Robotic surgery for gastric gastrointestinal stromal tumors: A single center case series.

Background And Objectives: The aim of surgical treatment of gastrointestinal stromal tumors (GIST) is a microscopically complete resection. Initial indications for laparoscopic surgery were limited to smaller tumors, in favorable locations. Over time, indications for minimal invasive surgery (MIS) have expanded, however concerns remain when considering resection of larger GISTs.

Antiretroviral Adherence, Drug Resistance, and the Impact of Social Determinants of Health in HIV-1 Patients in the US.

Adherence to antiretroviral therapy (ART) is critical to achieving viral suppression. However, social determinants of health (SDoH) can undermine patient adherence to ART, resulting in drug resistance that compromises future treatment options. We assessed ART adherence and HIV-1 drug resistance at the national and state levels in the US and investigated their associations with SDoH and other HIV-related outcomes.

Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'.

Background: Gastrointestinal stromal tumour (GIST) is commonly treated with tyrosine kinase inhibitors (TKIs), but most patients ultimately develop secondary resistance. Cabozantinib, a multi-targeted TKI inhibitor, has activity in patient-derived GIST mouse xenograft models and can overcome compensatory MET signalling occurring on TKI treatment. European Organisation for Treatment of Cancer (EORTC) 1317 'CaboGIST' assessed the safety and activity of cabozantinib in patients with GIST who had progressed on imatinib and sunitinib.

Ureteroenteric anastomosis in orthotopic neobladder creation: do urinary tract infections impact stricture rate?

Purpose: Radical cystectomy (RC) and urinary diversion in the treatment of muscle-invasive bladder cancer is associated with peri-operative complication rates as high as 60%. Ureteroenteric anastomotic stricture (UEAS) is a potential source significant morbidity often requiring secondary interventions. We sought to evaluate our experience with benign UEAS in our open ileal orthotopic neobladder (ON) population.

ASICs are required for immediate exercise-induced muscle pain and are downregulated in sensory neurons by exercise training.

Exercise training is an effective therapy for many pain-related conditions, and trained athletes have lower pain perception compared with unconditioned people. Some painful conditions, including strenuous exercise, are associated with elevated levels of protons, metabolites, and inflammatory factors, which may activate receptors and/or ion channels, including acid-sensing ion channels (ASICs), on nociceptive sensory neurons. We hypothesized that ASICs are required for immediate exercise-induced muscle pain (IEIP) and that exercise training diminishes IEIP by modulating ASICs within muscle afferents.

Long term outcomes of one-stage augmentation anterior urethroplasty: a systematic review and meta-analysis.

Objective: The objective is to summarize and characterize the long-term success of anterior augmentation urethroplasty (AU) in published series. The current literature on AU consists largely of retrospective series reporting intermediate follow-up and incompletely characterize the long term outcomes of AU.

Materials And Methods: A systematic literature review was performed consistent with PRISMA guidelines to characterize long-term outcomes of AU with a minimum upper limit follow-up of 100 months.

Real-world experience with doxorubicin and olaratumab in soft tissue sarcomas in England and Northern Ireland.

Background: A randomised phase II trial demonstrated that the addition of olaratumab to doxorubicin significantly increased overall survival (OS) in patients with advanced soft tissue sarcomas (STS) compared to doxorubicin alone. The recently presented phase III study of doxorubicin and olaratumab in advanced soft tissue sarcoma was discordant with this finding.

Methods: We performed a retrospective analysis of adult patients with advanced-/metastatic STS treated with at least two cycles of doxorubicin and olaratumab at eight sarcoma units across England and Northern Ireland between May 2017 and March 2019.

Metastatic Soft Tissue Sarcomas in Adolescents and Young Adults: A Specialist Center Experience.

Soft tissue sarcomas (STS) account for 8% of all cancers in adolescents and young adults (AYAs). Metastatic STS contribute significantly to disease-related mortality in this age group; however, data are limited due to under-representation in clinical trials. AYAs aged 18-39 years, diagnosed with metastatic STS between 1990 and 2012, were identified from The Royal Marsden Hospital database.

Dendritic Spine Dynamics after Peripheral Nerve Injury: An Intravital Structural Study.

