tbuckley/cabot-search huggingface dataset:
Prescribed Exercise With Compression vs Compression Alone in Treating Patients With Venous Leg Ulcers
Authors: Andrew Jull, Julia Slark, John Parsons
Journal: JAMA Dermatology (2018)

Exercise is recommended as an adjuvant treatment for venous leg ulceration (VLU) to improve calf muscle pump function. However, the association of exercise with VLU healing has not been properly aggregated, and the effectiveness of different exercise interventions has not been characterized.To summarize the association of different exercise interventions with VLU healing when used as an adjuvant to any form of compression.The Cochrane Controlled Trials Register, MEDLINE, Embase, CINAHL, PsycInfo, and SCOPUS databases were searched through October 9, 2017.Randomized clinical trials (RCTs) of any exercise compared with no exercise in participants with VLU were included, where compression was used as standard therapy and a healing outcome was reported. Independent title screening and full text review by 2 authors (A.J., J.S.) with appeal to a third author (J.P.) if disagreement was unresolved. Of the 519 articles screened, a total of 6 (1.2%) studies met the inclusion criteria for systematic review, including 5 for meta-analysis.Independent quality assessment for Cochrane risk of bias and data extraction by 2 authors with appeal to third author if disagreement unresolved (PRISMA). Data pooled using fixed effects model.The a priori primary outcome was any healing outcome (proportion healed, time to healing, or change in ulcer area). Secondary outcomes (adverse events, costs, and health-related quality of life) were only collected if a primary outcome was reported.Six RCTs were identified and 5 (190 participants) met inclusion criteria for meta-analysis. The exercise interventions were progressive resistance exercise alone (2 RCTs, 53 participants) or combined with prescribed physical activity (2 RCTs, 102 participants), walking only (1 RCT, 35 participants), or ankle exercises (1 RCT, 40 participants). Overall, exercise was associated with increased VLU healing at 12 weeks although the effect was imprecise (additional 14 cases healed per 100 patients; 95% CI, 1-27 cases per 100; P = .04). The combination of progressive resistance exercise plus prescribed physical activity appeared to be most effective, again with imprecision (additional 27 cases healed per 100 patients; 95% CI, 9-45 cases per 100; P = .004).The evidence base may now be sufficiently suggestive for clinicians to consider recommending simple progressive resistance and aerobic activity to suitable patients with VLU while further research is produced.
Empowering clinicians to complain about system failures
Authors: Katherine Hall, Clare Short, Katrina Graham, Priya Rajyaguru
Journal: BMJ (2018)

Restoration of the Medical Practitioners Tribunal’s decision to allow Hadiza Bawa-Garba to remain on the medical register, though highly welcome, has not erased the sense of alarm felt by the medical profession throughout the handling of this case.1 Frontline medical staff have made clear their fear that they are increasingly acting as scapegoats for services that are …
Abstract 14826: Association of Computed Tomography-Derived Left Ventricle Size With Major Cardiovascular Events in the General Population: The Heinz Nixdorf Recall Study
Authors: Iryna Dykun, Amir A Mahabadi, Marie H Berg, Hagen Kälsch, Nils Lehmann, Marcus Bauer, Susanne Moebus, Karl-Heinz Jöckel, Stefan Möhlenkamp, Raimund Erbel
Journal: Circulation (2013)

Background: Echocardiography data suggest a link of left ventricular (LV) size with CV morbidity and mortality. With the advent of cardiac CT, information on LV is readily available and may enhance...
Treatment with 5-azacytidine induces a sustained response in patients with angioimmunoblastic T-cell lymphoma
Authors: François Lemonnier, Jehan Dupuis, Pierre Sujobert, Olivier Tournillhac, Morgane Cheminant, Clémentine Sarkozy, Laura Pelletier, Ambroise Marçais, Cyrielle Robe, Virginie Fataccioli, Corinne Haioun, Olivier Hermine, Philippe Gaulard, Richard Delarue
Journal: Blood (2018)
Interferon-induced epithelial response to rhinovirus 16 in asthma relates to inflammation and FEV1
Authors: Abilash Ravi, Jan Koster, Annemiek Dijkhuis, Suzanne M. Bal, Yanaika S. Sabogal Piñeros, Peter I. Bonta, Christof J. Majoor, Peter J. Sterk, René Lutter
Journal: Journal of Allergy and Clinical Immunology (2018)
LOW GRADE GLIOMA CLINIC - ESTABLISHING AN INNOVATIVE SERVICE BASED ON A MULTIDISCIPLINARY APPROACH
Authors: José Pedro Lavrador, Charlotte Robinson, Victoria Hurwitz, Anastasios Giamouriadis, Francesco Vergani, Keyoumars Ashkan, Ranj Bhangoo, Hussein Kandeel
Journal: Neuro-Oncology (2018)

