We present a case of acute respiratory distress syndrome (ARDS) secondary to COVID-19 who required venovenous extracorporeal membrane oxygenation (V-V ECMO). Initially, a right ventricular assist ...device (RVAD), the ProtekDuo with an oxygenator, was placed in an outside heart center and the patient was transferred to us for ECMO management. Due to severe hypoxia, the configuration was later modified, and a 25 Fr femoral drainage cannula was inserted for venous drainage only. The arterial return tubing was spliced and using a Y-connector, arterialized blood was returned through both limbs of the ProtekDuo resulting in a significantly increased oxygenation and flow.
Changes in receptor signaling, excessive production of nitric oxide, and absolute or relative deficiencies of vasoactive hormones, including cortisol, vasopressin, and angiotensin II, play a role. ...Interest was re-ignited following the Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3) study, a randomized controlled trial in patients with refractory shock which confirmed that Ang II was effective at maintaining mean arterial pressure and reducing norepinephrine requirements without an increase in side effects 1. Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in acute lung injury.
Low dose direct acting oral anticoagulants (LDDOACS) were approved for elderly atrial Fibrillation (AF) patients with limited information. A retrospective analysis collecting baseline characteristics ...and outcomes in AF patients ≥ 80 prescribed LDDOAC or warfarin (W), from a multidisciplinary practice between 1/1/11 (First LDDOAC available) and 5/31/17 was conducted. From 9660 AF patients, 514 ≥ 80 received a LDDOAC and 422 W. A multivariable comparison found LDDOAC patients were older (p <0.001), had lower creatinine clearance (CrCl) (p = 0.006), used more anti-platelet drugs (p <0.001), and more often had new onset AF verses those prescribed W (p <0.001). There were no clinically significant differences among those patients receiving Dabigatran 75 mgs BID (D), Rivaroxaban 15mgs (R) or Apixaban 2.5mgs BID (A). Forty-eight and 50% of the patients remained on their LDDOAC or W for the observation period (p = 0.55). Stroke/systemic embolism (SSE) and CNS bleeds were 1.16 vs 2.22%/yr., (p = 0.143) and 1.46 vs 0.93%/yr., (p = 0.24). Mortality and major bleeds were 6.26 vs 1.67%/yr., and 12.3vs 3.77%/yr. (p <0.001). SSE were 1.1%/yr for D, R, and A (p = 0.94). CNS bleeds were 2.2 for D, 1.7 for R and 0.8%/yr. for A: p = 0.53. Major bleeding was: 14.3 for D, 14.1 for R and 9.1%/yr. for A, p = 0.048 (with A < R, p = 0.01). Mortality was 5.5 for D, 4.2 for R and 9.5% for A, p = 0.031. In conclusion, half the patients remained on their assigned anti-coagulant. SSE and intracranial bleed rates were similar and low. Major bleeds and deaths were different between groups emphasizing the need for prospective randomized trials in this growing population with AF.
While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in ...parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size.
Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome.
6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32-1.44), and mortality (RR 0.82, 0.41-1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28-0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33-0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control.
There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.
Ovarian cancer is the sixth leading cause of cancer-related death in women, and both occurrence and mortality are increased in women over the age of 60. There are documented age-related changes in ...the ovarian cancer microenvironment that have been shown to create a permissive metastatic niche, including the formation of advanced glycation end products, or AGEs, that form crosslinks between collagen molecules. Small molecules that disrupt AGEs, known as AGE breakers, have been examined in other diseases, but their efficacy in ovarian cancer has not been evaluated. The goal of this pilot study is to target age-related changes in the tumor microenvironment with the long-term aim of improving response to therapy in older patients. Here, we show that AGE breakers have the potential to change the omental collagen structure and modulate the peritoneal immune landscape, suggesting a potential use for AGE breakers in the treatment of ovarian cancer.
Heart and lung transplant recipients require care provided by clinicians from multiple different specialties, each contributing unique expertise and perspective. The period the patient spends in the ...intensive care unit is one of the most critical times in the perioperative trajectory. Various organizational models of intensive care exist, including those led by intensivists, surgeons, transplant cardiologists, and pulmonologists. Coordinating timely efficient intensive care is an essential and logistically difficult goal. The present work product of the American Society of Transplantation's Thoracic and Critical Care Community of Practice, Critical Care Task Force outlines operational guidelines and principles that may be applied in different organizational models to optimize the delivery of intensive care for the cardiothoracic organ recipient.
