Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease in ruminants. The "gold standard" of MAP detection is by culture, DNA sequencing possibly supplemented by identification of Ziehl–Neels...
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Σάββατο 21 Ιουλίου 2018
Failure to detect M. avium subspecies paratuberculosis in Johne’s disease using a proprietary fluorescent in situ hybridization assay
A novel inhibitor targets both Wnt signaling and ATM/p53 in colorectal cancer
For 2017, the estimated lifetime risk of developing colorectal cancer (CRC) was 1 in 22. Even though preventative colonoscopy screening and standard of care surgery, radiation, and chemotherapy have decreased the death rate from CRC, new therapies are needed for metastatic CRC. Here we developed a novel small molecule, compound 2, that inhibited proliferation and viability of human CRC cells (HCT-116, DLD-1, SW480, and 10.1). Compound 2 inhibited cell migration, invasion, and EMT processes and potently increased cell apoptosis in human CRC cells. Compound 2 also modulated mitotic stress signaling, leading to both inhibition of Wnt responsiveness and stabilization and activation of p53 to cause cell cycle arrest. In mouse xenografts, treatment with compound 2 (20 mg/kg/day, i.p.) induced cell death and inhibited tumor growth >4-fold compared to vehicle at day 34. Neither acute cytotoxicity nor toxicity in animals (up to 1000 mg/kg, i.p.) were observed for compound 2. To our knowledge, compound 2 is the first reported potent small molecule that inhibits Wnt/β-catenin signaling, activates p53 signaling regardless of p53 mutation status and binds microtubules without detectable toxicity. Thus, compound 2 offers a novel mechanism of action and a new strategy to treat CRC.
https://ift.tt/2O6mKN3
Rapid Fire
Emergency providers are likely to encounter sickle cell disease–related emergencies. The pathophysiology of emergent complaints are usually related to either an acute anemia or a vasoocclusive crisis. Differentiating between the two is the first step in the workup. Anemic crises must then be differentiated by the source. Vasoocclusive crises must be appropriately treated with aggressive pain management, gentle hydration, and other appropriate adjuncts. Early recognition and treatment are key in providing excellent emergency care to those with sickle cell disease.
https://ift.tt/2uFlgkF
Hematologic and Oncologic Emergencies
In the past two decades of practicing emergency medicine, there are probably only two major conditions that seem to have markedly increased in my practice: the number of elderly patients we care for and the number of patients with cancer (in their current or past history) that we care for. The increase in elderly patients in our practice has been strongly addressed in recent years in educational conferences, textbooks and journals, and national guidelines. But cancer still seems to be a relatively ignored clinical condition in emergency medicine.
https://ift.tt/2uC44wA
The Heme-Onc Tidal Wave: Are You Prepared?
The cancer population in the United States continues to grow and is projected to do so for the foreseeable future. Patients with hematologic and oncologic emergencies are presenting in increasing numbers to all types of emergency departments…academic, community, and rural. These patients bring a unique set of illnesses and complications, both of their primary disease and of its treatment. A functional understanding of some of the more frequently encountered emergencies in this unique population is mandatory for all practicing emergency providers.
https://ift.tt/2A3DGky
Rapid Fire
Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency, characterized by a constellation of hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia. The spectrum ranges from patients who are asymptomatic to those who go into cardiac arrest and die. Prompt recognition and initiation of treatment by emergency physicians are key, especially in the early stages of the syndrome. This case-based review presents an overview of the key points in pathophysiology, diagnosis, and management of TLS that are key to emergency physicians.
https://ift.tt/2uE3xdA
Anticoagulation Reversal
Today a variety of anticoagulants and antiplatelet agents are available on the market. Given the propensity for bleeding among patients prescribed these medications, the emergency medicine physician must be equipped with a working knowledge of hemostasis, and anticoagulant and antiplatelet reversal. This article reviews strategies to address bleeding complications occurring secondary to warfarin, low-molecular-weight heparin, and direct oral anticoagulant therapy.
https://ift.tt/2zY8nYb
The Cancer Emergency Department—The Ohio State University James Cancer Center Experience
In 2015, The James Cancer Hospital's Emergency Department (ED) opened at The Ohio State University Wexner Medical Center's ED. Careful planning was undertaken to assure that the needs of patients with cancer would be addressed. Strong relationships between experts in hematology, oncology, and emergency medicine were built to maximize the positive impact. Ongoing reevaluation of operational needs facilitates optimal patient flow, resource use, and opportunities to build and develop new resources. The results are evident in improved patient satisfaction in the cancer ED and a much smoother flow of patients into the system.
https://ift.tt/2LDKnL9
Hematologic and Oncologic Emergencies
EMERGENCY MEDICINE CLINICS OF NORTH AMERICA
https://ift.tt/2uB1cAe
Ictal asystole: a case presentation
Epileptic seizures can lead to cardiac arrhythmias. The arrhythmias may be in the form of tachycardia, bradycardia or asystole. Ictal bradycardia and asystole can lead to sudden unexpected death.
https://ift.tt/2JIQKeu
Miller Fisher syndrome, Bickerstaff brainstem encephalitis and Guillain-Barré syndrome overlap with persistent non-demyelinating conduction blocks: a case report
Miller Fisher syndrome (MFS) and Bickerstaff's Brainstem Encephalitis (BBE) share some clinical features and a common immunological profile characterized by anti-GQ1b antibodies. Some MFS patients overlap with...
https://ift.tt/2Lc5UP4
Granular Cell Tumour in Stomach: a Case Report
Abstract
Granular cell tumours are uncommon, usually benign soft tissue tumours. They are thought to be neural, arising from Schwann cells and can occur at various sites. Their occurrence in gastrointestinal tract is rare, the commonest site being oesophagus followed by large intestine. Gastric localization is unusual. A young female presented with abdominal discomfort since 3 months. Endoscopy showed a nodule in the body of stomach. Biopsy revealed features of granular cell tumour on microscopy, which was confirmed by immunohistochemical positivity for S100 and CD68. Wide excision of the tumour was performed. At the 6-month follow-up, patient was asymptomatic. The diagnosis of gastric granular cell tumour is based on endoscopic biopsy. Unless there is histological evidence of malignancy, wide local excision is an adequate surgical treatment.
https://ift.tt/2NywvCw
Serial FLT PET imaging to discriminate between true progression and pseudoprogression in patients with newly diagnosed glioblastoma: a long-term follow-up study
Abstract
Purpose
Response evaluation in patients with glioblastoma after chemoradiotherapy is challenging due to progressive, contrast-enhancing lesions on MRI that do not reflect true tumour progression. In this study, we prospectively evaluated the ability of the PET tracer 18F-fluorothymidine (FLT), a tracer reflecting proliferative activity, to discriminate between true progression and pseudoprogression in newly diagnosed glioblastoma patients treated with chemoradiotherapy.
Methods
FLT PET and MRI scans were performed before and 4 weeks after chemoradiotherapy. MRI scans were also performed after three cycles of adjuvant temozolomide. Pseudoprogression was defined as progressive disease on MRI after chemoradiotherapy with stabilisation or reduction of contrast-enhanced lesions after three cycles of temozolomide, and was compared with the disease course during long-term follow-up. Changes in maximum standardized uptake value (SUVmax) and tumour-to-normal uptake ratios were calculated for FLT and are presented as the mean SUVmax for multiple lesions.
Results
Between 2009 and 2012, 30 patients were included. Of 24 evaluable patients, 7 showed pseudoprogression and 7 had true progression as defined by MRI response. FLT PET parameters did not significantly differ between patients with true progression and pseudoprogression defined by MRI. The correlation between change in SUVmax and survival (p = 0.059) almost reached the standard level of statistical significance. Lower baseline FLT PET uptake was significantly correlated with improved survival (p = 0.022).
