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Παρασκευή 8 Ιουνίου 2018

Costs of Invasive Meningococcal Disease: A Global Systematic Review

Abstract

Background

Invasive meningococcal disease remains a public health concern because of its rapid onset and significant risk of death and long-term disability. New meningococcal serogroup B and combination serogroup ACWY vaccines are being considered for publicly funded immunization programs in many countries. Contemporary costing data associated with invasive meningococcal disease are required to inform cost-effectiveness analyses.

Objective

The objective of this study was to estimate costs and resource utilization associated with acute infection and the long-term care of invasive meningococcal disease.

Data Sources and Methods

PubMed, EMBASE, The Cochrane Library, health economic databases, and electronically available conference abstracts were searched. Studies reporting any costs associated with acute infection and long-term sequelae of invasive meningococcal disease in English were included. All costs were converted into purchasing power parity-adjusted estimates [international dollars (I$)] using the Campbell and Cochrane Economics Methods Group and the Evidence for Policy and Practice Information and Coordinating Centre cost converter.

Results

Fourteen studies met our eligibility criteria and were included. The mean costs of acute admission ranged from I$1629 to I$50,796, with an incremental cost of I$16,378. The mean length of hospital stay was reported to be 6–18 days in multiple studies. The average costs reported for readmissions ranged from I$7905 to I$15,908. Key variables such as the presence of sequelae were associated with higher hospitalization costs and longer inpatient stay. No studies estimated direct non-healthcare costs and productivity loss. Ten studies reported only unadjusted mean values without using appropriate statistical methods for adjustment.

Conclusions

Invasive meningococcal disease can result in substantial costs to healthcare systems. However, costing data on long-term follow-up and indirect costs used to populate health economic models are lacking.



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Economic Evaluation for USA of Systemic Chemotherapies as First-Line Treatment of Metastatic Pancreatic Cancer

Abstract

Background

Treatments for metastatic pancreatic cancer include monotherapy with gemcitabine (GEM); combinations of GEM with oxaliplatin (OX + GEM), cisplatin (CIS + GEM), capecitabine (CAP + GEM), or nab-paclitaxel (NAB-P + GEM); and the non-GEM combination FOLFIRINOX. Combination therapies have yielded better survival outcomes than GEM alone. A sponsor-independent economic evaluation of these regimens has not been conducted for USA.

Objective

The objective of this study was to estimate the cost utility and cost effectiveness of these regimens from the payer perspective for USA.

Methods

A three-state Markov model (progression-free, progressed disease, death) simulating the total costs and health outcomes (quality-adjusted life-years; life-years) was developed to estimate the incremental cost-utility and cost-effectiveness ratios. FOLFIRINOX clinical data were obtained from trial and indirect estimates were obtained from network meta-analyses. Lifetime horizon and 3%/year discount rates were used.

Results

FOLFIRINOX was the most expensive regimen and GEM the least costly regimen. Compared to GEM, all but one (CIS + GEM) regimen were found to be more effective in quality-adjusted life-years and life-years. Compared to GEM, the incremental cost-utility ratios for CAP + GEM, OX-GEM, NAB-P + GEM, and FOLFIRINOX, were US$180,503, US$197,993, US$204,833, and US$265,718 per additional quality-adjusted life-year, respectively; and the incremental cost-effectiveness ratios were US$88,181, US$87,620, US$135,683, and US$167,040 per additional life-year, respectively. A probabilistic sensitivity analysis confirmed the base-case analysis.

Conclusions

This sponsor-independent economic evaluation for USA found that OX + GEM, CAP + GEM, FOLFIRINOX, and NAB-P + GEM, but not CIS + GEM, were more expensive but also more effective than GEM alone in terms of quality-adjusted life-years and life-years gained. The NAB-P + GEM regimen appears to be the most cost effective in USA at a willingness-to-pay threshold of US$200,000/quality-adjusted life-year.



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RAMP3 is a prognostic indicator of liver cancer and might reduce the adverse effect of TP53 mutation on survival

Future Oncology, Ahead of Print.


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Associations of Estrogen Receptor Alpha Gene Polymorphisms with Type 2 Diabetes Mellitus and Metabolic Syndrome: A Systematic Review and Meta-Analysis

Horm Metab Res 2018; 50: 469-477
DOI: 10.1055/a-0620-8553

The associations between PvuII (T>C) and XbaI (A>G) polymorphisms of estrogen receptor alpha (ESR1) gene with type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) are reported in many studies, but the results are inconsistent. This present work aims to assess the associations by performing a comprehensive meta-analysis. Relevant studies were searched through several databases. The pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations of PvuII and XbaI polymorphisms with the risk of T2DM and MetS by using the STATA 14.0 software. Eight studies for T2DM and three articles about MetS were included in this meta-analysis. The overall results indicated that PvuII, rather than XbaI polymorphism, was associated with T2DM (regressive model: OR=0.673, 95% CI=0.550 to 0.823, praw<0.001, pFDR<0.003). The subgroup analysis based on race revealed an association of PvuII polymorphism with the decreased T2DM risk in Chinese population and a relationship between XbaI polymorphism and the reduced T2DM susceptibility in Caucasians. The difference of country may be one source of the heterogeneity for PvuII polymorphism and T2DM. However, neither PvuII nor XbaI polymorphism was related to the risk of MetS. The C allele of PvuII polymorphism presents a protective role in T2DM risk, especially in Chinese people. The G allele of XbaI polymorphism is related to a reduced risk for T2DM in Caucasian population. Nevertheless, neither of PvuII nor XbaI polymorphism is associated with MetS risk.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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An Overview of FGF19 and FGF21: The Therapeutic Role in the Treatment of the Metabolic Disorders and Obesity

Horm Metab Res 2018; 50: 441-452
DOI: 10.1055/a-0623-2909

Fibroblast growth factors (FGFs) are responsible for the regulation of a wide range of biological functions, among which cellular proliferation, survival, migration, and differentiation could be pointed out. FGF19 controls the enterohepatic bile acid/cholesterol system, and FGF21 modulates fatty acid/glucose metabolism. Obesity, type 2 diabetes, coronary artery disease, and cancer, all can alter FGF21 circulating concentrations. In contrast to FGF21, metabolic diseases exhibit reduced serum FGF19 levels. Accordingly, FGF19 and FGF21 play important roles in regulating glucose and lipid metabolism. Hence, we present here a timely review on the relationship between FGF19/21 and metabolic diseases, especially obesity, and their probable role in development and treatment of obesity seems necessary.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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The Effects of Vitamin D Supplementation on Biomarkers of Inflammation and Oxidative Stress in Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Horm Metab Res 2018; 50: 429-440
DOI: 10.1055/a-0630-1303

In this systematic review and meta-analysis of randomized controlled trials (RCTs), the effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress in diabetic patients are summarized. The following databases were searched up to December 2017: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as mean difference with 95% Confidence Intervals (95% CI). Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I2). Overall, 33 studies were included in the meta-analyses. Vitamin D supplementation were found to significantly reduce serum high-sensitivity C-reactive protein (hs-CRP) (WMD 0.27; 95% CI, – 0.35, – 0.20; p<0.001) and malondialdehyde (MDA) levels (WMD – 0.43, 95% CI – 0.62, – 0.25, p<0.001) in diabetic patients. In addition, vitamin D supplementation were found to increase markers of nitric oxide (NO) release (WMD 4.33, 95% CI 0.96, 7.70), total serum antioxidant capacity (TAC) (WMD 57.34, 95% CI 33.48, 81.20, p<0.001) and total glutathione (GSH) levels (WMD 82.59, 95% CI 44.37, 120.81, p<0.001). Overall, this meta-analysis shows that in diabetic patients, taking vitamin D had significant effects on hs-CRP and MDA levels, and significantly increased NO, TAC and GSH levels.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Correlation Between the Responses to Growth Hormone (GH) Treatment During Childhood and Adulthood in a Monocentric Cohort of GH-Deficient Patients

Horm Metab Res 2018; 50: 462-468
DOI: 10.1055/a-0620-8517

Our aim was to analyze a cohort of patients with childhood-onset growth hormone deficiency (GHD) to evaluate if there is some correlation between the response to GH treatment during childhood and adulthood, respectively. This was an observational retrospective monocentric cohort study of 47 patients treated with GH during childhood and adulthood. Changes in growth parameters during childhood were compared with the increase of IGF-I z-score and other indexes of GH response (body composition, lipid profile) after 1 year of treatment in adulthood. The only significant positive correlation was observed between final growth velocity during the last year of childhood GH treatment and increase in IGF-I z-score in GH-treated adults (r=0.592, p=< 0.01). No correlation was observed between growth-promoting effects of GH as child and metabolic changes induced by GH as adult. We also observed a negative correlation between weight at the end of childhood GH treatment and the IGF-I response during first year of treatment in adults (r=− 0.335, p <0.05). No significant positive correlation could be observed between the main parameters that evaluate response to GH treatment in children and adults. However, the final growth velocity, which may be considered as one of the main criteria of end of GH treatment in children, was identified as parameter that could predict future response to GH treatment in adulthood.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Cardiovascular Effects of Stress During Acutely Increased Free Fatty Acids in a Randomized, Double-Blind, Cross-Over Study in Humans

Horm Metab Res 2018; 50: 478-484
DOI: 10.1055/a-0620-8438

Increased free fatty acids stimulate sympathetic nervous system activity, impair endothelium-dependent vasodilation, and increase regional blood flow. The aim of this study was to assess if fatty acids acutely elevated by infusion of intralipid/heparin affect cardiovascular reactivity employing two stressors eliciting either a cardiac (Stroop test) or vascular (Cold Face test) dominated pressor response. Two stress tasks were performed in 20 healthy subjects (10 women, 10 men) before and during a 180-min intralipid/heparin or saline infusion as placebo on alternate trial days in a randomized crossover study design. Blood pressure, heart rate, cardiac index, and total peripheral resistance index were measured. At baseline, the Stroop test did not affect hemodynamic parameters, and the Cold Face test had an impact on hemodynamic parameters except for heart rate. Plasma fatty acids concentrations increased to 810% (t=11.0, p<0.001) of baseline and C-peptide increased by 17% (t=4.66, p<0.001) during intralipid/heparin infusion. This was paralleled by increased cardiac index (F=9.98; p<0.005 vs. saline) and reduced total peripheral resistance index (F=4.46; p<0.05 vs saline). There was no effect of intralipid/heparin or saline infusion on Stroop test or Cold Face test reactivity of hemodynamic parameters. An acute increase in free fatty acids does not affect the magnitude or pattern of stress response in healthy volunteers, but primarily alter the underlying cardiovascular tone by decreasing total peripheral resistance index and increasing cardiac index to maintain a constant blood pressure.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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



