Lower Glycosylated Hemoglobin Is Associated With Lower In-Hospital Mortality in Patients With COVID-19: A Systematic Review of the Literature and Meta-Analysis.

OBJECTIVE: Poor glycemic control during COVID-19 hospitalization is associated with higher mortality. However, the association between long-term glycemic control, as reflected by the glycosylated hemoglobin (HbA1c) and outcomes has yet to be clarified, with some studies reporting no association. The aim of this study is to determine the association between HbA1c and in-hospital mortality in patients with COVID-19. METHODS: Pubmed, Embase, and Web of Science databases were searched for studies examining the association between HbA1c level and in-hospital COVID-19 mortality. Random-effects meta-analysis was performed. Heterogeneity was assessed using the I2 statistic. Publication bias was assessed using funnel plots. RESULTS: Among 4142 results, 22 studies were included in the final analysis with a total of 11 220 patients. Lower Hba1c was associated with lower in-hospital mortality [odds ratio (OR), 0.53; 95% CI, 0.37-0.76; I2 81%], in using HbA1c as a dichotomous variable. When only patients with diabetes were included in the analysis, the association remained statistically significant (OR, 0.67; 95% CI, 0.47-0.96). In the subgroup analysis, the association remained statistically significant in studies using as cutoff the HbA1c value of 6.5% (OR, 0.34; 95% CI, 0.15-0.77) and 7% (OR, 0.54; 95% CI 0.32-0.90), but not with greater HbA1c cutoff values; 7.5% and ≥8%. In studies using HbA1C as a continuous variable, HbA1c level did not have a statistically significant association with in-hospital mortality, either in univariate or multivariate analyses. CONCLUSION: A better glycemic control prior to hospitalization, as reflected by lower HbA1c, is associated with lower in-hospital mortality in patients with COVID-19.

Factors Associated With Enrollment into Inpatient Coronavirus Disease 2019 Randomized Controlled Trials: A Cross-sectional Analysis.

Background: Clinical trials for coronavirus disease 2019 (COVID-19) have struggled to achieve diverse patient enrollment, despite underrepresented groups bearing the largest burden of the disease and, presumably, being most in need of the treatments under investigation. Methods: To assess the willingness of patients to enroll into inpatient COVID-19 clinical trials when invited, we conducted a cross-sectional analysis of adults hospitalized with COVID-19 who were approached regarding enrollment. Associations between patient and temporal factors and enrollment were assessed by multivariable logistic regression analysis. Results: A total of 926 patients were included in this analysis. Overall, Hispanic/Latinx ethnicity was associated with a nearly half-fold decrease in the likelihood to enroll (adjusted odds ratio [aOR], 0.60 [95% confidence interval {CI}, .41-.88]). Greater baseline disease severity (aOR, 1.09 [95% CI, 1.02-1.17]), age 40-64 years (aOR, 1.83 [95% CI, 1.03-3.25]), and age ≥65 years (aOR, 1.92 [95% CI, 1.08-3.42]) were each independently associated with higher likelihood to enroll. Over the course of the pandemic, patients were less likely to enroll during the summer 2021 wave in COVID-19-related hospitalizations (aOR, 0.14 [95% CI, .10-.19]) compared with patients from the first wave in winter 2020. Conclusions: The decision to enroll into clinical trials is multifactorial. Amid a pandemic disproportionately affecting vulnerable groups, Hispanic/Latinx patients were less likely to participate when invited, whereas older adults were more likely. Future recruitment strategies must consider the nuanced perceptions and needs of diverse patient populations to ensure equitable trial participation that advances the quality of healthcare for all.

A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection.

BACKGROUND: Thymosin-α-1 (Tα1) may be a treatment option for coronavirus disease 2019 (COVID-19), but efficacy and safety data remain limited. METHODS: Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of Tα1), compared with the standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. RESULTS: A total of 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68-3.25]) or baseline high-flow oxygen (1.28 [.35-4.63]), although neither difference was significant. Among patients with baseline low-flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4+ T cells on day 5 than on day 1 (P = .01). Nine serious adverse events among treated patients were deemed not related to Tα1. CONCLUSIONS: Tα1 increases CD4+ T-cell count among patients with baseline low-flow oxygen support faster than the standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. CLINICAL TRIALS REGISTRATION: NCT04487444.