Conclusion
Baseline FLT uptake appears to be predictive of overall survival. Furthermore, changes in SUVmax over time showed a tendency to be associated with improved survival. However, further studies are necessary to investigate the ability of FLT PET imaging to discriminate between true progression and pseudoprogression in patients with glioblastoma.
https://ift.tt/2O8GuQn
Histological features of autoimmune hepatitis: a critical appraisal
We speculate that the 'typical' histological features (lymphoplasmacytic interface hepatitis, emperipolesis and hepatocyte rosettes) of autoimmune hepatitis (AIH) are related to severity of hepatitis rather than etiology. We critically appraised various histologic features of AIH and compared them to cases of chronic hepatitis with similar inflammatory grade and fibrosis stage. Fifty one patients with clinically confirmed AIH were identified at our institution, of which 43 biopsies (from 42 patients) were taken prior to initiation of therapy and formed the study group.
https://ift.tt/2Lg1Ugn
Testicular germ cell tumors: revisiting a series in light of the new WHO classification and AJCC staging systems, focusing on challenges for pathologists
Testicular germ cell tumors (TGCTs) are strikingly heterogeneous, reflecting a complex tumor model, posing serious challenges for pathologists. Accurate classification and staging, according to most recent systems, is fundamental. We aimed to revise a series of consecutively diagnosed TGCTs (2005–2016) in light of the new World Health Organization (WHO) classification and American Joint Committee on Cancer (AJCC) staging systems, discussing dilemmas imposed to pathologists. All 164 patients' clinical files/histological slides were reviewed.
https://ift.tt/2LCibsl
Genotype-phenotype correlation of patients with tuberous sclerosis complex-associated renal angiomyolipoma: a descriptive study
TSC2 gene mutation was repeatedly reported associated with a more severe phenotype in patients of tuberous sclerosis complex (TSC). Our current study aims to further explore whether there is such a correlation in patients with TSC-associated renal angiomyolipoma (TSC-RAML). TSC1/TSC2 gene mutation was screened by high throughput sequencing in 25 TSC-RAML patients from two medical centers. Clinical data were also carefully collected. Linear-regression analysis and student t-test were conducted by IBM SPSS Statistics Version 21.0 to analyze the genotypic-phenotypic relationship.
https://ift.tt/2LbzjsB
Distribution of dysplasia and cancer in the gallbladder: an analysis from a high cancer-risk population
Gallbladder dysplasia can progress to cancer and may be associated with increased cancer risk at other biliary tract sites. Thus, its accurate identification is relevant both for etiologic understanding and for clinical purposes. Data on the frequency and distribution of gallbladder dysplasia are lacking due to limited gallbladder sampling and inability to visualize dysplasia grossly. An expert pathology group used consensus criteria to review 140 totally sampled consecutive cholecystectomy specimens from Chilean women.
https://ift.tt/2LEAdu2
Benign vascular tumors, cysts and pseudocysts of the adrenal gland: a contemporary multi-institutional clinicopathologic analysis of 55 cases
Benign adrenal vascular tumors, cysts and pseudocysts are a heterogeneous group of relatively uncommon entities that may pose diagnostic challenges radiologically and pathologically. However, there are only a few small cases series, systematically characterizing the clinicopathologic features of these lesions. We identified 55 cases of benign adrenal vascular tumors, cysts and pseudocysts (23 pseudocysts, 17 hemangiomas, 8 lymphangiomas, 6 angiomatous endothelial cysts and 1 arteriovenous malformation) from a multi-institutional Urologic Pathology database between 2000–2017, and retrospectively analyzed their clinicopathologic features.
https://ift.tt/2LguHS8
Investigating the impact of TB case-detection strategies and the consequences of false positive diagnosis through mathematical modelling
Increasing case notifications is one of the top programmatic priorities of National TB Control Programmes (NTPs). To find more cases, NTPs often need to consider expanding TB case-detection activities to popul...
https://ift.tt/2O91Ht9
Hepatitis C seropositivity among newly incarcerated prisoners in Estonia: data analysis of electronic health records from 2014 to 2015
Hepatitis C virus (HCV) infection is a widespread problem in prisons. The present study aimed to assess the prevalence of HCV seropositivity, HCV genotypes, factors associated with HCV seropositivity in newly ...
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Total yield of reactive species originating from an atmospheric pressure plasma jet in real time
Journal Name: Biological Chemistry
Issue: Ahead of print
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Physical plasma and leukocytes – immune or reactive?
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2uEIuYt
MAC30 knockdown involved in the activation of the Hippo signaling pathway in breast cancer cells
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2zXGwaJ
Involvement of mitophagy in cisplatin-induced cell death regulation
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2uG5h5Z
Activation and activity of glycosylated KLKs 3, 4 and 11
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2zZZSvN
Effects of Body Size and Composition on Sex Differences in Measured GFR in a US Community-Based Older Cohort (MESA-Kidney)
Extensive evidence suggests that normal measured glomerular filtration rate (mGFR) indexed for body surface area (BSA) may be slightly lower in young and middle-aged women than men.1-3 A recent substudy of a US community-based older cohort, Multi-Ethnic Study of Atherosclerosis (MESA-Kidney), reported a 12% lower mGFR in women than men.4 This difference was not observed in a prior substudy of an Icelandic community-based older cohort, Aging Genes Environment Susceptibility (AGES-Kidney), using similar methods for GFR measurement.
https://ift.tt/2NzVHJ7
Mercury Intoxication as a Rare Cause of Membranous Nephropathy in a Child
In adults, membranous nephropathy is the second most common cause of nephrotic syndrome. In contrast, minimal change disease and focal segmental glomerulosclerosis constitute the most common forms of nephrotic syndrome in children, while membranous nephropathy accounts for <5% of cases. In adults, causes of membranous nephropathy include autoantibodies directed against phospholipase A2 receptor and thrombospondin type 1 containing 7A, various infections, environmental toxicities, autoimmune disorders, malignancies, and other secondary forms.
https://ift.tt/2O7Fvzz
Postcontrast Acute Kidney Injury in Pediatric Patients: A Cohort Study
The risks of iodinated contrast material administered to pediatric patients are not well defined. The purpose of this study was to examine the rates of postcontrast acute kidney injury (AKI), dialysis therapy, and death following administration of intravenous contrast material to pediatric patients.
https://ift.tt/2NzVyFz
Monoclonal Antibodies for Waldenström Macroglobulinemia
For the last 2 decades, anti-CD20 monoclonal antibodies have revolutionized the treatment of patients with B-cell lymphomas. These agents have shown efficacy when used as single agents and also have improved response and survival rates when added to chemotherapy. Monoclonal antibodies are safe and effective as well in patients with Waldenström macroglobulinemia (WM). The purpose of this article is to review the mechanism of action of monoclonal antibodies and to discuss current clinical data supporting their use in patients with WM. This review focuses on retrospective and prospective studies and clinical trials on anti-CD20 antibodies, anti-CD38 antibody, and anti-CXCR4 antibody.
https://ift.tt/2LumhFO
Anaerobic Growth and Maintenance of Mammalian Cell Lines
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Syringe-injectable Mesh Electronics for Stable Chronic Rodent Electrophysiology
Mesh electronics probes seamlessly integrate and provide stable, long-term, single-neuron level recording within the brain. This protocol uses mesh electronics for in vivo experiments, involving the fabrication of mesh electronics, loading into needles, stereotaxic injection, input/output interfacing, recording experiments, and histology of tissue containing mesh probes.
https://ift.tt/2zXwVRf
Early anal gland adenocarcinoma with a characteristic submucosal tumor-like appearance: a case report
Abstract
Background
The clinical findings of early anal gland carcinoma (AGC) have not been well delineated because AGC is a rare malignancy usually diagnosed at an advanced stage. Knowledge of the characteristic findings will be helpful for both diagnosis and determination of the treatment options for early AGC.
