Background Decline in mitochondrial function occurs with aging and may increase mortality. We discuss mitochondrial contribution to Covid-19 sepsis, specifically the complex interaction of innate immune function, viral replication, hyperinflammatory state, and HIF-α/Sirtuin pathways. Methods Articles from PubMed/Medline searches were reviewed using the combination of terms "SARS-CoV-2, Covid-19, sepsis, mitochondria, aging, and immunometabolism". Results Evidence indicates that mitochondria in senescent cells may be dysfunctional and unable to keep up with hypermetabolic demands associated with Covid-19 sepsis. Mitochondrial proteins may serve as damage-associated molecular pattern (DAMP) activating innate immunity. Disruption in normal oxidative phosphorylation pathways contributes to elevated ROS which activates sepsis cascade through HIF-α/Sirtuin pathway. Viral-mitochondrial interaction may be necessary for replication and increased viral load. Hypoxia and hyper-inflammatory state contribute to increased mortality associated with Covid-19 sepsis. Conclusions Aging is associated with worse outcomes in sepsis. Modulating Sirtuin activity is emerging as therapeutic agent in sepsis. HIF-α, levels of mitochondrial DNA, and other mitochondrial DAMP molecules may also serve as useful biomarker and need to be investigated. These mechanisms should be explored specifically for Covid-19-related sepsis. Understanding newly discovered regulatory mechanisms may lead to the development of novel diagnostic and therapeutic targets.

AIMTo identify factors differentiating pathologic adult intussusception (AI) from benign causes and the need for an operative intervention. Current evidence available from the literature is discussed.METHODSThis is a case series of eleven patients over the age of 18 and a surgical consultation for “Intussusception” at a single veteran’s hospital over a five-year period (2011-2016). AI was diagnosed on computed tomography (CT) scan and or flexible endoscopy (colonoscopy). Surgical referrals were from the emergency room, endoscopy suites and the radiologists.RESULTSA total of 11 cases, 9 males and 2 females were diagnosed with AI. Median age was 58 years. Abdominal pain and change in bowel habits were most common symptoms. CT scan and or colonoscopy diagnosed AI, in ten/eleven (90%) patients. There were 6 small bowel-small bowel, 4 ileocecal, and 1 sigmoid-rectal AI. 8 patients (72%) needed an operation. Bowel resection was required and definitive pathology was diagnosed in 7 patients (63%). Five patients had malignant and 2 patients had benign etiology. Small bowel enteroscopy excluded pathology in 4 cases (37%) with AI. Younger patients tend to have a benign diagnosis.CONCLUSIONMajority of AI have malignant etiology however idiopathic intussusception is being seen more frequently. Operative intervention remains the mainstay however, certain small bowel intussusception especially in younger patients may be a benign, physiological, transient phenomenon and laparoscopy with reduction or watchful waiting may be an acceptable strategy. These patients should undergo endoscopic or capsule endoscopy to exclude intrinsic luminal lesions.

IntroductionGermline mutation in CDH1 (E-cadherin) tumor suppressor gene is associated with hereditary diffuse gastric cancer (HDGC) and lobular breast cancers (LBC). E-Cadherin protein is necessary for physiological signaling pathways, such as cell proliferation, maintenance of cell adhesion, cell polarity and epithelial-mesenchymal transition. Dysregulation leads to tumor proliferation, invasion, migration and metastases. We review current perspectives in CDH1 genetics with molecular mechanisms and also discuss management strategies for this aggressive form of gastric cancer.MethodsRelevant articles from PubMed/Medline and Embase (1994–2019) were searched and collected using the phrases “Hereditary diffuse gastric cancer, Familial gastric cancer, CDH1 mutation, E-Cadherin, Lobular breast cancer, Prophylactic total gastrectomy”.ResultsCurrent guidelines suggest maintaining a high degree of suspicion of hereditary etiology and recommend testing for CDH1 mutations in patients with familial clustering of HDGC and LBC, especially onset at an early age (before 40 years). In families lacking CDH1 mutations but with high suspicion for hereditary predisposition, testing of CTNNA1 and other closely related HDGC susceptibility genes could be considered. Prophylactic total gastrectomy is recommended for individuals with identified pathogenic germline variants. Endoscopic surveillance with biopsies is recommended for those choosing to delay prophylactic gastrectomy.ConclusionMutation or transcriptional silencing of the CDH1 gene is associated with familial diffuse gastric cancer. Further studies on the expression and the alteration in the proteins in the E-cadherin pathways may serve as biomarkers for early detection; stratify risk and selection of appropriate therapy in these families. Until then prophylactic total gastrectomy is recommended for individuals with CDH1 mutations and family history of diffuse gastric cancer. Endoscopic surveillance and biopsies by experienced gastroenterologists is recommended for those choosing not to have prophylactic gastrectomy and in individuals with CDH1 variants.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is diagnosed via real time reverse transcriptase polymerase chain reaction (RT-PCR) and reported as a binary assessment of the test being positive or negative. High SARS-CoV-2 viral load is an independent predictor of disease severity and mortality. Quantitative RT-PCR may be useful in predicting the clinical course and prognosis of patients diagnosed with coronavirus disease 2019 (COVID-19). AIM To identify whether quantitative SARS-CoV-2 viral load assay correlates with clinical outcome in COVID-19 infections. METHODS A systematic literature search was undertaken for a period between December 30, 2019 to December 31, 2020 in PubMed/MEDLINE using combination of terms “COVID-19, SARS-CoV-2, Ct values, Log 10 copies, quantitative viral load, viral dynamics, kinetics, association with severity, sepsis, mortality and infectiousness’’. After screening 990 manuscripts, a total of 60 manuscripts which met the inclusion criteria were identified . Data on age, number of patients, sample sites, RT-PCR targets, disease severity, intensive care unit admission, mortality and conclusions of the studies was extracted, organized and is analyzed. RESULTS At present there is no Food and Drug Administration Emergency Use Authorization for quantitative viral load assay in the current pandemic. The intent of this research is to identify whether quantitative SARS-CoV-2 viral load assay correlates with severity of infection and mortality? High SARS-CoV-2 viral load was found to be an independent predictor of disease severity and mortality in majority of studies, and may be useful in COVID-19 infection in susceptible individuals such as elderly, patients with co-existing medical illness such as diabetes, heart diseases and immunosuppressed. High viral load is also associated with elevated levels of TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10 and C reactive protein contributing to a hyper-inflammatory state and severe infection. However there is a wide heterogeneity in fluid samples and different phases of the disease and these data should be interpreted with caution and considered only as trends. CONCLUSION Our observations support the hypothesis of reporting quantitative RT-PCR in SARS-CoV-2 infection. It may serve as a guiding principle for therapy and infection control policies for current and future pandemics.