Patients diagnosed with a low grade glioma (LGG) are unique in terms of the uncertainty they experience with the disease, its prognosis and the different treatment approaches. In recognition of these needs, the low-grade glioma clinic aims to provide an individualized approach provided by a specialised multidisciplinary team which includes neuro-surgeons, neuro-psychologist, neurologist, speech therapist and clinical nurse specialist that is able to plan the patient’s treatment pathway. The nature of the clinic is to allow for longer consultations tailored to patients’ need in recognition of difficult treatment decisions considering the high psychological burden they may have in patients’ lives. To maximise time and potentiate the care provided by this specialised team, the clinic is divided into two group of patients: those who require physical assessment or treatment decisions attend in person and those in regular follow-up who do not attend but a proper feedback is provided. This clinic happens once every month. During the first 3 months, 20 patients were considered (10 attendants, 9 virtually reviewed and 1 patient did not attend); 4 patients had a previous histological diagnosis (2 oligodendrogliomas WHO grade II, 1 pilocytic astrocytoma WHO grade I and 1 ganglioglioma WHO grade I) and 16 patients were consider after initial presentation or follow-up of an incidental finding. As the main outcomes of this clinic: 12 patients were listed for surgery, 6 patients for follow-up (repeat imaging – 4 patients, neurology review – 1 patient, oncology review – 1 patient), and 1 was discharged. The EORTC QLQ - BN20 is completed prior to their consultation. We have found that 45% of patients feel ‘very uncertain about the future’ and 54% were ‘quite concerned about disruption to family life’. Overall, these statistics highlight the importance of this clinic in the global therapeutic approach of LGG patients.
Chronic lymphocytic leukemia treatment algorithm 2018
Authors: Sameer A. Parikh
Journal: Blood Cancer Journal (2018)

Abstract The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as ibrutinib, idelalisib, and venetoclax), and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in CLL, even among patients with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain ( IGHV ) genes. Each of these treatments is associated with a unique toxicity profile; in the absence of randomized data, the choice of one type of treatment over another depends on the co-morbidities of the patient. Chemoimmunotherapy still plays an important role in the management of previously untreated CLL patients, particularly among young fit patients who have standard risk FISH profile and mutated IGHV genes. Richter’s transformation of CLL remains a difficult complication to treat, although therapy with programmed death 1 inhibitors such as pembrolizumab and nivolumab has shown impressive responses in a subset of patients. Our ability to risk stratify CLL patients continues to evolve; the CLL-International Prognostic Index (CLL-IPI) is the best validated tool in predicting time to first therapy among previously untreated patients. This review summarizes the current approach to risk stratification and management of CLL patients.
Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses’ Health Studies
Authors: Mollie E. Barnard, Elizabeth M. Poole, Gary C. Curhan, A. Heather Eliassen, Bernard A. Rosner, Kathryn L. Terry, Shelley S. Tworoger
Journal: JAMA Oncology (2018)

