African Americans Possessed High Prevalence of Comorbidities and Frequent Abdominal Symptoms, and Comprised A Disproportionate Share of Covid-19 Mortality among 9,873 Us- Hospitalized Patients Early in the Pandemic.

Background and aim: Identifying clinical characteristics and outcomes of different ethnicities in the US may inform treatment for hospitalized COVID-19 patients. Aim of this study is to identify predictors of mortality among US races/ethnicities. Design Setting and participants: We retrospectively analyzed de-identified data from 9,873 COVID-19 patients who were hospitalized at 15 US hospital centers in 11 states (March 2020-November 2020). Main Outcomes and Measures: The primary outcome was to identify predictors of mortality in hospitalized COVID-19 patients. Results: Among the 9,873 patients, there were 64.1% African Americans (AA), 19.8% Caucasians, 10.4% Hispanics, and 5.7% Asians, with 50.7% female. Males showed higher in-hospital mortality (20.9% vs. 15.3%, p=0.001). Non- survivors were significantly older (67 vs. 61 years) than survivors. Patients in New York had the highest in-hospital mortality (OR=3.54 (3.03 - 4.14)). AA patients possessed higher prevalence of comorbidities, had longer hospital stay, higher ICU admission rates, increased requirement for mechanical ventilation and higher in-hospital mortality compared to other races/ethnicities. Gastrointestinal symptoms (GI), particularly diarrhea, were more common among minority patients. Among GI symptoms and laboratory findings, abdominal pain (5.3%, p=0.03), elevated AST (n=2653, 50.2%, p=<0.001, OR=2.18), bilirubin (n=577, 12.9%, p=0.01) and low albumin levels (n=361, 19.1%, p=0.03) were associated with mortality. Multivariate analysis (adjusted for age, sex, race, geographic location) indicates that patients with asthma, COPD, cardiac disease, hypertension, diabetes mellitus, immunocompromised status, shortness of breath and cough possess higher odds of in-hospital mortality. Among laboratory parameters, patients with lymphocytopenia (OR2=2.50), lymphocytosis (OR2=1.41), and elevations of serum CRP (OR2=4.19), CPK (OR2=1.43), LDH (OR2=2.10), troponin (OR2=2.91), ferritin (OR2=1.88), AST (OR2=2.18), D-dimer (OR2=2.75) are more prone to death. Patients on glucocorticoids (OR2=1.49) and mechanical ventilation (OR2=9.78) have higher in-hospital mortality. Conclusion: These findings suggest that older age, male sex, AA race, and hospitalization in New York were associated with higher in-hospital mortality rates from COVID-19 in early pandemic stages. Other predictors of mortality included the presence of comorbidities, shortness of breath, cough elevated serum inflammatory markers, altered lymphocyte count, elevated AST, and low serum albumin. AA patients comprised a disproportionate share of COVID-19 death in the US during 2020 relative to other races/ethnicities.

Gastrointestinal Manifestations and Their Association with Neurologic and Sleep Problems in Long COVID-19 Minority Patients: A Prospective Follow-Up Study.

