Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans.

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected. RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, EA and AS were 14.8, 7.3, 16.3 and 2.2%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation (p = 0.001), shortness of breath (SOB) (p < 0.01), fatigue (p = 0.04), diarrhea (p = 0.02), and increased AST (p < 0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables among the demographics of study population were age (over 45 years old), male sex, EA, and patients hospitalized in New York. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID-19 death in our cohort. CONCLUSION: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, our study findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to high frequency of comorbidities and older age among AA. Glucocorticoids should be used carefully considering the poor outcomes associated with it. Special focus in treating patients with elevated liver enzymes and other inflammatory biomarkers such as CRP, troponin, ferritin, procalcitonin, and D-dimer are required to prevent poor outcomes.

Utility of a High-Resolution Superficial Diagnostic Ultrasound System for Assessing Skin Thickness: A Cross-Sectional Study.

BACKGROUND: Compared with other imaging modalities, ultrasound is relatively deeply penetrating and can be used to evaluate deep dermal and subcutaneous structures. OBJECTIVE: Image skin thickness of the face and neck using high-frequency diagnostic ultrasound devices. MATERIALS AND METHODS: Skin overlying 20 different predesignated face and neck anatomic sites in 32 individuals was imaged using 2 commercially available high-frequency diagnostic ultrasound devices, a dedicated imaging device and a diagnostic device bundled with a therapeutic device. At each site, the subcutaneous and combined epidermal and dermal layer thicknesses were assessed by blinded expert raters. RESULTS: Similar skin thickness measurements were obtained. Notably, subcutaneous fat depth was measured to be 0.2 cm at the forehead; 0.5 cm at the mental eminence; and 0.6 cm at the submental, supraglenoid, and temporal regions. The combined epidermal and dermal thickness was approximately 0.1 cm at the zygomatic process, suborbital area, inferior malar region, gonion, supraglenoid area, and nasolabial-buccal, and nasolabial fold regions. CONCLUSION: This is the first study using high-resolution superficial diagnostic ultrasound to map skin thickness of the face and neck at standard anatomic locations. Ultrasound is an inexpensive, noninvasive, and convenient means to monitor dermatologic conditions and guide their treatment.

Blockade of transforming growth factor-ß signaling enhances oncolytic herpes simplex virus efficacy in patient-derived recurrent glioblastoma models.

Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-ß) plays vital roles in maintaining GSC stemness and GBM pathogenesis. We hypothesized that oHSV and TGF-ß inhibitors would synergistically exert antitumor effects for recurrent GBM. Here we established a panel of patient-derived recurrent tumor models from GBMs that relapsed after postsurgical radiation and chemotherapy, based on GSC-enriched tumor sphere cultures. These GSCs are resistant to the standard-of-care temozolomide but susceptible to oHSVs G47Δ and MG18L. Inhibition of TGF-ß receptor kinase with selective targeted small molecules reduced clonogenic sphere formation in all tested recurrent GSCs. The combination of oHSV and TGF-ßR inhibitor was synergistic in killing recurrent GSCs through, in part, an inhibitor-induced JNK-MAPK blockade and increase in oHSV replication. In vivo, systemic treatment with TGF-ßR inhibitor greatly enhanced the antitumor effects of single intratumoral oHSV injections, resulting in cures in 60% of mice bearing orthotopic recurrent GBM. These results reveal a novel synergistic interaction of oHSV therapy and TGF-ß signaling blockade, and warrant further investigations aimed at clinical translation of this combination strategy for GBM patients.

Initiation of Aripiprazole Lauroxil Long-Acting Injectable in Adolescents During Hospitalization: A Case Series.

Objective: The efficacy and safety of long-acting injectable (LAI) antipsychotics in the pediatric population is not well established due to limited evidence. This case series aims to describe off-label use of aripiprazole lauroxil (AL) LAI in adolescent inpatients, including findings on safety and readmission trends. Methods: This was a retrospective chart review of patients who were initiated on AL LAI while admitted at a county-based adolescent psychiatric unit between March 2021 and March 2023. Data comprised sociodemographic and clinical characteristics, such as psychiatric diagnoses, prior antipsychotic trials, and history of nonadherence. Other observations of interest included tolerability of AL LAI and time to readmission. Results: This analysis identified 12 adolescents who received AL LAI within a 2-year period. The mean age was 16 ± 1 years, and seven (58%) patients were female. There were varying primary psychiatric diagnoses, with the most common being bipolar disorder (25%), schizophrenia (17%), major depressive disorder with psychotic features (17%), and unspecified mood disorder (17%). Eleven (92%) patients had previously trialed at least one antipsychotic, with seven (58%) having exposure to oral aripiprazole before admission. Nonadherence was the driving factor for LAI consideration in all but one patient. AL LAI was well tolerated short term; one patient reported experiencing injection site pain, and one patient discontinued the LAI after discharge due to anxiety. Time to readmission ranged from 15 to 658 days for seven patients who were hospitalized again; two of the readmissions occurred within 1 month. Conclusion: This is the first case series to describe initiation of AL LAI at an inpatient adolescent psychiatric unit. Our study illustrates that AL LAI may hold potential as an acceptably tolerated treatment in adolescents with varying psychiatric diagnoses. Further studies are needed to evaluate long-term safety and effectiveness of AL LAI in youth.

COVID-19 among African Americans and Hispanics: Does gastrointestinal symptoms impact the outcome?

BACKGROUND: The coronavirus disease 2019 (COVID-19) disproportionately affected African Americans (AA) and Hispanics (HSP). AIM: To analyze the significant effectors of outcome in African American patient population and make special emphasis on gastrointestinal (GI) symptoms, laboratory values and comorbidities. METHODS: We retrospectively evaluated the medical records of 386 COVID-19 positive patients admitted at Howard University Hospital between March and May 2020. We assessed the symptoms, including the GI manifestations, comorbidities, and mortality, using logistic regression analysis. RESULTS: Of these 386 COVID-19 positive patients, 257 (63.7%) were AAs, 102 (25.3%) HSP, and 26 (6.45%) Whites. There were 257 (63.7%) AA, 102 (25.3%) HSP, 26 (6.45%) Whites. The mean age was 55.6 years (SD = 18.5). However, the mean age of HSP was the lowest (43.7 years vs 61.2 for Whites vs 60 for AAs). The mortality rate was highest among the AAs (20.6%) and lowest among HSP (6.9%). Patients with shortness of breath (SOB) (OR2 = 3.64, CI = 1.73-7.65) and elevated AST (OR2 = 8.01, CI = 3.79-16.9) elevated Procalcitonin (OR2 = 8.27, CI = 3.95-17.3), AST (OR2 = 8.01, CI = 3.79-16.9), ferritin (OR2 = 2.69, CI = 1.24-5.82), and Lymphopenia (OR2 = 2.77, CI = 1.41-5.45) had a high mortality rate. Cough and fever were common but unrelated to the outcome. Hypertension and diabetes mellitus were the most common comorbidities. Glucocorticoid treatment was associated with higher mortality (OR2 = 5.40, CI = 2.72-10.7). Diarrhea was prevalent (18.8%), and GI symptoms did not affect the outcome. CONCLUSION: African Americans in our study had the highest mortality as they consisted of an older population and comorbidities. Age is the most important factor along with SOB in determining the mortality rate. Overall, elevated liver enzymes, ferritin, procalcitonin and C-reactive protein were associated with poor prognosis. GI symptoms did not affect the outcome. Glucocorticoids should be used judiciously, considering the poor outcomes associated with it. Attention should also be paid to monitor liver function during COVID-19, especially in AA and HSP patients with higher disease severity.