocellular carcinoma", Published online: 12 September 2018; doi:10.1038/s41416-018-0250-3
Reply to 'Comment on 'Circulating Neutrophils in patients with hepatocellular carcinoma"https://ift.tt/2O6dIPI
Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I study
Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I study
Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I study, Published online: 12 September 2018; doi:10.1038/s41416-018-0244-1
Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I studyhttps://ift.tt/2QocK2Y
Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo
Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo
Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo, Published online: 12 September 2018; doi:10.1038/s41416-018-0216-5
Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivohttps://ift.tt/2QocIrS
Comment on ‘Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?’
Comment on 'Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?'
Comment on 'Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?', Published online: 12 September 2018; doi:10.1038/s41416-018-0241-4
Comment on 'Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?'https://ift.tt/2OhHgtC
AHA: Update on Diagnosis, Tx for Chagas Cardiomyopathy
TUESDAY, Sept. 11, 2018 -- Health care providers need to be equipped to recognize, diagnose, and treat Chagas disease, which is growing in prevalence in the United States, according to an American Heart Association (AHA) scientific statement...
https://ift.tt/2x7dUHi
Chest Radiograph Effective for Excluding Pediatric Pneumonia
TUESDAY, Sept. 11, 2018 -- A negative chest radiograph (CXR) accurately excludes pneumonia in the majority of children, according to a study published in the September issue of Pediatrics. Susan C. Lipsett, M.D., from Harvard University in Boston,...
https://ift.tt/2N4diNe
Rituximab + Lenalidomide Effective in Follicular Lymphoma
TUESDAY, Sept. 11, 2018 -- Rituximab plus lenalidomide has similar efficacy to rituximab plus chemotherapy among patients with previously untreated follicular lymphoma, according to a study published in the Sept. 6 issue of the New England Journal...
https://ift.tt/2x7dS28
Tai Chi Effective at Reducing Number of Falls in Older Adults
TUESDAY, Sept. 11, 2018 -- Tai chi is more effective than conventional exercise at preventing falls among high-risk, older adults, according to a study published online Sept. 10 in JAMA Internal Medicine. Fuzhong Li, Ph.D., from the Oregon Research...
https://ift.tt/2N7mZe2
One in Five Pot Products Fails Potency, Purity Tests in California
TUESDAY, Sept. 11, 2018 -- Close to 20 percent of marijuana products in California have failed to pass tests for potency or purity since the state began mandating such testing July 1, a new report finds. Cannabis-infused cookies, candies, and...
https://ift.tt/2x7dOiU
Incidence, Risk Factors, and Epidemiology of Cystic Echinococcosis: A Complex Socioecological Emerging Infectious Disease in Khyber Pakhtunkhwa, Province of Pakistan
Cystic echinococcosis is a serious zoonotic disease caused by Echinococcus granulosus species complex. The current study is the first attempt to determine the level of infection in domestic livestock and to explore the CE-related knowledge and awareness among livestock farmers in different districts of Khyber Pakhtunkhwa, province of Pakistan. A total of 1297 animals were examined for hydatid cysts including 538 cows, 428 buffaloes, 208 sheep, and 123 goats, at different slaughter houses in different districts of Khyber Pakhtunkhwa in 2 years from September 2015 to September 2017. For epidemiological investigations, prevalence in association with various factors (climate, age, and gender), organ specificity, types of cysts (fertile, sterile, or calcified), and viability of cysts parameters was recorded. Basing on the results obtained, areas with high prevalence were selected for further follow-ups and administration of questionnaires to the farmers and dog owners, to provide baseline data about this parasitic disease and to identify potential areas of emergence with correspondence animal and of public health significance. The finding of this study revealed the presence of CE in livestock of KP, Pakistan. The prevalence of hydatid cysts was the highest in buffaloes (15.88%) followed by cows (15.79%), sheep (15.38%), and goats (3.25%). Our investigation revealed close relationship between prevalence and animal age and gender in different months of the year. These findings also showed the highest prevalence of hydatid cysts in liver (63.49%), followed by lungs (23.80%) and mesentery (2.64%). Fertile and viable cysts were observed in all animal species except goats. The highest percentage of fertile and viable cysts was reported from the liver and lungs of sheep. For evaluation of risk factors, a total of 384 respondents were investigated. The results of current study revealed that 97.9% of farmers are not familiar with CE and transmission of this infection from dogs to human and livestock. The present study shows that CE will continue to be of medical and veterinary importance in Pakistan.
https://ift.tt/2x27VDw
Biochemical Changes and Biological Origin of Key Odor Compound Generations in Pig Slurry during Indoor Storage Periods: A Pyrosequencing Approach
Production of odors is a complex process. Many bacterial species are involved in the production of an extensive array of key odor compounds in stored pig slurry. Understanding of basic microbial communities and their role during storage periods is an essential way to control and prevent the odors generations. In this aspect, the pig slurry samples were taken directly from deep pits of finisher pig building every two weeks, their biochemical changes were analysed, and the indigenous bacterial communities that involve in offensive odor producing compounds were identified. The SCFA, BCFA, phenols, and indoles levels altered drastically in the slurry during storage periods. The COD, BOD, SS, P2O5, TKN, and NH4-N were increased in the stored slurry. Bacterial ecology indicates Firmicutes and Bacteroidetes phyla were dominantly found in pig slurry. Odorants produced in pig slurry were correlated with bacterial communities. Phenols, indoles, SCFA, and BCFA productions were positively correlated with bacteria species which comes under phyla of Firmicutes and Bacteroidetes. It seems that bacterial species under Firmicutes and Bacteroidetes phyla play an important role in the offensive odor compounds production. Taken together, the prevention of these phyla bacterial growth and early discharge of pig slurry might reduce the offensive odor production.