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Short-Term and Long-Term Effects of Bisphenol A (BPA) Exposure During Breastfeeding on the Biochemical and Endocrine Profiles in Rats

Horm Metab Res 2018; 50: 491-503
DOI: 10.1055/a-0628-6708

Neonates can be exposed to bisphenol A (BPA) through placenta and milk, and BPA is associated with disorders such as precocious puberty and obesity. We evaluated the effects of BPA exposure during breastfeeding on the biochemical and endocrine profiles in young and adult rat progeny. From postnatal day (PND) 3 to 15 dams were divided into low-dose BPA treatment [50 μg/kg/day s.c. (BPA-LD)], high-dose BPA treatment [5 mg/kg/day s.c. (BPA-HD)], and Control (vehicle) groups. Milk was collected at PND15 and 21, which represents the end of exposure and 6 days after withdrawal, respectively. Dams were euthanized at weaning. Offspring of both genders were euthanized at PND15, 21, and 180. Milk estradiol levels were lower in the BPA-HD group than in the control group at PND 15; however, they were higher at PND21. Female rats whose mothers were BPA-exposed showed more significant differences from those in the control group, including better glycemic control and lipid profiles and higher food intake without higher adiposity, in adulthood than in the weaning period, when they presented with higher adiposity and hyperestrogenism. Conversely, male rats showed more abnormalities after BPA exposure compared to control rats, including insulin, leptin, testosterone, and thyroid hormone changes, when young but exhibited fewer alterations in adulthood, with increase only in LDLc in the BPA-HD rats. Taken together, the present findings suggest that exposure to BPA exclusively through milk affects adiposity, metabolism, and/or hormones of offspring in the short and long term, possibly compromising normal development in both sexes.
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© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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A Variable Polyglutamine Repeat Affects Subcellular Localization and Regulatory Activity of a Populus ANGUSTIFOLIA Protein

Polyglutamine (polyQ) stretches have been reported to occur in proteins across many organisms including animals, fungi and plants. Expansion of these repeats has attracted much attention due their associations with numerous human diseases including Huntington's and other neurological maladies. This suggests that the relative length of polyQ stretches is an important modulator of their function. Here, we report the identification of a Populus C-terminus binding protein (CtBP) ANGUSTIFOLIA (PtAN1) which contains a polyQ stretch whose functional relevance had not been established. Analysis of 917 resequenced Populus trichocarpa genotypes revealed three allelic variants at this locus encoding 11-, 13- and 15-glutamine residues. Transient expression assays using Populus leaf mesophyll protoplasts revealed that the 11Q variant exhibited strong nuclear localization whereas the 15Q variant was only found in the cytosol, with the 13Q variant exhibiting localization in both subcellular compartments. We assessed functional implications by evaluating expression changes of putative PtAN1 targets in response to overexpression of the three allelic variants and observed allele-specific differences in expression levels of putative targets. Our results provide evidence that variation in polyQ length modulates PtAN1 function by altering subcellular localization.



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A Dual sgRNA Approach for Functional Genomics in Arabidopsis thaliana

Reverse genetics uses loss-of-function alleles to interrogate gene function. The advent of CRISPR/Cas9-based gene editing now allows the generation of knock-out alleles for any gene and entire gene families. Even in the model plant Arabidopsis thaliana, gene editing is welcomed as T-DNA insertion lines do not always generate null alleles. Here, we show efficient generation of heritable mutations in Arabidopsis using CRISPR/Cas9 with a workload similar to generating overexpression lines. We obtain for several different genes Cas9 null-segregants with bi-allelic mutations in the T2 generation. While somatic mutations were predominantly generated by the canonical non-homologous end joining (cNHEJ) pathway, we observed inherited mutations that were the result of synthesis-dependent microhomology-mediated end joining (SD-MMEJ), a repair pathway linked to polymerase (PolQ). We also demonstrate that our workflow is compatible with a dual sgRNA approach in which a gene is targeted by two sgRNAs simultaneously. This paired nuclease method results in more reliable loss-of-function alleles that lack a large essential part of the gene. The ease of the CRISPR/Cas9 workflow should help in the eventual generation of true null alleles of every gene in the Arabidopsis genome, which will advance both basic and applied plant research.



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Influence of Telomere Length in Hepatocytes on Liver Regeneration after Partial Hepatectomy in Rats

Background: The aim of this study was to investigate telomere length in hepatocytes as a biomarker for liver regeneration after partial hepatectomy (PH) in rats. Materials and Methods: Sixty male Wistar rats underwent a 70% PH. One-month-old rats were assigned to group Y (n = 30) and 4-month-old rats were assigned to group O (n = 30). The rats were euthanized, and their livers were then harvested at postoperative day (POD) 1, 2, 3, 4, or 7. Telomere lengths and established parameters for liver regeneration (residual liver weight and levels of proliferating cell nuclear antigen [PCNA], Ki67, and interleukin [IL]-6) were measured. Results: We observed a significant increase in residual liver weight in group Y compared to that in group O (p = 0.001). The levels of Ki67 (p = 0.016), PCNA (p #x3c; 0.0001), and IL-6 (p #x3c; 0.001) were significantly higher in group Y. Furthermore, the rats in group Y had significantly earlier peak values of Ki67 and PCNA. Telomeres were significantly longer at the time of PH in group Y (p = 0.001). We showed a correlation between telomere length at the day of PH and liver regeneration. Animals with longer telomeres at the time of PH had better liver regeneration (p = 0.015). In group Y, animals with increased liver regeneration (median cut-off: #x3e; 122%) did not show any significant difference in telomere length (p = 0.587) compared to rats with regular regeneration (#x3c; 122%). However, in the older animals, rats with increased regeneration had significantly longer telomeres (p = 0.019) than rats with regular regeneration. Conclusion: Telomere length in rat hepatocytes depends on age, and animals with long telomeres had earlier and better regeneration of healthy liver tissue than rats with short telomeres. Our data confirms that telomere length in rat hepatocytes could be used as a possible predictive marker for liver regeneration, and could help to identify older individuals with a high capacity for hepatic regeneration.
Eur Surg Res 2018;59:83–90

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An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors [Research Articles]

By leveraging tumorgraft (PDX) RNA-Seq data, we developed an empirical approach, DisHet, to dissect the tumor microenvironment (eTME). We found that 65% of previously defined immune signature genes are not abundantly expressed in Renal Cell Carcinoma (RCC), and identified 610 novel immune/stromal transcripts. Using eTME, genomics, pathology and medical record data involving >1,000 patients, we established an inflamed pan-RCC subtype (IS) enriched for Tregs, NK cells, Th1 cells, neutrophils, macrophages, B cells, and CD8+ T cells. IS is enriched for aggressive RCCs, including BAP1-deficient clear-cell and type 2 papillary tumors. The IS subtype correlated with systemic manifestations of inflammation such as thrombocytosis and anemia, which are enigmatic predictors of poor prognosis. Furthermore, IS was a strong predictor of poor survival. Our analyses suggest that tumor cells drive the stromal immune response. These data provide a missing link between tumor cells, the TME, and systemic factors.



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Squamous NSCLC Improves with Atezolizumab Plus Chemo [News in Brief]

Patients treated with drug combination had longer PFS and higher ORR than those who received chemotherapy alone.



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The lncRNA ARLNC1 Promotes Prostate Tumorigenesis [Research Watch]

ARLNC1 is expressed in prostate cancer and stabilizes the AR transcript to promote AR signaling.



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SS18-SSX Retargets the BAF Complex to Drive Synovial Sarcoma [Research Watch]

SS18–SSX targets BAF complexes away from enhancers to broad domains where they activate bivalent genes.



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Erasing CD33 in Normal Myeloid Cells Averts CAR T Cell-Driven Toxicity [Research Watch]

Inactivation of CD33 in HSPCs permits CD33-directed CAR T-cell treatment of AML.



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An Immunosuppressive Role for Eya3 in TNBC [News in Brief]

Protein suppresses CD8+ T cells, upregulates PD-L1 to drive their exhaustion and spur tumor growth.



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TET2 Disruption Enhances the Efficacy of CD19 CAR T-cell Therapy [Research Watch]

Expansion of a single CAR T-cell clone triggers a complete remission in a patient with CLL.



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Targeted therapy for premenopausal women with HR+, HER2- advanced breast cancer: focus on special considerations and latest advances

The incidence of advanced breast cancer in premenopausal women is increasing, and breast cancer in younger women is often more aggressive and has a worse prognosis compared with older women. Premenopausal women with hormone receptor-positive (HR+) breast cancer are frequently under-represented in clinical trials, and treatment strategies in the premenopausal setting are usually extrapolated from data from postmenopausal patients, with the addition of ovarian function suppression to endocrine therapy in HR+ disease. However, the underlying biology of breast cancer in premenopausal women can be different from postmenopausal women, and treatment strategies should ideally be specifically tested in premenopausal patients. Recent phase III trials have now investigated cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in premenopausal patients with HR+, human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer: palbociclib and abemaciclib have been tested in a subset of premenopausal patients in the PALOMA-3 and MONARCH-2 studies, and ribociclib has been tested in the phase III MONALEESA-7 trial, which was entirely dedicated to premenopausal women. This comprehensive review summarizes the differences in biology of HR+, HER2- breast cancer in the premenopausal population compared with the postmenopausal population, discusses special considerations for treatment of premenopausal women, and reviews the evidence from clinical trials investigating endocrine therapy, other targeted treatments, and ovarian function suppression in the HR+, HER2- advanced breast cancer setting.



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Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies

The activity of T cell mediated immunotherapies in B cell lymphoma has been limited to date. The novel bi-specific antibody CD20-TCB, has a 2:1 antibody design to maximize T cell engagement, and demonstrates activity in preclinical models. This may represent a novel therapeutic approach for patients with relapsed/refractory NHL.



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Primary Care Physicians Report Top Administrative Hassles

FRIDAY, June 8, 2018 -- Primary care physicians report that the worst administrative hassles include pre-authorization for medications and tests and managing specialty care, according to an article published in Medical Economics. The most common...

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American Society of Clinical Oncology, June 1-5

The 54th Annual Meeting of the American Society of Clinical Oncology The annual meeting of the American Society of Clinical Oncology was held from June 1 to 5 in Chicago and attracted approximately 20,000 participants from around the world,...