Neuropathic pain is an intractable medical condition with few or no options for effective treatment. Emerging evidence shows a strong structure-function relationship between dendritic spine dysgenesis and the presence of neuropathic pain. Postmortem tissue analyses can only imply dynamic structural changes associated with injury-induced pain.

Hippocampal Synaptic Dysfunction in a Mouse Model of Huntington Disease Is Not Alleviated by Ceftriaxone Treatment.

Glutamate transporters, particularly glutamate transporter 1 (GLT-1), help to prevent the adverse effects associated with glutamate toxicity by rapidly clearing glutamate from the extracellular space. Since GLT-1 expression and/or function are reduced in many neurodegenerative diseases, upregulation of GLT-1 is a favorable approach to treat the symptoms of these diseases. Ceftriaxone, a β-lactam antibiotic reported to increase GLT-1 expression, can exert neuroprotective effects in a variety of neurodegenerative diseases; however, many of these diseases do not exhibit uniform brain pathology.

Use of Direct In-Person Observation in the Care of Hospitalized Older Adults with Cognitive Impairment: A Systematic Review.

Hospitalized older adults with cognitive impairment (CI) due to dementia and/or delirium may require individualized care strategies such as direct observation to mitigate safety concerns and manage behavioral symptoms. Despite common use of direct observation as a strategy, little is known about its practice and outcomes. A systematic review was conducted to identify, appraise, and synthesize literature on direct observation among hospitalized older adults with CI.

Impact of Latent Tuberculosis Infection on Neurocognitive Functioning and Inflammation in HIV-Infected and Uninfected South Indians.

Background: HIV-associated neurocognitive disorder persists in some people living with HIV despite optimal antiretroviral therapy. Latent tuberculosis infection (LTBI) may cause systemic inflammation and immune activation that may impair brain function. We assessed cognition and biomarkers of inflammation in both HIV+ and HIV- South Indians with and without LTBI.

Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome: A Decision Analysis.

Background: Fetal aortic valvuloplasty (FAV) may prevent progression of midgestation aortic stenosis to hypoplastic left heart syndrome. However, FAV has well-established risks, and its survival benefit remains unknown. Our primary aim was to determine whether FAV for midgestation aortic stenosis increases survival from fetal diagnosis to age 6 years.

The impact of pressure, moisture and temperature on pyrolysis of municipal solid waste under simulated landfill conditions and relevance to the field data from elevated temperature landfill.

Experiments were conducted with simulated Municipal Solid Waste (MSW) to understand the impact of pressure, moisture, and temperature on MSW decomposition under simulated landfill conditions. Three experimental phases were completed, where the first two phases provided baseline results and assisted in fine tuning parameters such as pressure, temperature, gas composition, and moisture content for phase three. The manuscript focuses on the results from third phase.

Effects of exposure to large sharks on the abundance and behavior of mobile prey fishes along a temperate coastal gradient.

Top predators can exert strong influences on community structure and function, both via direct, consumptive effects, as well as through non-consumptive, fear-based effects (i.e. predation risk).

Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib: a Phase 1b, multicentre study.

Background: The majority of patients with advanced gastrointestinal stromal tumours (GISTs) develop resistance to imatinib and sunitinib, the standard of care for these patients. This study evaluated the combination of buparlisib, an oral phosphoinositide 3-kinase (PI3K) inhibitor, with imatinib in patients with advanced GIST, who have failed prior therapy with imatinib and sunitinib.

Methods: This Phase 1b, multicentre, open-label study aimed to determine the maximum tolerated dose (MTD) and/or a recommended Phase 2 dose of buparlisib in combination with 400 mg of imatinib through a dose-escalation part and a dose-expansion part, and also evaluated the clinical profile of the combination.

Hydraulic and mechanical behavior of municipal solid waste and high-moisture waste mixtures.

The objective of this study was to investigate how addition of high-moisture waste (HMW) affects the hydraulic and mechanical behavior of municipal solid waste (MSW). Direct shear and hydraulic conductivity tests were conducted on MSW, HMW, and MSW-HMW mixtures prepared with HMW contents ranging from 20% to 80% (by total mass). Direct shear tests were conducted at normal stress between 22 and 168 kPa and hydraulic conductivity tests were conducted at vertical effective stresses of approximately 50, 100, and 200 kPa.