https://ift.tt/2NBXVv5
Optimization of Ultrasound-Assisted Extraction Followed by Macroporous Resin Purification for Maximal Recovery of Functional Components and Removal of Toxic Components from Ginkgo biloba Leaves
In the present study, the process of ultrasound-assisted extraction (UAE) followed by macroporous resin purification was successfully developed to achieve maximal recovery of functional components (flavonoids and ginkgolides) with minimal contents of toxic components (alkylphenols) from Ginkgo biloba leaves. Three effective extracted factors including HAc%, EtOH%, and UAE power were screened by Plackett–Burman design (PBD). The important variables were further optimized by rotatable central composite design (RCCD). By combination of PBD and RCCD, the resulting optimal UAE conditions were as follows: HAc% of 1.8%, EtOH% of 63%, ultrasound power of 303 W, G. biloba leaves powder amount of 1.0 g (solvent-to-solid ratio 40 mL/g), particle size of 60 mesh, extraction time of 40 min, and extraction temperature of 45°C. Under the optimum conditions, the yield of flavonoids was 25.1 ± 0.81 mg/g, ginkgolides was 10.6 ± 0.57 mg/g, and alkylphenols was 3.96 ± 0.31 mg/g. Moreover, the further enriching the functional components and removing toxic components from the obtained extracts of G. biloba leaves using the above optimum UAE condition was successfully achieved by macroporous resin DA-201. After column adsorption and desorption on DA-201, the content of total flavonoids was 36.51 ± 1.53%, ginkgolides was 13.24 ± 0.85%, and alkylphenols was 7.0 ± 1.0 μg/g from the obtained dry extracts (drug to extract ratio of 45-50:1) of G. biloba leaves which were complied with Chinese pharmacopoeias.
https://ift.tt/2x9xMta
The Antimicrobial Peptide Nal-P-113 Exerts a Reparative Effect by Promoting Cell Proliferation, Migration, and Cell Cycle Progression
Objective. The primary purpose of this study was to evaluate the reparative efficacy of a novel antimicrobial peptide, Nal-P-113, in shortening the healing time of oral mucosal ulcers by promoting cell proliferation and migration and accelerating the cell cycle. Methods. Cell counting kit-8 (CCK-8) and wound-healing assays were used to evaluate the proliferation and migration of human immortalized oral epithelial cells (HIOECs). The cell cycle distribution of HIOECs was analyzed by flow cytometry. Additionally, the RNA levels of EGF, FGF-2, and TGF-β1 of HIOECs were assessed by real-time PCR. Rats were divided into three groups randomly: (a) blank control group; (b) 20 μg/mL Nal-P-113; and (c) 10 ng/mL rhEGF. An oral mucosal ulcer was induced in every rat by the application of 30% acetic acid. An immunohistochemical assay was used to assess the expression of EGF, FGF-2, and TGF-β1 in the rat oral mucosa. Results. In the CCK-8 assay, the optical density values in the Nal-P-113 and rhEGF groups were found to be significantly higher than that in the blank control group. In addition, the scratch areas in the Nal-P-113 and rhEGF groups were found to be significantly smaller (P
https://ift.tt/2NxqnON
Combined Celiac Ganglia and Plexus Neurolysis Shortens Survival, Without Benefit, vs Plexus Neurolysis Alone
Pancreatic cancer produces debilitating pain that opioids often ineffectively manage. The suboptimal efficacy of celiac plexus neurolysis (CPN) might result from brief contact of the injectate with celiac ganglia. We compared the effects of endoscopic ultrasound-guided celiac ganglia neurolysis (CGN) vs the effects of CPN on pain, quality of life (QOL), and survival.
https://ift.tt/2x6avIR
CAN anterior cervical fusion procedures prevent the progression of the natural course of Hirayama disease? An ambispective cohort analysis
Hirayama disease (HD) is a special neurological disease that is characterised by muscular weakness and atrophy in the upper extremities without sensory involvement (Hirayama, 2008; Zhou et al., 2010; Hassan and Sahni, 2013). The main hypotheses for the aetiology of HD implicates chronic ischemia of cervical motor neurons caused by neck flexion (Hirayama et al., 1987; Imai et al., 1999; Zheng et al., 2016). Furthermore, some previous studies suggest that the disease progression of HD may stop at 2-4 years after the onset (Tan, 1985; Tashiro et al., 2006; Huang et al., 2008).
https://ift.tt/2x0RU1q
The Pain Divide: a cross-sectional analysis of chronic pain prevalence, pain intensity and opioid utilisation in England
Objectives
Our central research question was, in England, are geographical inequalities in opioid use driven by health need (pain)? To answer this question, our study examined: (1) if there are regional inequalities in rates of chronic pain prevalence, pain intensity and opioid utilisation in England; (2) if opioid use and chronic pain are associated after adjusting for individual-level and area-level confounders.
DesignCross-sectional study design using data from the Health Survey for England 2011.
SettingEngland.
Primary and secondary outcome measuresChronic pain prevalence, pain intensity and opioid utilisation.
ParticipantsParticipant data relating to chronic pain prevalence, pain intensity and opioid usage data were obtained at local authority level from the Health Survey for England 2011; in total, 5711 respondents were included in our analysis.
MethodsRegional and local authority data were mapped, and a generalised linear model was then used to explore the relationships between the data. The model was adjusted to account for area-level and individual-level variables.
ResultsThere were geographical variations in chronic pain prevalence, pain intensity and opioid utilisation across the English regions—with evidence of a 'pain divide' between the North and the South, whereby people in the North of England more likely to have 'severely limiting' or 'moderately limiting' chronic pain. The intensity of chronic pain was significantly and positively associated with the use of opioid analgesics.
ConclusionsThere are geographical differences in chronic pain prevalence, pain intensity and opioid utilisation across England—with evidence of a 'pain divide'. Given the public health concerns associated with the long-term use of opioid analgesics—and their questionable activity in the management of chronic pain—more guidance is needed to support prescribers in the management of chronic pain, so the initiation of opioids can be avoided.
https://ift.tt/2N7a23R
Are noise and air pollution related to the incidence of dementia? A cohort study in London, England
Objective
To investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London.
DesignRetrospective cohort study using primary care data.
Setting75 Greater London practices.
Participants130 978 adults aged 50–79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence.
Primary and secondary outcome measuresA first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer's disease and vascular dementia during 2005–2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20x20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.
Results2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer's disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2 concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5 specifically from primary traffic sources only and Lnight, but only NO2 and PM2.5 remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer's disease than vascular dementia.