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Topical Rapamycin Effective for TSC-Related Facial Angiofibromas

FRIDAY, June 8, 2018 -- Topical rapamycin seems effective for tuberous sclerosis complex (TSC)-related facial angiofibromas, according to a study published online May 23 in JAMA Dermatology. Mary Kay Koenig, M.D., from The University of Texas Health...

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Negative Social Media Ups Risk of Depression in Young Adults

FRIDAY, June 8, 2018 -- Negative experiences on social media are more impactful than positive interactions as it relates to depressive symptoms in young adults, according to a study published online June 6 in Depression and Anxiety. Brian A....

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Medicaid Expansion Ups Access to Rehab in Young Adults With Injury

FRIDAY, June 8, 2018 -- For young adults hospitalized for injury, the first year of implementation of Medicaid expansion under the Affordable Care Act correlated with significant increases in Medicaid coverage, reductions in lack of insurance, and...

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Crosstalk between type I and II interferons in regulation of myeloid cell responses during bacterial infection

William J Crisler | Laurel L Lenz

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Painful transient edema in the tibial diaphysis: the challenges and the essence of biopsy in treatment

Abstract

Background

Some patients experience a non-traumatic pain in the tibial diaphysis similar to that in the clinical and radiological findings of a tumor, an infection or a stress fracture and cannot be definitively diagnosed even after biopsy.

In this study, our aim was to exhibit the challenges in the diagnosis of this patient group and to evaluate this type of patients with a limited population in the literature.

Methods

Eighteen extremities of 16 patients, whose complaints of non-traumatic pain in the tibial diaphysis were evaluated by our tumor council and T2-weighted MR scans of the medullary bone had shown hyperintense signal changes or tumor-like appearances, were evaluated with histological, radiological, and clinical results.

Results

Lesions were detected in 18 extremities of the 16 patients (seven males, nine females; mean age 23 [range 7 to 51] years). Four of the lesions were in the right tibial diaphysis, ten were in the left, and two were bilateral. Laboratory findings of the patients were normal. Based on the decision of the tumor council, biopsy was performed on 12 patients. All patients' complaints were gone and MRI findings decreased during the follow-up period. The complaints of the three patients who did not have a biopsy decreased after a mean period of three months.

Conclusions

Medullary stress syndrome has been reported in the literature in various forms and in a limited number of cases, including longitudinal stress fracture and transient medullary edema of the bone. In light of our findings, we deduced that biopsy of the diaphyseal lesions in this patient group is essential and that the complaints of this patient group declined in the earlier term in comparison to the patients who were not performed biopsy.



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Second Generation Optical Coherence Tomography: Preliminary Experience in Pancreatic and Biliary Strictures

Evaluation of indeterminate biliary strictures remains a diagnostic challenge. Optical Coherence Tomography (OCT) provides in-vivo, wide-field, cross-sectional imaging at the microstructure level. We present the first preliminary data using a second-generation OCT system using volumetric laser endomicroscopy (VLE) in biliary and pancreatic duct strictures.

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Editorial introductions

imageNo abstract available

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Current questions in bone sarcomas

imagePurpose of review Osteosarcoma and Ewing sarcoma, the most common primary bone tumours in young people, are curable in most patients. However, these tumours remain a significant challenge due to the complexity and intensity of treatment and its long-term morbidity and the significant proportion of patients in whom treatment is unsuccessful. This review addresses questions about current management and emerging therapeutic targets for patients with osteosarcoma, Ewing sarcoma and chondrosarcoma, the commonest bone sarcoma but more common in older patients. Recent findings The largest collaborative international study in osteosarcoma, EURAMOS-1 determined that treatment of patients with resectable disease should not be altered on basis of pathological response to neoadjuvant chemotherapy. In view of little improvement in outcome being evident in recent years, novel therapeutic approaches are required. Putative targets and clinical trials of novel agents are discussed, including emerging targets such as poly (ADP-ribose) polymerase inhibition and isocitrate dehydrogenase inhibition in Ewing sarcoma and chondrosarcoma, respectively. Newer radiotherapy techniques including proton beam and particle ion therapy may be important for local tumour control in selected patients. Summary Collaborative studies are essential to answer current questions and investigate novel therapies in these malignancies to improve outcome and quality of life for patients.

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Supportive care in cancer: quo vadis

No abstract available

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What's new in systemic sarcoma treatments?

No abstract available

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Are we ready for intercultural cancer care?

imagePurpose of review Migration is increasing worldwide, with accumulating evidence of health disparities. At the same time, oncology faces new challenges within a fast-changing care landscape. These two developments raise the question of integration of migrants and ethnic minorities (MEMs) and cultural influences in oncology. Recent findings Perceptions of health and disease differ substantially across and within societies and cultures. However, health needs of MEMs and cultural influences seem often out of the scope of cancer care. The purpose of this thematic review is to consider three major challenges of current and future oncology through the prism of culture and ethnicity: enrollment in cancer clinical trials, therapeutic adherence, and new models and paradigms of care. We found inconsistent literature highlighting gaps in knowledge, research, and clinical practice. This confirms unequal situations for MEMs in cancer and asserts interactions between culture influences and therapeutic transactions. Summary To eliminate the burden of health disparities and ensure the best outcomes in MEM's cancer patients, a collaborative approach from research and clinical practice is necessary. Only robust research from all countries exploring unmet needs of MEMs and striving for functional understanding can inform and innovate clinical practice.

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The concept of oligometastases in colorectal cancer: from the clinical evidences to new therapeutic strategies

imagePurpose of review The concept of oligometastases, defining cancers with limited metastatic capacity and attaining a limited number of secondary sites, is now widely accepted, particularly in colorectal cancer. Currently, however, accurate predictive markers for oligometastatic tumors are still lacking. For this reason, it remains challenging to translate this concept into clinical recommendations. In the present work, we review recent publications on oligometastases in colorectal cancer, showing the evidences for such presentation and underlying the need for the identification of biomarkers, necessary to further develop new therapeutic strategies. Recent findings This review of recently published series confirms that long-term survival and cure could be obtained in patients undergoing surgical resection for colorectal metastases, particularly in the cases of liver metastases. Similar results are observed in other secondary sites such as in pulmonary metastases. Furthermore, in patients with unresectable metastases, significant survival benefit could be still obtained using nonresectional targeted approaches, as thermal ablation or stereotactic radiotherapy. Although these clinical evidences could now serve as proof-of-concept for the existence of an oligometastatic phenotype in colorectal cancer, neither clinical characteristics nor biological biomarkers have been established to be able to prospectively define the patients that will benefit from such therapeutic approaches targeting the metastatic sites. This emphasizes the need for further studies aiming at better defining early clinical and biological characteristics of these patients. As, currently, the reliable identification of the oligometastatic patients could only rely on the demonstration of favorable long-term outcomes after metastases-directed therapies, we propose that retrospective studies will be pivotal to analyze this question. Summary Extensive research is undergoing to define biologically the oligometastatic phenotype in colorectal cancer. Currently, the selection of the patients for potentially curative metastasectomy remains mostly empirical.

https://ift.tt/2MbQKq0

Spiritual care in cancer patients: a need or an option?

imagePurpose of review Because of cancer is generally perceived as a life-threatening illness, patients often develop spiritual needs upon the diagnosis. Spirituality impacts patient quality of life (QoL) and provides a context in which to derive hope and meaning to cope with illness. The goal of this review is to give an overview of the most relevant studies with a focus on the relationship between spiritual well being, QoL and hope in patients with cancer, in addition to exploring the importance of spiritual issues both for patients and healthcare professionals. Recent findings Spiritual well being with its dimensions of faith, meaning, and peace is a central component for the overall QoL. A strong spiritual well being decreases symptom severity, the level of hopelessness and the desire for hastened death in cancer patients. However, in the medical setting the provision of spiritual care remains poor, although patients, especially at the end of life, would like their spiritual needs to be addressed as part of the global care. Summary Care for cancer patients goes beyond just caring for the person's body. The assessment of spiritual/religious needs can be considered the first step in designing needs-tailored interventions.

https://ift.tt/2xRDeVc

Management of sarcoma patients: centralization in reference centers to fragmentation of systemic treatment

No abstract available

https://ift.tt/2JDPgq6

Fatigue, a major still underestimated issue

imagePurpose of review Cancer-related fatigue (CRF) is a frequent and distressing symptom present at any stage of the disease. However, it is still underreported, rarely properly assessed and undertreated. Recent findings There are international guidelines available, but also several barriers to their implementation into clinical practice. Summary According to guidelines, all patients should be clinically screened for CRF on regular basis, at the initial cancer visit and at intervals during every clinic visit, also at posttreatment follow-up visits. Generally, any treatable contributing factors should be identified and possibly treated. After the concomitant factors have been improved or removed, pharmacological and or nonpharmacological treatments of CRF can be considered. Further research is needed to better understand the causes, the better treatments, the easier assessment tool for CRF for clinical practice and to identify barriers and facilitators to implementing CRF guidelines.

https://ift.tt/2JxzWbi

Gynecological sarcomas: what's new in 2018, a brief review of published literature

imagePurpose of review In this article, we focus on recent published data (2017) on the management of gynecologic sarcomas. Recent findings The most significant data published in 2017 develop definition of a new molecular subtype of high grade endometrial stromal sarcoma (ESS) using molecular technics added to histological analysis. The identification of a new translocation on presumed uterine leiomyosarcoma (LMS) points to refinement of nosological classification, with fragmentation of even rare tumors into distinct molecular entities: gynecologic sarcomas are now distinguished into distinct entities from a heterogeneous group of tumors. Other articles have discussed the real incidence of unsuspected sarcomas after fibroid mini-invasive surgery and evaluate the risk of relapse and dissemination after morcellation. Among several criteria, preoperative imagery could become a useful tool. For systemic treatment, no clinical trials changing practices were published, only one positive nonrandomized phase II with carboplatin and pegylated liposomal doxorubicin (PLD) in the treatment of uterine sarcomas after the conventional first line, especially in LMSs and ESSs. Summary Many articles were published on this confidential domain in oncology demonstrating interests on rare sarcomas. All specialties were represented in the literature, even though we are still waiting for urgent improvements in early diagnosis and therapeutic strategies to transform the poor prognostic of these tumors.

