Longitudinal Trend of Plasma Concentrations of Extracellular Vesicles in Patients Hospitalized for COVID-19

Plasma concentrations of extracellular vesicles (EVs) originating from cells involved in COVID-19-associated coagulopathy (CAC), their longitudinal trend and association with clinical outcomes were evaluated. Blood samples of consecutive COVID-19 patients admitted to a medical Unit were longitudinally collected within 48 h of admission, at discharge and 30 days post-discharge. EVs were analyzed using high sensitivity flow cytometry and phospholipid-dependent clotting time (PPL). The following EVs were measured: endothelium-, platelet-, leukocyte-derived, bearing tissue factor (TF)+, angiotensin-converting enzyme (ACE2)+, platelet-derived growth factor receptor-β (PDGF-β)+ and SARS-CoV-2-nucleoprotein (NP)+. 91 patients were recruited for baseline EV analysis (mean age 67 ± 14 years, 50.5% male) and 48 underwent the longitudinal evaluation. From baseline to 30-days post-discharge, we observed significantly decreased plasma concentrations of endothelium-derived EVs (E-Selectin+), endothelium-derived bearing TF (E-Selectin+ TF+), endothelium-derived bearing ACE2 (E-Selectin+ACE2+) and leukocyte-EVs bearing TF (CD45+TF+), p < 0.001, p = 0.03, p = 0.001, p = 0.001, respectively. Conversely, platelet-derived (P-Selectin+) and leukocyte-derived EVs (CD45+) increased from baseline to 30-days post-discharge (p = 0.038 and 0.032, respectively). EVs TF+, ACE2+, PDGF-β+, and SARS-CoV-2-NP+ did not significantly change during the monitoring. PPL increased from baseline to 30-days post-discharge (+ 6.3 s, p = 0.006). P-Selectin + EVs >1,054/µL were associated with thrombosis (p = 0.024), E-Selectin + EVs ≤531/µL with worsening/death (p 0.026) and 30-days P-Selectin+ and CD45 + EVs with persistent symptoms (p < 0.0001). We confirmed increased EVs originating from cells involved in CAC at admission and discharge. EVs derived from activated pericytes and expressing SARS-CoV-2-NP were also detected. 30-days post-discharge, endothelium-EVs decreased, while platelet- and leukocyte-EVs further increased, indicating that cellular activation persists long after the acute phase.

Prediction and Clinically Important Factors of Acute Kidney Injury Non-recovery

ObjectiveThis study aimed to identify phenotypic clinical features associated with acute kidney injury (AKI) to predict non-recovery from AKI at hospital discharge using electronic health record data.MethodsData for hospitalized patients in the AKI Recovery Evaluation Study were derived from a large healthcare delivery system in Taiwan between January 2011 and December 2017. Living patients with AKI non-recovery were used to derive and validate multiple predictive models. In total, 64 candidates variables, such as demographic characteristics, comorbidities, healthcare services utilization, laboratory values, and nephrotoxic medication use, were measured within 1 year before the index admission and during hospitalization for AKI.ResultsAmong the top 20 important features in the predictive model, 8 features had a positive effect on AKI non-recovery prediction: AKI during hospitalization, serum creatinine (SCr) level at admission, receipt of dialysis during hospitalization, baseline comorbidity of cancer, AKI at admission, baseline lymphocyte count, baseline potassium, and low-density lipoprotein cholesterol levels. The predicted AKI non-recovery risk model using the eXtreme Gradient Boosting (XGBoost) algorithm achieved an area under the receiver operating characteristic (AUROC) curve statistic of 0.807, discrimination with a sensitivity of 0.724, and a specificity of 0.738 in the temporal validation cohort.ConclusionThe machine learning model approach can accurately predict AKI non-recovery using routinely collected health data in clinical practice. These results suggest that multifactorial risk factors are involved in AKI non-recovery, requiring patient-centered risk assessments and promotion of post-discharge AKI care to prevent AKI complications.

A COVID-19 Patient with Simultaneous Renal Infarct, Splenic Infarct and Aortic Thrombosis during the Severe Disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with a high incidence of arterial and venous thrombotic complications. However, thromboembolic events in unusual sites such as limb and visceral arterial ischemia are reported rarely in the literature. Herein, we describe a rare case of a patient with severe coronavirus disease 2019 (COVID-19) infection who experienced severe abdominal pain during the hospitalization and presented simultaneously renal artery, splenic artery and vein as well as aortic thrombi despite prophylactic antithrombotic treatment. Information about his follow-up post discharge is also provided. This case report raises significant clinical implications regarding the correct dose of antithrombotic treatment during the acute phase of the severe COVID-19 infection and highlights the need for incessant vigilance in order to detect thrombosis at unusual sites as a possible diagnosis when severe abdominal pain is present in severe COVID-19 patients.