ConclusionsWe have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.
https://ift.tt/2MmHL3P
Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study
Anti-synthetase (AS) and dermato-pulmonary associated with anti-MDA-5 antibodies (aMDA-5) syndromes are near one of the other autoimmune inflammatory myopathies potentially responsible for severe acute interst...
https://ift.tt/2Qng7XN
A randomized-controlled trial evaluating general endotracheal anesthesia versus monitored anesthesia care and the incidence of sedation-related adverse events during ERCP in high-risk patients
ERCP is a complex procedure and often performed in patients at high risk for sedation-related adverse events (SRAE). However, there is no current standard of care with regard to mode of sedation and airway management during ERCP. The aim of this study was to assess the safety of general endotracheal anesthesia (GEA) versus propofol-based monitored anesthesia care without endotracheal intubation (MAC) in patients undergoing ERCP at high risk for SRAE.
https://ift.tt/2p12iSx
Quantification of Circulating miR-125b-5p Predicts Survival in Chronic Hepatitis B Patients with Acute-on-Chronic Liver Failure
To analyze the role of serum miR-125b-5p in reflecting liver damage and predicting outcomes in chronic hepatitis B (CHB) patients with acute-on-chronic liver failure (ACLF).
https://ift.tt/2QnhPbx
What to Consider in a Culturally Tailored Technology-Based Intervention?
The purpose of this article is to identify practical issues in implementing a culturally tailored technology-based intervention among Asian American survivors of breast cancer. In a large-scale technology-based breast cancer intervention study, research team members wrote memos on issues in implementing a culturally tailored technology-based intervention and plausible reasons for the issues. Then, the content of the research diaries was analyzed, along with written records of the research team. The practical issues found in the research process included those related to (1) technology literacy and preferences; (2) language issues; (3) cultural attitudes, beliefs, and values; (4) intervention staff competence; (5) security and confidentiality issues; and (6) time and geographical constraints. Based on the issues, several recommendations are proposed for future research using culturally tailored technology-based interventions among racial and ethnic minorities.
https://ift.tt/2x3qfNv
https://ift.tt/2x3qfNv
Educational Analytics: A New Frontier for Gamification?
To determine the effects of gamification on student education, researchers implemented "Kaizen," a software-based knowledge competition, among a first-year class of undergraduate nursing students. Multiple-choice questions were released weekly or biweekly during two rounds of play. Participation was voluntary, and students could play the game using any Web-enabled device. Analyses of data generated from the game included (1) descriptive, (2) logistic regression modeling of factors associated with user attrition, (3) generalized linear mixed model for retention of knowledge, and (4) analysis of variance of final examination performance by play styles. Researchers found a statistically significant increase in the odds of a correct response (odds ratio, 1.8; 95% confidence interval, 1.0–3.4) for a round 1 question repeated in round 2, suggesting retention of knowledge. They also found statistically significant differences in final examination performance among different play styles. To maximize the benefits of gamification, researchers must use the resulting data both to power educational analytics and to inform nurse educators how to enhance student engagement, knowledge retention, and academic performance.https://ift.tt/2x7cvBf
Association of Electronic Health Literacy With Health-Promoting Behaviors in Patients With Type 2 Diabetes: A Cross-sectional Study
It is important to know how well patients with type 2 diabetes understand and use health information available online in relation to health-promoting behaviors. Thus, the purposes of this study were to examine the association among electronic health literacy, perceived benefits, self-efficacy, and health-promoting behaviors in patients with type 2 diabetes, and to identify factors that affect health-promoting behaviors. A cross-sectional survey was conducted in a diabetes center in Seoul, South Korea. It was found that health-promoting behaviors were significantly correlated with electronic health literacy (r = 0.15, Phttps://ift.tt/2Mn4DjI
Customizing Functionality in an Electronic Health Record to Capture Value of Provider-Specific Services
No abstract availablehttps://ift.tt/2Miibx6
Ontology Development for Patient Education Documents Using a Professional- and Patient-Oriented Delphi Method
Written patient education materials are essential to motivate and help patients to participate in their own care, but the production and management of a large collection of high-quality and easily accessible patient education documents can be challenging. Ontologies can aid in these tasks, but the existing resources are not directly applicable to patient education. An ontology that models patient education documents and their readers was constructed. The Delphi method was used to identify a compact but sufficient set of entities with which the topics of documents may be described. The preferred terms of the entities were also considered to ensure their understandability. In the ontology, readers may be characterized by gender, age group, language, and role (patient or professional), whereas documents may be characterized by audience, topic(s), and content, as well as the time and place of use. The Delphi method yielded 265 unique document topics that are organized into seven hierarchies. Advantages and disadvantages of the ontology design, as well as possibilities for improvements, were identified. The patient education material ontology can enhance many applications, but further development is needed to reach its full potential.https://ift.tt/2MowUqt
Electronic Charting During Simulation: A Descriptive Study
Informatics is a core competency for nursing students recognized by several national organizations in healthcare and nursing education. Nurses must be able to use information and technology to communicate and manage knowledge in support of clinical decisions. Many hospitals either limit or deny nursing students' access to the electronic health record during traditional clinical learning. Simulation-based learning experiences are an alternative to traditional clinical experiences. What remains unclear is how nursing programs are incorporating electronic health record platforms within simulation. This study used a descriptive design to survey nursing programs exploring electronic health record use within simulation-based learning experiences in the classroom, skills laboratory, or simulation laboratory settings. Findings of the survey show that 56.2% of participants used an electronic health record in the classroom, skills laboratory, or simulation laboratory for simulation. Electronic health record use is gaining momentum via simulation-based learning experiences and students are not only documenting but also gathering data and appraising patient data for meaningful use to inform patient care decisions and promote clinical readiness.https://ift.tt/2x4nhbn