https://ift.tt/2JHAlen

Photobiomodulation or low-level laser therapy in the management of cancer therapy-induced mucositis, dermatitis and lymphedema

imagePurpose or review There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT) also known as PhotoBioModulation (PBM) when used for the prevention and/or treatment of oral mucositis in patients undergoing radiotherapy for head and neck cancer, or high-dose chemotherapy regimens. This review aims at giving the state of the art of this technique in this indication. Recent findings Recent advances in LLLT/PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with cancer treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. Summary The article discusses LLLT/PBM mechanisms of action, dosimetry, and safety, and aims to identify some cancer treatment side-effects for which LLLT/PBM may prove to be effective (oral mucositis, radiation dermatitis, lymphedema). In addition, LLLT/PBM parameters for each of these complications are suggested and future research directions are discussed.

https://ift.tt/2JtM9NX

The unbearable lightness of therapeutic algorithms in colorectal liver metastasis

No abstract available

https://ift.tt/2M886no

The latest consensus on antiemetics

imagePurpose of review The present review summarizes and discuss the most recent updated antiemetic consensus. Recent findings Two new neurokinin (NK)1-receptor antagonists, netupitant and rolapitant, have been approved by the Food and Drug Administration and the European Medicines Agency and incorporated in the latest versions of the MASCC/ESMO, ASCO, and NCCN guidelines. Guidelines all recommend a combination of a serotonin (5-HT)3-receptor antagonist, dexamethasone, and a NK1-receptor antagonist in patients receiving highly emetogenic chemotherapy (HEC) with the addition of the multireceptor targeting agent, olanzapine, as an option in cisplatin or anthracycline-cyclophosphamide chemotherapy. A combination of a 5-HT3-receptor antagonist, dexamethasone, and a NK1-receptor antagonist is also recommended in patients receiving carboplatin-based chemotherapy, although based on a lower level of evidence. In spite of the development of new antiemetics, nausea has remained a significant adverse effect. Olanzapine is an effective antinausea agent, but sedation can be a problem. Therefore, the effect and tolerability of multitargeting, nonsedative agents like amisulpride, should be explored. Summary Guidelines recommend a combination of a 5-HT3-receptor antagonist, dexamethasone, and an NK1-receptor antagonist in HEC and carboplatin-based chemotherapy. The addition of olanzapine can be useful in cisplatin-based and anthracycline-cyclophosphamide-based chemotherapy in particular if the main problem is nausea.

https://ift.tt/2JrnJVq

Pseudoadjuvant chemotherapy in resectable metastatic colorectal cancer

imagePurpose of review In this article, we focus on the potential benefits and risks of chemotherapy administration before (perioperative) or after (pseudoadjuvant) a curative resection of colorectal cancer (CRC) metastases. Recent findings In the published evidence, there is a lack of survival benefit from peri or postoperative chemotherapy in the context of resectable metastatic CRC. However, high-risk patients may have a certain benefit when receiving a postoperative cytotoxic treatment. Apart from, according to the published data, the administration of a preoperative chemotherapy has been associated with serious parenchymal liver damage and an increase in the postoperative morbidity-mortality rate. Summary Surgery is the only potentially curative treatment for metastatic CRC, but the risk of recurrence remains high. The current guidelines recommend the administration of either a perioperative or a pseudoadjuvant chemotherapy in this setting despite the absence of survival benefit. A better selection of patients who may require and gain an advantage from chemotherapy in the setting of resectable metastasis is highly needed. In this view, a prospective trial enrolling patients at high risk of recurrence is ongoing.

https://ift.tt/2M87X3k

Prior trauma exposure and serious illness at end of life: A national study of children in the US foster care system from 2005 to 2015

Children in foster care suffer with serious illness at end of life. However, the relationship between prior trauma exposure and serious illness has received little empirical attention.

https://ift.tt/2HyaznC

Survival benefit of adjuvant brachytherapy after hysterectomy with positive surgical margins in cervical cancer

We analyzed a cohort of patients from the National Cancer Database who underwent hysterectomy for cervical cancer with positive surgical margins followed by adjuvant radiation therapy. We found that the addition of brachytherapy to external beam radiation therapy was associated with improved overall survival compared to external beam radiation therapy alone. However, only 45% of patients in this cohort received brachytherapy.

https://ift.tt/2xVfXSx

Do scalp-recorded slow potentials during neuro-feedback training reflect the cortical activity?

Neuro-feedback (NFB) is a therapy for treating various neurological diseases such as epilepsy, attention-deficit hyperactivity disorder, and migraine (Wyckoff and Strehl, 2011). The regulation of slow potentials (SPs) can be applied for alleviating the symptoms of brain disorders. The SPs recorded by the scalp electrodes area are generated in the cerebral cortex and are therefore called as slow cortical potentials (SCPs).

https://ift.tt/2JHrFoc

Incidence of epileptiform discharges in children during induction of anaesthesia using Propofol versus Sevoflurane

Since the implementation of electroencephalography (EEG) for anaesthetic procedures in children, epileptiform discharges have been frequently observed during general anaesthesia with Sevoflurane (Vakkuri et al., 2001; Schultz et al., 2012; Gibert et al., 2012; Kreuzer et al., 2014). Additionally, it has been shown that lower Sevoflurane concentrations and shorter administration time can reduce the incidence of epileptiform discharges (Kreuzer et al., 2014). Sevoflurane and Propofol are currently the most popular agents used for anaesthesia induction in children (Habre et al., 2017).

https://ift.tt/2LBmjYS

Usefulness of EEG-EMG coherence analysis to confirm epileptic nature of spells mimicking hemifacial spasms

Focal seizures mimicking hemifacial spasm have rarely been reported (Towfigh et al., 1997; Espay et al., 2008). Differential diagnosis may be difficult, especially if ictal EEG is normal. We report the utility of EEG-EMG coherence analysis to confirm the epileptic nature of these spells in a patient with a minor pre-rolandic stroke.

https://ift.tt/2JJghZj

Atypical Auditory Language Processing in Adolescents with Autism Spectrum Disorders

Autism spectrum disorder (ASD) is characterized by a variety of abnormalities in auditory processing, which play an important role in verbal communication. For example, individuals with ASD have shown abnormal auditory perception and processing, including phonological processing deficits (Tuchman et al., 1991; Kjelgaard et al., 2001; Rapin et al., 2009; O'Connor, 2012; Schelinski et al., 2016). Two major approaches have been used to investigate the pathophysiology underlying atypical auditory processing in ASD: structural and functional imaging.

https://ift.tt/2HwYgrU

Association of Medicare's Bundled Payment Reform With Changes in Use of Vitamin D Among Patients Receiving Maintenance Hemodialysis: An Interrupted Time-Series Analysis

Medicare's 2011 prospective payment system (PPS) was introduced to curb overuse of separately billable injectable drugs. After epoietin, intravenous (IV) vitamin D analogues are the biggest drug cost drivers in hemodialysis (HD) patients, but the association between PPS introduction and vitamin D therapy has been scarcely investigated.

https://ift.tt/2sSoyzA

Epidemiology of Lower Extremity Deep Venous Thrombosis in Critically Ill Adolescents

To determine the epidemiology of lower extremity deep venous thrombosis (DVT) in critically ill adolescents, which currently is unclear.

https://ift.tt/2M9Myqs

Unilateral Neck Mass in a Neonate

A previously healthy 3-week-old child presented to the emergency room for evaluation of acute-onset left-sided neck swelling. The parents initially noticed it during the previous week and had brought him to the pediatrician, who felt it was a reactive lymph node. However, owing to a concern about the increasing size, they brought him in for reevaluation. Examination revealed a 2 × 2 cm, firm, nontender mass in the lower left neck with no overlying skin changes (Figure 1). There was no obvious limitation in range of motion.

https://ift.tt/2sTLH4s

Cutaneous Smooth Muscle Tumors: A Review

imageSmooth muscle tumors occur infrequently in the skin. They consist of a diverse group of lesions representing hamartomas as well as benign and malignant neoplasms. They may arise from arrector pili muscle, specialized smooth muscle of the genitalia, or vascular smooth muscle. Although rare, accurate diagnosis and classification of cutaneous smooth muscle proliferations is important as they can exhibit a range of clinical behavior and may be associated with underlying syndromes. This review summarizes the clinicopathologic spectrum of smooth muscle tumors involving the skin.

https://ift.tt/2sSsbVX

Recent Advances in the Classification of Low-grade Papillary-like Thyroid Neoplasms and Aggressive Papillary Thyroid Carcinomas: Evolution of Diagnostic Criteria

imagePapillary thyroid carcinomas account for ∼80% of well-differentiated thyroid tumors. During the past decade, several new variants of papillary-like thyroid neoplasms and papillary thyroid carcinomas have been recognized. Some of these neoplasms that were previously classified as malignant have been reclassified as low-grade neoplasms, as the diagnostic criteria have evolved. Similarly, some of the papillary thyroid carcinomas that were previously classified as conventional or classic papillary thyroid carcinomas have now been recognized as more aggressive variants of papillary thyroid carcinomas. Recognizing these differences becomes more important for the proper medical, surgical, and radiotherapeutic management of patients with these neoplasms

https://ift.tt/2sIlgiR

Tumor Syndromes Predisposing to Osteosarcoma

imageOsteosarcoma (OS) is the most common primary bone tumor affecting predominantly adolescents and young adults. It accounts for about 5% of all childhood cancers. Although the majority of OSs are sporadic, a small percentage occur as a component of hereditary cancer syndromes. Early onset, bilateral, multifocal, and metachronous tumors suggest genetic predisposition. The inheritance patterns can be autosomal dominant or recessive. These syndromes predispose to a wide variety of mesenchymal and epithelial cancers with propensity for certain mutations being prevalent in specific cancer subtypes. Li-Fraumeni syndrome, retinoblastoma, Rothmund-Thompson syndrome (type 2), Werner syndrome, and Bloom syndrome, constitute the majority of the tumor syndromes predisposing to OS and will be the focus for this review.

https://ift.tt/2M59IhX

Fluorescent In Situ Hybridization in Surgical Pathology Practice

imageThere have been rapid and significant advances in diagnostic and predictive molecular techniques in recent years with profound impact on patient care. In situ hybridization (ISH) studies have become well entrenched in surgical pathology practice and their role in the evaluation of HER2 in breast carcinoma and their diagnostic utility in soft tissue pathology are well known. Fluorescent ISH is being increasingly used in other sites such as the head and neck and the gynecologic tract. Like most tests in surgical pathology, ISH studies require good quality tissue, correlation with clinical and histopathologic findings, and adherence to guidelines for optimal assay performance and interpretation. Although ISH studies are largely performed in tertiary centers, the tissue is often processed by a variety of laboratories and the referring pathologists are required to discuss the need, relevance, and significance of these tests and the results with their clinical colleagues. Here we review the predictive and diagnostic utility of fluorescent ISH studies in a variety of organ systems, the preanalytical factors that may affect the results, and the pitfalls in the interpretation that all practicing surgical pathologists should be aware of.