Case presentation
A 62-year-old man was referred to our hospital for treatment of a rectal submucosal tumor (SMT) detected during a medical checkup at another hospital. Trans-sacral resection of the tumor was performed under the diagnosis of a rectal benign cyst. Pathological examination of the resected tumor showed a mucin-producing adenoma. About 14 months later, a new cystic lesion was found by follow-up examination, and trans-sacral resection of the tumor was performed again. The second pathological diagnosis was a mucinous adenocarcinoma with a possible remnant tumor at the local site. After providing sufficient informed consent, the patient underwent intersphincteric resection (ISR) of the rectum to preserve anal function. The final diagnosis was mucinous adenocarcinoma of the anal gland, T1N0M0. The patient remained alive without recurrence or complications for 6 years 7 months postoperatively.
Conclusion
We have herein reported a case of early AGC with a characteristic SMT-like appearance. Because the anal gland is located within both the submucosal layer and the internal sphincter muscle, ISR may be selected when the tumor is limited to inside the gland.
https://ift.tt/2zXBj2t
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
In this protocol, we describe how to utilize [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (18F-FDG PET/CT) imaging to measure the tumor metabolic response to the targeted therapy MLN0128 in a Kras/Lkb1 mutant mouse model of lung cancer and coupled imaging with high resolution ex vivo autoradiography and quantitative histology.
https://ift.tt/2Lr7sEc
A Behavioral Assay for Investigating the Role of Spatial Memory During Instinctive Defense in Mice
https://ift.tt/2uE3xds
Determination of the Excitation and Coupling Rates Between Light Emitters and Surface Plasmon Polaritons
https://ift.tt/2zZGZZR
Novel insights on m 6 A RNA methylation in tumorigenesis: a double-edged sword
Abstract
N6-methyladenosine (m6A), the most prevalent modification of mammalian RNA, has received increasing attention. Although m6A has been shown to be associated with biological activities, such as spermatogenesis modulation, cell spermatogenesis and pluripotency, Drosophila sex determination, and the control of T cell homeostasis and response to heat shock, little is known about its roles in cancer biology and cancer stem cells. Recent articles have noted that some genes have abnormal m6A expression after tumorigenesis, including genes ABS2, RARA, MYB, MYC, ADAM19 and FOX1. Abnormal changes in the m6A levels of these genes are closely related to tumour occurrence and development. In this review, we summarized the 'dual edge weapon' role of RNA methylation in the tumorigenesis. We discussed RNA methylation could lead to not only tumour progression but also tumour suppression. Moreover, we clarified that the abnormal changes in the m6A enrichment of specific loci contribute to tumour occurrence and development, thereby representing a novel anti-cancer strategy by restoration to balanced RNA methylation in tumour cells.
https://ift.tt/2LE4WYa
Presurgical localization of infected avascular bone segments in chronic complicated posttraumatic osteomyelitis in the lower extremity using dual-tracer PET/CT
Abstract
Background
Localizing and removing the infected sequestrum in long-standing trauma-related chronic osteomyelitis remains a clinical challenge. PET/CT with 18F-fluorodeoxyglucose (FDG-PET) has a high sensitivity for chronic osteomyelitis and 18F-sodium-fluoride PET/CT (NaF-PET) has a high specificity for identifying non-viable bone. Combining both, high signal on FDG-PET in the bone without signal on NaF-PET could potentially guide surgery to become more precise with curative intent.
Eight patients with long-standing (average 22 years) posttraumatic (n = 7) or postoperative (n = 1) chronic osteomyelitis in the lower extremity and with multiple futile attempts for curative surgery were recruited in this prospective pilot study. FDG-PET and NaF-PET were performed within a week in between using standard scanning protocols. The most likely location of the culprit sequestrum was identified and was surgically removed. Based on perioperative tissue cultures, antibiotics were given for 6–8 months. Dual-tracer (FDG- and NaF-PET/CT) was performed again after 12 months to rule out persisting signs of infection.
Results
A likely culprit sequestrum could preoperatively be identified by dual-tracer PET in all eight cases and in four cases an additional sequestrum was identified at a location with no clinical sign of infection. The infected necrotic tissue was removed during surgery. Follow-up dual-tracer PET revealed no signs of persistent infection. All patients recovered with no clinical signs of recurrence for a follow-up of mean 4.5 (SD 1.3) years.
Conclusions
Dual-tracer PET/CT with FDG and NaF allows successful precise surgery with curative intent in patients with long-standing complicated posttraumatic chronic osteomyelitis with severely deranged anatomy.
https://ift.tt/2mwEDYL
18 F-FDG and 68 Ga-somatostatin analogs PET/CT in patients with Merkel cell carcinoma: a comparison study
Abstract
Background
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18F-FDG and 68Ga-somatostatin analog PET/CT in MCC patients.
Results
Fifteen patients (12 males, 3 females; median age 73 years; range 41–81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both 18F-FDG and 68Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, 18F-FDG and 68Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, 18F-FDG detected 67/75 lesions (89%) and 68Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site.
Conclusions
Our preliminary data suggest that 18F-FDG and 68Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that 18F-FDG PET/CT should be replaced by 68Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of "personalized medicine."
https://ift.tt/2uRGXxi
Activity and clinical relevance of autotaxin and lysophosphatidic acid pathways in high-grade serous carcinoma
Abstract
The aim of this study was to analyze the expression, biological role and clinical relevance of autotaxin (ATX), the enzyme synthetizing lysophosphatidic acid (LPA), and LPA receptors (LPAR) in high-grade serous carcinoma (HGSC). mRNA expression by qRT-PCR of LPAR1-6 was analyzed in 155 HGSC specimens (88 effusions, 67 solid lesions). ATX mRNA expression was analyzed in 97 specimens. ATX, ERK, and AKT protein expression was studied by Western blotting. LPAR2 mRNA was overexpressed in HGSC cells in effusions compared to solid lesions, with opposite findings for LPAR3 and LPAR6 mRNA and ATX protein. Higher LPAR1 levels were significantly related to longer overall survival (OS) in pre-chemotherapy effusions (p = 0.027). Conversely, higher expression of LPAR1, LPAR2, and LPAR5 in post-chemotherapy effusions was significantly associated with shorter OS (p = 0.037, p = 0.025 and p = 0.021, respectively) and progression-free survival (PFS) (p < 0.001, p = 0.007 and p < 0.001, respectively) in univariate survival analysis. LPAR1 mRNA expression was an independent prognosticator of OS in patients with pre-chemotherapy effusions and PFS in patients with post-chemotherapy effusions (p = 0.013 both). In conclusion, LPAR mRNA and ATX protein levels are anatomic site-dependent in HGSC and the former are informative of disease outcome.
https://ift.tt/2uPbkVb
Higher Recurrence Rate After Endoscopic Totally Extraperitoneal (TEP) Inguinal Hernia Repair With Ultrapro Lightweight Mesh: 5-Year Results of a Randomized Controlled Trial (TULP-trial)
Objective: The aim of this study was to determine inguinal hernia recurrence rates 5 years after endoscopic totally extraperitoneal (TEP) inguinal hernia repair when either lightweight or heavyweight mesh was used. Background: Recurrence is an important complication of inguinal hernia surgery. Higher recurrence rates of Ultrapro lightweight meshes after TEP repair have been demonstrated, yet data regarding long-term follow-up are limited. Methods: From 2010 to 2012, 950 male adult patients with primary unilateral hernias were randomized to TEP hernia repair with heavyweight (Prolene) or lightweight (Ultrapro) mesh. Five years postoperatively, the validated PINQ-PHONE telephone questionnaire was carried out. Participants with a positive questionnaire reply were scheduled for a clinical visit. A recurrence was defined as a clinically detectable bulge in the operated groin on physical examination. Results: Data on development of recurrence could be obtained from 790 patients (83.2% 5-year follow–up rate). Four patients presented with a recurrence at the outpatient clinic between 2 and 5 years postoperatively. Thirty-five patients (4.6%) with a positive PINQ-PHONE reply (60.0% lightweight vs 40.0% heavyweight) were physically examined at the outpatient clinic. In 2 patients (lightweight) a recurrence was detected. The total 5-year recurrence rate after TEP hernia repair was 2.4% (3.8% lightweight, 1.1% heavyweight, P = 0.01). A significantly higher recurrence rate for lightweight mesh in primary direct hernias was found (P = 0.003). Conclusions: The overall recurrence rate 5 years after TEP repair was low. Ultrapro lightweight meshes showed higher recurrence rates than heavyweight meshes and are not recommended for endoscopic TEP inguinal hernia repair.https://ift.tt/2uaImj4
The expansion of targetable biomarkers for CAR T cell therapy
Abstract
Biomarkers are an integral part of cancer management due to their use in risk assessment, screening, differential diagnosis, prognosis, prediction of response to treatment, and monitoring progress of disease. Recently, with the advent of Chimeric Antigen Receptor (CAR) T cell therapy, a new category of targetable biomarkers has emerged. These biomarkers are associated with the surface of malignant cells and serve as targets for directing cytotoxic T cells. The first biomarker target used for CAR T cell therapy was CD19, a B cell marker expressed highly on malignant B cells. With the success of CD19, the last decade has shown an explosion of new targetable biomarkers on a range of human malignancies. These surface targets have made it possible to provide directed, specific therapy that reduces healthy tissue destruction and preserves the patient's immune system during treatment. As of May 2018, there are over 100 clinical trials underway that target over 25 different surface biomarkers in almost every human tissue. This expansion has led to not only promising results in terms of patient outcome, but has also led to an exponential growth in the investigation of new biomarkers that could potentially be utilized in CAR T cell therapy for treating patients. In this review, we discuss the biomarkers currently under investigation and point out several promising biomarkers in the preclinical stage of development that may be useful as targets.