Preclinical testing of 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide: a potent protein kinase C-ι inhibitor as a potential prostate carcinoma therapeutic
Protein kinase C-iota (PKC-ι) is an oncogene overexpressed in many cancer cells including prostate, breast, ovarian, melanoma, and glioma. Previous in-vitro studies have shown that 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1s), a PKC-ι specific inhibitor, is effective against some cancer cell lines by decreasing cell growth and inducing apoptosis. To assess ICA-1s as a possible therapeutic, in-vivo studies using a murine model were performed. ICA-1s was tested for stability in blood serum and results demonstrated that ICA-1s was stable in human plasma at 25 and 37°C over a course of 2 h. Toxicity of ICA-1s was tested for both acute and subacute exposure. The acute exposure showed patient surviving after 48 h of doses ranging from 5 to 5000 mg/kg. Subacute tests exposed the patients to 14 days of treatment and were followed by serum and tissue collection. Aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, troponin, and C-reactive protein serum levels were measured to assess organ function. ICA-1s in plasma serum was measured over the course of 24 h for both oral and intravenous treatments. Heart, liver, kidney, and brain tissues were analyzed for accumulation of ICA-1s. Finally, athymic nude mice were xenografted with DU-145 prostate cancer cells. After tumors reached ~0.2 cm2, they were either treated with ICA-1s or left as control and measured for 30 days or until the tumor reached 2 cm2. Results showed tumors in treated mice grew at almost half the rate as untreated tumors, showing a significant reduction in growth. In conclusion, ICA-1s is stable, shows low toxicity, and is a potential therapeutic for prostate carcinoma tumors. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. https://ift.tt/1hexVwJ *André H. Apostolatos and Christopher A. Apostolatos contributed equally to the writing of this article. Correspondence to Mildred Acevedo-Duncan, PhD, Research Professor, University of South Florida, 4202 E. Fowler Ave., CHE 205 Tampa, FL 33620, USA Tel: +1 813 748 4715; fax: +1 813 974 3203; e-mail: macevedo@usf.edu Received May 23, 2018 Accepted August 20, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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An Adolescent with Left Ventricular Noncompaction and Ebstein Anomaly Presenting with Advanced Heart Failure: Discharge from Hospital with a Biventricular Assist Device
A 15-year-old adolescent presented to our emergency department (ED) for evaluation of shortness of breath, nonbilious, nonbloody vomiting, and abdominal pain that began 3 weeks before presentation. He also reported weight loss and constant fatigue for about 1 month, which prevented him from attending school. He complained of difficulty breathing with minimal exertion and could not perform many activities of daily living. He had not been able to sleep lying flat. He denied experiencing chest pain, palpitations, near syncope, or syncope.
https://ift.tt/2MkThNr
Predicting Risk of Infection in Infants with Congenital Diaphragmatic Hernia
To predict incident bloodstream infection and urinary tract infection (UTI) in infants with congenital diaphragmatic hernia (CDH).
https://ift.tt/2wZ1O3J
Regrowing dental tissue with stem cells from baby teeth
In a clinical trial stem cells extracted from children's baby teeth were used to regrow the living tissue in teeth damaged by injury. The promising findings highlight the potential of dental stem cells, which could one day be used in a wide range of dental procedures or even for treating certain systemic diseases.
https://ift.tt/2NywXnZ
Handheld Metal Detector Screening for Metallic Foreign Body Ingestion in Children
Here, we present a protocol to use the handheld metal detector, to screen for the presence of ingested metallic foreign bodies in children who present to the pediatric emergency medicine department with a history of foreign body ingestion.
https://ift.tt/2QnPF0o
Multiscale Structures Aggregated by Imprinted Nanofibers for Functional Surfaces
Presented is an easy method to fabricate nano-micro multiscale structures, for functional surfaces, by aggregating nanofibers fabricated using an anodic aluminum oxide filter.
https://ift.tt/2MkJjM1
Determining Tribocorrosion Rate and Wear-Corrosion Synergy of Bulk and Thin Film Aluminum Alloys
https://ift.tt/2Qnys7e
Total of 43,371 New Cases of HPV-Associated Cancers in 2015
TUESDAY, Sept. 11, 2018 -- A total of 43,371 new cases of human papillomavirus (HPV)-associated cancers were reported in 2015, with oropharyngeal squamous cell carcinoma (SCC) being the most common HPV-associated cancer, according to research...
https://ift.tt/2Mrhgus
Racial/Ethnic Disparity in Use of Low-Vision Devices
TUESDAY, Sept. 11, 2018 -- Among Medicare beneficiaries with self-reported vision impairment, Hispanic individuals and those from other races/ethnicities are less likely to report using low-vision devices than white individuals in a model adjusted...
https://ift.tt/2p1DTfn
Mediterranean Diet Tied to Lower Risk of Rheumatoid Arthritis
TUESDAY, Sept. 11, 2018 -- High adherence to the Mediterranean diet score is tied to lower risk of rheumatoid arthritis (RA) in some populations, according to a study published online Aug. 9 in Arthritis Research & Therapy. Kari Johansson,...
https://ift.tt/2Mrhcec
Opioids Often Prescribed in the Absence of Pain Diagnosis
TUESDAY, Sept. 11, 2018 -- Many outpatient opioid prescriptions have no documented medical indication, according to a research letter published online Sept. 11 in the Annals of Internal Medicine. Tisamarie B. Sherry, M.D., Ph.D., from the RAND...
https://ift.tt/2p0hkrM
Early Talk, Interaction Predicts School-Age Language Outcomes
TUESDAY, Sept. 10, 2018 -- Talk and interaction during early childhood, especially during 18 to 24 months, is associated with language and cognitive outcomes, according to a study published online Sept. 10 in Pediatrics. Jill Gilkerson, Ph.D., from...
https://ift.tt/2Mlzz47
Algorithm Can Discriminate Cardiovascular Disease Risk
TUESDAY, Sept. 11, 2018 -- The Cardiovascular Disease Population Risk Tool (CVDPoRT) algorithm, which includes 12 variables, can discriminate cardiovascular disease risk, according to a study recently published in CMAJ, the journal of the Canadian...
https://ift.tt/2oYUlNL
Shift Seen From EDs to Urgent Care for Low-Acuity, Acute Care
TUESDAY, Sept. 11, 2018 -- From 2008 through 2015, there was a substantial shift in venue in which acute care for low-acuity conditions was sought, according to a study published online Sept. 4 in JAMA Internal Medicine. Sabrina J. Poon, M.D., from...
