Medicine and surgery residents\u27 perspectives on the impact of COVID-19 on graduate medical education.

The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisis-related stressors on residents\u27 professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after \u3e6 weeks of a modified schedule. The primary outcome was to determine which factors or resident characteristics were related to stress during the pandemic. Our secondary goals were to examine which resident characteristics were related to survey responses. Data were analyzed with regression analyses. Ninety-six of 205 residents completed the survey (47% response rate). For our primary outcome, anxiety about PP

Risk factors for venous thromboembolism in hospitalized patients with hematological malignancy: an analysis of the National Inpatient Sample, 2011-2015

Hospitalized patients with hematological malignancy (HM) suffer an increased incidence of venous thromboembolism (VTE). We sought to identify risk factors and rate of VTE in hospitalized patients with HM using National Inpatient Sample (NIS) for the years 2011 to 2015. We used ICD-9 codes to identify patients with HM as the primary diagnosis and VTE as a secondary diagnosis for hospitalization. The rate of VTE was highest in patients with acute myeloid leukemia (6.6%) followed by acute lymphocytic leukemia (6.1%) and non-Hodgkin\u27s lymphoma (6.0%). The highest risk of VTE occurred among patients with HM receiving chemotherapy (OR 1.68; 95% CI 1.567-1.809) followed by infection such as pneumonia (OR 1.31; 95% CI 1.201-1.436) and sepsis (OR = 1.66; 95% CI = 1.524-1.621). Chemotherapy had the highest risk of developing VTE during hospitalization followed by sepsis and pneumonia. The identification of patients with HM most at risk for VTE could be used to design and test prophylactic strategy

In-hospital complications and outcomes of autologous stem cell transplantation in multiple myeloma patients older than 65-years old in the United States: National inpatient sample analysis, 2011-2015

Background: Use of Autologous Stem Cell Transplantation (ASCT) continues to increase in elderly patients with multiple myeloma. The main goal of our study was to describe in-hospital complications and outcomes after ASCT in patients younger and older than 65-years old utilizing the Nationwide Inpatient Sample (NIS) database. Methods: Cohort selection. The NIS database for the years 2011 to 2015 was queried for the analysis. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) in order to identify patients with MM as a primary diagnosis for the hospitalization, and ASCT as a primary diagnosis of the hospitalization. In order to determine comorbidities in selected population we used Clinical Classifications Software (CCS) in conjunction with ICD-9-CM codes. Statistical Analysis: Complex weights were used throughout all calculations, enabling appropriate national projections. Chi-squared and independent t-tests were used for univariate analysis where appropriate. In our study p-value Results: A total of 3,664 patients with MM receiving ASCT were identified in our cohort. Males represented 57.1% of the population, majority of the patients were white, with private insurance, located at the urban teaching hospitals (Table 1). Main insurance in patients older than 65 years old was Medicare. Main comorbidities during hospitalization were anemia, hypertension, electrolyte abnormalities, acute kidney injury, cardiac dysrhythmias, sepsis and pneumonia (Table 2). Overall in-hospital mortality was low, 0.7%, and was significantly higher in patients older than 65 years old (1.3% vs 0.4%, p-value 0.002), however when adjusted for the baseline characteristics with multivariate logistic regression analysis in-hospital mortality was no longer statistically significant (Table 3). Conclusions: We found that patients older than 65 years with MM receiving ASCT are more susceptible to in-hospital complications. However we found that in-hospital outcomes are not statistically significant when adjusted to baseline characteristics, suggesting that the procedure is safe even in the elderly population. Findings of our study can be used to design future randomized controlled trials. No relevant conflicts of interest to declare

Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate

Dichloroacetate-induced metabolic reprogramming improves lifespan in a Drosophila model of surviving sepsis.

Sepsis is the leading cause of death in hospitalized patients and beyond the hospital stay and these long-term sequelae are due in part to unresolved inflammation. Metabolic shift from oxidative phosphorylation to aerobic glycolysis links metabolism to inflammation and such a shift is commonly observed in sepsis under normoxic conditions. By shifting the metabolic state from aerobic glycolysis to oxidative phosphorylation, we hypothesized it would reverse unresolved inflammation and subsequently improve outcome. We propose a shift from aerobic glycolysis to oxidative phosphorylation as a sepsis therapy by targeting the pathways involved in the conversion of pyruvate into acetyl-CoA via pyruvate dehydrogenase (PDH). Chemical manipulation of PDH using dichloroacetic acid (DCA) will promote oxidative phosphorylation over glycolysis and decrease inflammation. We tested our hypothesis in a Drosophila melanogaster model of surviving sepsis infected with Staphylococcus aureus. Drosophila were divided into 3 groups: unmanipulated, sham and sepsis survivors, all treated with linezolid; each group was either treated or not with DCA for one week following sepsis. We followed lifespan, measured gene expression of Toll, defensin, cecropin A, and drosomycin, and levels of lactate, pyruvate, acetyl-CoA as well as TCA metabolites. In our model, metabolic effects of sepsis are modified by DCA with normalized lactate, TCA metabolites, and was associated with improved lifespan of sepsis survivors, yet had no lifespan effects on unmanipulated and sham flies. While Drosomycin and cecropin A expression increased in sepsis survivors, DCA treatment decreased both and selectively increased defensin

