Sunday, January 24, 2021

Effectiveness of Eribulin in Metastatic Breast Cancer:

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Abstract

Introduction

Eribulin was approved in the United States (US) in 2010 for patients with metastatic breast cancer (MBC) who previously received at least two chemotherapeutic regimens, including anthracycline and taxane in the adjuvant or metastatic setting. With significant changes to the treatment landscape over the past decade, assessment of the real-world effectiveness of eribulin in clinical practice when used according to the approved US indication is valuable.

Methods

Patients with MBC were identified by community oncologists through a retrospective, multi-site patient chart review; de-identified data were abstracted into electronic case report forms. Eligible patients initiated eribulin consistent with approved US indication between 1 January 2011 and 31 December 2017. Clinical outcomes assessed included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in all patients and those with triple negative breast cancer (TNBC).

Results

The analysis included 513 patients (median 59.0 years; 38.8% with Eastern Cooperative Oncology Group status ≥ 2). Eribulin was third-line therapy for 78.0% of patients, and fourth-line or later for the remainder. ORR was 54.4%, median PFS was 6.1 months (95% CI: 5.8, 6.6), and median OS was 10.6 months (95% CI 9.9, 11.7) in all patients. Among the 49.9% of patients with TNBC, ORR was 55.5%, median PFS was 5.8 months (95% CI 5.1, 6.4), and median OS was 9.8 months (95% CI 8.6, 11.0).

Conclusion

The current retrospective chart review study reinforces the clinical effectiveness of eribulin in patients with MBC, including those with TNBC, when used according to the approved US indication in real-world clinical practice.

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Comparison Between Fusion and Non-Fusion Surgery for Lumbar Spinal Stenosis: A Meta-analysis

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Abstract

Introduction

A large number of studies have shown that, for severe lumbar spinal stenosis, decompression surgery can often obtain better results than non-surgical treatment. However, whether the lumbar spine is fixed after decompression is still controversial. The results of biomechanical studies indicate that there is a correlation between the range of decompression and postoperative spinal instability.

Methods

The multiple databases like Pubmed, Embase, Cochrane databases and China National Knowledge database were used to search for the relevant studies, and full-text articles involved in the evaluation of fusion and nonfusion surgery for lumbar spinal stenosis. Review Manager 5.2 was adopted to estimate the effects of the results among selected articles. Forest plots, sensitivity analysis and bias analysis for the articles included were also conducted.

Results

A total of nine relevant studies were eventually satisfied the included criteria. There were significant differences in length of stay [mean difference (MD) = 3.04, 95% CI (2.00, 4.08), P < 0.000]1), but there were no differences in Oswestry Disability Index (ODI score) [MD = − 1.14, 95% CI (− 2.92, 0.63), P = 0.21; I2 = 87%] and complications [RR = 1 with 95% CI (0.69, 1.46), P value of overall effect was 0.98]. The study was robust and limited publication bias was observed in this study.

Conclusion

Our research supported that fusion and nonfusion surgeries had no differences in clinical effects and complications for lumbar spinal stenosis, while fusion surgery involved a longer length of stay than nonfusion surgery.

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Diagnostic Criteria for Gastro-esophageal Reflux Following Sleeve Gastrectomy

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Abstract

Background

Gastro-esophageal reflux disease (GERD) post-sleeve gastrectomy (SG) is a controversial issue and diagnostic dilemma. Strong heterogeneity exists in the assessment of reflux post-SG, and better diagnostic tools are needed to characterize symptomatic reflux. We aimed to determine the discriminant factors of symptomatic reflux and establish diagnostic thresholds for GERD following SG.

Materials and Methods

Patients post-SG were categorized into asymptomatic and symptomatic cohorts and completed validated symptom questionnaires. All patients underwent stationary esophageal manometry and 24-h ambulatory pH monitoring. Univariate and multivariate analyses were conducted to determine the strongest discriminant factors for GERD.

Results

Baseline characteristics of the asymptomatic cohort (n = 48) and symptomatic cohort (n = 76) were comparable. The median post-operative duration was 7.3 (14.1) vs 7.5 (10.7) months (p = 0.825). The symptomatic cohort was more female predominant (90.8 vs 72.9%, p = 0.008). Reflux scores were significantly higher in the symptomatic group (36.0 vs 10.5, p = 0.003). Stationary manometry parameters were similar, including hiatus hernia prevalence and impaired esophageal motility. The symptomatic cohort had significantly higher total acid exposure, especially while supine (11.3% vs 0.6%, p < 0.001). Univariate and multivariate regressions delineated reflux score and supine acid exposure as discriminant factors for symptomatic reflux. The thresholds for distinguishing symptomatic reflux are as follows: reflux score of 11.5 (sensitivity 84.0%, specificity 68.2%) and supine acid exposure of 2.65% (sensitivity 67.1%, specificity 70.8%).

Conclusion

A reflux score of 11.5 or more or supine acid exposure of 2.65% or more should be considered diagnostic in defining symptomatic reflux following SG.