Lassa fever in pregnancy: a systematic review and meta-analysis.

Lassa fever is a zoonotic infection endemic to West Africa and is known to have adverse effects in pregnancy. We sought to synthesize and critically appraise currently available evidence on the effects of Lassa fever in pregnancy. An exhaustive bibliographic search from dates of inception to 30 September 2019 yielded 13 studies, from which individual patient data were extracted.

A Case of Biopharmaceutical-Induced Catatonia and the Implication of a Novel Mechanism.

Catatonia can be described structurally as a motor dysregulation syndrome with a concomitant behavioral component. However, despite its initial recognition nearly 150 years ago, the exact pathophysiological causes underlying this syndrome are still somewhat unknown and are potentially variable. This report reviews a case of a patient with multiple catatonic episodes precipitated by the use of an immunomodulator medication, and in doing so suggests a possible mechanism speaking to the immune system's role in the etiology of some cases of catatonia.

The role of the pharmacist in mental health: An investigation of the impact of pharmacist-led interventions on psychotropic medication adherence in patients with diabetes.

Objective: To evaluate the impact of targeted telepharmacist mental health adherence interventions for patients with type 2 diabetes.

Methods: This retrospective review involved the analysis of a telepharmacist-led mental health intervention. The subjects included: patients aged 18 years or more with type 2 diabetes, enrolled in an adherence service and who had been prescribed psychotropics.

Shared Learnings on the New EMA First-in-Human and Early Clinical Trial Guideline: Proceedings From a DIAlogue Session at DIA Europe 2018.

The EU is a member of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), and therefore adopts the ICH Guidelines, including the ICH M3 Guideline on Nonclinical Safety Studies. Following the 2016 incident in France with BIA 10-2474, and in light of the substantial evolvement of how early clinical development has been undertaken during the last 10 years, for example, conducting integrated (FIH) studies that include multiple parts (eg, single ascending doses, multiple ascending doses, food effect), EMA decided to update the existing 2007 FIH guideline. The key revisions to the 2007 guideline, now titled "Guideline on Strategies to Identify and Mitigate Risks for First-in-Human and Early Clinical Trials With Investigational Medicinal Products," include additional information.

Primary iliocaval leiomyosarcomas: The path beyond surgery.

Introduction: Iliocaval leiomyosarcoma (ICLM) is a rare and aggressive form of sarcoma within the retroperitoneum. Surgery is the mainstay of treatment, with no consensus on the benefit of chemoradiotherapy in the neo/adjuvant setting. This study aims to describe the natural history of a chemotherapy-naïve ICLM treated in a tertiary cancer centre and to explore potential directions to improve oncological outcome.

"Pseudogestational Sac" and Other 1980s-Era Concepts in Early First-Trimester Ultrasound: Are They Still Relevant Today?

Objectives: To determine whether an intrauterine round or oval fluid collection ("saclike structure") can prove to be either an intrauterine pregnancy or intrauterine fluid in conjunction with an ectopic pregnancy (sometimes termed "pseudogestational sac") and whether ultrasound features, including the presence or absence of an echogenic rim, "double sac sign" (DSS), or "intradecidual sign" (IDS), are helpful for establishing the diagnosis or predicting the prognosis.

Methods: We identified all sonograms obtained from women with positive serum human chorionic gonadotropin results at our institution between January 1, 2012, and June 30, 2018, meeting the following criteria: presence of an intrauterine saclike structure without a yolk sac or embryo; no extraovarian adnexal mass; and follow-up information identifying the location of the pregnancy as intrauterine or ectopic. Study authors reviewed sonograms in all cases and recorded the following information: presence or absence of each of an echogenic rim around the collection, a DSS, and an IDS, as well as the mean sac diameter.

Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens.

Aim: To assess the efficacy and tolerability of tirzepatide treatment using three different dose-escalation regimens in patients with type 2 diabetes.

Materials And Methods: In this double-blind, placebo-controlled study, patients were randomized (1:1:1:1) to receive either once-weekly subcutaneous tirzepatide or placebo. The tirzepatide dose groups and dose-escalation regimens were: 12 mg (4 mg weeks 0-3; 8 mg weeks 4-7; 12 mg weeks 8-11), 15 mg-1 (2.