https://ift.tt/2JGsBFB
Exosomal TRIM3 is a novel marker and therapy target for gastric cancer
Abstract
Background
Exosomes are critically involved in cancer development and progression. The exosomal contents have been suggested as ideal cancer biomarkers. In this study, we investigated the expression of exosomal proteins in the serum of gastric cancer patients and their roles in gastric cancer.
Methods
The proteomic profile of exosomes from the serum of gastric cancer patients was detected by using LC-MS/MS. The expression of TRIM3 in exosomes from the serum of gastric cancer patients and healthy controls was assessed by ELISA and western blot. Immunohistochemistry was used to detect TRIM3 expression in gastric cancer tissues and their matching adjacent tissues. The growth and migration abilities of gastric cancer cells with TRIM3 overexpression or knockdown in vitro were evaluated by colony formation assay and transwell migration assay. The effects of TRIM3 overexpression or knockdown on gastric cancer growth and metastasis in vivo were investigated by using subcutaneous xenograft tumor and peritoneal metastasis mouse model. The effects of TRIM3-overexpressing exosomes on gastric cancer growth and metastasis in vitro and in vivo were also evaluated.
Results
We found that the expression levels of TRIM3 mRNA and protein were decreased in gastric cancer tissues compared to the matched control tissues. In addition, the levels of TRIM3 protein in the serum exosomes of gastric cancer patients were lower than that in healthy controls. We demonstrated that TRIM3 overexpression reduced while TRIM3 knockdown promoted the growth and metastasis of gastric cancer in vitro and in vivo through the regulation of stem cell factors and EMT regulators. Moreover, exosomes-mediated delivery of TRIM3 protein could suppress gastric cancer growth and metastasis in vitro and in vivo.
Conclusions
Taken together, our findings suggest that exosomal TRIM3 may serve as a biomarker for gastric cancer diagnosis and the delivery of TRIM3 by exosomes may provide a new avenue for gastric cancer therapy.
https://ift.tt/2Le6egf
Investigation of the key chemical structures involved in the anticancer activity of disulfiram in A549 non-small cell lung cancer cell line
Abstract
Background
Disulfiram (DS), an antialcoholism medicine, demonstrated strong anticancer activity in the laboratory but did not show promising results in clinical trials. The anticancer activity of DS is copper dependent. The reaction of DS and copper generates reactive oxygen species (ROS). After oral administration in the clinic, DS is enriched and quickly metabolised in the liver. The associated change of chemical structure may make the metabolites of DS lose its copper-chelating ability and disable their anticancer activity. The anticancer chemical structure of DS is still largely unknown. Elucidation of the relationship between the key chemical structure of DS and its anticancer activity will enable us to modify DS and speed its translation into cancer therapeutics.
Methods
The cytotoxicity, extracellular ROS activity, apoptotic effect of DS, DDC and their analogues on cancer cells and cancer stem cells were examined in vitro by MTT assay, western blot, extracellular ROS assay and sphere-reforming assay.
Results
Intact thiol groups are essential for the in vitro cytotoxicity of DS. S-methylated diethyldithiocarbamate (S-Me-DDC), one of the major metabolites of DS in liver, completely lost its in vitro anticancer activity. In vitro cytotoxicity of DS was also abolished when its thiuram structure was destroyed. In contrast, modification of the ethyl groups in DS had no significant influence on its anticancer activity.
Conclusions
The thiol groups and thiuram structure are indispensable for the anticancer activity of DS. The liver enrichment and metabolism may be the major obstruction for application of DS in cancer treatment. A delivery system to protect the thiol groups and development of novel soluble copper-DDC compound may pave the path for translation of DS into cancer therapeutics.
https://ift.tt/2LyEC1o
The LEAD study protocol: a mixed-method cohort study evaluating the lung cancer diagnostic and pre-treatment pathways of patients from Culturally and Linguistically Diverse (CALD) backgrounds compared to patients from Anglo-Australian backgrounds
Abstract
Background
Lung cancer is the leading cause of cancer mortality worldwide. Early diagnosis and treatment is a key factor in reducing mortality and improving patient outcomes. To achieve this, it is important to understand the diagnostic pathways of cancer patients. Patients from Culturally and Linguistically Diverse (CALD) are a vulnerable group for lung cancer with higher mortality rates than Caucasian patients. The aim of this study is to explore differences in the lung cancer diagnostic pathways between CALD and Anglo-Australian patients and factors underlying these differences.
Methods
This is a prospective, observational cohort study using a mixed-method approach. Quantitative data regarding time intervals in the lung cancer diagnostic pathways will be gathered via patient surveys, General practitioner (GP) review of general practice records, and case-note analysis of hospital records. Qualitative data will be gathered via structured interviews with lung cancer patients, GPs, and hospital specialists. The study will be conducted in five study sites across three states in Australia. Anglo-Australian patients and patients from five CALD groups (i.e., Arabic, Chinese, Greek, Italian and Vietnamese communities) will mainly be identified through the list of new cases presented at lung multidisciplinary team meetings. For the quantitative component, it is anticipated that 724 patients (362 Anglo-Australian and 362 CALD patients) will be recruited to obtain a final sample of 290 (145 per group) assuming a 50% patient survey completion rate and a 80% GP record review completion rate. For the qualitative component, 60 interviews with lung cancer patients (10 Anglo-Australian and 10 patients per CALD group), 20 interviews with GPs, and 20 interviews with specialists will be conducted.
Discussion
This is the first Australian study to compare the time intervals along the lung cancer diagnostic pathway between CALD and Anglo-Australian patients. The study will also explore the underlying patient, healthcare provider, and health system factors that influence the time intervals in the two groups. This information will improve our understanding of the effect of ethnicity on health outcomes among lung cancer patients and will inform future interventions aimed at early diagnosis and treatment for lung cancer, particularly patients from CALD backgrounds.
Trial registration
The project was retrospectively registered with Australian New Zealand Clinical Trials Registry (registration number: ACTRN12617000957392, date registered: 4th July 2017).
https://ift.tt/2L9kiaG
Congenital Myasthenic Syndromes: a Clinical and Treatment Approach
Abstract
Purpose of review
Congenital myasthenia syndromes are clinically and genetically heterogeneous but treatable conditions. Careful selection of drug therapy is paramount as the same drug can be effective, ineffective, and even harmful in different congenital myasthenia syndromes. The purpose of this article is to review current treatment options for these conditions.