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Data Age in Clinical Trials Is About Three Years at Publication
TUESDAY, Sept. 11, 2018 -- The median data age in clinical trials in journals with a high impact factor is about three years at publication, according to a study published in the Aug. 10 issue of JAMA Network Open. John Welsh, from Yale-New Haven...
https://ift.tt/2oZL5Zx
Medicaid Work Requirements Don't Impact Many Enrollees
TUESDAY, Sept. 11, 2018 -- Medicaid work requirements will only impact a small proportion of persons and may only generate minimal savings, according to two research letters published online Sept. 10 in JAMA Internal Medicine. Anna L. Goldman, M.D.,...
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Case Report Describes 4 Breast Cancer Cases Post Transplant
TUESDAY, Sept. 11, 2018 -- A single multiorgan donor transmitted breast cancer to four transplant recipients, according to a case report published recently in the American Journal of Transplantation. Yvette A.H. Matser, from the VU University...
https://ift.tt/2p0hkbg
Integrating Geriatric Assessment into Cancer Care: A Conversation with Dr. Supriya Mohile
Dr. Supriya Mohile discusses the unique issues experienced by older adults with cancer and efforts to incorporate geriatric assessment into patient care, including the publication of recent ASCO clinical guidelines on geriatric cancer care.
https://ift.tt/2CJydk7
The Effect of Nonoperative Management of Chronic Anal Fissure and Hemorrhoid Disease on Bowel Function Patient-Reported Outcomes
BACKGROUND: Nonoperative management has been reported to decrease symptoms from common anorectal conditions such as chronic anal fissures and hemorrhoids. The effects of these interventions on bowel function are unknown. OBJECTIVE: This study aims to perform a prospective evaluation of patient-reported outcomes of bowel function on nonoperative management for chronic anal fissures and hemorrhoid disease. DESIGN: This is a prospective, observational study. SETTINGS: Patient-reported outcome measures were collected from the clinical practice of the division of colon and rectal surgery at a tertiary colon and rectal surgery referral center. INTERVENTION: All patients received standardized dietary counseling including fiber supplementation as well as toileting strategies. Those with chronic anal fissures were also prescribed topical calcium channel blockers. The Colorectal Functional Outcome questionnaire was administered at baseline and at first follow-up visit. MAIN OUTCOME MEASURES: The primary outcomes measured were the mean change in patient-reported bowel function scores after nonoperative management for each disease and in aggregate. RESULTS: A cohort of 64 patients was included, 37 patients (58%) with chronic anal fissure and 27 patients with hemorrhoid disease. Incontinence, social impact, stool-related aspects, and the global score were observed to have statistically significant improvement in the aggregate group. When analyzed by diagnosis, hemorrhoid disease demonstrated a statistically significant improvement in incontinence and stool-related aspects, whereas chronic anal fissure was associated with a statistically significant change in social impact, stool-related aspects, and the global score. LIMITATIONS: This study was limited by the small cohort size and unclear patient adherence to medical management. CONCLUSIONS: Nonoperative management of chronic anal fissures and hemorrhoid disease is associated with significant improvement in patient-reported outcome scores in several domains, suggesting that dietary counseling and medical therapy should be the first-line outpatient therapy for these diseases. See Video Abstract at https://ift.tt/2x6O1Hl.https://ift.tt/2NBD4Id
Benefits and Early Outcomes of a New Mock Oral Examination for Colorectal Surgery
No abstract availablehttps://ift.tt/2NzFlDW
The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Chronic Radiation Proctitis
No abstract availablehttps://ift.tt/2NAI5AM
Intraperitoneal Local Anesthetic Instillation and Postoperative Infusion Improves Functional Recovery Following Colectomy: A Randomized Controlled Trial
BACKGROUND: Intraperitoneal local anesthetic is an analgesic technique for inclusion in the polypharmacy approach to postoperative pain management in enhanced recovery after surgery programs. Previously, augmentation of epidural analgesia with intraperitoneal local anesthetic was shown to improve functional postoperative recovery following colectomy. OBJECTIVE: This study determines whether intraperitoneal local anesthetic improves postoperative recovery in patients undergoing colectomy, in the absence of epidural analgesia, with standardized enhanced recovery after surgery perioperative care. DESIGN: This is a multisite, double-blinded, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier NCT02449720). SETTINGS: This study was conducted at 3 hospital sites in South Australia. PATIENTS: Eighty-six adults undergoing colectomy were stratified by approach (35 open; 51 laparoscopic), then randomly assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42) groups. INTERVENTIONS: Patients in the intraperitoneal local anesthetic group received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and postdissection and 20 mg/h continuous postoperative infusion for 48 hours. Patients in the control group received a normal saline equivalent. MAIN OUTCOME MEASURES: Functional postoperative recovery was assessed by using the surgical recovery scale for 45 days; postoperative pain was assessed by using a visual analog scale; and opioid consumption, use of rescue ketamine, recovery of bowel function, time to readiness for discharge, and perioperative complications were recorded. RESULTS: The intraperitoneal local anesthetic group reported improved surgical recovery scale scores at day 1 and 7, lower pain scores, required less rescue ketamine, and passed flatus earlier than the control group (phttps://ift.tt/2x6o62H
Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial
BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response. OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Four sequential study groups with stage II or III rectal cancer were included. INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9–125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004,https://ift.tt/2NGwm3X
Liposomal Bupivacaine Transversus Abdominis Plane Block Versus Epidural Analgesia in a Colon and Rectal Surgery Enhanced Recovery Pathway: A Randomized Clinical Trial
BACKGROUND: Multimodal pain management is an integral part of enhanced recovery pathways. The most effective pain management strategies have not been determined. OBJECTIVE: The purpose of this study was to compare liposomal bupivacaine transversus abdominis plane block with epidural analgesia in patients undergoing colorectal surgery. DESIGN: This is a single-institution, open-label randomized (1:1) trial. SETTING: This study compared liposomal bupivacaine transversus abdominis plane block with epidural analgesia in patients undergoing elective open and minimally invasive colorectal surgery in an enhanced recovery pathway. PATIENTS: Two hundred were enrolled. Following randomization, allocation, and follow-up, there were 92 patients with transversus abdominis plane block and 87 patients with epidural analgesia available for analysis. INTERVENTIONS: The interventions comprised liposomal bupivacaine transversus abdominis plane block versus epidural analgesia. MAIN OUTCOME MEASURES: The primary outcomes measured were numeric pain scores and the overall benefit of analgesia scores. RESULTS: There were no significant differences in the Numeric Pain Scale and Overall Benefit of Analgesia Score between groups. Time trend analysis revealed that patients with transversus abdominis plane block had higher numeric pain scores on the day of surgery, but that the relationship was reversed later in the postoperative period. Opioid use was significantly less in the transversus abdominis plane block group (206.84 mg vs 98.29 mg, phttps://ift.tt/2x2ocIE