The present article introduces RetFM-J, a semi-automated ImageJ-based module that detects, counts, and collects quantitative data on nuclei of the inner retina from H&E-stained whole-mounted retinas. ...To illustrate performance, computer-derived outputs were analyzed in inbred C57BL/6J mice. Automated characterization yielded computer-derived outputs that closely matched manual counts. As a method using open-source software that is freely available, inexpensive staining reagents that are robust, and imaging equipment that is routine to most laboratories, RetFM-J could be utilized in a wide variety of experiments benefiting from high-throughput, quantitative, uniform analyses of total cellularity in the inner retina.
•RetFM-J counts and quantifies features for all nuclei in the inner retina.•RetFM-J is packaged as a freely available plugin on the open ImageJ-based platform.•Protocols for dissection and H&E staining of mouse retinal whole-mounts are detailed.
Background
Patients with combined circulatory shock and respiratory failure may benefit from veno‐arteriovenous (V‐AV) extracorporeal membrane oxygenation support (ECMO). We report our center’s ...experience with V‐AV ECMO and propose an algorithm to help identify patients that may benefit from early V‐AV ECMO support.
Methods
Clinical data were extracted from electronic medical records between November 1, 2016 and November 1, 2019.
Results
Out of a total of 369 patients placed on extracorporeal life support (ECLS), we identified a total of 26 patients who underwent hybrid ECMO placement. Three patients were excluded from our analysis due to veno‐venoarterial extracorporeal membrane oxygenation (V‐VA ECMO) configuration, therefore 23 patients were included in our analysis. The median age was 53 (range 25–73) years. Hybrid ECMO support was instituted most commonly for differential hypoxemia in patients on venoarterial (V‐A) ECMO support, and cardiogenic shock in patients who were initially started on venovenous (V‐V) ECMO. The initial ECMO cannulation was V‐A in 12 patients, V‐V in 8 patients, and directly V‐AV in 3 patients. Nine out of 23 patients were successfully decannulated (39.1%) and survived until hospital discharge. The main ECMO‐related complications included bleeding (n = 10), circuit exchange either due to hemolysis or oxygenator failure (n = 4), ECMO cannula site infection (n = 2), deep venous thrombosis (n = 2), and death during ECMO cannula exchange (n = 1).
Conclusions
V‐AV ECMO represents a rescue strategy in critically ill patients with combined respiratory failure and cardio‐circulatory shock.
Out of 369 patients placed on extracorporeal life support between November 1, 2016 and November 1, 2019, we identified a total of 23 patients who underwent V‐AV ECMO placement. The initial ECMO cannulation was V‐A in 12 patients, V‐V in 8 patients and V‐AV in 3 patients. Nine out of 23 patients were successfully decannulated (39.1%) and survived to hospital discharge. In conclusion, V‐AV ECMO represents a rescue strategy in critically ill patients with combined respiratory failure and cardio‐circulatory shock. ECMO, extracorporeal membrane oxygenation; V‐A, venoarterial; V‐AV, veno‐arteriovenous; V‐V, venovenous; V‐VA, veno‐venoarterial.
Asymmetric disassembly of the synaptonemal complex (SC) is crucial for proper meiotic chromosome segregation. However, the signaling mechanisms that directly regulate this process are poorly ...understood. Here we show that the mammalian Rho GEF homolog, ECT-2, functions through the conserved RAS/ERK MAP kinase signaling pathway in the C. elegans germline to regulate the disassembly of SC proteins. We find that SYP-2, a SC central region component, is a potential target for MPK-1-mediated phosphorylation and that constitutively phosphorylated SYP-2 impairs the disassembly of SC proteins from chromosomal domains referred to as the long arms of the bivalents. Inactivation of MAP kinase at late pachytene is critical for timely disassembly of the SC proteins from the long arms, and is dependent on the crossover (CO) promoting factors ZHP-3/RNF212/Zip3 and COSA-1/CNTD1. We propose that the conserved MAP kinase pathway coordinates CO designation with the disassembly of SC proteins to ensure accurate chromosome segregation.
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