The SGLT2 inhibitor empagliflozin reduces mortality and prevents progression in experimental pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a rare, but progressive and devastating vascular disease with few treatment options to prevent the advancement to right ventricular dysfunction hypertrophy and failure. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion as well as reduces cardiovascular events and mortality in individuals with type 2 diabetes. While empagliflozin has been reported to lower systemic hypertension due to increased diuresis, the effect of empagliflozin on PAH is unknown.

Development and validation of machine learning models to predict gastrointestinal leak and venous thromboembolism after weight loss surgery: an analysis of the MBSAQIP database.

Background: Postoperative gastrointestinal leak and venous thromboembolism (VTE) are devastating complications of bariatric surgery. The performance of currently available predictive models for these complications remains wanting, while machine learning has shown promise to improve on traditional modeling approaches. The purpose of this study was to compare the ability of two machine learning strategies, artificial neural networks (ANNs), and gradient boosting machines (XGBs) to conventional models using logistic regression (LR) in predicting leak and VTE after bariatric surgery.

Establishment of an internationally agreed minimum data set for acute telestroke.

Introduction: Globally, the use of telestroke programmes for acute care is expanding. Currently, a standardised set of variables for enabling reliable international comparisons of telestroke programmes does not exist. The aim of the study was to establish a consensus-based, minimum dataset for acute telestroke to enable the reliable comparison of programmes, clinical management and patient outcomes.

Particle control reduces fine and ultrafine particles greater than HEPA filtration in live operating rooms and kills biologic warfare surrogate.

Background: Controlling indoor air quality and the airborne transmission of infectious agents in hospitals is critical. The most hazardous particles and pathogens are not easily eliminated by traditionally passive air cleansing.

Methods: We studied the effect of a novel particle control technology on airborne particulate matter in 2 live real-world operating room settings and on pathogen survival in a microbiology laboratory.

Use of Chest Computed Tomography for Blunt Pediatric Chest Trauma: Does It Change Clinical Course?

Introduction: Given the concern for radiation-induced malignancy in children and the fact that risk of severe chest injury in children is low, the risk/benefit ratio must be considered in each child when ordering a computed tomography (CT) scan after blunt chest trauma.

Methods: The study included pediatric blunt trauma patients (age, <15 years) with chest radiograph (CR) before chest CT on admission to our adult and pediatric level I trauma center. Surgeons were asked to view the blinded images and reads and indicate if they felt CT was warranted based on CR findings, if their clinical management change based on additional findings on chest CT, and how they might change management.

Characterization of a Vimentin /Nestin proteome and tissue regenerative secretome generated by human pancreas-derived mesenchymal stromal cells.

Multipotent/mesenchymal stromal cells (MSCs) exist within a variety of postnatal tissues; however, global proteomic analyses comparing tissue-specific MSC are limited. Using human bone marrow (BM)-derived MSCs as a gold standard, we used label-free mass spectrometry and functional assays to characterize the proteome, secretome, and corresponding function of human pancreas-derived MSCs (Panc-MSCs) with a classical phenotype (CD90+/CD73+/CD105+/CD45-/CD31-). Both MSC subtypes expressed mesenchymal markers vimentin, α-SMA, and STRO-1; however, expression of nestin was increased in Panc-MSCs.

Short-Term Acute Exercise Preconditioning Reduces Neurovascular Injury After Stroke Through Induced eNOS Activation.

Physical exercise is known to reduce cardiovascular risk but its role in ischemic stroke is not clear. It was previously shown that an acute single bout of exercise reduced increased eNOS activation in the heart and reduced myocardial infarction. However, the impact of a single bout or short-term exercise on eNOS-induced neuroprotection after stroke was not previously studied.

Droplet-based optofluidic systems for measuring enzyme kinetics.

The study of enzyme kinetics is of high significance in understanding metabolic networks in living cells and using enzymes in industrial applications. To gain insight into the catalytic mechanisms of enzymes, it is necessary to screen an enormous number of reaction conditions, a process that is typically laborious, time-consuming, and costly when using conventional measurement techniques. In recent times, droplet-based microfluidic systems have proved themselves to be of great utility in large-scale biological experimentation, since they consume a minimal sample, operate at high analytical throughput, are characterized by efficient mass and heat transfer, and offer high levels of integration and automation.