Recent findings
Next-generation sequencing has accelerated the discovery of new genes and facilitated the description of novel congenital myasthenic syndromes. Retrospective therapy data from these newly identified syndromes has provided additional insight on the management of these conditions. Cholinergic agents, β-adrenergic agonists, and open-channel blockers remain the principal treatment modalities, and their optimal use depends on an accurate genetic diagnosis and the timely clinical recognition of the disease. In particular, pyridostigmine, usually a first-line agent, should be avoided in DOK7, acetylcholinesterase deficiency, and slow-channel congenital myasthenic syndromes. Beta-adrenergic agonists have been recognized as a first-line agent for a number of congenital myasthenic syndromes, particularly DOK7 and acetylcholinesterase deficiency, whereas long-lived open-channel blockers of the acetylcholine receptor (AChR) ion channel are indicated for the slow-channel congenital myasthenic syndrome. Beta-adrenergic agonists additionally have an important adjunct treatment for congenital myasthenia syndrome due to glycosylation defects, fast channel syndrome, AChR deficiency, and choline acetyltransferase deficiency (ChaT) and therefore may be particularly important in the treatment of syndromes due to defects in motor endplate development and repair.
Summary
Unlike in autoimmune myasthenia gravis, there is no role for immunotherapy in congenital myasthenic syndromes. If available, a genetic diagnosis should drive the choice for a first-line treatment agent between cholinergic agents, β-adrenergic agents, and open-channel blockers. Evaluation and supportive care at centers with experience in these rare syndromes likely are paramount in achieving optimal outcomes. Furthermore, gene discovery for congenital myasthenic syndromes has provided novel insights on the role of protein glycosylation, endplate maintenance and repair, and synaptic vesicle exocytosis in neuromuscular transmission. These insights may lead to new therapeutic strategies in both congenital and autoimmune myasthenic diseases in the future.
https://ift.tt/2L9urUZ
Orthostatic Tremor: Pathophysiology Guiding Treatment
Abstract
Purpose of review
Orthostatic tremor (OT) is a rare disorder characterized by tremor and a feeling of unsteadiness while standing that resolve upon walking or sitting. A pathognomonic 13–18 Hz tremor is seen on surface EMG while standing. Though its clinical features have been better defined over time, much of its pathophysiology remains unknown and treatment options are limited. We review here recent developments in both of these areas.
Recent findings
Several recent studies have furthered our understanding of the central oscillatory network involved in OT. fMRI and 18F-FDG-PET studies have identified a ponto-cerebello-thalamo-cortical network underlying OT, though the nature of its dysfunction remains unknown.
Randomized trials of treatments for OT are few, so most data are from case reports or small case series. Clonazepam and gabapentin are likely the most effective medical therapies, while bilateral ventral intermediate nucleus deep brain stimulation shows promise for refractory cases.
Summary
Though much about OT remains unknown, our understanding of its pathophysiology has improved through recent studies. Treatment benefit is overall modest and inconsistent, though better understanding of the disease could lead to new avenues for treatment.
https://ift.tt/2LBrR6m
Diagnosis of isolated extensor carpi radialis longus (ECRL) tendon avulsion fracture using ultrasound: a paradigm shift
Abstract
Isolated avulsion fracture of the extensor carpi radialis longus (ECRL) tendon is a rare and poorly understood injury. We present a unique case of a 45-year-old male who fell on his flexed right hand. He presented with a subtle but extremely painful mass on the dorsum of his wrist. Ultrasound (U/S) imaging of the mass revealed an avulsed bone fragment attached to the ECRL tendon, confirming the clinical suspicion of an ECRL avulsion injury. Computed tomography and magnetic resonance imaging are well-documented imaging modalities to detect tendon avulsions. As demonstrated by this case report, U/S is an excellent diagnostic tool for ECRL rupture, a cost-effective alternative that provides real-time dynamic examination of hand injuries. To our knowledge, this is the first case of ECRL avulsion diagnosed by U/S. The purpose of this case report is to educate the reader on detection and diagnosis of ECRL tendon avulsion using U/S, a time-efficient and cost-effective imaging modality that is infrequently used for this purpose.
https://ift.tt/2uQHcbR
MRI findings associated with medial patellofemoral capsuloligamentous plication
Abstract
Objective
To review the MRI appearance of medial patellofemoral capsuloligamentous plication (also known as reefing or imbrication) for proximal patellar realignment in patients with patellofemoral instability.
Materials and methods
Retrospective analysis of our surgical and PACS databases identified cases of medial plication performed between June 2011 and July 2016. Pre- and postoperative MRI characteristics were reviewed. Correlation was made with operative reports and clinical records to define postoperative appearances on MRI.
Results
Forty-one patients underwent medial plication during the study period; 29 were excluded owing to a lack of postoperative imaging. Ultimately, 12 knees were included in 11 patients who had postoperative MRI studies available (8 women and 3 men, mean age 27.3 ± 10.2 years). Ten (83%) of the surgeries were performed open and 2 (17%) arthroscopically. There were differences in the post-surgical MRI appearance of medial plications carried out after surgery using the open and arthroscopic techniques. The open technique produces a "heaped up" distal vastus medialis obliquus (VMO) with centralized patellar insertion (100%), which was absent in the case of arthroscopic plication, where subtle medial retinaculum thickening was demonstrated without alteration of its patellar insertion. The mean postoperative lateral patellar and patellofemoral congruence angles measured 2.5° ± 5.6° and 12.4° ± 19.9° respectively. A significant association was found regarding change in patellofemoral alignment (p = 0.018 and p = 0.004 respectively).
Conclusion
The MRI appearance of medial plication is not well described in the radiology literature; radiologists should be familiar with anticipated post-plication findings to avoid potential confusion for pathology and allow more accurate interpretation of postoperative imaging findings from this common surgery.
https://ift.tt/2mvsJye
Lymphangiomatosis: a rare entity presenting with involvement of the sacral plexus
Abstract
Lymphangiomatosis is an uncommon disease process characterized by multisystem lymphatic malformations that can involve numerous body systems, including organs, muscles, soft tissues, and bones. Involvement of the nervous system is rare and has even been previously described as a site of sparing. We present a case of a 24-year-old female with known lymphangiomatosis, presenting with acute onset of lower extremity paresthesias, weakness, and new urinary retention. MRI of the pelvis revealed lymphangiomatosis of the sacral plexus, which has not been previously reported. We will review the clinical and imaging manifestations of lymphangiomatosis and provide a differential diagnosis for masses of the lumbosacral plexus. Although lower extremity pain and weakness encountered in the emergency department or outpatient setting is most frequently caused by lumbar spine pathology, occasionally, abnormalities of the lumbosacral plexus may prove to be the cause. While peripheral nerve sheath tumors lead the differential diagnosis of tumor or tumor-like entities involving the lumbosacral plexus, lymphangiomatosis is a rare differential consideration.
https://ift.tt/2uTcb7h
Giant fibroepithelial polyp of the thigh and retroperitoneal fibromatosis in a young woman: a rare case
Abstract
We present a case of 20-year-old woman who presented with a large pedunculated skin covered mass lesion arising from the left thigh, measuring 40 × 25 cm, with no history of pain or skin ulceration and a feeling of a lump with dragging pain in the left side of the abdomen for about 7 years. Subsequently, ultrasound, contrast-enhanced computed tomography, and magnetic resonance imaging of abdomen and left thigh region were carried out. The lesion was broad-based toward the left upper thigh with a central core of interspersed fat supplied by branches of the superficial and deep femoral arteries. Another lesion was seen in the left retroperitoneum anterior to the psoas muscle in a left paravertebral location encasing the left common iliac vessels extending into the left pelvic cavity and inguinal region inferiorly. The lesion showed dense post-acoustic shadowing on ultrasound, mild enhancement on contrast-enhanced computed tomography, and appeared hypointense on T1- and T2-weighted images. A left thigh lesion was excised, whereas incisional biopsy was done for the left retroperitoneal lesion. The diagnosis of a giant fibroepithelial polyp arising from the left thigh and left retroperitoneal fibromatosis was made. This is the first report of such a giant fibroepithelial polyp arising from the thigh with associated retroperitoneal fibromatosis.
https://ift.tt/2mxIhS7
Normal imaging laterality on magnetic resonance imaging of the medial epicondyle of the elbow on the dominant side of adolescent male baseball players
Abstract
Objective
Multimodality elbow screening of adolescent baseball players shows apparent laterality in morphology and signal intensity of the medial epicondyle on dedicated magnetic resonance imaging. We aimed to elucidate actual imaging laterality in the medial epicondyle by comparing magnetic resonance images of the dominant and contradominant elbows and to clarify the clinical meaning and mechanism of this phenomenon.