BACKGROUND: Long-COVID is a condition post SARS-CoV-2 infection with persistent or recurring symptoms affecting multiple organs, and may involve viral persistence, changes to the microbiome, coagulopathies, and alterations to neuro-immune interactions. These factors can disrupt the Gut-Brain Axis, which is a complex system involving bidirectional communication between the central nervous system and the gastrointestinal (GI) system. As a result of these disruptions, individuals with long-COVID may develop post-infectious functional GI disorders, which can cause a range of symptoms affecting the digestive system. AIM: To understand frequency of GI manifestations of Long-COVID and to determine association with sleep or neurological symptoms in a predominantly minority population. METHODS: We included patients with positive SARS-CoV-2 PCR (n = 747) who were hospitalized from Feb. 2020 to May 2021 at Howard University Hospital and followed between 6 and 12 months from discharge. GI, sleep, and neurological symptoms (via the Montreal Cognitive Assessment (MoCA) scoring system) were assessed using a standardized questionnaire. Linear regression analysis, χ2 and Fisher's exact test were utilized to determine the statistical significance of correlations of GI/Neuro/COVID. RESULTS: The mean age of patients was 58, with 51.6% females and a predominant African American ethnicity (73.6%, n = 550). A total of 108 patients died during their initial hospital stay, with the remaining 639 patients followed-up. Three hundred fifty (350) patients responded to the questionnaire (57 patients died during the follow-up period). Overall, 39 (13.3%) patients reported GI-related symptoms, out of which 19 (6.4%) had persistent symptoms and 20 (6.8%) developed new onset GI symptoms. Nausea and vomiting were the most common 24/39 (61.5%), followed by abdominal pain 7/39 (18%), diarrhea 5/39 (12.8%), and others 3/39 (7.6%). Patients who presented with vomiting during acute SARS-CoV-2 infection were more likely to have Long-COVID GI manifestations (P = 0.023). Use of ACE inhibitors, abnormal lymphocyte count and elevated ferritin are other variables that showed significant associations with Long-COVID GI manifestations (P = 0.03, 0.006 and 0.03, respectively). During follow-up, a total of 28 (9.5%) patients reported difficulty with sleep and 79 (27%) patients had abnormal MoCA assessment. With further analysis, there was a trend between presentation of GI symptoms on admission with abnormal MoCA assessment, and an association between abnormal LFTs and history of liver disease during hospitalization with subsequent sleep problems. Baseline characteristics, clinical comorbidities, other laboratory values, hospital length of stay, mechanical ventilation, medications during hospitalization, re-admission and Flu or COVID-19 vaccination have not shown any association with Long-COVID GI symptoms in our cohort. CONCLUSION: Dyspeptic symptoms were common GI manifestations in the acute and post COVID periods. GI symptoms, abnormal LFTs and a history of liver disease during the acute infectious phase associates with abnormal MoCA and sleep problems during follow-up. Further large population studies are needed to determine if COVID-19 leads to a GI symptoms-associated Long-COVID phenotypes and other symptoms through the Gut-Brain-Axis.

The importance of patient-partnered research in addressing long COVID: Takeaways for biomedical research study design from the RECOVER Initiative's Mechanistic Pathways taskforce.

The NIH-funded RECOVER study is collecting clinical data on patients who experience a SARS-CoV-2 infection. As patient representatives of the RECOVER Initiative's Mechanistic Pathways task force, we offer our perspectives on patient motivations for partnering with researchers to obtain results from mechanistic studies. We emphasize the challenges of balancing urgency with scientific rigor. We recognize the importance of such partnerships in addressing post-acute sequelae of SARS-CoV-2 infection (PASC), which includes 'long COVID,' through contrasting objective and subjective narratives. Long COVID's prevalence served as a call to action for patients like us to become actively involved in efforts to understand our condition. Patient-centered and patient-partnered research informs the balance between urgency and robust mechanistic research. Results from collaborating on protocol design, diverse patient inclusion, and awareness of community concerns establish a new precedent in biomedical research study design. With a public health matter as pressing as the long-term complications that can emerge after SARS-CoV-2 infection, considerate and equitable stakeholder involvement is essential to guiding seminal research. Discussions in the RECOVER Mechanistic Pathways task force gave rise to this commentary as well as other review articles on the current scientific understanding of PASC mechanisms.

Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts.

BACKGROUND: The respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a multi-organ disorder, with long-term effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease (COVID). AIM: To examine the current knowledge and outcomes of long-term neurological and gastrointestinal (GI) symptoms in adult cohorts, including United States minority populations. METHODS: PubMed and Google Scholar were searched using relevant terms, and data from five studies were analyzed, comprising 27383 patients with persistent neurological and GI sequelae. RESULTS: The main symptoms included anxiety, depression, dysphagia, headache, vomiting, nausea, gastroesophageal reflux, fatigue, and abdominal pain. Patients with comorbidities and metabolic syndromes were at higher risk for long COVID. While most patients were European Americans, there was a need for further study on African Americans. CONCLUSION: The underlying causes of these symptoms remain unclear, warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.

Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC).