Clinical Outcomes of Adult Patients Hospitalized with COVID-19 after Vaccination.

Vaccination remains the most effective way to prevent COVID-19. The aim of the present study was to assess the incidence of COVID-19 hospitalizations after vaccination, as well as the effect of prior vaccination on hospitalization outcomes among patients with COVID-19. We analyzed and compared all consecutive patients, with or without prior vaccination, who were admitted to our hospital network due to COVID-19 from January to April 2021. Our primary outcome was to identify and describe cases of COVID-19 hospitalized after vaccination. We also utilized a multivariate logistic regression model to investigate the association of previous vaccination with hospitalization outcomes. We identified 915 consecutive patients hospitalized due to COVID-19 with 91/915 (10%) previously vaccinated with at least one dose of a COVID-19 vaccine. Utilizing our multivariate logistic regression model, we found that prior vaccination, regardless of the number of doses or days since vaccination, was associated with decreased mortality (aOR 0.44, 95% CI: 0.20-0.98) when compared to unvaccinated individuals. Our study showed that COVID-19 related hospitalization after vaccination may occur to a small percentage of patients, mainly those who are partially vaccinated. However, our findings underline that prior vaccination, even when partial, is associated with a decreased risk of death. Ongoing vaccination efforts should remain an absolute priority.

Mortality in mechanically ventilated patients with COVID-19: a systematic review.

Introduction: The use of mechanical ventilation associated with acute hypoxemic respiratory failure, the most common complication in critically ill COVID-19 patients, defines a high risk population that requires specific consideration of outcomes and treatment practices.Areas covered: This review evaluates existing information about mortality rates and effectiveness of antiviral, immune-modulating, and anticoagulation treatments in COVID-19 patients who received mechanical ventilation. The mortality rate and follow-up periods in patients receiving mechanical ventilation ranged widely. Antivirals, including remdesivir and convalescent plasma, have shown no definitive mortality benefit in this population despite positive results in other COVID-19 patients. Dexamethasone was associated with an absolute reduction in 28-day mortality by 12.3% (95% CI, 6.3 to 17.6), after adjusting for age. Reduced mortality has been demonstrated with tocilizumab use alongside corticosteroids. Evidence is inconclusive for therapeutic anticoagulation, and further studies are needed to determine the comparative benefit of prophylactic anticoagulation.Expert opinion: Significant variation and high mortality rates in mechanically ventilated patients necessitate more standardized outcome measurements, increased consideration of risk factors to reduce intubation, and improved treatment practices. Anticoagulation and dexamethasone should be incorporated in the treatment of patients receiving invasive mechanical ventilation, while more rigorous studies are required for other potential treatments.

Impact of Influenza Infection Among Adult and Pediatric Populations With Hematologic Malignancy and Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis.

PURPOSE: Influenza is increasingly recognized as a leading cause of morbidity and mortality in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation (HSCT). However, the impact of influenza on this population has not been previously evaluated in a systematic review. This study systematically reviewed and summarized the outcomes of influenza infection as to in-hospital influenza-related mortality, development of lower respiratory tract infection and acute respiratory distress syndrome, need for hospitalization, intensive care unit admission, and mechanical ventilation. METHODS: We conducted a systematic search of literature using the PubMed and EMBASE databases for articles published from January 1989 through January 19, 2020, reporting laboratory-confirmed influenza in patients of any age with hematologic malignancies and HSCT. Time from transplantation was not included in the search criteria. The impact of antiviral therapy on influenza outcomes was not assessed due to heterogeneity in antiviral treatment provision across the studies. Patients with influenza-like illness, solid-tumor cancers, or nonmalignant hematologic diseases were excluded from the study. A random-effects meta-analysis was performed to estimate the prevalences and 95% CIs of each outcome of interest. A subgroup analysis was carried out to assess possible sources of heterogeneity and to evaluate the potential impact of age on the influenza infection outcomes. Heterogeneity was assessed using the I2 statistic. FINDINGS: Data from 52 studies providing data on 1787 patients were included in this analysis. During seasonal epidemics, influenza-related in-hospital mortality was 16.60% (95% CI, 7.49%-27.7%), with a significantly higher death rate in adults compared to pediatric patients (19.55% [95% CI, 10.59%-29.97%] vs 0.96% [95% CI, 0%-6.77%]; P < 0.001). Complications from influenza, such as lower respiratory tract infection, developed in 35.44% of patients with hematologic malignancies and HSCT recipients, with a statistically significant difference between adults and children (46.14% vs 19.92%; P < 0.001). However, infection resulted in a higher hospital admission rate in pediatric patients compared to adults (61.62% vs 22.48%; P < 0.001). For the 2009 H1N1 pandemic, no statistically significant differences were found between adult and pediatric patients when comparing the rates of influenza-related in-hospital mortality, lower respiratory tract infection, and hospital admission. Similarly, no significant differences were noted in any of the outcomes of interest when comparing H1N1 pandemic with seasonal epidemics. IMPLICATIONS: Regardless of influenza season, patients, and especially adults, with underlying hematologic malignancies and HSCT recipients with influenza are at risk for severe outcomes including lower respiratory tract infection and in-hospital mortality.

Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

OBJECTIVES: Observational and experimental studies suggest that the use of antibiotics close to administration of immune checkpoint inhibitors (ICI) can have a negative effect on tumour response and patient survival, due to microbiome dysbiosis and the resultant suppression of host immune response against neoplastic cells. METHODS: A systematic search of PUBMED and EMBASE was undertaken for studies published between 1 January 2017 and 1 June 2020, evaluating the association between the use of antibiotics and clinical outcomes in patients with cancer treated with ICIs. A meta-analysis of the association between the use of antibiotics and clinical outcomes was also performed. RESULTS: Forty-eight studies met the inclusion criteria (12,794 patients). Use of antibiotics was associated with shorter overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.59-2.22; adjusted HR 1.87, 95% CI 1.55-2.25] and progression-free survival (HR 1.52, 95% CI 1.36-1.70; adjusted HR 1.93, 95% CI 1.59-2.36), decreased response rate [odds ratio (OR) 0.54, 95% CI 0.34-0.86] and more disease progression (OR 2.00, 95% CI 1.27-3.14). The negative association between the use of antibiotics and progression-free survival was stronger in patients with renal cell carcinoma or melanoma compared with lung cancer. Only antibiotic administration >1 month prior to ICI initiation was associated with increased disease progression. Heterogeneity was substantial for all outcomes. CONCLUSIONS: Recent use of antibiotics in patients with cancer treated with ICIs was associated with worse clinical outcomes. Such patients may benefit from dedicated antimicrobial stewardship programmes.

Clinical Presentation, Course, and Risk Factors Associated with Mortality in a Severe Outbreak of COVID-19 in Rhode Island, USA, April-June 2020.

Long-term care facilities (LTCFs) have had a disproportionally high mortality rate due to COVID-19. We describe a rapidly escalating COVID-19 outbreak among 116 LTCF residents in Rhode Island, USA. Overall, 111 (95.6%) residents tested positive and, of these, 48 (43.2%) died. The most common comorbidities were hypertension (84.7%) and cardiovascular disease (84.7%). A small percentage (9%) of residents were asymptomatic, while 33.3% of residents were pre-symptomatic, with progression to symptoms within a median of three days following the positive test. While typical symptoms of fever (80.2%) and cough (43.2%) were prevalent, shortness of breath (14.4%) was rarely found despite common hypoxemia (95.5%). The majority of patients demonstrated atypical symptoms with the most common being loss of appetite (61.3%), lethargy (42.3%), diarrhea (37.8%), and fatigue (32.4%). Many residents had increased agitation (38.7%) and anxiety (5.4%), potentially due to the restriction measures or the underlying mental illness. The fever curve was characterized by an intermittent low-grade fever, often the first presenting symptom. Mortality was associated with a disease course beginning with a loss of appetite and lethargy, as well as one more often involving fever greater than 38 °C, loss of appetite, altered mental status, diarrhea, and respiratory distress. Interestingly, no differences in age or comorbidities were noted between survivors and non-survivors. Taking demographic factors into account, treatment with anticoagulation was still associated with reduced mortality (adjusted OR 0.16; 95% C.I. 0.06-0.39; p < 0.001). Overall, the clinical features of the disease in this population can be subtle and the symptoms are commonly atypical. However, clinical decline among those who did not survive was often rapid with patients expiring within 10 days from disease detection. Further studies are needed to better explain the variability in clinical course of COVID-19 among LTCF residents, specifically the factors affecting mortality, the differences observed in symptom presentation, and rate of clinical decline.