Ovarian cancer is a highly fatal malignant neoplasm with few modifiable risk factors. Case-control studies have reported a modest reduced risk of ovarian cancer among women who frequently use aspirin or regularly use low-dose aspirin.To evaluate whether regular aspirin or nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use and patterns of use are associated with lower ovarian cancer risk.This cohort study analyzed NSAID use and ovarian cancer diagnosis data from 2 prospective cohorts, 93 664 women in the Nurses' Health Study (NHS), who were followed up from 1980 to 2014, and 111 834 in the Nurses' Health Study II (NHSII), who were followed up from 1989 to 2015. Follow-up was completed on June 30, 2014, for the NHS and June 30, 2015, for NHSII. Data were analyzed from June 13, 2016, to September 18, 2017.For each analgesic type (aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen), timing, duration, frequency, and number of tablets used were evaluated; exposure information was updated every 2 to 4 years.Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of aspirin, nonaspirin NSAIDs, and acetaminophen with risk of epithelial ovarian cancer. All statistical tests were 2-sided, with a significance level of .05.In the NHS, the mean (SD) age at baseline (1980) was 45.9 (7.2) years, and 93% of participants identified as non-Hispanic white. In the NHSII, the mean age at baseline (1989) was 34.2 (4.7) years, and 92% identified as non-Hispanic white. Among the 205 498 women in both cohorts, there were 1054 cases of incident epithelial ovarian cancer. Significant associations between aspirin and ovarian cancer risk were not observed when current vs nonuse of any aspirin was evaluated regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). However, when low-dose (≤100-mg) and standard-dose (325-mg) aspirin were evaluated separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96), but no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49) was observed. Current use of nonaspirin NSAIDs was positively associated with risk of ovarian cancer compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and significant positive trends for duration of use (P = .02 for trend) and cumulative average tablets per week (P = .03 for trend) were observed. There were no clear associations for the use of acetaminophen.These results appear to be consistent with case-control studies that show a reduced risk of ovarian cancer among regular users of low-dose aspirin. An increased risk of ovarian cancer with long-term high-quantity use of other analgesics, particularly nonaspirin NSAIDs, was observed, although this finding requires confirmation.
Abstract 16182: Diabetics With Acute Chest Pain Have Similar Length of ED Stay From Early CCTA Compared to Standard Evaluation but More Downstream Testing and Radiation Exposure: The ROMICAT II Trial
Authors: Quynh Truong, Joshua Schulman-Marcus, Pearl Zakroysky, Eric T Chou, John T Nagurney, Stephen D Wiviott, Jerome L Fleg, David A Schoenfeld, James E Udelson, Udo Hoffman, Pamela K Woodard
Journal: Circulation (2014)

Objective: In the evaluation of acute chest pain (ACP), early cardiac computed tomographic angiography reduces emergency department (ED) length of stay (LOS) compared with standard evaluation. It is unknown whether patients with diabetes mellitus (DM) have similar benefits. Methods: In the ROMICAT II multicenter trial, we randomized 1000 patients (17.3% DM) 40-74 years old with symptoms suggestive of acute coronary syndrome (ACS) but without ischemic ECG changes or initial positive troponin to early CCTA or standard ED evaluation. In this pre-specified analysis, we compared differences between the two strategies for the primary endpoint of LOS in DM and non-DM patients. Secondary endpoints were examined in Table 1. Results: ACS rate was similar between DM and non-DM (both 7.5%, p=1.0). DM (70% on oral hypoglycemics, 25% insulin) were older (57 vs 54 years) with more cardiac risk factors, though more frequently female (56%) and on cardiac medications than non-DM (all p&lt;0.001). Table 1 shows the effects of early CCTA versus standard evaluation in DM and non-DM groups. LOS was unaffected by CCTA strategy in DM, whereas LOS was significantly reduced in non-DM. Early CCTA was associated with higher rates of direct ED discharge in both groups, but hospital admissions were significantly reduced with CCTA only in non-DM. Although both groups had more downstream testing and higher radiation dose with CCTA, these differences were accentuated in DM (all p-interaction≤0.04). There was no missed ACS. More DM had abnormal CCTA than non-DM (68% vs 50%, p=0.003), but among DM with no CAD or non-obstructive CAD (69%) by CCTA, LOS was similar compared to non-DM patients (p=NS). Conclusions: An early CCTA strategy in the ED was associated with shorter LOS in non-DM but not in the DM group. The higher prevalence of CAD in DM and direct visualization of atherosclerosis by CCTA may explain the increased testing and radiation exposure with CCTA that were accentuated in DM.
Genetic Variants in SGLT1, Glucose Tolerance, and Cardiometabolic Risk
Authors: Sara B. Seidelmann, Elena Feofanova, Bing Yu, Nora Franceschini, Brian Claggett, Mikko Kuokkanen, Hannu Puolijoki, Tapani Ebeling, Markus Perola, Veikko Salomaa, Amil Shah, Josef Coresh, Elizabeth Selvin, Calum A. MacRae, Susan Cheng, Eric Boerwinkle, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2018)