https://ift.tt/2sTiMxk

Pathologic Features of Infectious Gastritis

imageThis manuscript presents a review of infectious causes of gastritis aimed at the practicing anatomic pathologist. We shall highlight unique histologic findings and clinical attributes that will assist those analyzing endoscopically obtained mucosal biopsies of the stomach or resection specimens.

https://ift.tt/2sQFTZG

An Update on the Clinicopathologic Features and Pathologic Diagnosis of Hepatitis E in Liver Specimens

imageInfection with the hepatitis E virus (HEV) is globally seen a leading cause of hepatitis. Now increasingly recognized also in industrialized countries, hepatitis E constitutes a significant health problem worldwide. The patient's immune status determines the clinical course and histopathology of hepatitis E. In immunocompetent patients, hepatitis E usually follows an asymptomatic or subclinical course, but may also present with acute hepatitis. In contrast, immunocompromised patients may develop chronic hepatitis, and patients with preexisting liver diseases are at risk for liver decompensation with potentially fatal outcome. Whereas pathologists only occasionally encounter liver biopsies from immunocompetent individuals with hepatitis E, they are more likely exposed to biopsies from patients with preexisting liver disease or immunocompromised individuals. Histopathologic hallmarks of hepatitis E in immunocompetent patients comprise lobular disarray, lobular, and portal inflammation, as well as hepatocyte necrosis of varying extend and regeneration. Thus, it is similar to acute non–E viral hepatitis, yet further differential diagnoses include autoimmune hepatitis and drug-induced liver injury. Histopathologic findings of hepatitis E in preexisting liver disease are determined by the underlying pathology, but may be more severe. Histopathologic presentation of hepatitis E in immunocompromised patients is highly variable, ranging from minimal active hepatitis to chronic hepatitis with severe activity and progressive fibrosis. Taken together, the variability of the histologic features depending on the clinical context and the overlap with other liver diseases make the histopathologic diagnosis of hepatitis E challenging. Immunohistochemistry for HEV open reading frame 2 protein and molecular testing for HEV RNA are useful tissue-based ancillary tools.

https://ift.tt/2sGNbQf

Atypical Hepatocellular Neoplasms: Review of Clinical, Morphologic, Immunohistochemical, Molecular, and Cytogenetic Features

imageThe distinction of hepatocellular adenoma from well-differentiated hepatocellular carcinoma (HCC) can be difficult in some cases, especially on biopsy specimens. These borderline cases often occur in men or older patients and may have β-catenin activation or focal atypical morphologic features (such as small cell change, prominent pseudoacinar formation, cytologic atypia, focally thick plates, and/or focal reticulin loss) that are insufficient for an unequivocal diagnosis of HCC. The term "atypical hepatocellular neoplasm" has been advocated for these tumors, but a number of other terms, including "atypical adenoma," "hepatocellular neoplasm of uncertain malignant potential," and "well-differentiated hepatocellular neoplasm with atypical or borderline features" have also been proposed. This review proposes guidelines for designating tumors as atypical hepatocellular neoplasm and describes clinical, morphologic, immunohistochemical, molecular, and cytogenetic features that distinguish these tumors from typical hepatocellular adenoma and HCC.

https://ift.tt/2sS8T3j

Disclosure of Harmful Medical Error to Patients: A Review With Recommendations for Pathologists Erratum

No abstract available

https://ift.tt/2MdNyd8

Cytokeratin 5/6 and cytokeratin 8/18 expression in triple negative breast cancers: clinicopathologic significance in South-Asian population

Cytokeratin 5/6 and Cytokeratin 8/18 are basal and luminal markers of breast cancer and they have pathological and prognostic significance in breast cancer. We performed Cytokeratin 5/6 and CK8/18 immunohistoc...

https://ift.tt/2JEbTuw

The association of latent toxoplasmosis and level of serum testosterone in humans

Latent toxoplasmosis modifies various hormones and behaviors in infected hosts and possibly involves in etiology of different neurologic and psychiatric disorders. The aim of the current study was to assess po...

https://ift.tt/2JtyAOx

Male size, not female preferences influence female reproductive success in a poeciliid fish (Poecilia latipinna): a combined behavioural/genetic approach

We investigated the potential role of indirect benefits for female mate preferences in a highly promiscuous species of live-bearing fishes, the sailfin molly Poecilia latipinna using an integrative approach that ...

https://ift.tt/2MbH7HS

Self-rated health, quality of life and appetite as predictors of initiation of dialysis and mortality in patients with chronic kidney disease stages 4–5: a prospective cohort study

Patient-reported health status, including symptom burden, functional status and quality of life, are important measures of health in patients with chronic kidney disease. We aimed to investigate patient-report...

https://ift.tt/2xVPVOZ

Comparison of TPLO tibial tuberosity fractures with and without an in situ rotational pin

Cranial cruciate ligament (CCL) rupture is a common cause of pelvic limb lameness in dogs. The tibial plateau leveling osteotomy (TPLO) is a well-described surgical procedure that treats CCL ruptures. The obje...

https://ift.tt/2M80EZv

Selumetinib Continues to Show Promise in Children with NF1

In a phase 2 clinical trial, the investigational drug selumetinib shrank tumors in some children with the genetic syndrome neurofibromatosis type 1 (NF1). The tumors, called neurofibromas, can cause pain, difficulty breathing or walking, and disfigurement.



https://ift.tt/2MbWH6c

Oroxylum indicum (L.) Kurz extract inhibits adipogenesis and lipase activity in vitro

Oroxylum indicum (L.) Kurz (O. indicum) is found in Thailand. It has been used for the treatment of obesity. This study aimed to investigate the effects of an O. indicum extract (OIE) on the adipogenic and biomol...

https://ift.tt/2JxvbOA

Computer-assisted rehabilitation of attention in pediatric multiple sclerosis and ADHD patients: a pilot trial

The treatment of cognitive deficits is challenging in pediatric onset multiple sclerosis (POMS) and in patients with attention deficit hyperactivity disorder (ADHD). We performed a pilot double-blind RCT to ev...

https://ift.tt/2JnY0kL

The TreadWheel: Interval Training Protocol for Gently Induced Exercise in Drosophila melanogaster

The TreadWheel uses rotational motion to gently induce exercise in adult Drosophila melanogaster by exploiting flies' innate, negative geotaxis. It allows for analysis of the interactions between exercise and factors, such as genotype, sex, and diet, and their effect on physiological and molecular assays to assess metabolic health.

https://ift.tt/2sSgDlz

Homochronic Transplantation of Interneuron Precursors into Early Postnatal Mouse Brains

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Challenging young neurons in new brain regions can reveal important insights into how the environment sculpts neuronal fate and maturation. This protocol describes a procedure to harvest interneuron precursors from specific brain regions and transplant them either homotopically or heterotopically into the brain of postnatal pups.

https://ift.tt/2sI6tER

Synthetic Cannabis May Increase Ischemic Cardiomyopathy Risk

FRIDAY, June 8, 2018 -- A case of severe ischemic cardiomyopathy in the absence of traditional risk factors and attributed to synthetic cannabinoid use is described in a report published online June 7 in BMJ Case Reports. Sumera Khan, from the...

https://ift.tt/2sD5uWH

Infant Omega-3 Supplementation Tied to Decreased Waist Size

FRIDAY, June 8, 2018 -- Omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation in infancy is associated with reduced insulin concentrations and insulin resistance in boys and reduced waist circumference in both sexes at age 5...

https://ift.tt/2JBPqOv

Prostate Cancer Treatment Side Effects Linked to Distress

FRIDAY, June 8, 2018 -- For prostate cancer survivors, dysfunction due to treatment side effects has a bidirectional association with emotional distress, according to a study published in the June issue of The Journal of Urology. Heather Orom,...

https://ift.tt/2LA9s9E

Some Common Allergies Linked to Odds of Autism in Children

FRIDAY, June 8, 2018 -- Common allergic conditions, especially food allergy, are associated with autism spectrum disorder (ASD) in children, according to a study published online June 8 in JAMA Network Open. Guifeng Xu, M.D., from the University of...

https://ift.tt/2HvAVa7

Malpractice Damage Caps Associated With Change in CAD Testing, Tx

FRIDAY, June 8, 2018 -- Following adoption of damage caps, physicians alter their approach to coronary artery disease testing and follow-up after initial ischemic evaluations, according to a study published online June 6 in JAMA Cardiology. Steven...

https://ift.tt/2sD5shx

Adenoid, Tonsil Removal May Affect Later Respiratory Risks

FRIDAY, June 8, 2018 -- Adenoidectomy and tonsillectomy in children are associated with increased long-term risks of respiratory, infectious, and allergic diseases, according to a study published online June 7 in JAMA Otolaryngology-Head & Neck...

https://ift.tt/2LyFbI1

Web Program Tied to Better Salt Knowledge, Behaviors in Children

FRIDAY, June 8, 2018 -- A web-based salt reduction program is associated with improvement in salt-related knowledge, self-efficacy, and behaviors among children ages 7 to 10 years, according to a study published online June 7 in the Journal of...

https://ift.tt/2HwiL83

Noninvasive Blood Test Can Predict Gestational Age

FRIDAY, June 8, 2018 -- Noninvasive blood tests can predict gestational age and can identify women at risk for preterm delivery using cell-free RNA, according to a study published in the June 8 issue of Science. Thuy T.M. Ngo, from Stanford...

https://ift.tt/2JEudDv

Older Age Tied to Poorer Course of Major Depressive Disorder

FRIDAY, June 8, 2018 -- Older age is associated with poorer course of major depressive disorder (MDD), according to a study published online June 7 in The Lancet Psychiatry. Roxanne Schaakxs, Ph.D., from VU University Medical Center in Amsterdam,...

https://ift.tt/2sITgvD

Case Volume Affects Mortality for Immunosuppressed With Sepsis

FRIDAY, June 8, 2018 -- At hospitals with the lowest volume of immunosuppressed patients with sepsis, the risk of death from sepsis due to a suppressed immune state is highest, according to a study published online June 1 in the Annals of the...

https://ift.tt/2Hyd35A

Efficacy of introducing a checklist to reduce central venous line associated bloodstream infections in the ICU caring for adult patients