Fatal Mucormycosis and Aspergillosis in an Atypical Host: What Do We Know about Mixed Invasive Mold Infections?

Mixed invasive mold infections (MIMIs) are considered rare. We present a case of fatal aspergillosis and mucormycosis in an elderly host with history of chronic lymphocytic leukemia (CLL) and potential mold exposures. Notably, he had no classic risk factors for IMI other than high-dose corticosteroids, which may be an important risk factor for (M)IMI, based on the current and previous reports. There is an urgent need for studies on the "net state of immunosuppression," environmental exposure as risk factors for (M)IMIs, and noninvasive fungal diagnostics.

Bloodstream infections by gram-negative bacteria in kidney transplant patients: Incidence, risk factors, and outcome.

BACKGROUND: Kidney transplant recipients (KTRs) are at increased risk of infections. METHODS: The aims of this study were to describe the incidence of bloodstream infections (BSIs) by gram-negative bacteria in a cohort of KTRs, the risk factors for BSI due to multi-drug-resistant (MDR) gram-negative bacteria, and the predictors for unfavorable outcome, defined as death or nephrectomy or return to dialysis, within 30 days from BSI. We conducted a retrospective cohort study at the renal transplant unit of a tertiary care hospital in Athens, Greece. RESULTS: In a total of 1962 KTRs, we recorded 195 BSI episodes in 182 single patients (male/female = 97/85), with a median (interquartile range) age of 57.2 (44-64.9) years. The incidence was 1.393/100 patient-years. The most common source of infection was urinary tract (70.9%), and Escherichia coli (63.7%) was the most common pathogen. 19.2% of the infecting organisms were MDR; previous antibiotic use (OR 8.2; CI 2.1-32.9) and previous stay in the intensive care unit (OR 34.2; CI 1.6-730.2) were associated with MDR BSIs. 6% of patients died, and 2.2% underwent nephrectomy, while no patients had to return to dialysis. Diabetes mellitus (OR 8.1; 95% CI 1.3-50.3), Pseudomonas aeruginosa BSI (OR 46.1; 95% CI 3.9-552.3), and septic shock (OR 46.7; 95% CI 1.7-1304.9) were independent predictors of unfavorable outcome. CONCLUSION: Bloodstream infections in KTRs have a significant impact on allograft and patients outcome.

Emerging Technologies for Use in the Study, Diagnosis, and Treatment of Patients with COVID-19.

INTRODUCTION: The COVID-19 pandemic has caused an unprecedented health and economic worldwide crisis. Innovative solutions are imperative given limited resources and immediate need for medical supplies, healthcare support and treatments. AIM: The purpose of this review is to summarize emerging technologies being implemented in the study, diagnosis, and treatment of COVID-19. RESULTS: Key focus areas include the applications of artificial intelligence, the use of Big Data and Internet of Things, the importance of mathematical modeling for predictions, utilization of technology for community screening, the use of nanotechnology for treatment and vaccine development, the utility of telemedicine, the implementation of 3D-printing to manage new demands and the potential of robotics. CONCLUSION: The review concludes by highlighting the need for collaboration in the scientific community with open sharing of knowledge, tools, and expertise.

Integrase Strand Transfer Inhibitors and the Emergence of Immune Reconstitution Inflammatory Syndrome (IRIS).