Loss-of-function mutations in the SGLT1 (sodium/glucose co-transporter-1) gene result in a rare glucose/galactose malabsorption disorder and neonatal death if untreated. In the general population, variants related to intestinal glucose absorption remain uncharacterized.The goal of this study was to identify functional SGLT1 gene variants and characterize their clinical consequences.Whole exome sequencing was performed in the ARIC (Atherosclerosis Risk in Communities) study participants enrolled from 4 U.S. communities. The association of functional, nonsynonymous substitutions in SGLT1 with 2-h oral glucose tolerance test results was determined. Variants related to impaired glucose tolerance were studied, and Mendelian randomization analysis of cardiometabolic outcomes was performed.Among 5,687 European-American subjects (mean age 54 ± 6 years; 47% male), those who carried a haplotype of 3 missense mutations (frequency of 6.7%)-Asn51Ser, Ala411Thr, and His615Gln-had lower 2-h glucose and odds of impaired glucose tolerance than noncarriers (β-coefficient: -8.0; 95% confidence interval [CI]: -12.7 to -3.3; OR: 0.71; 95% CI: 0.59 to 0.86, respectively). The association of the haplotype with oral glucose tolerance test results was consistent in a replication sample of 2,791 African-American subjects (β = -16.3; 95% CI: -36.6 to 4.1; OR: 0.39; 95% CI: 0.17 to 0.91) and an external European-Finnish population sample of 6,784 subjects (β = -3.2; 95% CI: -6.4 to -0.02; OR: 0.81; 95% CI: 0.68 to 0.98). Using a Mendelian randomization approach in the index cohort, the estimated 25-year effect of a reduction of 20 mg/dl in 2-h glucose via SGLT1 inhibition would be reduced prevalent obesity (OR: 0.43; 95% CI: 0.23 to 0.63), incident diabetes (hazard ratio [HR]: 0.58; 95% CI: 0.35 to 0.81), heart failure (HR: 0.53; 95% CI: 0.24 to 0.83), and death (HR: 0.66; 95% CI: 0.42 to 0.90).Functionally damaging missense variants in SGLT1 protect from diet-induced hyperglycemia in multiple populations. Reduced intestinal glucose uptake may protect from long-term cardiometabolic outcomes, providing support for therapies that target SGLT1 function to prevent and treat metabolic conditions.
LXRα Promotes Hepatosteatosis in Part Through Activation of MicroRNA‐378 Transcription and Inhibition of Ppargc1β Expression
Authors: Tianpeng Zhang, Jiangyan Duan, Lei Zhang, Zhuoyu Li, Clifford J. Steer, Guiqin Yan, Guisheng Song
Journal: Hepatology (2018)

Nonalcoholic fatty liver disease (NAFLD) is a major risk factor of many end‐stage liver diseases. Alterations in microRNA expression have been reported in patients with NAFLD. However, the transcriptional mechanism(s) of dysregulated microRNAs under the state of NAFLD is poorly described, and microRNAs that regulate the pathogenesis of NAFLD synergistically with their regulators remain unknown. Here we report that microRNA‐378 expression is significantly increased in fatty livers of mice and patients with NAFLD. Although microRNA‐378 locates within the intron of Ppargc1β (peroxisome proliferator‐activated receptor γ coactivator 1‐beta), there was a significant uncoupling of Ppargc1β mRNA and microRNA‐378 levels in both sources of fatty livers. Further studies identified a full‐length primary transcript of microRNA‐378. LXRα (liver X receptor alpha) functioned as a transcription activator of microRNA‐378 and a repressor of Ppargc1β transcription. It is known that miR‐378 is an inhibitor of fatty acid oxidation (FAO) and the function of Ppargc1β is opposite to that of miR‐378. GW3965 treatment (LXRα agonist) of murine hepatocytes and mice increased microRNA‐378 and reduced Ppargc1β , which subsequently impaired FAO and aggravated hepatosteatosis. In contrast, additional treatment of miR‐378 inhibitor or Ppargc1β , which knocked down increased miR‐378 or recovered expression of Ppargc1β , offset the effects of GW3965. Liver‐specific ablation of Lxrα led to decreased miR‐378 and increased Ppargc1β , which subsequently improved FAO and reduced hepatosteatosis. Conclusion: Our findings indicated that miR‐378 possesses its own transcription machinery, which challenges the well‐established dogma that miR‐378 transcription is controlled by the promoter of Ppargc1β . LXRα selectively activates transcription of miR‐378 and inhibits expression of Ppargc1β, which synergistically impairs FAO. In addition to lipogenesis, impaired FAO by miR‐378 in part contributes to LXRα‐induced hepatosteatosis.
Peripheral immune system in aging and Alzheimer’s disease
Authors: Wei Cao, Hui Zheng
Journal: Molecular Neurodegeneration (2018)