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Amitraz efficacy against Rhipicephalus microplus

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Abstract

Amitraz is an acaricide that is widely used in veterinary medicine to control the cattle tick Rhipicephalus microplus. However, controversy exists in the literature regarding the resistance of R. microplus to this product. The present work provides an update on the acaricidal efficacy of amitraz (Triatox®, 12.5 % amitraz) after 15 years without its use on a property. Two in vivo (bovines treated with amitraz and submitted to tick counts, n = 20 animals) and one in vitro (adult immersion test, n = 40 ticks) assays were performed to determine product efficacy. The efficacy of the commercial formulation tested in the first in vivo trial ranged from 14.1 to 47.0%, and in the second from 3.6 to 35.1%, for the 28 days of the experiments. Efficacy for the in vitro trial was 47.38%. The dose recommended by the manufacturer of the product did not cause mortality to most of the ticks of this strain, and efficacy/resistance was not rever ted or modified after 15 years (estimated 60 tick generations).

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Comparative evaluation of amniotic fluid as an alternative to fetal bovine serum in the maintenance of Leishmania major and Toxoplasma gondii

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Abstract

This study aimed to evaluate the efficacy of amniotic fluid (AF) as an alternative to fetal bovine serum (FBS) in the maintenance of Leishmania major promastigotes and Toxoplasma gondii tachyzoites. AF was collected by an obstetrician using sterile syringes during a cesarean section. The culture medium was supplemented with 5 different concentrations of FBS or AF including 2, 5, 10, 20, and 30%. These concentrations were used to maintain both mentioned parasites. L. major was maintained at temperatures 4 and 24 °C and examined once a week for 4 weeks, while T. gondii was maintained at temperatures 4, 24, and 37 °C and examined at hours 24, 48, 72, and 96. For L. major, at both 4 and 24 °C, we observed no significant difference between FBS and AF on day 7. However, on days 14, 21, and 28, the difference between FBS and AF was significant at both temperatures. For T. gondii, no significant difference was obse rved between FBS and AF at hour 24 and all temperatures. However, this difference was significant at hours 48, 72, and 96 and all temperatures. According to our results, although FBS had a greater efficacy than AF in the growth of L. major and the survival of T. gondii, the number of promastigotes increased over time in AF-containing medium and the number of tachyzoites reduced slowly with a mild slop. Therefore, AF can be a potential alternative to FBS.

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Process- and Outcome-Based Financial Incentives to Improve Self-Management and Glycemic Control in People with Type 2 Diabetes in Singapore: A Randomized Controlled Trial

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Abstract

Background

Sub-optimally controlled diabetes increases risks for adverse and costly complications. Self-management including glucose monitoring, medication adherence, and exercise are key for optimal glycemic control, yet, poor self-management remains common.

Objective

The main objective of the Trial to Incentivize Adherence for Diabetes (TRIAD) study was to determine the effectiveness of financial incentives in improving glycemic control among type 2 diabetes patients in Singapore, and to test whether process-based incentives tied to glucose monitoring, medication adherence, and physical activity are more effective than outcome-based incentives tied to achieving normal glucose readings.

Methods

TRIAD is a randomized, controlled, multi-center superiority trial. A total of 240 participants who had at least one recent glycated hemoglobin (HbA1c) being 8.0% or more and on oral diabetes medication were recruited from two polyclinics. They were block-randomized (blocking factor: current vs. new glucometer users) into the usual care plus (UC +) arm, process-based incentive arm, and outcome-based incentive arm in a 2:3:3 ratio. The primary outcome was the mean change in HbA1c at month 6 and was linearly regressed on binary variables indicating the intervention arms, baseline HbA1c levels, a binary variable indicating titration change, and other baseline characteristics.

Results

Our findings show that the combined incentive arms trended toward better HbA1c than UC + , but the difference is estimated with great uncertainty (difference − 0.31; 95% confidence interval [CI] − 0.67 to 0.06). Lending credibility to this result, the proportion of participants who reduced their HbA1c is higher in the combined incentive arms relative to UC + (0.18; 95% CI 0.04, 0.31). We found a small improvement in process- relative to outcome-based incentives, but this was again estimated with great uncertainty (difference − 0.05; 95% CI − 0.42 to 0.31). Consistent with this improvement, process-based incentives were more effective at improving weekly medication adherent days (0.64; 95% CI − 0.04 to 1.32), weekly physically active days (1.37; 95% CI 0.60–2.13), and quality of life (0.04; 95% CI 0.0–0.07) than outcome-based incentives.

Conclusion

This study suggests that both incentive types may be part of a successful self-management strategy. Process-based incentives can improve adherence to intermediary outcomes, while outcome-based incentives focus on glycemic control and are simpler to administer.

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Retained Endoscope: An Unexpected but Serious Complication of Hemospray®

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Hypofibrinogenemia can be estimated by the predictive formula in aortic surgery

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Abstract

Objective

Aortic surgery often causes massive bleeding due to hypofibrinogenemia. Predicting hypofibrinogenemia is useful for developing a hemostasis strategy, including preparing for blood transfusion. We made a formula for predicting the serum fibrinogen level (SFL) at the termination of cardiopulmonary bypass (CPB) in aortic surgery and examined its validity.