The ALCCaS Trial: A Randomized Controlled Trial Comparing Quality of Life Following Laparoscopic Versus Open Colectomy for Colon Cancer
BACKGROUND: This study reports the quality-of-life assessment of the ALCCaS trial. The ALCCaS trial compared laparoscopic and open resection for colon cancer. It reported equivalence of survival at 5 years. Quality of life was measured as a secondary outcome. OBJECTIVE: This study aimed to report on the quality of life data of the ALCCaS Trial. DESIGN: This study reports a randomized controlled trial comparing laparoscopic with open colonic resection. SETTINGS: The study was conducted in Australasia. PATIENTS: Patients with a single adenocarcinoma of the right, left, or sigmoid colon, presenting for elective treatment, were eligible for randomization. INTERVENTIONS: Open and laparoscopic colonic resections were performed. MAIN OUTCOME MEASURES: Patient symptoms and quality of life were measured using the Symptoms Distress Scale, the Quality of Life Index, and the Global Quality of Life Score preoperatively, and at 2 days, 2 weeks, and 2 months postoperatively. RESULTS: Of the 592 patients enrolled in ALCCaS, 425 completed at least 1 quality-of-life measure at 4 time points (71.8% of cohort). Those who received the laparoscopic intervention had better quality of life postoperatively in terms of the Symptoms Distress Scale (phttps://ift.tt/2NxMS6e
Life After Surgery: Surgeon Assessments of Quality of Life Among Patients With Familial Adenomatous Polyposis
BACKGROUND: Without prophylactic surgery, patients with familial adenomatous polyposis are at high risk for colorectal cancer development. Various surgical options for prophylaxis are available. Patient decision-making for preventative treatments is often influenced by the preferences of healthcare providers. OBJECTIVE: We determined surgeon preferences for the surgical options available to patients with familial adenomatous polyposis. DESIGN: We obtained preference estimates for postoperative health states from colorectal surgeons who had treated ≥10 patients with familial adenomatous polyposis. SETTINGS: Assessments were made at an annual meeting of the American Society of Colon and Rectal Surgeons. MAIN OUTCOME MEASURES: Utilities were measured through the time trade-off method. We determined utilities for 3 procedures used for prophylaxis, including total proctocolectomy with permanent ileostomy, colectomy with ileorectal anastomosis, and total proctocolectomy with IPAA. We also assessed utilities for 2 short-term health states: 90 days with a temporary ileostomy and 2 years with a poorly functioning ileoanal pouch. RESULTS: Twenty-seven surgeons who had cared for >1700 patients with familial adenomatous polyposis participated in this study. The highest utility scores were provided for colectomy with ileorectal anastomosis (0.98). Lower utility scores were provided for total proctocolectomy with permanent ileostomy (0.87) and IPAA (0.89). The number of patients with familial adenomatous polyposis who were treated by participating surgeons did not influence these estimates; however, more-experienced surgeons gave lower utility scores for a poorly functioning ileoanal pouch than less-experienced surgeons (0.15, 0.50, and 0.25 for high-, medium-, and low-volume surgeons; p = 0.02). LIMITATIONS: This study was limited by the sample size. CONCLUSIONS: For patients with familial adenomatous polyposis and relative rectal sparing, surgeon preferences are greatest for colectomy with ileorectal anastomosis. Utility estimates provided by this study are important for understanding surgical decision-making and suggest a role for ileorectal anastomosis in appropriately selected patients. See Video Abstract at https://ift.tt/2NCAl18.https://ift.tt/2x6lFxa
Radiologic Evaluation of Clinically Benign Rectal Neoplasms May Not Be Necessary Before Local Excision
BACKGROUND: Local excision may be curative for benign and malignant rectal neoplasms. Because many early rectal cancers are discovered incidentally after local excision of clinically benign lesions, it is unclear whether preoperative imaging with transrectal ultrasound or MRI affects management. OBJECTIVE: The purpose of this study was to determine the diagnostic characteristics and effect of preoperative imaging on the incidence of malignancy in benign rectal lesions undergoing local excision. DESIGN: Prospective data from 2 institutions were included. Coarsened exact matching created a balanced cohort comparing imaging and no-imaging groups. SETTING: The study was conducted at high-volume specialist referral hospitals. PATIENTS: Adult patients undergoing local excision via transanal endoscopic surgery between 1997 and 2016 for clinically benign rectal neoplasms were included. INTERVENTION: The study intervention included preoperative imaging with transrectal ultrasound and/or MRI. MAIN OUTCOME MEASURES: We measured the incidence of malignancy and diagnostic accuracy of preoperative imaging. RESULTS: A total of 620 patients were included (272 with preoperative imaging and 348 without). There were 250 patients undergoing transrectal ultrasound, and 24 patients undergoing MRI (2 patients underwent both). Transrectal ultrasound and MRI correctly identified malignant polyps in 50% (11/22) and 44% (8/18). Overall agreement for benign versus malignant polyps between preoperative imaging and final pathology was κ = 0.30 (95% CI, 0.18–0.41) for transrectal ultrasound and 0.29 (95% CI, 0.01–0.57) for MRI. In both the overall and unmatched cohorts, the incidence of malignancy, margin involvement, and proportion of patients requiring salvage surgery was similar. LIMITATIONS: Data were obtained from 2 institutions with different equipment over a long time period. CONCLUSIONS: Preoperative imaging did not accurately identify malignancy in clinically benign rectal lesions and did not affect the incidence of malignancy, margin involvement, or proportion of patients requiring salvage surgery. Therefore, preoperative imaging may not be necessary for clinically benign lesions undergoing local excision. See Video Abstract at https://ift.tt/2NxMKDM.https://ift.tt/2x2ocbC
Indocyanine Green Fluorescence Angiography and the Incidence of Anastomotic Leak After Colorectal Resection for Colorectal Cancer: A Meta-analysis