With a global tally of more than 500 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses are key determinants of the severity and outcomes of the initial SARS-CoV-2 infection as well as subsequent PASC. The complexity of the innate and adaptive immune responses in the acute and post-acute period requires in-depth mechanistic analyses to identify specific molecular signals as well as specific immune cell populations which promote PASC pathogenesis. In this review, we examine the current literature on mechanisms of immune dysregulation in severe COVID-19 and the limited emerging data on the immunopathology of PASC. While the acute and post-acute phases may share some parallel mechanisms of immunopathology, it is likely that PASC immunopathology is quite distinct and heterogeneous, thus requiring large-scale longitudinal analyses in patients with and without PASC after an acute SARS-CoV-2 infection. By outlining the knowledge gaps in the immunopathology of PASC, we hope to provide avenues for novel research directions that will ultimately lead to precision therapies which restore healthy immune function in PASC patients.

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

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.

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.

Integrative Analysis of DNA Methylation and microRNA Expression Reveals Mechanisms of Racial Heterogeneity in Hepatocellular Carcinoma.

Pathologic alterations in epigenetic regulation have long been considered a hallmark of many cancers, including hepatocellular carcinoma (HCC). In a healthy individual, the relationship between DNA methylation and microRNA (miRNA) expression maintains a fine balance; however, disruptions in this harmony can aid in the genesis of cancer or the propagation of existing cancers. The balance between DNA methylation and microRNA expression and its potential disturbance in HCC can vary by race. There is emerging evidence linking epigenetic events including DNA methylation and miRNA expression to cancer disparities. In this paper, we evaluate the epigenetic mechanisms of racial heterogenity in HCC through an integrated analysis of DNA methylation, miRNA, and combined regulation of gene expression. Specifically, we generated DNA methylation, mRNA-seq, and miRNA-seq data through the analysis of tumor and adjacent non-tumor liver tissues from African Americans (AA) and European Americans (EA) with HCC. Using mixed ANOVA, we identified cytosine-phosphate-guanine (CpG) sites, mRNAs, and miRNAs that are significantly altered in HCC vs. adjacent non-tumor tissue in a race-specific manner. We observed that the methylome was drastically changed in EA with a significantly larger number of differentially methylated and differentially expressed genes than in AA. On the other hand, the miRNA expression was altered to a larger extent in AA than in EA. Pathway analysis functionally linked epigenetic regulation in EA to processes involved in immune cell maturation, inflammation, and vascular remodeling. In contrast, cellular proliferation, metabolism, and growth pathways are found to predominate in AA as a result of this epigenetic analysis. Furthermore, through integrative analysis, we identified significantly differentially expressed genes in HCC with disparate epigenetic regulation, associated with changes in miRNA expression for AA and DNA methylation for EA.

Trends in the Incidence of Hepatocellular Carcinoma in Washington DC: A Single Institutional Cohort Study (1959-2013).

The African American (AA) community in Washington DC is at an elevated risk for hepatocellular carcinoma (HCC) that has a dismal prognosis. The recent rapid increase in the incidence and diagnosis of HCC and liver metastases (LM) in DC prompted us to evaluate the past six decades of this incidence and some of its underlying causes using a single institutional cohort in a hospital located in the center of the city. Electronic medical and pathology records of 454 liver cancer patients from 1959 to 2013 at Howard University Hospital (HUH) were reviewed. Demographic, clinical and pathology characteristics were examined, and statistical analysis was performed using Wilcoxon rank-sum test. Incidence of HCC rose substantially between 1959 and 2013, increasing eight-fold from 1.05 to 8.0 per 100,000 AAs. The rate of increase in the last decade was highest at 550%. Cases were disproportionately male (67.2%), and median age at diagnosis was 57 years. Towards the last decade, the most common etiology for HCC was nonalcoholic fatty liver disease (NAFLD) followed by NAFLD/HCV combination. Liver cancer was clustered in the eastern region of DC in wards 4, 5, 7, and 8. Cases of liver metastases clinically diagnosed and confirmed by biopsies increased 96.4% from 1959 to 1968 to 2009-2013. This study confirms that HCC incidence has been increasing (initially driven by HCV, and NAFLD in the latter decades) more rapidly in DC than previously believed, highlighting the impact of case definitions especially regarding NAFLD in the context of changing diagnostic approaches including the revised ICD10. The rising burden, disproportionate population distribution, and low survival rate among AAs emphasize the importance of prevention and early detection as a public health imperative.