Phase 1 Dose Escalation Study of the Allosteric AKT Inhibitor BAY 1125976 in Advanced Solid Cancer-Lack of Association between Activating AKT Mutation and AKT Inhibition-Derived Efficacy.

This open-label, phase I first-in-human study (NCT01915576) of BAY 1125976, a highly specific and potent allosteric inhibitor of AKT1/2, aimed to evaluate the safety, pharmacokinetics, and maximum tolerated dose of BAY 1125976 in patients with advanced solid tumors. Oral dose escalation was investigated with a continuous once daily (QD) treatment (21 days/cycle) and a twice daily (BID) schedule. A dose expansion in 28 patients with hormone receptor-positive metastatic breast cancer, including nine patients harboring the mutation, was performed at the recommended phase 2 dose (R2D) of 60 mg BID.

Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging.

This third in a series of vascular cognitive impairment (VCI) workshops, supported by "The Leo and Anne Albert Charitable Trust," was held from February 8 to 12 at the Omni Resort in Carlsbad, CA. This workshop followed the information gathered from the earlier two workshops suggesting that we focus more specifically on brain white matter in age-related cognitive impairment. The Scientific Program Committee (Frank Barone, Shawn Whitehead, Eric Smith, and Rod Corriveau) assembled translational, clinical, and basic scientists with unique expertise in acute and chronic white matter injury at the intersection of cerebrovascular and neurodegenerative etiologies.

Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2.

Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bidirectional regulator of cell state interconversion.

The Association Between Stroke Mortality and Time of Admission and Participation in a Telestroke Network.

Objectives: Acute ischemic stroke is one of the leading causes of death. Patient outcomes, such as in-patient mortality, may be impacted by the time of arrival to the hospital. Telestroke networks have been found to be effective and safe at treating acute ischemic strokes.

Anterior enterocele as an etiology for anterior vaginal wall prolapse: a magnetic resonance defecography case series.

Pelvic floor hernias from the posterior cul-de-sac most often contain small bowel and are called enteroceles, however may contain sigmoid colon (sigmoidocele) or only peritoneal fat (peritoneocele). These cul-de-sac hernias typically cause bulging of the posterior vaginal wall, while anterior vaginal wall bulges are typically secondary to bladder prolapse in patients with pelvic floor deficiency. We report a series of seven patients who presented with anterior vaginal wall "mass" or bulge after cystectomy and were found on magnetic resonance defecography (MRD) to have enteroceles or sigmoidoceles in the anterior rather than posterior compartment.

Resident involvement in minimally-invasive vs. open procedures.

Background: The objective of this study was to evaluate the impact of resident involvement on surgical outcomes in laparoscopic compared to open procedures.

Methods: The American College of Surgeons National Surgical Quality Improvement Program 2007-2012 was queried for open and laparoscopic ventral hernia repair (VHR), inguinal hernia repair (IHR), splenectomy, colectomy, or cholecystectomy (CCY). Multivariable regression analyses were performed to assess the impact of resident involvement on surgical outcomes.

Fabrication of fully enclosed paper microfluidic devices using plasma deposition and etching.

A fully enclosed paper microfluidic device has been fabricated using pentafluoroethane (PFE) plasma deposition followed by O plasma etching. Structures with one and two non-interacting, fully enclosed hydrophilic channels were generated in a single paper sheet using metal masks. Furthermore, by performing an additional O plasma step with a secondary mask, pinholes were created at the reaction zones for reagent loading.

SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus.

Hess et al. quantified circulating aldehyde dehydrogenase-expressing (ALDH) cell subsets in people with T2DM given either empagliflozin (EMPA) or placebo. EMPA treatment increased circulating pro-angiogenic CD133 progenitor cells, decreased pro-inflammatory ALDH granulocyte precursors, and increased ALDH monocytes with M2 polarization.

A Phase 1 study of BAL101553, a novel tumor checkpoint controller targeting microtubules, administered as 48-h infusion in adult patients with advanced solid tumors.

Purpose BAL101553, the prodrug of the microtubule-destabilizer BAL27862, previously showed signs of antitumor activity when administered as a 2-h infusion, but its use was limited by vascular toxicity. We investigated an alternative dosing strategy aimed at improving the safety profile of BAL101553. Methods This multicenter, open-label, Phase 1 dose-escalation study used a 3 + 3 design to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and antitumor activity of BAL101553 administered as a 48-h IV infusion on Days 1, 8, and 15 of a 28-day cycle.