Materials and methods
We used a 0.2-T dedicated magnetic resonance imaging scanner. Eighty adolescent baseball players were enrolled and divided into four age groups: 9–10 years (13 patients); 11 years (28 patients); 12 years (24 patients) and 13–14 years (15 patients). The long and short axes of the ossification center and distance of the epiphyseal plate and the cartilage of the lower pole of the medial epicondyle were measured. Signal intensity of the ossification center was visually evaluated.
Results
Owing to their age, ossification and cartilage size on the dominant side were significantly larger in all boys (P < 0.01). All age groups had larger ossification and cartilage in the dominant elbow (P < 0.01). Ossification showed an apparent lower signal intensity on the dominant side (P < 0.01).
Conclusions
Larger ossification and cartilage size of the medial epicondyle in the dominant elbow suggested that the medial collateral ligament to the medial epicondyle induces excessive repetitive tensile stress, but without clinical symptoms. Functional or microanatomical damage of the medial epicondyle may induce a lower ossification signal in the dominant elbow, thereby decreasing fatty bone marrow and inducing sclerotic changes.
https://ift.tt/2zZnctw
Clinical, radiological, and pathological features of extraskeletal osteosarcoma
Abstract
Objective
To evaluate clinical and radiological features of pathology-proven extraskeletal osteosarcomas.
Methods
This retrospective study was IRB-approved and HIPAA-compliant. Our pathology database was queried for cases of extraskeletal osteosarcoma. Tumor location, size, imaging appearance, presence of metastases, and clinical outcome were documented.
Results
Nineteen patients met inclusion criteria (age 59 ± 15 (range 28–85) years; 15 male, 4 female). Tumors occurred in the lower extremities (12 out of 19, 63%), pelvis/gluteal region (3 out of 19, 16%), upper extremity (2 out of 19, 5%), thorax (1 out of 19, 5%), and neck (1 out of 19, 5%). Two out of 19 (11%) patients had undergone radiation to the tumor site previously. According to pathology, 16 out of 19 tumors were high-grade (84%). Tumors presented as soft-tissue masses measuring 9.5 ± 6.8 (2–29) cm. Tumor mineralization was present in 5 out of 19 cases (26%) and local invasion was found in 1 out of 19 cases (6%). On MRI, tumors typically appeared hyperintense on T2-weighted sequences with enhancement in 15 out of 15 (100%) contrast-enhanced studies, and with central necrosis in 10 out of 19 (53%) cases. Low-grade tumors were smaller (<4 cm; 3 out of 3, 100%) and lacked central necrosis (3 out of 3, 100%). 8 out of 19 patients (42%) had metastases, most commonly to the lung (7 out of 19, 37%) and bone (2 out of 19,11%). Two out of 8 patients (25%) with metastases and 8 out of 11 (73%) without metastases achieved recurrence-free survival (mean follow-up 3.8 ± 4.0 [0.2–14.2]) years. No metastases or deaths occurred in patients with low-grade histology.
Conclusions
Extraskeletal osteosarcomas are rare, typically high-grade malignancies that commonly metastasize to lung and bones. Low-grade tumors and those without metastases have a good prognosis. MRI appearance is nonspecific, with T2 hyperintense signal and heterogeneous enhancement. Unlike conventional osteosarcoma, mineralization is rare.
https://ift.tt/2uP4GOP
Imaging of the post-operative shoulder: does injection of iodinated contrast in addition to MR contrast during arthrography improve diagnostic accuracy and patient throughput?
Abstract
Objective
Post-operative shoulder patients are often difficult to image due to scar tissue, metallic artifact, and residual irregularity of anatomic structures. The purpose of this study was to assess MR versus MR arthrography versus CT arthrography in the post-operative shoulder. Also, we assessed whether injecting CT contrast in addition to MR contrast during arthrography improved patient care.
Methods and materials
One hundred consecutive post-operative conventional shoulder MR and MR arthrography exams performed on the same patients were reviewed retrospectively by two musculoskeletal radiologists. A combination of gadolinium and CT contrast was injected at arthrography so CT imaging could be performed post arthrography if metallic artifact precluded MR imaging. Twenty-two of these patients also had CT exams performed post-arthrography due to metallic artifact on MR exam. Exams were assessed for labral tears and supraspinatus tendon tears. All patients went on to arthroscopy.
Results
Of these 100 patients, 35 had SLAP (superior labral anterior to posterior) tears, 22 had posterior labral tears, 24 had anterior labral tears, and 46 had full-thickness supraspinatus tendon tears on conventional MR exam. On MR arthrography, 48 patients had SLAP tears, 26 had posterior labral tears, 27 had anterior labral tears, and 54 had full-thickness supraspinatus tendon tears. MR arthrogram detected 12 SLAP tears, three posterior labral tears, three anterior labral tears, and nine supraspinatus tendon tears not detected on conventional MR exam. Twenty-two patients had additional imaging performed with CT arthrography due to metallic artifacts precluding MR assessment of shoulder pathology. There were four SLAP tears, six posterior labral tears, five anterior labral tears, and five supraspinatus tendon tear seen on CT arthrography not seen on MR exam.
Conclusions
MR arthrography is more accurate than conventional MR in assessment of post-operative shoulder pathology. CT arthrography can detect additional pathology when there is metallic artifact in post-operative patients. It is beneficial to inject a combination of gadolinium and CT contrast at arthrography so CT imaging can be performed post-arthrography if metallic artifact precludes imaging shoulder pathology by MR.
https://ift.tt/2mwVxGT
Radiological glenohumeral osteoarthritis in long-term type 1 diabetes. Prevalence and reliability of three classification systems. The Dialong shoulder study
Abstract
Objective
In the present study, we evaluate the intra- and interrater agreement of radiological glenohumeral OA using three different classification systems and estimate the prevalence of radiological and clinical glenohumeral OA in patients with type 1 diabetes mellitus (DM1), for over 45 years and controls (The Dialong study).
Materials and methods
We included 102 patients with DM1 (49% women, mean age, 61.9 years) and 73 controls (57% women, mean age, 62.6 years). Anterior-posterior shoulder radiographs were interpreted by two observers applying the Kellgren–Lawrence (K–L), Samilson–Prieto (S–P) and Samilson–Prieto Allain (S–PA) classifications.
Results
The interrater agreement was moderate (weighted kappa, 0.46 to 0.48) for all classifications and the intrarater agreement mainly substantial (0.48–0.86) for both observers. The agreed prevalence of radiological OA was 26 and 18% (OR 1.6 (0.8 to 3.3), p = 0.22, 44 and 26% (OR 2.2 (1.2 to 4.2), p = 0.02) and 30 and 17% (OR 2.1 (1.0 to 4.5), p = 0.05) for the K–L, S–P and S–PA classifications respectively in the diabetes and control groups. The prevalence of moderate or severe radiological OA was 1 to 6% and clinical OA 1 to 2% with no difference between the groups.