Novel Coronavirus Infection (COVID-19) Related Thrombotic and Bleeding Complications in Critically Ill Patients: Experience from an Academic Medical Center

Introduction: Thrombosis and bleeding are recognized complications of the novel coronavirus infection (COVID-19), with a higher incidence described particularly in the critically ill. Methods: A retrospective review of COVID-19 patients admitted to our intensive care units (ICU) between 1 January 2020 and 31 December 2020 was performed. Primary outcomes included clinically significant thrombotic and bleeding events (according to the ISTH definition) in the ICU. Secondary outcomes included mortality vis-a-vis the type of anticoagulation. Results: The cohort included 144 consecutive COVID-19 patients with a median age of 64 years (IQR 54.5–75). The majority were male (85 (59.0%)) and Caucasian (90 (62.5%)) with a median BMI of 30.5 kg/m2 (IQR 25.7–36.1). The median APACHE score at admission to the ICU was 12.5 (IQR 9.5–22). The coagulation parameters at admission were a d-dimer level of 109.2 mg/mL, a platelet count of 217.5 k/mcl, and an INR of 1.4. The anticoagulation strategy at admission included prophylactic anticoagulation for 97 (67.4%) patients and therapeutic anticoagulation for 35 (24.3%) patients, while 12 (8.3%) patients received no anticoagulation. A total of 29 patients (20.1%) suffered from thrombotic or major bleeding complications. These included 17 thrombus events (11.8%)—8 while on prophylactic anticoagulation (7 regular dose and 1 intermediate dose) and 9 while on therapeutic anticoagulation (p-value = 0.02)—and 19 major bleeding events (13.2%) (4 on no anticoagulation, 7 on prophylactic (6 regular dose and 1 intermediate dose), and 8 on therapeutic anticoagulation (p-value = 0.02)). A higher thrombosis risk among patients who received remdesivir (18.8% vs. 5.3% (p-value = 0.01)) and convalescent serum (17.3% vs. 5.8% (p-value = 0.03%)) was noted, but no association with baseline characteristics (age, sex, race, comorbidity), coagulation parameters, or treatments (steroids, mechanical ventilation) could be identified. There were 10 pulmonary embolism cases (6.9%). A total of 99 (68.8%) patients were intubated, and 66 patients (45.8%) died. Mortality was higher, but not statistically significant, in patients with thrombotic or bleeding complications—58.6% vs. 42.6% (p-value = 0.12)—and higher in the bleeding (21.2%) vs. thrombus group (12.1%), p-value = 0.06. It did not significantly differ according to the type of anticoagulation used or the coagulation parameters. Conclusions: This study describes a high incidence of thrombotic and bleeding complications among critically ill COVID-19 patients. The findings of thrombotic events in patients on anticoagulation and major bleeding events in patients on no or prophylactic anticoagulation pose a challenging clinical dilemma in the issue of anticoagulation for COVID-19 patients. The questions raised by this study and previous literature on this subject demonstrate that the role of anticoagulation in COVID-19 patients is worthy of further investigation

Cost of surviving sepsis: a novel model of recovery from sepsis in Drosophila melanogaster