Methods

We performed a retrospective observational study that consisted of 267 patients (group A) who underwent aortic surgery from July 2013 to December 2016 and made a formula for predicting the SFL at the termination of CPB in group A by a multiple linear regression analysis. The validity of this formula was then examined in another 60 patients (group B) who underwent aortic surgery from January 2017 to December 2017.

Results

We developed the following predictive formula: SFL at the termination of CPB (mg/dL) = 14.7 + 0.44 × preoperative SFL (mg/dL) + (− 0.14) × CPB time (min) + 0.64 × preoperative body weight (kg) + (− 17.3) × lateral thoracotomy (Yes/No, Yes: 1, No: 0). In group B, the predictive formula proved to be statistically valid in group B (R2 = 0.531, p < 0.001).

Conclusion

The SFL at the termination of CPB in aortic surgery can be predicted by the preoperative SFL, body weight, CPB time and surgical approach. The predictive formula is useful for developing a hemostasis strategy, including preparing for blood transfusion.

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Lenz microphthalmia syndrome in neurosurgical practice: a case report and review of the literature

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Abstract

Lenz microphthalmia syndrome (LMS) is an allelic X-linked syndrome correlated to a null mutation of B cell lymphoma (BCL-6) corepressor (BCOR) gene, which is essential in the early embryonic development. Phenotypically, this rare hereditary syndrome is characterized by microphthalmia/anophthalmia and other eye disorders; mental disability; dental, ear, and digital abnormalities; and variable malformations affecting the heart, skeleton (limbs and/or spine), and genitourinary tract. In this paper, a case of a young adult with LMS affected additionally by immuno-hematological disturbances was treated with decompressive craniectomy after domestic accidental fall. Case description and a brief review of the current literature about this rare condition are presented here.

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Biological evaluation of the modified nano-amorphous phosphate calcium doped with citrate/poly-amino acid composite as a potential candidate for bone repair and reconstruction

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Abstract

Large numbers of research works related to fabricating organic–inorganic composite materials have been carried out to mimic the natural structure of bone. In this study, a new modified n-ACP doped with citrate (n-ACP-cit)/poly (amino acids) (PAA) composite (n-ACP-cit/PAA) was synthesized by employing high bioactive n-ACP-cit and the biodegradable and biocompatible PAA copolymer. Its basic structure was characterized by X-ray diffraction spectroscopy, Fourier transformed infrared spectroscopy, and X-ray photoelectron spectroscopy. Moreover, the degradability, bioactivity, biocompatibility, and osteoconductivity of n-ACP-cit/PAA composite were evaluated in vitro and in vivo, using simulated body fluid (SBF) solution soaking test, mouse bone marrow mesenchymal stem cells proliferation and differentiation, morphological observation test, expression of genes associated with osteogenesis, and bone defect model repair test, respectively. The modified n-ACP-cit/PAA c omposite exhibited a much higher weight loss rate (36.01 wt.%) than that of PAA (23.99 wt.%) after immersing in SBF solution for 16 weeks and the pH values of local environment restored to neutral condition. Moreover, cells co-culturing with composites exhibited higher alkaline phosphatase activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes (Bmp-2, Colla I, OCN, OPN, and Runx-2) than that of PAA. Furthermore, the bone defect model repair test revealed that the composite could be intimately incorporated with the surrounding bone without causing any deleterious reaction and capable of guiding new bone formation. Together, these results indicated that the new modified bone repair n-ACP-cit/PAA composite material with specific characteristics may be designed for meeting diverse requirements from biomedical applications.

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Physical exercise effects on the brain during COVID-19 pandemic: links between mental and cardiovascular health

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Abstract

The current pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The quarantine period during corona virus disease 19 (COVID-19) outbreak might affect the quality of life leading thousands of individuals to diminish the daily caloric expenditure and mobility, leading to a sedentary behavior and increase the number of health disorders. Exercising is used as a non-pharmacological treatment in many chronic diseases. Here, we review the molecular mechanisms of physical exercise in COVID-19 pandemic on mental health. We also point links between exercise, mental, and cardiovascular health. The infection caused by SARS-CoV-2 affects host cells binding to angiotensin-converting enzyme-2 (ACE2), which is the receptor for SARS-CoV-2. If there is not enough oxygen supply the lungs and other tissues, such as the heart or brain, are affected. SARS-CoV-2 enhances ACE2 leading to inflammation and neuronal death with possible development of mo od disorders, such as depression and anxiety. Physical exercise also enhances the ACE2 expression. Conversely, the activation of ACE2/Ang 1-7/Mas axis by physical exercise induces an antiinflammatory and antifibrotic effect. Physical exercise has beneficial effects on mental health enhancing IGF-1, PI3K, BDNF, ERK, and reducing GSK3β levels. In addition, physical exercise enhances the activity of PGC-1α/ FNDC5/Irisin pathway leading to neuronal survival and the maintenance of a good mental health. Thus, SARS-CoV-2 infection leads to elevation of ACE2 levels through pathological mechanisms that lead to neurological and cardiovascular complications, while the physiological response of ACE2 to physical exercise improves cardiovascular and mental health.

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