Characteristics and resolution of hypertension in obese African American bariatric cohort.

Weight reduction continues to be first-line therapy in the treatment of hypertension (HTN). However, the long-term effect of bariatric malabsorptive surgical techniques such as Roux-en-Y Gastric Bypass (RYGB) surgery in the management of hypertension (HTN) is less clear. African Americans (AA) are disproportionately affected by obesity and hypertension and have inconsistent outcomes after bariatric surgery (BS). Despite a plethora of bariatric literature, data about characteristics of a predominantly AA bariatric hypertensive cohort including hypertension in obese (HIO) are scarce and underreported. The aims of this study were, (1) to describe the preoperative clinical characteristics of HIO with respect to HTN status and age, and (2) to identify predictors of HTN resolution one year after RYGB surgery in an AA bariatric cohort enrolled at the Howard University Center for Wellness and Weight Loss Surgery (HUCWWS). In the review of 169 AA bariatric patients, the average BMI was 48.50 kg/m2 and the average age was 43.86 years. Obese hypertensive patients were older (46 years vs. 37.89 years; p < .0001); had higher prevalence of diabetes mellitus (DM, 43.09% vs. 10.87%; p < .0001) and dyslipidemia (38.2% vs. 13.04%; p 0.002). Hypertensive AA who were taking ≥ 2 antihypertensive medications prior to RYGB were 18 times less likely to experience HTN resolution compared to hypertensive AA taking 0-1 medications, who showed full or partial response. Also, HIO was less likely to resolve after RYGB surgery in patients who needed ≥ 2 antihypertensive medications prior to surgical intervention.

A Comprehensive Analysis of COVID-19 Impact in Latin America.

Background: Latin America has now become the epicenter of the global coronavirus disease 2019 (COVID-19) pandemic. In the ongoing COVID -19 pandemic, a profound burden of SARS-COV-2 infection has been reported in Latin America. In the present study, we aim to determine the profiles that are associated with this disease in Latin America. We analyzed symptoms, morbidities and gastrointestinal (GI) manifestations by country. Methods: We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 Latin American countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia between March 1 and July 30, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and lethality were performed. Results: A total of 728,282 patients tested positive for COVID-19 across all the 8 Latin American countries. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years old and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivia had fever as the top symptom (83.3%). GI symptoms including diarrhea (highest in Mexico with 22.9%), nausea, vomiting, and abdominal pain were not associated with higher mortality.Hypertension was among the top (12.1%) comorbidities followed by diabetes with 8.3% and obesity 4.5%. In multivariable analyses, the leading and significant comorbidities were hypertension (r=0.83, p=0.02), diabetes (r=0.91, p=0.01), and obesity (r=0.86, p=0.03). Asthma (r=0.37, p=0.54) and increasing age (0.13 p=0.81) were not independently associated with higher mortality. Lethality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts. Conclusion: Nearly, 10.5%-53% of patients with COVID-19 have GI manifestations. Differential clinical symptoms were associated with COVID-19 in Latin America countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed. Country-specific management and prevention plans can be established from this meta-analysis.

A Comprehensive Meta-Analysis of COVID-19 in Latin America.

Background: Latin America has become the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. We aim to perform a systematic comparative review of the clinical characteristics that are associated with this disease in Latin American countries. Methods: We conducted a systematic review of published articles, journal and/or epidemiological reports of confirmed COVID-19 cases in Latin America. Data were obtained either through publicly available information from Ministries of Health, published journal reports and/or unpublished datasets. We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia, between March 1st and July 30th, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities, and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and mortality were performed. Results: A total of 728,282 COVID-19 patients were included in this study. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivian patients had fever as the top symptom (83.3%). GI symptoms included diarrhea which was highest in Mexico with 22.9%. Hypertension was among the top (12.1%) comorbidities, followed by diabetes with 8.3% and obesity at 4.5%. In multivariate analyses, the leading and significant comorbidities were hypertension (r = 0.83, p = 0.02), diabetes (r = 0.91, p = 0.01), and obesity (r = 0.86, p = 0.03). Mortality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts. Conclusion: Overall, COVID-19 patients in Latin America display cough, fatigue, and fever as main symptoms. Up to 53% of patients with COVID-19 have GI manifestations. Different clinical symptoms were associated with COVID-19 in Latin American countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed and can be established from this meta-analysis.

