Right heart overload – possible long-term sequelae of Covid-19: a narrative review

The United Nations announced the COVID-19 Pandemic in March 2019, and since then, many efforts have been made to understand better the multiple consequences of the virus on one's health. Notably, such viral infection leads to an increase in the formation of thrombi and microthrombi. However, mechanisms are not precise yet, neither are these complication consequences and management. It is essential to acknowledge these aspects of the disease, so patients receive better health care when dealing with COVID-19. This article's extensive search involved PubMed, SCOPUS, Cochrane, and Google Scholar databases; authors used keywords to find relevant studies on the subject. SARS-CoV2 creates a pro-thrombotic state through direct endothelial damage and a cytokine storm, affecting the lung, among other organs, leading to hypoxia and a rise in vascular resistance. Increased vascular resistance makes patients prone to cardiac stress, with a known association with right heart failure, among other insults to the heart. This condition affects both outpatients and inpatients, hypertension being a significant risk factor. The cardiac damage can be observed by cardiac injury biomarkers, imaging, and heart failure symptoms. Considering the massive number of infected during the pandemic, we suggest that right heart failure secondary to increased vascular resistance in the COVID/post-COVID state presents as a long-term sequel of the infection. Moreover, we believe it deserves attention so that patients may receive early and adequate health care

COVID-19 Pathophysiology and Clinical Effects on Multiple Organ Systems - A Narrative Review

Patients with comorbidities including Hypertension (HTN), Diabetes Mellitus (DM), Chronic Obstructive Pulmonary Disease (COPD), Asthma, Obesity, Cardiovascular Disease (CVD), Chronic Kidney Disease (CKD), and those who are immunocompromised are prone to more severe complications of COVID-19 and a higher rate of hospitalizations. In the United States, around 94% of COVID-19 deaths had an average of 2.6 additional conditions or causes per death. In a summary report published by the Chinese Centre for Disease Control and Prevention of 72,314 cases, case-fatality rate was elevated among those with preexisting comorbid conditions—10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for HTN, and 5.6% for cancer. The COVID-19 pandemic continues to threaten people and healthcare systems globally and therefore the global economy. Currently, there is no cure or vaccine for COVID-19 and there is an urgent need to develop target therapies as we continue to learn more about this novel virus. Without therapeutic interventions, much of how we contain the viral spread is prevention through mitigation strategies (social distancing, face masks, supportive care). Early suspicion of COVID-19 symptoms with radiological and laboratory assessments may play a major role in preventing severity of the COVID-19. With this literature review we aim to provide review of pathophysiology of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its clinical effects on multiple organ systems

Molecular differences with therapeutic implications in early-onset compared to average-onset cholangiocarcinoma

536 Background: Early-onset cholangiocarcinoma (eoCCA) is among early-onset cancers with the fastest rising rates, yet little is known about its biology. We sought to compare the molecular characteristics of eoCCA with average-onset CCA (aoCCA) with an age cut-off of 50 years, utilizing a real-world multi-omics dataset. Methods: The study comprised patients whose tumors underwent molecular analysis at Caris Life Sciences (Phoenix, AZ) using whole exome and whole transcriptome analyses. Patients were categorized by age as eoCCA defined as 50 years. Gene expression profiles were analyzed for transcriptional signatures predictive of immunotherapy response including the T-cell inflamed score (TIS) and interferon-gamma (IFG) score. P values (adjusted for multiple testing) were considered significant at False Discovery Rate (FDR) P<0.05 for molecular comparisons and FDR P<0.25 for Gene Set Enrichment Analysis (GSEA). Insurance claims data was used for survival comparison using Kaplan-Meier estimates. Results: The study included 5587 patients - 453 patients with eoCCA and 5134 with aoCCA (Table). Of targetable mutations ( FGFR2, IDH1, IDH2, ERBB2, BRCA, BRAF), FGFR2 fusion was significantly more prevalent in eoCCA (15.7% vs 5.9% in aoCCA, FDR P<0.001). Rates trended higher in eoCCAfor MSI-H tumors (4.1% vs 2.4%), and high tumor mutational burden (6.1% vs 5.1%) but not significantly different (FDR P=1). The IFG score (Fold Change FC: 1.1, FDR P=0.01) and TIS (FC:17.3, FDR P=0.03) were significantly higher in aoCCA vs eoCCA. On GSEA, angiogenesis was enriched in eoCCA (normalized enrichment score NES=1.51, FDR P=0.16) while IFG (NES= -1.58, FDR P =0.06) and inflammatory response (NES= -1.46, FDR P=0.18) were enriched in aoCCA. Median OS was longer in eoCCA (16.5 vs 13.3 months, Hazard Ratio (HR) 0.86, 95%CI 0.78-0.95, P=0.004). Among patients treated with immunotherapy, median OS was longer in patients with eoCCA (19.2 months, n=19) vs aoCCA (7.6 months, n=150) - HR 0.52, 95%CI 0.28-0.94, p=0.03. No survival difference was identified in patients on chemotherapy (HR 0.91, 95%CI 0.76-1.08, P=0.28). Conclusions: In the largest age-stratified analysis of molecular characteristics of CCA, we identified crucial differences, including higher prevalence of FGFR2 fusions and significant differences in immunotherapy-related markers, angiogenesis enrichment, and inflammatory response. Patients with eoCCA experienced better outcomes with immunotherapy even though immune-oncology-relevant markers favored aoCCA. Our findings, especially higher FGFR2 fusion prevalence in eoCCA, underscore the need for NGS testing and the potential for age-tailored therapeutic strategies. [Table: see text

COVID-19 Pathophysiology and Clinical Effects on Multiple Organ Systems: A Review

Patients with comorbidities including Hypertension (HTN), Diabetes Mellitus (DM), Chronic Obstructive Pulmonary Disease (COPD), Asthma, Obesity, Cardiovascular Disease (CVD), Chronic Kidney Disease (CKD), and those who are immunocompromised are prone to more severe complications of COVID-19 and a higher rate of hospitalizations. In the United States, around 94% of COVID-19 deaths had an average of 2.6 additional conditions or causes per death. In a summary report published by the Chinese Centre for Disease Control and Prevention of 72,314 cases, case-fatality rate was elevated among those with preexisting comorbid conditions—10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for HTN, and 5.6% for cancer. The COVID-19 pandemic continues to threaten people and healthcare systems globally and therefore the global economy. Currently, there is no cure or vaccine for COVID-19 and there is an urgent need to develop target therapies as we continue to learn more about this novel virus. Without therapeutic interventions, much of how we contain the viral spread is prevention through mitigation strategies (social distancing, face masks, supportive care). Early suspicion of COVID-19 symptoms with radiological and laboratory assessments may play a major role in preventing severity of the COVID-19. With this literature review we aim to provide review of pathophysiology of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its clinical effects on multiple organ systems