Alzheimer's disease (AD) represents an urgent public health mandate. AD is no longer considered a neural-centric disease; rather, a plethora of recent studies strongly implicate a critical role played by neuroinflammation in the pathogeneses of AD and other neurodegenerative conditions. A close functional connection between the immune system and central nervous system is increasingly recognized. In late-onset AD, aging represents the most significant risk factor. Here, from an immunological perspective, we summarize the prominent molecular and cellular changes in the periphery of aging individuals and AD patients. Moreover, we review the knowledge gained in the past several years that implicate specific arms of the peripheral immune system and other types of immune responses in modulating AD progression. Taken together, these findings collectively emphasize a dynamic role of a concert of brain-extrinsic, peripheral signals in the aging and degenerative processes in the CNS. We believe that a systematic view synthesizing the vast amounts of existing results will help guide the development of next-generation therapeutics and inform future directions of AD investigation.
Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells
Authors: Enming Zhang, Israa Mohammed Al-Amily, Sarheed Mohammed, Cheng Luan, Olof Asplund, Meftun Ahmed, Yingying Ye, Danya Ben-Hail, Arvind Soni, Neelanjan Vishnu, Pradeep Bompada, Yang De Marinis, Leif Groop, Varda Shoshan-Barmatz, Erik Renström, Claes B. Wollheim, Albert Salehi
Journal: Cell Metabolism (2018)

Type 2 diabetes (T2D) develops after years of prediabetes during which high glucose (glucotoxicity) impairs insulin secretion. We report that the ATP-conducting mitochondrial outer membrane voltage-dependent anion channel-1 (VDAC1) is upregulated in islets from T2D and non-diabetic organ donors under glucotoxic conditions. This is caused by a glucotoxicity-induced transcriptional program, triggered during years of prediabetes with suboptimal blood glucose control. Metformin counteracts VDAC1 induction. VDAC1 overexpression causes its mistargeting to the plasma membrane of the insulin-secreting β cells with loss of the crucial metabolic coupling factor ATP. VDAC1 antibodies and inhibitors prevent ATP loss. Through direct inhibition of VDAC1 conductance, metformin, like specific VDAC1 inhibitors and antibodies, restores the impaired generation of ATP and glucose-stimulated insulin secretion in T2D islets. Treatment of db/db mice with VDAC1 inhibitor prevents hyperglycemia, and maintains normal glucose tolerance and physiological regulation of insulin secretion. Thus, β cell function is preserved by targeting the novel diabetes executer protein VDAC1.
Intramedullary spinal cord tumours - a single centre retrospective 10 year analysis
Authors: Mr Oliver Richards, Mr Edward Goacher, Mr Christopher Derham
Journal: Neuro-Oncology (2018)

Intramedullary spinal cord tumours are relatively rare tumours of the central nervous system. Surgical outcomes are affected by many variables, including pre-operative neurological function, tumour histology and extent of resection. Emphasis remains on surgical treatment due to the limited adjunctive therapeutic options and poor drug penetration. To identify clinically relevant predictors of progression free survival by retrospectively analysing the anatomical location, pre- and post-operative function and histology in intramedullary spinal cord tumours from a single neurosurgical centre over 10 years. 49 patients were identified from a surgical database. Variables collected included pre-and post-operative Frankel Grade and Modified McCormick Scale assessments, tumour histology, extent of resection and length of follow up. Chi-Squared, Kaplan-Mier Survival and Mann-Whitney U-Tests were completed. Ependymoma, Haemangioblastoma and Pilocytic Astrocytoma were the commonest tumour histologies. In total 21 different histological tumours were identified in the series. There was a statistically significant relationship between identification of the tumour plane and extent of resection (p<0.01), along with the extent of resection and recurrence (p<0.01). Compared to the other histological subtypes, ependymoma’s demonstrated a significantly greater extent of resection (p=0.02). There was a significant relationship between the grade of tumour and progression free survival (p<0.01). We did not find a significant relationship between pre- and post-operative neurological function and survival. Tumour plane and the extent of tumour resection are significant determinants of progression free survival. Ependymoma, whilst being the commonest histology in our series were also the most resectable. Whilst complete resection reduces the rate of recurrence, tumour grade is the most important predictor of outcome.