Evaluation of the Clinical Impact of Thromboprophylaxis in Patients With COVID-19 Following Hospital Discharge

Background: Data are limited regarding the incidence of thromboembolism post-hospital discharge among COVID-19 patients. Guidelines addressing the role of extended thromboprophylaxis for COVID-19 patients are limited and conflicting. Objective: The purpose of this study was to evaluate the incidence of post-discharge thromboembolic and bleeding events and the role of thromboprophylaxis among COVID-19 patients. Methods: A retrospective analysis was conducted of hospitalized patients with symptomatic COVID-19 infection who were discharged from a University of Colorado Health (UCHealth) hospital between March 1, 2020, and October 31, 2020. The primary outcome was objectively confirmed thromboembolism within 35 days post-discharge. The main secondary outcome was the incidence of bleeding events within 35 days post-discharge. Outcomes were compared between those who received extended prophylaxis and those who did not. Results: A total of 1171 patients met the study criteria. A total of 13 (1.1%) of patients had a documented thromboembolic event and 10 (0.9%) patients had a documented bleeding event within 35 days post-discharge. None of the 132 patients who received extended prophylaxis had a thromboembolic event compared to 13 of 1039 who did not receive extended prophylaxis (0 and 1.3%, respectively; P = .383). The incidence of bleeding was higher among patients who received extended prophylaxis compared to those who did not (3.0% vs 0.6%, P = .019). Conclusions and Relevance: These results suggest that post-discharge extended prophylaxis may be beneficial for select COVID-19 patients, while carefully weighing the risk of bleeding. Application of our findings may assist institutions in development of thromboprophylaxis protocols for discharged COVID-19 patients.

A New Biomarker Tool for Risk Stratification in “de novo” Acute Heart Failure (OROME)

Background: Inflammation is one of the mechanisms involved in heart failure (HF) pathophysiology. Thus, the acute phase reactant protein, orosomucoid, was associated with a worse post-discharge prognosis in de novo acute HF (AHF). However, the presence of anti-inflammatory adipokine, omentin, might protect and reduce the severity of the disease. We wanted to evaluate the value of omentin and orosomucoid combination for stratifying the risk of these patients.Methods and Results: Two independent cohorts of patients admitted for de novo AHF in two centers were included in the study (n = 218). Orosomucoid and omentin circulating levels were determined by ELISA at discharge. Patients were followed-up for 317 (3–575) days. A predictive model was determined for the primary endpoint, death, and/or HF readmission. Differences in survival were evaluated using a Log-rank test. According to cut-off values of orosomucoid and omentin, patients were classified as UpDown (high orosomucoid and low omentin levels), equal (both proteins high or low), and DownUp (low orosomucoid and high omentin levels). The Kaplan Meier determined a worse prognosis for the UpDown group (Long-rank test p = 0.02). The predictive model that includes the combination of orosomucoid and omentin groups (OROME) + NT-proBNP values achieved a higher C-index = 0.84 than the predictive model with NT-proBNP (C-index = 0.80) or OROME (C-index = 0.79) or orosomucoid alone (C-index = 0.80).Conclusion: The orosomucoid and omentin determination stratifies de novo AHF patients into the high, mild, and low risk of rehospitalization and/or death for HF. Its combination with NT-proBNP improves its predictive value in this group of patients.

An open-label, pilot study to evaluate the benefits of using lyophilized human milk-derived nutritional product (NeoLact 70 – 1.55 g) as an immune-nutritional supplement in premature infants discharged from NICU