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting highly active anti-retroviral therapy (HAART) in new patients and especially late presenters. This study attempts to identify risk factors for IRIS and investigate whether certain treatment regimens increase the probability of IRIS for patients at risk. METHODS: Retrospective single-centre study of HIV patients treated with HAART. RESULTS: A total of 417 patients were included. We identified 45 cases of IRIS in 37 patients; an incidence of 13.3 cases over 1000 person-years. In univariate analysis, IRIS development was significantly associated with CDC stage, the presence of an opportunistic infection (OI) at diagnosis, CD4 cell count and viral load at diagnosis and HAART initiation and the use of integrase strand inhibitors (INSTIs). In multivariate analysis, INSTIs use (OR 2.89; 95%CI 1.26-6.64; p=0.012), CD4≤200/mm3 (OR 5.56; 95%CI 2.2-13.98; p<0.001), and the presence of an OI (OR 4.74; 95%CI 2.13-10.23; p=0.012) were independent risk factors. Among INSTI regimens, dolutegravir (OR 4.99 vs. NNRTI; 95%CI 1.11-22.55; p=0.037) and elvitegravir (OR 4.82 vs. NNRTI; 95%CI 1.43-16.19; p=0.011) seem to carry increased risk. Mortality was 18.9% (7/37) for IRIS patients compared to 9.7% (37/380) in the non-IRIS group. Mortality at any given time during follow-up was significantly higher in the IRIS group (HR 3.2; 95%CI 1.39-7.36; p=0.006). CONCLUSION: The use of INSTIs and especially DTG and EVG is associated with a higher probability for the development of IRIS in the background of late presentation and the presence of OIs. These data highlight the need for further research.

Prognostic Benefit of Surgical Management of Renal Cell Carcinoma Invading the Inferior Vena Cava.

Renal cell carcinoma (RCC) accounts for approximately 3 % of adult malignancies and 90-95 % of neoplasms arising from the kidney. One of the unique features of RCC is the tumor thrombus formation that migrates into the venous system including renal vein (RV) and inferior vena cava (IVC). Only 10 % of patients with RCC present with the classic triad of flank pain, hematuria and defined mass, while 25-30 % of affected patients are asymptomatic. Signs of para-neoplastic syndrome such as hypercalcemia, hypertension, anemia, cachexia and increased erythrocyte sedimentation rate (ESR) are often apparent. Extension of tumor thrombus into the venous system is depicted by radiological examinations, such as contrast enhanced Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and vena cavography. The level of the thrombus is mostly determined according to the Mayo classification. Despite recent research on the therapeutic strategies against advanced RCC, surgical resection appears the only potentially curative approach. Aggressive surgical management including nephrectomy with thrombectomy is currently the standard therapeutic approach for RCC patients with tumor thrombus extending to the RV or the IVC. Pre-surgical down-staging with the use of molecular targeted therapy has also been proposed. Alternative therapies, such as radio- and chemotherapy proved insufficient. The aim of this review is to evaluate the results of surgical treatment for RCC invading IVC with special reference to the extent of its histological spread. Review of recent world literature was accomplished to provide an update on the current concepts of surgical management of the disease.

Spondylodiscitis Associated with Major Abdominal Surgical Intervention: Challenging Diagnostic and Therapeutic Modalities.

Post-operative spondylodiscitis (PS) is a relatively rare infectious disease, with incidence varying from 0.21-3.6% in association with all surgical procedures. The entity appears insidiously, with non-specific symptoms such as neck or back pain, fever, muscle contractures, limited range of spinal motion, sciatica and neurological symptoms. C-reactive protein (CRP) remains the most reliable laboratory finding, while magnetic resonance imaging (MRI) has proven to be the most effective method for demonstrating the site of the infection. Treatment consists of immobilization along with antimicrobial therapy. The aim of this investigation was to analyse two isolated cases of PS presented in our institution. Into this retrospective survey were consecutively enrolled one patient with PS after complete common bile duct (CBD) obstruction and subsequent endoscopic retrograde cholangiopancreatography (ERCP) and Whipple operation along with one case of PS in a patient with vascular graft placement for therapeutic approach of an aortoenteric fistula as a consequence of an abdominal aorta pseudoaneurysm. PS is mainly associated with major surgical procedures and possesses a mortality rate of 11%. The most common etiological factor is Staphylococcus aureus but there is also evidence of gram-positive cocci, gram-negative bacilli, anaerobia bacteria, fungi, parasites and multi resistant microorganisms. Furthermore, there are many risk factors which contribute to this pathological situation such as advanced age, diabetes mellitus, smoking, steroid treatment, obesity, alcohol, malnutrition, concomitant infections, prolonged hospitalization and relevant serious co-morbidities. Also, the diagnosis is based on combination of clinical, haematological, microbiological and histopathologic findings.