Analysis of ß-catenin association with obesity in African Americans with premalignant and malignant colorectal lesions.

BACKGROUND: African Americans (AA) are at high risk for Colorectal Cancer (CRC). Studies report a 30-60% increase in CRC risk with physical inactivity, obesity and metabolic syndrome. Activation of the WNT/ß-catenin (CTNNB1) signaling pathway plays a critical role in colorectal carcinogenesis. Accumulating evidence also indicates a role of WNT-CTNNB1 signaling in obesity and metabolic diseases. AIM: To examine the association between obesity, ß-Catenin expression and colonic lesions in African Americans. METHODS: We reviewed the pathology records of 152 colorectal specimens from 2010 to 2012 (46 CRCs, 74 advanced adenomas and 32 normal colon tissues). Tissue Microarrays (TMA) were constructed from these samples. Immunohistochemistry (IHC) for CTNNB1 (ß-Catenin; clone ß-Catenin-1) was performed on the constructed TMAs. The IHC results were evaluated by 2 pathologists and the nuclear intensity staining was scored from 0 to 4. BMI, sex, age, location of the lesion and other demographic data were obtained. RESULTS: Positive nuclear staining in normal, advanced adenoma and CRC was 0, 24 and 41%, respectively (P < 0.001). CRC was asso ciated with positive status for nuclear CTNNB1 intensity (adjusted OR: 3.40, 95%CI = 1.42-8.15, P = 0.006 for positive nuclear staining) compared to non-CRC samples (Normal or advanced adenoma). Nuclear staining percentage has a fair diagnostic ability for CRC with an AUC of 0.63 (95%CI = 0.55-0.71). Overweight/obese patients (BMI > 25) did not show a significant difference in (p = 0.3) nuclear CTNNB1 staining (17% positive in normal weight vs. 27% positive in overweight/obese). The association between nuclear intensity and CRC was not different between normal and overweight patients (P for interaction = 0.6). The positive nuclear CTNNB1status in CRC stage III and IV (35% of all CRC) was not different from stage I and II (50% vs. 36%, respectively, P = 0.4). CONCLUSION: In our study, advanced adenoma and CRC were associated with activation of ß-catenin in physically fit, overweight and obese patients. Thus, obesity and WNT/ß-Catenin pathway seem to be independent in African American patients. WNT/ß-Catenin signaling pathway has a potential to be used as an effector in colon carcinogenic transformation. Whether or not BMI is a modifier of this pathway needs to be investigated further.

Inflammatory polyps occur more frequently in inflammatory bowel disease than other colitis patients.

BACKGROUND: Colitis is generally considered a risk factor for colon neoplasia. However, not all types of colitis seem to have equal neoplastic transformation potential. AIM: To determine the prevalence of colorectal polyps in a predominantly African American population with inflammatory bowel disease (IBD) and Non-IBD/Non-Infectious Colitis (NIC). METHODS: We retrospectively evaluated medical records of 1060 patients previously identified with colitis at Howard University Hospital, based on ICD-10 code. Among these, 485 patients were included in the study: 70 IBD and 415 NIC based on a thorough review of colonoscopy, pathology and clinical reports. Logistic regression analysis was applied to estimate the risk of polyps in patients with IBD compared to those with NIC after adjusting for age and sex. A subgroup analysis within the IBD group was performed. RESULTS: Of the 485 patients, 415 were NIC and 70 were IBD. Seventy-three percent of the NIC patients and 81% of the IBD patients were African Americans. Forty six percent of IBD and 41% of NIC cases were male. IBD patients were younger than NIC patients (median age of 38 years vs. 50, P < 0.001). The prevalence of all types of polyps was 15.7 and 8.2% in the IBD and NIC groups, respectively (P = 0.045). Among patients with polyps, the prevalence of inflammatory polyps was higher in the IBD group (55%) compared to the NIC group (12%). After adjusting for age, sex and race, odds ratio of inflammatory polyps in IBD patients was 6.0 (P = 0.016). Adenoma prevalence was 4.3% (3/70) in IBD patients and 3.9% (16/415) in the NIC patients (p = 0.75). The anatomic distribution of lesions and colitis shows that polyps occur predominantly in the colitis field regardless of colitis type. More polyps were present in the ulcerative colitis patients when compared to Crohn's disease patients (27% vs. 5%, P < 0.001) within the IBD group. CONCLUSION: Our study shows that inflammatory polyps are more common in IBD patients when compared to NIC patients. Most polyps were in the same location as the colitis.