Central line-associated bloodstream infections (CLABSI) are a major source of sepsis in modern intensive care medicine. Some years ago bundle interventions have been introduced to reduce CLABSI. The use of che...

https://ift.tt/2LzFwuc

Genetic structures of invasive Streptococcus pneumoniae isolates from Korean children obtained between 1995 and 2013

Understanding the population genetics of pneumococci will allow detection of changes in the prevalence of circulating genotypes and evidence for capsular switching. We aimed to analyze the genetic structure of...

https://ift.tt/2sJPiTq

Distribution of influenza virus types by age using case-based global surveillance data from twenty-nine countries, 1999-2014

Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data ...

https://ift.tt/2HykDgy

Adherence to antiretroviral therapy and associated factors among HIV positive adults attending care and treatment in University of Gondar Referral Hospital, Northwest Ethiopia

Antiretroviral therapy has an impressive clinical effect on the human immunodeficiency virus although its effectiveness depends mainly on the adherence of patients to the therapy. Therefore, this study aimed t...

https://ift.tt/2sGatG2

Whole genome sequencing reveals high clonal diversity of Escherichia coli isolated from patients in a tertiary care hospital in Moshi, Tanzania

Limited information regarding the clonality of circulating E. coli strains in tertiary care hospitals in low and middle-income countries is available. The purpose of this study was to determine the serotypes, ant...

https://ift.tt/2M7EvKR

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Repair of double-strand DNA breaks is a dynamic process, requiring not only formation of repair complexes at the breaks, but also their resolution after the lesion is addressed. Here, we use immunofluorescence microscopy for transient and long-lasting double-stranded breaks as a tool to dissect this genome maintenance mechanism.

https://ift.tt/2kZfbKU

Assessing the efficacy of peripherally acting mu-opioid receptor antagonists (PAMORAs) in the treatment of opioid-induced constipation

We read with interest the recent systematic review and network meta-analysis on the efficacy of pharmacological treatment of opioid-induced constipation (OIC).1 The authors reviewed 27 randomised controlled trials (RCTs) involving 9149 patients and concluded that naloxone was the best drug in patients with OIC, followed by naldemedine. We believe that several factors impacted the appraisal of relative efficacy and deserve discussion especially in network meta-analyses with no head-to-head drug trials.

Distribution and potential for opioid withdrawal: Naloxone is a lipophilic, non-selective and competitive opioid receptor antagonist. The oral formulation of naloxone has a bioavailability of ~2%; however, it is widely distributed, has a narrow therapeutic index and the oral doses required to treat OIC can increase the risk of opioid withdrawal symptoms. On the other hand, peripherally acting mu-opioid receptor antagonists such as naldemedine and naloxegol are extensively absorbed and excreted, do not cross the blood–brain barrier and are...



https://ift.tt/2HvyDb1

Beyond Oxalobacter: the gut microbiota and kidney stone formation

In the last decade, disease-association studies have dominated gut microbiome research. In many cases, the set-up of these studies has been explorative, screening faecal microbiomes for diagnostic signals with potential predictive or therapeutic perspectives. While such data-driven approaches contributed substantially to tool development and the establishment of metagenome research as a stand-alone field within microbial sciences, they also demonstrated that the untargeted characterisation of microbiome variation in the function of disease pathology is far from trivial.1 Researchers able to successfully establish microbiota–disease associations beyond microbiome background variation awaited the long and painful task to discriminate between causes and consequences, taking into account the continuously expanding list of microbiome covariates. Top-ranked among those covariates is the use of medication,2 emphasising a need for careful study design and cautious statistics when attempting to differentiate between drug and disease associations.3

Aside from data-driven gut microbiome research, far fewer studies have...



https://ift.tt/2JCmJ49

Subtypes of Barretts oesophagus and oesophageal adenocarcinoma based on genome-wide methylation analysis

Objective

To identify and characterise DNA methylation subtypes in oesophageal adenocarcinoma (EAC) and its precursor Barrett's oesophagus (BE).

Design

We performed genome-wide DNA methylation profiling on samples of non-dysplastic BE from cancer-free patients (n=59), EAC (n=23), normal squamous oesophagus (n=33) and normal fundus (n=9), and identified methylation subtypes using a recursively partitioned mixture model. We assessed genomic alterations for 9 BE and 22 EAC samples with massively parallel sequencing of 243 EAC-associated genes, and we conducted integrative analyses with transcriptome data to identify epigenetically repressed genes. We also carried out in vitro experiments treating EAC cell lines with 5-Aza-2'-Deoxycytidine (5-Aza-dC), short hairpin RNA knockdown and anticancer therapies.

Results

We identified and validated four methylation subtypes of EAC and BE. The high methylator subtype (HM) of EAC had the greatest number of activating events in ERBB2 (p<0.05, Student's t-test) and the highest global mutation load (p<0.05, Fisher's exact test). PTPN13 was silenced by aberrant methylation in the HM subtype preferentially and in 57% of EACs overall. In EAC cell lines, 5-Aza-dC treatment restored PTPN13 expression and significantly decreased its promoter methylation in HM cell lines (p<0.05, Welch's t-test). Inhibition of PTPN13 expression in the SK-GT-4 EAC cell line promoted proliferation, colony formation and migration, and increased phosphorylation in ERBB2/EGFR/Src kinase pathways. Finally, EAC cell lines showed subtype-specific responses to topotecan, SN-38 and palbociclib treatment.

Conclusions

We identified and characterised methylator subtypes in BE and EAC. We further demonstrated the biological and clinical relevance of EAC methylator subtypes, which may ultimately help guide clinical management of patients with EAC.



https://ift.tt/2LC4Wrg

Generation and Coherent Control of Pulsed Quantum Frequency Combs

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A protocol is presented for the practical generation and coherent manipulation of high-dimensional frequency-bin entangled photon states using integrated micro-cavities and standard telecommunications components, respectively.

https://ift.tt/2xUr2mH

A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation

Irreversible electroporation (IRE) is a non-thermal ablation technique used for the treatment of locally advanced pancreatic cancer. Being a relatively new technique, the effects of IRE on the tumor growth are poorly understood. We have developed a syngeneic mouse model that facilitates studying the effects of IRE on pancreatic cancer.

https://ift.tt/2MaiGKE

Detection of neuroinflammation before selective neuronal loss appearance after mild focal ischemia using [ 18 F]DPA-714 imaging

Abstract

Background

Translocator protein (TSPO) imaging can be used to detect neuroinflammation (including microglial activation) after acute cerebral infarction. However, longitudinal changes of TSPO binding after mild ischemia that induces selective neuronal loss (SNL) without acute infarction are not well understood. Here, we performed TSPO imaging with [18F]DPA-714 to determine the time course of neuroinflammation and SNL after mild focal ischemia.

Results

Mild focal ischemia was induced by middle cerebral artery occlusion (MCAO) for 20 min. In MCAO rats without acute infarction investigated by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, in vitro ARG revealed a significant increase of [18F]DPA-714 binding in the ipsilateral striatum compared with that in the contralateral side at 1, 2, 3, and 7 days after MCAO. Increased [18F]DPA-714 binding was observed in the cerebral cortex penumbra, reaching maximal values at 7 days after MCAO. Activation of striatal microglia and astrocytes was observed with immunohistochemistry of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) at 2, 3, and 7 days after MCAO. SNL was investigated with Nissl staining and neuronal nuclei (NeuN) immunostaining and observed in the ischemic core region of the striatum on days 3 and 7 after MCAO. We confirmed that total distribution volume of [18F]DPA-714 in the ipsilateral striatum was significantly increased at 2 and 7 days after MCAO using positron emission tomography (PET).

Conclusions

[18F]DPA-714 binding measured with in vitro ARG was increased before SNL appeared, and this change was detected by in vivo PET. These findings suggest that TSPO PET imaging might be useful for detection of neuroinflammation leading to SNL after focal ischemia.



https://ift.tt/2LxVk0p

Systematic literature review of methodologies and data sources of existing economic models across the full spectrum of Alzheimers disease and dementia from apparently healthy through disease progression to end of life care: a systematic review protocol.

Introduction

Dementia is one of the greatest health challenges the world will face in the coming decades, as it is one of the principal causes of disability and dependency among older people. Economic modelling is used widely across many health conditions to inform decisions on health and social care policy and practice. The aim of this literature review is to systematically identify, review and critically evaluate existing health economics models in dementia. We included the full spectrum of dementia, including Alzheimer's disease (AD), from preclinical stages through to severe dementia and end of life. This review forms part of the Real world Outcomes across the Alzheimer's Disease spectrum for better care: multimodal data Access Platform (ROADMAP) project.

Methods and analysis

Electronic searches were conducted in Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Economic Literature Database, NHS Economic Evaluation Database, Cochrane Central Register of Controlled Trials, Cost-Effectiveness Analysis Registry, Research Papers in Economics, Database of Abstracts of Reviews of Effectiveness, Science Citation Index, Turning Research Into Practice and Open Grey for studies published between January 2000 and the end of June 2017. Two reviewers will independently assess each study against predefined eligibility criteria. A third reviewer will resolve any disagreement. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed using the Phillips checklist for decision analytic modelling. A narrative synthesis will be used.

Ethics and dissemination

The results will be made available in a scientific peer-reviewed journal paper, will be presented at relevant conferences and will also be made available through the ROADMAP project.

PROSPERO registration number

CRD42017073874.



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Educational inequalities in subjective health in Germany from 1994 to 2014: a trend analysis using the German Socio-Economic Panel study (GSOEP)

Introduction

As trend studies have shown, health inequalities by income and occupation have widened or remained stable. However, research on time trends in educational inequalities in health in Germany is scarce. The aim of this study is to analyse how educational inequalities in health evolved over a period of 21 years in the middle-aged population in Germany, and whether the trends differ by gender.

Methods

Data were obtained from the German Socio-Economic Panel covering the period from 1994 to 2014. In total, n=16 339 participants (106 221 person years) aged 30–49 years were included in the study sample. Educational level was measured based on the 'Comparative Analysis of Social Mobility in Industrial Nations' (CASMIN) classification. Health outcomes were self-rated health (SRH) as well as (mental and physical) health-related quality of life (HRQOL, SF-12v2). Absolute Index of Inequality (Slope Index of Inequality (SII)) and Relative Index of Inequality (RII) were calculated using linear and logarithmic regression analyses with robust SEs.