Submitted by Janaína Nascimento ([email protected]) on 2019-04-10T13:14:51Z No. of bitstreams: 1 ve_Kaynar_Ata_etal_INI_2016.pdf: 1792156 bytes, checksum: fd4ed5589dce0b49eaa9636408521f8b (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-04-17T20:05:04Z (GMT) No. of bitstreams: 1 ve_Kaynar_Ata_etal_INI_2016.pdf: 1792156 bytes, checksum: fd4ed5589dce0b49eaa9636408521f8b (MD5)Made available in DSpace on 2019-04-17T20:05:05Z (GMT). No. of bitstreams: 1 ve_Kaynar_Ata_etal_INI_2016.pdf: 1792156 bytes, checksum: fd4ed5589dce0b49eaa9636408521f8b (MD5) Previous issue date: 2016University of Pittsburgh. School of Medicine. Department of Critical Care Medicine. Clinical Research, Investigation, and Systems Modeling of Acute Illness. Laboratory. Pittsburgh, PA, USA.University of Pittsburgh. School of Medicine. Department of Critical Care Medicine. Clinical Research, Investigation, and Systems Modeling of Acute Illness. Laboratory. Pittsburgh, PA, USA.University of Pittsburgh. School of Medicine. Department of Medicine. Pittsburgh, PA, USA.Université Paris Descartes. Paris, France.Eulji University. Department of Pulmonology and Allergy. Seoul, Korea.University of Pittsburgh. Department of Pharmacology and Chemical Biology. Pittsburgh, PA, USA / The Children’s Hospital of Philadelphia. Center of Mitochondrial and Epigenomic Medicine. Philadelphia, PA, USA.University of Pittsburgh. School of Medicine. Department of Medicine. Pittsburgh, PA, USA.University of Western Australia. School of Population Health. Perth, WA, Australia.University of Pittsburgh. Department of Pharmacology and Chemical Biology. Pittsburgh, PA, USA.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.University of Pittsburgh. School of Medicine. Department of Medicine. Pittsburgh, PA, USA.University of Pittsburgh. School of Medicine. Department of Critical Care Medicine. Clinical Research, Investigation, and Systems Modeling of Acute Illness. Laboratory. Pittsburgh, PA, USA.Background: Multiple organ failure, wasting, increased morbidity, and mortality following acute illness complicates the health span of patients surviving sepsis. Persistent inflammation has been implicated, and it is proposed that insulin signaling contributes to persistent inflammatory signaling during the recovery phase after sepsis. However, mechanisms are unknown and suitable pre-clinical models are lacking. We therefore developed a novel Drosophila melanogaster model of sepsis to recapitulate the clinical course of sepsis, explored inflammation over time, and its relation to impaired mobility, metabolic disturbance, and changes in lifespan. Methods: We used wild-type (WT), Drosomycin-green fluorescent protein (GFP), and NF-κB-luc reporter male Drosophila melanogaster 4–5 days of age (unmanipulated). We infected Drosophila with Staphylococcus aureus (infected without treatment) or pricked with aseptic needles (sham). Subsets of insects were treated with oral linezolid after the infection (infected with antibiotics). We assessed rapid iterative negative geotaxis (RING) in all the groups as a surrogate for neuromuscular functional outcome up to 96 h following infection. We harvested the flies over the 7-day course to evaluate bacterial burden, inflammatory and metabolic pathway gene expression patterns, NF-κB translation, and metabolic reserve. We also followed the lifespan of the flies. Results: Our results showed that when treated with antibiotics, flies had improved survival compared to infected without treatment flies in the early phase of sepsis up to 1 week (81 %, p = 0.001). However, the lifespan of infected with antibiotics flies was significantly shorter than that of sham controls (p = 0.001). Among infected with antibiotic sepsis survivors, we observed persistent elevation of NF-κB in the absence of any obvious infection as shown by culturing flies surviving sepsis. In the same group, geotaxis had an early (18 h) and sustained decline compared to its baseline. Geotaxis in infected with antibiotics sepsis survivors was significantly lower than that in sham and age-matched unmanipulated flies at 18 and 48 h. Expression of antimicrobial peptides (AMP) remained significantly elevated over the course of 7 days after sepsis, especially drosomycin (5.7-fold, p = 0.0145) on day 7 compared to that of sham flies. Infected with antibiotics flies had a trend towards decreased Akt activation, yet their glucose stores were significantly lower than those of sham flies (p = 0.001). Sepsis survivors had increased lactate levels and LDH activity by 1 week, whereas ATP and pyruvate content was similar to that of the sham group. Conclusions: In summary, our model mimics human survivors of sepsis with persistent inflammation, impaired motility, dysregulated glucose metabolism, and shortened lifespan

Additional file 2: Figure S2. of Cost of surviving sepsis: a novel model of recovery from sepsis in Drosophila melanogaster

Weight of flies over a course of 1 week after sepsis. Drosophila were harvested at baseline, 18, 48, and 168 h after induction of sepsis and weighed in groups of five flies in triplicate. The weights (0.8 ± 0.053 μg/fly) were unchanged within and between groups over a 1-week period following sepsis. (PDF 67 kb