Conclusion
The prevalence of radiological glenohumeral OA was higher in the diabetes group with the Samilson–Prieto classification systems, but not associated with clinical OA. The interrater agreement was moderate. We recommend the Samilson–Prieto Allain classification for glenohumeral OA to avoid interpretation of osteophytes < 1 mm as OA in patient groups with a low pre-test likelihood of glenohumeral OA.
https://ift.tt/2A7uE67
Intra-articular solitary fibrous tumor of the knee
Abstract
A rare case of intra-articular solitary fibrous tumor of the knee in an 84-year-old man is presented. This case report illustrates that solitary fibrous tumor should be included in the extended differential diagnosis of an intra-articular soft tissue mass.
https://ift.tt/2myrUFb
Radiographic morphology of normal ring apophyses in the immature cervical spine
Abstract
Background
The ring apophyses of the cervical spine have a variable appearance that changes with age. The times at which they appear and fuse at each level are not fixed. In this study, we aim to detail normal ranges of appearance of these ossification centers for each age group.
Materials and methods
One hundred and eighty patients under the age of 21 attending the Royal Stoke University Hospital for cervical spine radiographs were retrospectively identified. The presence or absence of ring apophyses at each cervical level and whether these had undergone fusion was reported, as were the thickness, length, and craniocaudal and anteroposterior distance of the apophysis from the vertebral body. The angulation of the apophysis relative to the endplate was also noted.
Results
The youngest patient in which apophyses were seen was aged 3, but apophyses were otherwise rarely seen before the age of 6. All apophyses were present from age 14, and the superior apophyses fused by the age of 18, although unfused inferior apophyses were still seen in the 20-year age group. It was observed that apophyses were rarely separated from the vertebral body by greater than 1 mm in craniocaudal distance (1%) or 2.5 mm in anteroposterior distance (2.6%) and the anterior apophysis was angulated towards the endplate in only 1% of cases.
Conclusions
We have detailed the range of normal appearances of the ring apophyses of the developing cervical spine. Cervical spine apophyseal injury is thought to be rare, but knowledge of normative morphological features should help in this diagnosis.
https://ift.tt/2mzwRh0
Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease
Abstract
Alzheimer's disease is characterized by the histopathological presence of amyloid-β plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized pathological component. The relationship between microglial activation and protein aggregation is still debated. We investigated the relationship between amyloid plaques, tau tangles and activated microglia using PET imaging. Fifty-one subjects (19 healthy controls, 16 mild cognitive impairment and 16 Alzheimer's disease subjects) participated in the study. All subjects had neuropsychometric testing, MRI, amyloid (18F-flutemetamol), and microglial (11C-PBR28) PET. All subjects with mild cognitive impairment and Alzheimer's disease and eight of the controls had tau (18F-AV1451) PET. 11C-PBR28 PET was analysed using Logan graphical analysis with an arterial plasma input function, while 18F-flutemetamol and 18F-AV1451 PET were analysed as target:cerebellar ratios to create parametric standardized uptake value ratio maps. Biological parametric mapping in the Statistical Parametric Mapping platform was used to examine correlations between uptake of tracers at a voxel-level. There were significant widespread clusters of positive correlation between levels of microglial activation and tau aggregation in both the mild cognitive impairment (amyloid-positive and amyloid-negative) and Alzheimer's disease subjects. The correlations were stronger in Alzheimer's disease than in mild cognitive impairment, suggesting that these pathologies increase together as disease progresses. Levels of microglial activation and amyloid deposition were also correlated, although in a different spatial distribution; correlations were stronger in mild cognitive impairment than Alzheimer's subjects, in line with a plateauing of amyloid load with disease progression. Clusters of positive correlations between microglial activation and protein aggregation often targeted similar areas of association cortex, indicating that all three processes are present in specific vulnerable brain areas. For the first time using PET imaging, we show that microglial activation can correlate with both tau aggregation and amyloid deposition. This confirms the complex relationship between these processes. These results suggest that preventative treatment for Alzheimer's disease should target all three processes.https://ift.tt/2mvHdyh
Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia
Abstract
Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1–90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63–80 Hz) in occipital regions and upregulated low frequency (5–28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.https://ift.tt/2uPbBHG
Bubble Trouble: Venous Air Embolism in Endoscopic Retrograde Cholangiopancreatography
No abstract availablehttps://ift.tt/2JH58Us
The Stress Hormone Cortisol Enhances Interferon-υ–Mediated Proinflammatory Responses of Human Immune Cells
BACKGROUND: Cortisol is a prototypical human stress hormone essential for life, yet the precise role of cortisol in the human stress response to injury or infection is still uncertain. Glucocorticoids (GCs) such as cortisol are widely understood to suppress inflammation and immunity. However, recent research shows that GCs also induce delayed immune effects manifesting as immune stimulation. In this study, we show that cortisol enhances the immune-stimulating effects of a prototypical proinflammatory cytokine, interferon-υ (IFN-υ). We tested the hypothesis that cortisol enhances IFN-υ–mediated proinflammatory responses of human mononuclear phagocytes (monocyte/macrophages [MOs]) stimulated by bacterial endotoxin (lipopolysaccharide [LPS]). METHODS: Human MOs were cultured for 18 hours with or without IFN-υ and/or cortisol before LPS stimulation. MO differentiation factors granulocyte-macrophage colony stimulating factor (GM-CSF) or M-CSF were added to separate cultures. We also compared the inflammatory response with an acute, 4-hour MO incubation with IFN-υ plus cortisol and LPS to a delayed 18-hour incubation with cortisol before LPS exposure. MO activation was assessed by interleukin-6 (IL-6) release and by multiplex analysis of pro- and anti-inflammatory soluble mediators. RESULTS: After the 18-hour incubation, we observed that cortisol significantly increased LPS-stimulated IL-6 release from IFN-υ–treated undifferentiated MOs. In GM-CSF–pretreated MOs, cortisol increased IFN-υ–mediated IL-6 release by >4-fold and release of the immune stimulant IFN-α2 (IFN-α2) by >3-fold, while suppressing release of the anti-inflammatory mediator, IL-1 receptor antagonist to 15% of control. These results were reversed by either the GC receptor antagonist RU486 or by an IFN-υ receptor type 1 antibody antagonist. Cortisol alone increased expression of the IFN-υ receptor type 1 on undifferentiated and GM-CSF–treated MOs. In contrast, an acute 4-hour incubation of MOs with IFN-υ and cortisol showed classic suppression of the IL-6 response to LPS. CONCLUSIONS: These results reveal a surprisingly robust proinflammatory interaction between the human stress response hormone cortisol and the immune activating cytokine IFN-υ. The results support an emerging physiological model with an adaptive role for cortisol, wherein acute release of cortisol suppresses early proinflammatory responses but also primes immune cells for an augmented response to a subsequent immune challenge. These findings have broad clinical implications and provide an experimental framework to examine individual differences, mechanisms, and translational implications of cortisol-enhanced immune responses in humans.https://ift.tt/2LnuHz3
Rashomon Effect and the Contradiction of Data, Practice, and Regulations
No abstract availablehttps://ift.tt/2JH50UY
Adding to Our Competitive Advantage: Making the Case for Teaching Communication and Professionalism
No abstract availablehttps://ift.tt/2LnuETT
Vascular Air Embolism and Endoscopy: Every Bubble Matters
No abstract availablehttps://ift.tt/2uNNHMw
Beyond Emergence: Understanding postoperative Cognitive Dysfunction (POCD)
No abstract availablehttps://ift.tt/2LqJk4w
Repeated Measures Designs and Analysis of Longitudinal Data: If at First You Do Not Succeed—Try, Try Again