Results

Significant educational inequalities in SRH and physical HRQOL were found for almost every survey year from 1994 to 2014. Relative inequalities in SRH ranged from 1.50 to 2.10 in men and 1.25 to 1.87 in women (RII). Regarding physical HRQOL, the lowest educational group yielded 4.5 to 6.6 points (men) and 3.3 to 6.1 points (women) lower scores (SII). Although educational level increased over time, absolute and relative health inequalities remained largely stable over the last 21 years. For mental HRQOL, only few educational inequalities were found.

Discussion

This study found persistent educational inequalities in SRH and physical HRQOL among adults in Germany from 1994 to 2014. Our findings highlight the need to intensify efforts in social and health policies to tackle these persistent inequalities.



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Evaluation of different infant vaccination schedules incorporating pneumococcal vaccination (The Vietnam Pneumococcal Project): protocol of a randomised controlled trial

Introduction

WHO recommends the use of pneumococcal conjugate vaccine (PCV) as a priority. However, there are many countries yet to introduce PCV, especially in Asia. This trial aims to evaluate different PCV schedules and to provide a head-to-head comparison of PCV10 and PCV13 in order to generate evidence to assist with decisions regarding PCV introduction. Schedules will be compared in relation to their immunogenicity and impact on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae.

Methods and analysis

This randomised, single-blind controlled trial involves 1200 infants recruited at 2 months of age to one of six infant PCV schedules: PCV10 in a 3+1, 3+0, 2+1 or two-dose schedule; PCV13 in a 2+1 schedule; and controls that receive two doses of PCV10 and 18 and 24 months. An additional control group of 200 children is recruited at 18 months that receive one dose of PCV10 at 24 months. All participants are followed up until 24 months of age. The primary outcome is the post-primary series immunogenicity, expressed as the proportions of participants with serotype-specific antibody levels ≥0.35 µg/mL for each serotype in PCV10.

Ethics and dissemination

Ethical approval has been obtained from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (EC00153) and the Vietnam Ministry of Health Ethics Committee. The results, interpretation and conclusions will be presented to parents and guardians, at national and international conferences, and published in peer-reviewed open access journals.

Trial registration number

NCT01953510; Pre-results.



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Effectiveness of amoxicillin alone in the treatment of uncomplicated acute otitis media: a systematic review protocol

Introduction

Amoxicillin is the first-line antibiotic recommended by most scientific societies for the treatment of uncomplicated acute otitis media (AOM) in children and adults. In low-income and middle-income countries however, absence of setting-specific recommendations and antibiotic resistance, promoted by higher population density and over-the-counter antibiotic availability, could hamper the effectiveness of amoxicillin. We aim to provide updated information to enable evidence-based decisions for first-line therapy of uncomplicated AOM in our setting.

Methods and analysis

We will conduct a systematic review of all randomised controlled trials on the clinical effectiveness of amoxicillin for the treatment of uncomplicated AOM in children above 6 months and adults. The search will include studies published from the generation of the included databases to 31 December 2017. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and study quality will be assessed by the Risk of Bias Assessment Tool from the Cochrane Handbook for randomised trials. A meta-analysis will be conducted for homogeneous studies, eventually, using the fixed-effect model. Subgroup analysis will include age groups, amoxicillin dosage, treatment duration, effectiveness criteria, time of trial realisation, study quality and region of the world involved.

Ethics and dissemination

Formal ethical approval is not required, as primary data will not be collected. The results will be disseminated through a peer-reviewed publication and presented at scientific meetings.

PROSPERO registration number

CRD42017080029.



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Epidemiology of overweight and obesity in early childhood in the Gulf Cooperation Council countries: a systematic review and meta-analysis protocol

Introduction

There has been a notable increase in the prevalence of overweight and obesity in school-aged children in many industrialised regions. The worldwide prevalence of childhood overweight and obesity increased from 4.2% in 1990 to 6.7% in 2010. Although many studies have been published, the epidemiological burden of overweight and obesity in the Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates) is unclear. There is a need to bring together and appraise relevant studies in order to estimate the epidemiological burden (including incidence, prevalence, risk factors, trend over time) of overweight and obesity in this region and thus help to inform national and regional policies.

Methods and analysis

We will conduct a systematic review and meta-analysis on the epidemiology of overweight and obesity in early childhood including incidence, prevalence, risk factors and trends over time in the GCC countries. We will search international electronic databases including MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, CINAHL, Google Scholar, AMED, Psych INFO, CAB International and WHO Global Health Library for published, unpublished and in-progress epidemiological studies of interest published from inception to 2017. In addition, we will contact an international panel of experts on the topic. There will be no restriction on the language of publication of studies. We will use the Effective Public Health Practice Project (EPHPP) to appraise the methodological quality of included studies. Meta-analysis will be undertaken using random effects models.

Ethics and dissemination

Ethical approval is not required. The outcome of the review will be disseminated through conference presentations and peer-reviewed journal publication.

PROSPERO registration number

CRD42017073189.



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Subcutaneous emphysema to the head and neck: an unlikely traumatic origin

Subcutaneous emphysema to the neck represents a rare entity mainly derived from iatrogenic and traumatic origin. We report a case of a subcutaneous emphysema resulted from an intraoral injury aiming to emphasise the significance of precise medical history to identify an unlikely mechanism. A 40-year-old female patient was presented with subcutaneous emphysema extending from the region underneath the left eye up to the submandibular area of the neck. The patient complained of painful, swollen neck. The patient mentioned that the symptoms began after an intraoral injury accidentally caused by the use of a high-pressure water jet device meant for car wash. The patient was managed conservatively and was discharged after 2 days. This case highlights the urgency for clinical suspicion for unlikely mechanisms. Moreover, the manufacturer companies should alert and give official warning for the contingency of injury due to incorrect or careless usage.



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Terminal deoxynucleotidyl transferase (TdT)-negative T-cell lymphoblastic lymphoma with loss of the T-cell lineage-specific marker CD3 at relapse: a rare entity with an aggressive outcome

Terminal deoxynucleotidyl transferase (TdT)-negative T-cell lymphoblastic lymphoma is a variant of T-cell lymphoblastic lymphoma/T-cell lymphoblastic leukaemia. TdT is a marker of immaturity expressed in 90%–95% cases of lymphoblastic lymphoma and useful in differentiating it from other mature lymphomas/leukaemias. It has been associated with poorer response to chemotherapy and a more aggressive outcome. Here we present a case of TdT-negative T-cell lymphoblastic lymphoma in a 28-year-old man who presented with superior vena cava syndrome. The patient was treated with hyper-cyclophosphamide,vincristine, Adriamycin, dexamethasone (CVAD), however unfortunately suffered a relapse 1 year later. A unique feature of our case was that on relapse, the patient lost expression of the T-cell lineage-specific marker CD3, which has previously not been reported in association with TdT-negative T-cell lymphoblastic lymphoma. The patient failed to respond to chemotherapy on his relapse and died.



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Histiocytic necrotising lymphadenitis identical to Kikuchi-Fujimoto disease in CNS lupus

Description 

A 36-year-old woman presented after a first generalised tonic–clonic seizure. On clinical examination, prominent cervical and axillary lymphadenopathy was noted. Brain MRI showed diffuse, partially enhancing, hyperintense lesions (figure 1). An axillary lymph node biopsy revealed typical findings of histiocytic necrotising lymphadenitis, compatible with Kikuchi-Fujimoto disease (figure 2).1 Laboratory studies showed positive antinuclear antibodies, low complement levels and pancytopenia. In the cerebrospinal fluid (CSF), lymphocytic pleocytosis (34/μL), elevated lactate (3.3 mmol/L) and protein (104 mg/dL) levels were noted. Investigations for lymphoma were negative. Furthermore, negative serological and PCR findings for Epstein-Barr virus, cytomegalovirus and HIV were found. Interferon-gamma release assay and PCR for tuberculosis, along with serological investigations for toxoplasmosis and syphilis, were negative. The cytological examination of the CSF revealed activated lymphocytes and plasma cells. CSF and blood cultures remained negative. On diagnostic evidence of pericarditis and a positive history for photosensitivity and...



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Bilateral ocular paralysis in an ocular emergency

Description Case description

A 70-year-old female patient was brought to the ocular emergency department with the chief complaints of bilateral severe ptosis and total external ophthalmoplegia (L>R) for the past 1 week (figure 1). There was no history of any significant medical or surgical intervention. On evaluation, there was a 6 mm ptosis in the right eye and complete ptosis in the left eye along with an axial proptosis of 20 mm in the right eye and 21 mm in the left eye as measured using a Hertel exophthalmometer. Both eyes had complete restriction of extraocular movements in all gazes (figure 1) along with mildly dilated pupils with a sluggish reaction to light. Conjunctiva showed severe chemosis in both eyes (L>R). The anterior segment was slightly shallow on both sides with nuclear sclerosis of grade I to II. Intraocular pressures were 18 and 20 mm Hg in the right and...



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Novel psychoactive substances: overdose of 3-fluorophenmetrazine (3-FPM) and etizolam in a 33-year-old man

Though illegal in the UK, in many countries novel psychoactive substances are quasi-legal synthetic compounds that are widely available online under the guise of research chemicals. These substances are relatively cheap and are often undetectable in standard drug screens. Nearly 200 such compounds are introduced yearly, and little is usually known about their metabolism or physiological effects. Consequently, managing patients in overdose situations on largely unknown substances usually involves supportive care, however anticipating and managing atypical side effects are challenging in the absence of knowledge of these compounds. In this report, we discuss our encounter with a 33-year-old unconscious man presenting with coingestion of a novel stimulant 3-fluorophenmetrazine with a rarely used benzodiazepine etizolam. This patient developed seizure-like activity and delayed widespread T-wave inversions, both of which ultimately resolved without sequelae.



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Chronic calcified subdural haematoma found after presentation of symptomatic glioma

Description 

A patient with neurofibromatosis 1 and childhood ventriculoperitoneal (VP) shunt insertion for hydrocephalus presented with 4 weeks of short-term and working memory impairment. Apart from right-hand tremor, he denied headache, visual changes, weakness and dyscoordination. A CT head showed a right-sided subdural lesion with 22 mm midline shift. The MRI head showed a right inferior-frontal enhancing mass suspicious of high-grade glioma and right extensively calcified subdural extra-axial collection, with mixed heterogeneous predominantly T1-hyperintense contents (figure 1A).