BACKGROUND: Anastomotic leak is a life-threatening complication of colorectal surgery. Recent studies showed that indocyanine green fluorescence angiography might be a method to prevent anastomotic leak. OBJECTIVE: The purpose of this study was to investigate whether intraoperative indocyanine green fluorescence angiography can reduce the incidence of anastomotic leak. DATA SOURCES: Potential relevant studies were identified from the following databases: PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. STUDY SELECTION: This meta-analysis included comparative studies investigating the association between indocyanine green fluorescence angiography and anastomotic leak in patients undergoing surgery for colorectal cancer where the diagnosis of anastomotic leak was confirmed by CT and the outcomes of the indocyanine green group were compared with a control group. INTERVENTION: Indocyanine green was injected intravenously after the division of the mesentery and colon but before anastomosis. MAIN OUTCOME MEASURES: The Newcastle–Ottawa Scale was used to assess methodologic quality of the studies. ORs and 95% CIs were used to assess the association between indocyanine green and anastomotic leak. RESULTS: In 4 studies with a total sample size of 1177, comparing the number of anastomotic leaks in the indocyanine green and control groups, the ORs were 0.45 (95% CI, 0.18–1.12), 0.30 (95% CI, 0.03–2.98), 0.17 (95% CI, 0.01–3.69), and 0.12 (95% CI, 0.03–0.52). The combined OR was 0.27 (95% CI, 0.13–0.53). The difference was statistically significant (phttps://ift.tt/2x8cNqy
Extended Venous Thromboembolism Prophylaxis After Elective Surgery for IBD Patients: Nomogram-Based Risk Assessment and Prediction from Nationwide Cohort
BACKGROUND: Identification of risk factors for postoperative venous thromboembolism is an important step to reduce the morbidity associated with this potentially preventable complication after elective surgery for patients with IBD. OBJECTIVE: This study aimed to determine the risk factors for 30-day venous thromboembolism after abdominal surgery for patients with venous thromboembolism, identify potential indications for extended thromboprophylaxis, and develop a nomogram for prediction of risk. DESIGN: This is a retrospective cohort study from a prospectively collected database. SETTING: The American College of Surgeons National Surgical Quality Improvement Program Participant User File from 2005 to 2016 was used for data analysis. PATIENTS: All patients with IBD undergoing elective abdominopelvic bowel surgery were included. MAIN OUTCOME MEASURES: The primary outcomes were the incidence of in-hospital and postdischarge venous thromboembolism within 30 days of the index abdominopelvic surgery. RESULTS: A total of 24,182 patients met the inclusion criteria. Thirty-day total and postdischarge rates of venous thromboembolism were 2.5% (n = 614) and 1% (n =252). Forty-one percent (252/614) of venous thromboembolism events occurred after hospital discharge. Univariate analysis assessed 37 variables for association with study outcomes. On multivariate logistic regression analysis, older age, steroid use, bleeding disorders, open surgery, hypertension, longer operative time, and preoperative hospitalization were associated with venous thromboembolism before discharge and also postoperative transfusion, steroid use, pelvic and enterocutaneous fistula surgery, and longer operative time were associated with venous thromboembolism after discharge. A nomogram was constructed for each outcome, translating multivariate model parameter estimates into a visual scoring system where the estimated probability of venous thromboembolism can be calculated. LIMITATIONS: This study was limited by its retrospective nature and the limitations inherent to a database. CONCLUSION: Given the higher risk of venous thromboembolism in patients with IBD after elective abdominopelvic surgery compared with other indications, an accurate prediction of venous thromboembolism before and after discharge using the proposed nomogram can facilitate decision making for individualized extended thromboprophylaxis in the preoperative setting as a screening tool. See Video Abstract at https://ift.tt/2xdImzF.https://ift.tt/2NA7n1P
Lateral Node Dissection in Rectal Cancer in the Era of Minimally Invasive Surgery: A Step-by-Step Description for the Surgeon Unacquainted with This Complex Procedure with the Use of the Laparoscopic Approach
INTRODUCTION: Lateral node dissection in rectal cancer has been routinely performed in Eastern countries. Technical and anatomical challenges and potential significant postoperative morbidity associated with the procedure have prevented its implementation into clinical practice in Western countries. However, the minimally invasive approach may offer the opportunity of performing this complex procedure with precise anatomical dissection and minimal intraoperative blood loss. In this setting, proper training and standardization of technical steps is highly warranted for surgeons not fully acquainted with the procedure. TECHNIQUE: Access to the lateral nodes along the obturator and internal iliac vessels is described by using specific anatomical landmarks. Opening of the peritoneum along the ureter provides access to the region of interest. Dissection of the medial limit is performed preserving the neurovascular bundle and ureter. The lateral dissection is performed along the external iliac vein to provide access to the obturator muscle. Identification of the obturator nerve with blunt dissection of the fat is a critical part of the procedure. Once the lymphatic connections between the inguinal and iliac nodes are transected, dissection is performed along the internal iliac vessels, and branches are separated from the lymphadenectomy specimen. RESULTS: Evidence supports that lateral node dissection performed for highly selected patients with minimally invasive access leads to less intraoperative blood loss and similar oncological outcomes. Technical steps illustrated in the present video may aid surgeons in performing this procedure with precise anatomical landmarks and minimal risk for intraoperative complications. CONCLUSIONS: Lateral node dissection for rectal cancer is a procedure that may follow standardized technical steps by using precise anatomical landmarks with the use of minimally invasive approach.
https://ift.tt/2Nybs6O
https://ift.tt/2Nybs6O
Quantifying Acute Changes in Renal Sympathetic Nerve Activity in Response to Central Nervous System Manipulations in Anesthetized Rats
Methods for measuring sympathetic and cardiovascular responses to central nervous system (CNS) manipulations are important for advancing neuroscience. This protocol was developed to assist scientists with measuring and quantifying acute changes in renal sympathetic nerve activity (RSNA) in anesthetized rats (non-survival).
https://ift.tt/2QkqLyt
Spectrophotometric Determination of Phycobiliprotein Content in Cyanobacterium Synechocystis
https://ift.tt/2CGMgXD
Predicting Responses to Pregabalin for Painful Diabetic Peripheral Neuropathy Based on Trajectory-Focused Patient Profiles Derived from the First 4 Weeks of Treatment
Abstract
Introduction
Prediction of final clinical outcomes based on early weeks of treatment can enable more effective patient care for chronic pain. Our goal was to predict, with at least 90% accuracy, 12- to 13-week outcomes for pregabalin-treated painful diabetic peripheral neuropathy (pDPN) patients based on 4 weeks of pain and pain-related sleep interference data.