Factors influencing treatment outcome in hepatitis C virus minority patients at an inner-city hospital: A STROBE-complaint article.

Chronic hepatitis C virus (HCV) infection disproportionately affects African-Americans (AAs) and is a major contributor to liver failure and mortality. Genetic factors may not be the only cause in outcome disparity. We retrospectively investigated whether genetic host factors, viral genotypes, and treatment compliance in AA patients impacted the efficacy and the sustained virological response (SVR) rate of the interferon (IFN)-based treatment regimen. The medical chart review included 76 African-American patients (age ranging from 26 to 76) with varying levels of hepatitis condition. Fifty-seven (75%) of them had a clinically verifiable HCV infection and were followed by a hepatologist for 2 years at Howard University Hospital in Washington, DC. Both comprehensive metabolic profile and complete blood count analyses were performed. Among the 57 patients whose viral and IL28B genotypes were determined, sixty-eight percent (68%) were infected with viral genotype 1 and 71% harbored the CT allele of the IL28B gene. Among the 12 patients who completed treatment with IFN-based dual or triple therapy, 58% had achieved SVR 12 weeks following completion of treatment; 33% had a partial response with under 6000 viral count after 16 weeks of treatment; and there was one patient with viral genotype 1a and CT allele who did not respond to the medications. The results of this study prove that the PEG IFN-based regimen was effective in treating HCV-infected AA patients despite the current availability of new direct-acting antivirals. The major obstacles contributing to a low reduction in HCV infection and outcome in the AA community were avoidance or lack of treatment or compliance; contraindications, medication side effects, non-adherence, and payer eligibility restrictions.

Identification of miRNA-mRNA associations in hepatocellular carcinoma using hierarchical integrative model.

BACKGROUND: The established role miRNA-mRNA regulation of gene expression has in oncogenesis highlights the importance of integrating miRNA with downstream mRNA targets. These findings call for investigations aimed at identifying disease-associated miRNA-mRNA pairs. Hierarchical integrative models (HIM) offer the opportunity to uncover the relationships between disease and the levels of different molecules measured in multiple omic studies. METHODS: The HIM model we formulated for analysis of mRNA-seq and miRNA-seq data can be specified with two levels: (1) a mechanistic submodel relating mRNAs to miRNAs, and (2) a clinical submodel relating disease status to mRNA and miRNA, while accounting for the mechanistic relationships in the first level. RESULTS: mRNA-seq and miRNA-seq data were acquired by analysis of tumor and normal liver tissues from 30 patients with hepatocellular carcinoma (HCC). We analyzed the data using HIM and identified 157 significant miRNA-mRNA pairs in HCC. The majority of these molecules have already been independently identified as being either diagnostic, prognostic, or therapeutic biomarker candidates for HCC. These pairs appear to be involved in processes contributing to the pathogenesis of HCC involving inflammation, regulation of cell cycle, apoptosis, and metabolism. For further evaluation of our method, we analyzed miRNA-seq and mRNA-seq data from TCGA network. While some of the miRNA-mRNA pairs we identified by analyzing both our and TCGA data are previously reported in the literature and overlap in regulation and function, new pairs have been identified that may contribute to the discovery of novel targets. CONCLUSION: The results strongly support the hypothesis that miRNAs are important regulators of mRNAs in HCC. Furthermore, these results emphasize the biological relevance of studying miRNA-mRNA pairs.