Figure 1

(A) Preoperative MRI shows a right inferior frontal mass suspicious of high-grade glioma and the extra-axial collection with mixed heterogeneous predominantly T1-hyperintense contents, and extensive calcification. (B) Postoperative MRI showing more than 90% debulking of the enhancing tumour (glioblastoma, WHO grade IV) and the right subdural evacuation.

He underwent right fronto-temporo-parietal craniotomy with chronic calcified subdural haematoma evacuation, right frontal mass resection plus duraplasty (figure...



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Acyclovir-induced thrombocytopaenia in a patient with SLE

Acyclovir has been used in the treatment of herpes simplex and varicella zoster viral infections for over 30 years. The side effects of oral treatment at standard doses are rare and include headache, diarrhoea, dizziness and malaise. We report a patient with a new diagnosis of systemic lupus erythematosus (SLE) who developed thrombocytopaenia within days on a therapeutic dose with acyclovir. Prompt discontinuation of acyclovir and treatment with intravenous immunoglobulin resulted in reversal of the above potentially serious complication. Therefore a high index of suspicion should be exercised in patients with SLE who require treatment with acyclovir for herpes viral infections. In these patients regular platelet count measurement should be considered while on treatment with the above antiviral agent.



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Symptomatic hyperthyroidism in metastatic testicular mixed germ cell tumour

This is a case of a young 34-year-old man who had symptomatic hyperthyroidism from an extremely high serum beta HCG level in the setting of a metastatic stage IIIC mixed germ cell tumour. The patient's thyroid function normalised with treatment of the cancer as the beta HCG levels declined.



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Orbital cysticercosis

A young male patient presented to our ocular emergency department with chief complaints of progressive pain, redness, diplopia and a right-sided face turn. Ocular examination revealed severely restricted extraocular movements along with retinal folds in the left eye. Initial orbital ultrasound and CT findings were equivocal; however, serology favoured an infective cause. Considering the endemicity of the disease and equivocal investigation findings, a diagnosis of orbital cysticercosis with an atypical presentation was made. The patient was managed medically with a combination of oral albendazole and steroids over a period of 6 weeks to achieve optimal results.



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Babesiosis as a cause of false-positive HIV serology

This is a case of a 71-year-old homosexual man who presented with a 4-day history of fever, weakness and headaches, near syncope, nausea and poor oral intake. The patient denied recent travel or sick contacts but had significant tick bites in the last 4 weeks. A peripheral blood smear showed 0.5% parasitaemia with signet ring appearance organisms consistent with Babesia microti. Serology testing for HIV 1 and 2 by ELISA and western blot were positive. Treatment for Babesia was started and the patient improved. Repeat serology testing for HIV was negative. To the best of our knowledge, this is the first case of false-positive HIV serology that is associated with active babesiosis. In this case, the positive HIV serology turned negative after successful treatment of babesiosis.



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Salvage therapy for acute severe ulcerative colitis during pregnancy

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with an age of onset that affects young people during the peak of their reproductive years. Management of flares of disease during pregnancy can be complex and there are few case reports of pregnant women with acute severe ulcerative colitis (ASUC). We present the case of a 31-year-old pregnant woman who at 16 weeks gestation developed ASUC in the context of primary non-response to infliximab therapy. She subsequently underwent an emergency laparoscopic colectomy after failing to respond to hydrocortisone and cyclosporine salvage therapy. Her pregnancy was further complicated by HELLP (Haemolysis, Elevated liver enzymes and Low Platelets) syndrome resulting in premature delivery at 27 weeks gestation. This case highlights the management issues involved in ASUC during pregnancy and the assessment of disease activity, use of salvage therapies, and provides a framework to approach this complex medical emergency.



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Obstructive hydrocephalus caused by colloid cyst presenting as a schizophrenia-like psychosis

This report presents a young woman with psychotic symptoms that were highly suspicious of schizophrenia. Previous attempts of antidepressant therapy of mood symptoms had been ineffective. However, she also presented with discrete signs of an underlying neurological condition, and as a part of the diagnostic workup, neuroimaging revealed ventriculomegaly. She was diagnosed with obstructive hydrocephalus and experienced full remission of psychotic symptoms after neurosurgical intervention with a ventriculoperitoneal shunt. This atypical presentation of obstructive hydrocephalus underlines the importance of neuroimaging in psychiatric differential diagnostics. Otherwise, this young woman had been diagnosed with schizophrenia, instead of organic delusional disorder secondary to a neurological condition, with possible irreversible damage to brain tissue as a consequence.



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Concomitant sarcoidosis and papillary thyroid cancer with severe hypercalcaemia as the main symptom

A 65-year-old Caucasian man was admitted to our hospital due to incidental finding of plasma ionised calcium=1.83 mmol/L. During the previous months, he had felt more tired and had experienced an unintended weight loss of 6–8 kg. A CT scan revealed an inhomogeneous thyroid gland and enlarged lymph nodes along the cervical vessels and in the mediastinum. The patient underwent total thyroidectomy and, at the same time, two lymph nodes were removed. Histological examination of the thyroid gland revealed papillary thyroid carcinoma (PTC), T1aN0M0, and histological examination of the lymph nodes showed non-caseating granulomatous inflammation. After further investigation, a diagnosis of sarcoidosis (SA) was made.

Coexistence of SA and PTC may yield a diagnostic challenge as both diseases might involve the lymph nodes of the neck. Furthermore, the case illustrates the importance of close follow-up of even moderate hypercalcaemia, since it may evolve into a hypercalcaemic crisis.



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Staphylococcus aureus modulation of innate immune responses through Toll-like (TLRs), (NOD)-like (NLRs) and C-type lectin (CLRs) receptors

Abstract
Early recognition of pathogens by the innate immune system is crucial for bacterial clearance. Many pattern recognition receptors (PRRs) such as Toll-like (TLRs) and (NOD)-like (NLRs) receptors have been implicated in initial sensing of bacterial components. The intracellular signaling cascades triggered by these receptors result in transcriptional upregulation of inflammatory pathways. Although this step is crucial for bacterial elimination, it is also associated with the potential for substantial immunopathology, which underscores the need for tight control of inflammatory responses. The leading human bacterial pathogen Staphylococcus aureus expresses over 100 virulence factors that exert numerous effects upon host cells. In this manner, the pathogen seeks to avoid host recognition or perturb PRR-induced innate immune responses to allow optimal survival in the host. These immune system interactions may result in enhanced bacterial proliferation but also provoke systemic cytokine responses associated with sepsis. This review summarizes recent findings on the various mechanisms applied by S. aureus to modulate or interfere with inflammatory responses through PRRs. Detailed understanding of these complex interactions can provide new insights toward future immune-stimulatory therapeutics against infection or immunomodulatory therapeutics to suppress or correct dysregulated inflammation.

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New Research From Psychological Science

Read about the latest research published in Psychological Science:

A Cognitive-Ecological Explanation of Intergroup Biases
Hans Alves, Alex Koch, and Christian Unkelbach

People often evaluate minorities and out-groups negatively. These are usually novel groups and thus tend to be associated with unique attributes that differentiate them from other groups. But unique attributes are also more negative than positive because of their higher diversity and lower frequency. The authors propose a model that combines these two theories to explain the negative evaluation of minorities and out-groups. They showed participants information about two alien tribes and asked them to choose their favorite tribe. Most participants preferred the first tribe over the second when the unique attributes were negative but not when the unique attributes were positive. Participants also preferred the first tribe over the second when the negative traits were more diverse and when the positive traits were more frequent. When the positive traits were more diverse or the negative traits were more frequent, there was no evaluation bias favoring the first tribe. These results show that the information environment, in the form of how attributes are distributed, interacts with cognitive processing of group novelty to create intergroup biases.

Object-Based Attention on Social Units: Visual Selection of Hands Performing a Social Interaction
Jun Yin, Haokui Xu, Jipeng Duan, and Mowei Shen

Recent studies have suggested that information structure and object boundaries constrain visual attention selection. But can multiple objects in a social interaction be integrated for selective attention? In two experiments, the authors tested whether a handshake can be selected as a single object of attentional selection (rather than as two hands, separately). In several trials, they showed participants two pairs of hands. In each pair, one hand was in a handshake position with either the palm or the back of the hand facing out; the other hand was either also in the handshake position or was reversed (i.e., the thumb was pointed downward). When the hands returned to their initial positions, a cue flashed on the center of one hand, and then a target letter or a distractor symbol appeared on the center of each hand. Participants had to report the target by pressing a key. When the cue appeared in the wrong hand, participants identified the target faster if cue and target were in the same pair than if they were in different pairs. However, this effect occurred only when the pair was in the handshake position and in motion. These results show that the handshake selected attention. Thus, attention can select a grouped object whose components are connected by a social interaction.

The Napoleon Complex: When Shorter Men Take More
Jill E. P. Knapen, Nancy M. Blaker, and Mark Van Vugt

A popular belief known as the Napoleon complex holds that short men compensate for their height disadvantage by displaying dominant behavior. The authors examined whether shorter men were more aggressive toward taller competitors in economic games. They tested pairs of men and compared their behavior in two games: a dictator game in which the player had unconditional power over the division of resources and an ultimatum game in which the player's division of resources could be rejected and incite retaliation. Shorter men kept more resources for themselves in the dictator game, regardless of the opponent's height. In the ultimatum game, shorter men kept more resources only if the opponent was not taller. When participants were also asked to prepare a hot sauce mixture for their opponents, as a measure of physically aggressive behavior, height had no effect. These results show that the Napoleon complex manifests itself in indirect aggressive behavior but not necessarily in direct or physically aggressive behavior. Thus, height predicts competitive behaviors in an absolute-power situation.

Sameness May Be a Natural Concept That Does Not Require Learning
Thomas R. Zentall, Danielle M. Andrews, and Jacob P. Case

Pigeons can learn how to peck colors that match or mismatch a stimulus. Does this behavior reflect learning the simple association between stimulus and response or might it reflect the concept of sameness? The authors trained pigeons to respond to colors by choosing either the matching or the mismatching color from a pair of colors. In the test phase, they replaced the matching or mismatching stimulus with a familiar stimulus to avoid pigeons' fear of novelty. Pigeons performed at the chance level when the matching stimulus was replaced (i.e., the correct stimulus in the matching task and the incorrect one in the mismatching task) but performed above chance when the mismatching stimulus was replaced (i.e., the incorrect stimulus in the matching task and the correct one in the mismatching task). These results show that pigeons learned to locate the matching color and either choose it or avoid it, depending on the task. This effect demonstrates that pigeons can use the natural concept of sameness and that their responses in a matching task are not exclusively stimulus-response associations.



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