Background: Premature and low birth weight (LBW) infants are at increased risk of having inadequate growth in post-discharge periods. In this study, lyophilized human milk was used as an immune-nutrition supplement along with breastfeeding for a period of 1 month in preterm infants discharged from neonatal intensive care unit (NICU). Objectives: Primary objective was to assess the percentage change in serum immunoglobulins for the duration of supplementation, and secondary objectives were to correlate changes in immunoglobulins to number of episodes of infections including respiratory infections and diarrhea, requirement of antibiotics, weight gain, and episodes of feed intolerance during the study period. Methods: A total of 10 preterm and LBW infants were included in the study at the time of discharge from NICU after satisfying the inclusion and exclusion criteria. The serum immunoglobulins were estimated at baseline and at end of the study, other parameters such as episodes of infections, feed intolerance, and weight gain were recorded on the weekly follow-up visits. All the infants received supplementation with NeoLact 70 – 1.55 g on a TID frequency along with the regular breastfeeding for a period of 1-month post-discharge from NICU and were followed up on a weekly basis. Results: Ten infants completed the study, mean birth weight and gestational age were 1779.4±576 gm and 33.5±4.9 weeks, respectively. There was increase in immunoglobulins IgA, IgE, IgG, and IgM by 38.29%, 85.36%, 17.45%, and 48.25%, respectively, from baseline to end of study. None of the infants experienced feeding intolerance, diarrhea, abdominal distension, fever, respiratory infections, or rehospitalizations, none of the infants required antibiotics or probiotics during the study period. The average weight gain in the 1st, 2nd, 3rd, and 4th week of supplementation was 28.42 g/day, 31.57 g/day, 35.17 g/day, and 39.24 g/day, respectively, with a mean weight gain of 30.4 g/day achieved for the entire duration of the study. Conclusion: The immune-nutritional supplementation with lyophilized human milk (NeoLact 70 – 1.55 g) helps to ensure exclusive human milk diet post-discharge and reduce the risk of infections, diarrhea, and rehospitalization through the enhancement of immunoglobulins and ensuring optimal weight gain. However, these results should be confirmed through multicentric studies with larger sample size. Supplementation with NeoLact 70 – 1.55 g can clinically benefit premature and LBW infants post-discharge.

Improving smoking cessation after myocardial infarction by systematically implementing evidence-based treatment methods

We compared the odds of smoking cessation at 2-months post-myocardial infarction (MI), before and after implementing routines optimizing use of evidence-based smoking cessation methods, with start during admission. The following routines were implemented at six Swedish hospitals: cardiac rehabilitation nurses offering smokers consultation during admission, optimizing nicotine replacement therapy and varenicline prescription, and contacting patients by telephone during the 1st week post-discharge. Using logistic regression, odds for smoking cessation at 2-months before (n smokers/n admitted = 188/601) and after (n = 195/632) routine implementation were compared. Secondary outcomes included adherence to implemented routines and assessing the prognostic value of each routine on smoking cessation. After implementation, a larger proportion of smokers (65% vs. 54%) were abstinent at 2-months (OR 1.60 [1.04–2.48]). Including only those counselled during admission (n = 98), 74% were abstinent (2.50 [1.42–4.41]). After implementation, patients were more often counselled during admission (50% vs. 6%, p < 0.001), prescribed varenicline (23% vs. 7%, p < 0.001), and contacted by telephone post-discharge (18% vs. 2%, p < 0.001). Being contacted by telephone post-discharge (adjusted OR 2.74 [1.02–7.35]) and prescribed varenicline (adjusted OR 0.39 [0.19–0.83]) predicted smoking cessation at 2-months. In conclusion, readily available methods for aiding smoking cessation can be implemented effectively in routine practice, with beneficial effects for post-MI patients.

Substance Use/Dependence in Psychiatric Emergency Setting Leading to Hospitalization: Predictors of Continuity of Care

Background: Poor adherence to treatment is a common clinical problem in individuals affected by mental illness and substance use/dependence. In Italy, mental care is organized in a psychiatric service and addiction unit (SERD), characterized by dual independent assets of treatment. This difference, in the Emergency Room setting, leads to a risk of discontinuity of treatment in case of hospitalization. In this study we clinically characterized individuals who decided to attend hospital post-discharge appointments at SERD, in accordance with medical advice. Methods: This is a retrospective study, based on two years of discharged records of patients entering “Versilia Hospital” (Viareggio, Italy) emergency room, with urinalyses testing positive for substance use, and hospitalization after psychiatric consultation. The sample was divided according to the presence or absence of SERD consultation after discharge. Results: In the 2-year period of the present study, 1005 individuals were hospitalized. Considering the inclusion criterion of the study, the sample consisted of 264 individuals. Of these, 128 patients attended post-discharge appointments at SERD showing urinalyses positive to cocaine, opiates, and poly use; they were more frequently diagnosed as personality disorder and less frequently as bipolar disorder. The prediction was higher for patients that had already been treated at SERD, for patients who received SERD consultation during hospitalization, and for patients with positive urinalyses to cocaine and opiates at treatment entry. Conversely, patients who did not attend SERD consultation after discharge were affected by bipolar disorders. Limitations: Small sample size. Demographical data are limited to gender and age due to paucity of data in hospital information systems. SERD is located far from the hospital and is open only on weekdays; thus, it cannot ensure a consultation with all inpatients. Conclusions: Mental illness diagnosis, the set of substance use positivity at hospitalization, and having received SERD consultation during hospitalization appeared to have a critical role in promoting continuity of care. Moreover, to reduce the gap between the need and the provision of the treatment, a more effective personalized individual program of care should be implemented.