Nelfinavir and lenalidomide/dexamethasone in patients with lenalidomide-refractory multiple myeloma. A phase I/II Trial (SAKK 39/10).

The antiretroviral agent nelfinavir has antimyeloma activity and can overcome resistance to bortezomib. Our phase I/II trial investigated whether adding nelfinavir to lenalidomide-dexamethasone can overcome lenalidomide resistance in lenalidomide-refractory multiple myeloma (MM). Twenty-nine patients were included (high-risk cytogenetic aberrations 31%; ≥2 prior therapy lines 93%; lenalidomide-bortezomib double-refractory 34%).

Fat-Specific Protein 27 Regulation of Vascular Function in Human Obesity.

Background Pathophysiological mechanisms that connect obesity to cardiovascular disease are incompletely understood. FSP27 (Fat-specific protein 27) is a lipid droplet-associated protein that regulates lipolysis and insulin sensitivity in adipocytes. We unexpectedly discovered extensive FSP27 expression in human endothelial cells that is downregulated in association with visceral obesity.

Are there specific clinical characteristics associated with physician's treatment choices in COPD?

Background: The number of pharmacological agents and guidelines available for COPD has increased markedly but guidelines remain poorly followed. Understanding underlying clinical reasoning is challenging and could be informed by clinical characteristics associated with treatment prescriptions.

Methods: To determine whether COPD treatment choices by respiratory physicians correspond to specific patients' features, this study was performed in 1171 patients who had complete treatment and clinical characterisation data.

Trends over time in COPD treatment choices by respiratory physicians: An analysis from the COLIBRI-COPD French cohort.

Introduction: Over the last decade, new evidence and many guidelines have been published on COPD pharmacological treatments; prescriptions are often not in accordance with guidelines.

Materials And Methods: Trends in physician treatment choices from February 2012 to November 2018 (Feb.2012/Nov.

Domain Comparison Between 6 Validated Questionnaires Administered to Women With Urinary Incontinence.

Objectives: To compare patients' questionnaire-reported urinary incontinence (UI) symptoms to determine which have the best concordance.

Methods: Women with self-reported mixed UI were asked to report quality of life (QoL) due to urinary problems on a visual analog scale and complete 6 standardized validated questionnaires with questions on mixed UI (Medical Epidemiological and Social Aspects of Aging questionnaire, the Urogenital Distress Inventory short form [UDI-6], the Incontinence impact questionnaire short form [IIQ-7], the International Consultation on Incontinence Questionnaire Urinary Incontinence short form [ICIQ-SF], the King's Health Questionnaire [KHQ], and Patient Global Impression of Severity Scale [PGI-S]). Specific questions related to stress urinary incontinence (SUI), urgency urinary incontinence (UUI), UI severity, and QoL were compared within surveys from each patient with a Pearson correlation coefficient.

Burnout and its relationship with perceived stress, self-efficacy, depression, social support, and programmatic factors in general surgery residents.

Background: Burnout affects surgical residents' well-being.

Objective: We sought to identify factors associated with burnout among surgery residents.

Methods: An electronic/anonymous survey was sent to surgical residents at 18 programs, consisting of demographic/programmatic questions and validated scales for burnout, depression, perceived stress, self-efficacy, and social support.

Fibrous hamartoma of infancy associated with bony remodeling and muscle atrophy.

Fibrous hamartoma of infancy (FHI) is a benign, poorly demarcated, unencapsulated hamartoma contiguous with surrounding fat. This case highlights pronounced bony remodeling and muscle atrophy associated with FHI in a 6-week-old girl. Emphasis is placed on pathologic diagnosis and mechanisms, treatment considerations, and the multidisciplinary approach utilized in the management of the disorder.

Tumor suppressor role of cytoplasmic polyadenylation element binding protein 2 (CPEB2) in human mammary epithelial cells.

Background: Over-expression of cyclooxygenase (COX)-2 promotes breast cancer progression by multiple mechanisms, including induction of stem-like cells (SLC). Combined gene expression and microRNA microarray analyses of empty vector vs COX-2- transfected COX-2 low MCF7 breast cancer cell line identified two COX-2-upregulated microRNAs, miR-526b and miR-655, both found to be oncogenic and SLC-promoting. Cytoplasmic Polyadenylation Element-Binding Protein 2 (CPEB2) was the single common target of both microRNAs, the functions of which remain controversial.