Methods
We utilized active treatment data from six placebo-controlled randomized controlled trials (n = 939) designed to evaluate efficacy of pregabalin for reducing pain in patients with pDPN. We implemented a three-step, trajectory-focused analytics approach based upon patient responses collected during the first 4 weeks using monotonicity, path length, frequency domain (FD), and k-nearest neighbor (kNN) methods. The first two steps were based on combinations of baseline pain, pain at 4 weeks, weekly monotonicity and path length during the first 4 weeks, and assignment of patients to one of four responder groups (based on presence/absence of 50% or 30% reduction from baseline pain at 4 and at 12/13 weeks). The third step included agreement between prediction of logistic regression of daily FD amplitudes and assignment made from kNN analyses.
Results
Step 1 correctly assigned 520/939 patients from the six studies to a responder group using a 3-metric combination approach based on unique assignment to a 50% responder group. Step 2 (applied to the remaining 419 patients) predicted an additional 121 patients, using a blend of 50% and 30% responder thresholds. Step 3 (using a combination of FD and kNN analyses) predicted 204 of the remaining 298 patients using the 50% responder threshold. Our approach correctly predicted 90.0% of all patients.
Conclusion
By correctly predicting 12- to 13-week responder outcomes with 90% accuracy based on responses from the first month of treatment, we demonstrated the value of trajectory measures in predicting pDPN patient response to pregabalin.
Trial Registration
www.clinicaltrials.gov identifiers, NCT00156078/NCT00159679/NCT00143156/NCT00553475.
Funding
Pfizer.
Plain Language Summary
Plain language summary available for this article.
https://ift.tt/2MlnxaL
72-Week Safety and Tolerability of Dimethyl Fumarate in Japanese Patients with Relapsing-remitting Multiple Sclerosis: Analysis of the Randomised, Double Blind, Placebo-Controlled, Phase III APEX Study and its Open-Label Extension
Abstract
Introduction
The long-term safety of dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (RRMS) has been studied in mainly Caucasian patients. The present interim analysis aimed to evaluate the 72-week safety of DMF in Japanese patients with RRMS.
Methods
Safety data of Japanese subjects enrolled in the 24-week randomised, double-blind, placebo-controlled APEX study (Part I) and its following open-label extension (Part II) were analysed at 72 weeks from the beginning of Part I. In Part I, subjects were randomised to DMF treatment or matching placebo while all subjects received DMF treatment during Part II. Adverse events (AEs) reported throughout the study period were recorded.
Results
Overall, 109 Japanese subjects completed 72 weeks of treatment. The incidence of AEs and serious AEs was 95% and 19%, respectively, in the DMF group compared with 84% and 18%, respectively, in the placebo group at 24 weeks. Common AEs (at least 5%) reported with treatment included nasopharyngitis, flushing, hot flush, gastrointestinal events, pruritus, rash, headache, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). AEs led to discontinuation of DMF in 5% of patients and included MS relapse, flushing, abdominal pain, liver disorder and increased ALT/AST. After an initial decrease from baseline of 17% in the DMF group at week 24, the mean lymphocyte counts stabilised and were maintained until week 72. No opportunistic/serious infections nor malignancies were reported with DMF treatment. The incidences of AEs, serious AEs, and discontinuation due to AEs were similar between the DMF and the placebo groups.
Conclusion
The 72-week safety profile of DMF in Japanese patients with RRMS was consistent with previous studies that enrolled mostly Caucasian patients, with a lower incidence of flushing and related symptoms and a lower reduction in the lymphocyte count compared with previous reports.
Trial Registration
ClinicalTrials.gov identifier NCT01838668.
Funding
Biogen Japan Ltd.
https://ift.tt/2MksZL3
Does ‘Strong Analgesic’ Equal ‘Strong Opioid’? Tapentadol and the Concept of ‘µ-Load’
Abstract
Introduction
The distinct properties of the centrally-acting analgesic tapentadol derive from the combined contributions of an opioid component and a nonopioid component. However, the opioid component's relative contribution to analgesic and adverse effects has not previously been elucidated. Tapentadol's analgesic effect derives from the combined contribution of an opioid mechanism and a nonopioid mechanism, the extent of which can vary for different pains. Likewise, the interaction can vary for various adverse effects. Hence, the contribution of each mechanism to adverse effects can be different from the contribution to analgesia. We here estimate the percent contribution of each component of the mechanism of action to analgesia and to adverse effects.
Areas Covered
Several approaches to in vitro and in vivo data to estimate the contribution of tapentadol's opioid component to analgesia and to the two important opioid adverse effects, respiratory depression and constipation. The results are then compared with clinical data.
Expert Opinion
Traditional opioids, such as morphine, oxycodone, and others, produce their analgesic effects primarily through a single mechanism—the activation of µ-opioid receptors (MOR). Therefore, the contribution of the opioid component to adverse effects is 100%. In contrast, the newer strong analgesic tapentadol produces its analgesic effect via two separate and complementary analgesic mechanisms, only one of which is µ-opioid. We applied standard drug–receptor theory and novel techniques to in vitro and in vivo data to estimate by several different ways the μ-load of tapentadol (the % contribution of the opioid component to the adverse effect magnitude relative to a pure/classical µ-opioid at equianalgesia) in respiratory depression and constipation, and we compared the results to clinical evidence. The estimate is remarkably consistent over the various approaches and indicates that the μ-load of tapentadol is ≤ 40% (relative to pure MOR agonists, which have, by definition, a µ-load of 100%).
Funding
Grünenthal GmbH.
https://ift.tt/2Qm36O4
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