Anesthesia, critical care, perioperative, and pain research often involves study designs in which the same outcome variable is repeatedly measured or observed over time on the same patients. Such repeatedly measured data are referred to as longitudinal data, and longitudinal study designs are commonly used to investigate changes in an outcome over time and to compare these changes among treatment groups. From a statistical perspective, longitudinal studies usually increase the precision of estimated treatment effects, thus increasing the power to detect such effects. Commonly used statistical techniques mostly assume independence of the observations or measurements. However, values repeatedly measured in the same individual will usually be more similar to each other than values of different individuals and ignoring the correlation between repeated measurements may lead to biased estimates as well as invalid P values and confidence intervals. Therefore, appropriate analysis of repeated-measures data requires specific statistical techniques. This tutorial reviews 3 classes of commonly used approaches for the analysis of longitudinal data. The first class uses summary statistics to condense the repeatedly measured information to a single number per subject, thus basically eliminating within-subject repeated measurements and allowing for a straightforward comparison of groups using standard statistical hypothesis tests. The second class is historically popular and comprises the repeated-measures analysis of variance type of analyses. However, strong assumptions that are seldom met in practice and low flexibility limit the usefulness of this approach. The third class comprises modern and flexible regression-based techniques that can be generalized to accommodate a wide range of outcome data including continuous, categorical, and count data. Such methods can be further divided into so-called "population-average statistical models" that focus on the specification of the mean response of the outcome estimated by generalized estimating equations, and "subject-specific models" that allow a full specification of the distribution of the outcome by using random effects to capture within-subject correlations. The choice as to which approach to choose partly depends on the aim of the research and the desired interpretation of the estimated effects (population-average versus subject-specific interpretation). This tutorial discusses aspects of the theoretical background for each technique, and with specific examples of studies published in Anesthesia & Analgesia, demonstrates how these techniques are used in practice.https://ift.tt/2LmlYNB
A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology
The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplants. Since its initial conception in 1991 for renal transplants, it has undergone review every 2 years, with attendant updated publications. The rapid expansion of knowledge in the field has led to numerous revisions of the classification. The resultant dispersal of relevant content makes it difficult for novices and experienced pathologists to faithfully apply the classification in routine diagnostic work and in clinical trials. This review shall provide a complete and simple illustrated reference guide of the Banff Classification of Kidney Allograft Pathology based on all publications including the 2017 update. It is intended as a concise desktop reference for pathologists and clinicians, providing definitions, Banff Lesion Scores and Banff Diagnostic Categories. An online website reference guide hosted by the Banff Foundation for Allograft Pathology (www.banfffoundation.org) is being developed, which will be updated with future refinement of the Banff Classification from 2019 onwards. 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. Received 19 February 2018. Revision received 7 May 2018. Accepted 23 May 2018. Corresponding author: Jan U. Becker, MD, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Germany, Phone: +4922147898803, Fax: +492214786360, E-mail: janbecker@gmx.com Authors' contribution All authors contributed the discussion of the content, the collation of images and illustrations and to writing of the manuscript. Disclosure: The authors declare no conflicts of interest. Funding Dr. Roufosse's and Dr. Simmond's contribution to this research is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Alexandre Loupy is supported by a research grant ATIP AVENIR from the National French Institute of Research. Jan U. Becker is supported by the European Rare Kidney Disease Network (ERKNet); the content of this manuscript is the sole responsibility of the authors. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2mwHEZ9
https://ift.tt/2mwHEZ9
Transplant-free Survival in Chronic Liver Disease Presenting as Acute Liver Failure in Childhood
Background in adults, the absence of a preexisting chronic liver disease (CLD) is required to diagnose acute liver failure (ALF). The paediatric classification does not considered this aspect, thus previous studies pooled together children with ALF and children with unknown CLD presenting with acute hepatic decompensation (ALF-CLD). We aimed to compare prevalence, features and outcome of children with ALF-CLD to those with a proper ALF. Methods Patients admitted between 1996-2017 because of ALF defined by PALF criteria (raised transaminases, INR ≥2.0, no history of liver disease) were classified as ALF-CLD if diagnosed with autoimmune hepatitis (AIH), Wilson disease (WD), Budd-Chiari syndrome, HBV reactivation, inborn errors of metabolism (IEM). The others were classified as ALF. Results 74 children [median age 4 years, 1.0-8.8, M/F =36/38] with ALF were found ; 18 of
https://ift.tt/2uQAjr1
https://ift.tt/2uQAjr1
From dynamics to membrane organization: Experimental breakthroughs occasion a "modeling manifesto"
New experimental techniques, especially in the context of observing molecular dynamics, reveal the plasma membrane to be heterogeneous and "scale-rich," from nanometers to microns, and from microseconds to seconds. This is critical information, as heterogeneous, scale-dependent transport governs the molecular encounters that underlie cellular signaling. The data are rich, and reaffirm the importance of the cortical cytoskeleton, protein aggregates, and lipidomic complexity on the statistics of molecular encounters.
https://ift.tt/2mz2Duc
Partition of repeat-induced point mutations reveals structural aspects of homologous DNA-DNA pairing
In some fungi, a premeiotic process known as Repeat-Induced Point mutation (RIP) can accurately identify and mutate nearly all gene-sized DNA repeats present in the haploid germline nuclei. Studies in Neurospora crassa have suggested that RIP detects sequence homology directly between intact DNA double helices, without strand separation and without participation of RecA-like proteins. Those studies used the aggregated number of RIP mutations as a simple quantitative measure of RIP activity. Additional structural information about homologous DNA-DNA pairing during RIP can be extracted by analyzing spatial distributions of RIP mutations converted into profiles of a new parameter called partitioned RIP propensity (PRP).
https://ift.tt/2uOP51J
Maintenance Therapy in Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma
Opinion statement
Maintenance therapy has evolved as a strategy to prolong remissions in patients with diffuse large B cell lymphoma (DLBCL) or mantle cell lymphoma (MCL), typically following a more intensive therapy, such as induction therapy or stem cell transplantation. In randomized, controlled clinical trials, this approach has successfully prolonged overall survival in some MCL clinical settings, including after autologous stem cell transplantation and after R-CHOP induction, but has generally been unsuccessful in DLBCL. This most likely reflects differences in the biology and natural history of each disease. In DLBCL, a majority of patients are cured with frontline therapy, leaving fewer who can potentially benefit from maintenance. When the disease relapses, it is usually within the first 2 years and is usually clinically aggressive and difficult to control with low-intensity therapy. In contrast, nearly all patients with MCL will eventually relapse, and the disease may remain quiescent for many years. There may also be differences in sensitivity of minimal residual disease to maintenance treatments. Thus, future strategies to improve DLBCL treatments should focus on improved induction and possibly consolidation regimens rather than maintenance. In MCL, maintenance therapy will continue to play a role in the near future, although in both diseases, applying novel immunotherapies with the potential to eradicate residual disease clones persisting after induction may be the most successful strategy to improve patient outcomes.
https://ift.tt/2mvT92V
Reducing radiation dermatitis during ongoing radiation therapy: an innovative film-forming wound dressing
Abstract
Objective
This multicenter study focuses on the use of a film-forming wound dressing in the form of a gel that can be applied directly to the area affected by radiation dermatitis, especially after skin breakdown. The primary objective of the study was to validate the efficacy of an innovative film-forming wound dressing used as monotherapy in the treatment of radiation dermatitis in patients with RTOG score 2.5 (± 0.5) confirmed by the investigator.
Methods
Fifty-four patients undergoing radiation therapy for different cancer types and developing radiation dermatitis were recruited in the study; they were treated with the film-forming wound dressing when reaching an RTOG score of 2.5 (± 0.5). The evaluation of radiation dermatitis during ongoing radiation therapy was performed using the RISRAS, which includes investigator-assessed items (erythema, dry desquamation, moist desquamation, necrosis) and patient-assessed items (pain, itch, burning sensation, affection of daily activities).
Results
The following study shows a statistically significant clinical improvement (p < 0.05) of the RISRAS score (− 16.9%), as well as of specific clinical outcomes, such as erythema (− 20.6%), pain (− 20.5%), itch (− 22.2%), and burning sensation (−24.7%), after the treatment with the film-forming wound dressing during ongoing radiation therapy. Other radiation dermatitis markers, such as inflammation (− 28.9%) and hydration (26.0%), appeared to be significantly influenced.
Conclusion
The use of the innovative film-forming wound dressing for radiation dermatitis treatment shows first time evidence of improving the RISRAS score during ongoing radiation therapy, showing major improvements in patients' quality of life.
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