The incidence of cirrhosis is rising, and identification of these patients prior to undergoing any surgical procedure is crucial. The preoperative risk stratification using validated scores, such as Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease, perioperative optimization of hemodynamics and metabolic derangements, and postoperative monitoring to minimize the risk of hepatic decompensation and complications are essential components of medical management. The advanced stage of cirrhosis, emergency surgery, open surgeries, old age, and coexistence of medical comorbidities are main factors influencing the clinical outcome of these patients. Perioperative management of patients with cirrhosis warrants special attention to nutritional status, fluid and electrolyte balance, control of ascites, excluding preexisting infections, correction of coagulopathy and thrombocytopenia, and avoidance of nephrotoxic and hepatotoxic medications. Transjugular intrahepatic portosystemic shunt may improve the CTP class, and semielective surgeries may be feasible. Emergency surgery, whenever possible, should be avoided.

Patient: Female, 56Final Diagnosis: Colonic MALT lymphomaSymptoms: Epigastric painMedication: —Clinical Procedure: Colonoscopy and biopsySpecialty: Gastroenterology and HepatologyObjective:Rare diseaseBackground:Non-Hodgkin lymphoma (NHL) is a well-known hematologic malignancy. The gastrointestinal (GI) tract is the most commonly involved extra nodal site. MALT lymphomas are uncommon, accounting for 5% of all NHL. Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the prototype seen in association with Helicobacter pylori. Colonic MALT lymphoma is rare and comprises only 2.5% of the MALT lymphomas. Its etiology and treatment is not well established.Case Report:A 56-year-old Hispanic woman presented to the clinic with symptoms of chronic epigastric pain for the past three years and a 13-pound weight loss over the past two months. The patient did not have any prior medical conditions. Her systemic examination was unremarkable, while her routine labs revealed mild anemia. An upper endoscopy and colonoscopy for colorectal cancer screening were performed revealing erosive gastropathy with duodenal ulcers and a 5 cm broad based polypoid mass in the hepatic flexure respectively. Computed tomography (CT) of the abdomen revealed a round, well demarcated mass at the hepatic flexure of the colon. The histopathology and immunophenotyping were consistent with extra nodal marginal zone of MALT lymphoma. Stool testing for H. pylori was positive. The patient received two weeks of H. pylori eradication therapy and four cycles of rituximab. Repeat colonoscopy after completion of chemotherapy showed complete resolution of the MALT lymphoma.Conclusions:Unlike gastric MALT lymphoma, treatment of colonic MALT lymphoma is not standardized. Chemotherapy and surgical resection have been utilized to successfully treat it. Only a handful of cases have reported successful treatment of colonic MALT lymphoma with rituximab monotherapy.

BackgroundTumor glycolysis is a target for cancer chemotherapy. Methylglyoxal (MG) is a reactive metabolite formed mainly as a by-product in anaerobic glycolysis, metabolized by glyoxalase 1 (Glo1) of the glyoxalase system. We investigated the role of MG and Glo1 in cancer chemotherapy related in multidrug resistance (MDR).MethodsHuman Glo1 was overexpressed in HEK293 cells and the effect on anticancer drug potency, drug-induced increase in MG and mechanism of cytotoxicity characterized. Drug-induced increased MG and the mechanisms driving it were investigated and the proteomic response to MG-induced cytotoxicity explored by high mass resolution proteomics of cytoplasmic and other subcellular protein extracts. Glo1 expression data of 1,040 human tumor cell lines and 7,489 tumors were examined for functional correlates and impact of cancer patient survival.ResultsOverexpression of Glo1 decreased cytotoxicity of antitumor drugs, impairing antiproliferative activity of alkylating agents, topoisomerase inhibitors, antitubulins, and antimetabolites. Antitumor drugs increased MG to cytotoxic levels which contributed to the cytotoxic, antiproliferative mechanism of action, consistent with Glo1-mediated MDR. This was linked to off-target effects of drugs on glycolysis and was potentiated in hypoxia. MG activated the intrinsic pathway of apoptosis, with decrease of mitochondrial and spliceosomal proteins. Spliceosomal proteins were targets of MG modification. Spliceosomal gene expression correlated positively with Glo1 in human tumor cell lines and tumors. In clinical chemotherapy of breast cancer, increased expression of Glo1 was associated with decreased patient survival, with hazard ratio (HR) = 1.82 (logrank p < 0.001, n = 683) where upper quartile survival of patients was decreased by 64% with high Glo1 expression.ConclusionsWe conclude that MG-mediated cytotoxicity contributes to the cancer chemotherapeutic response and targets the spliceosome. High expression of Glo1 contributes to multidrug resistance by shielding the spliceosome from MG modification and decreasing survival in the chemotherapy of breast cancer. Adjunct chemotherapy with Glo1 inhibitor may improve treatment outcomes.

BACKGROUND There is little evidence about the association of pre-existing hepatitis C infection (HCV) with outcomes in patients with coronavirus disease 2019 (COVID-19). AIM To assess the prevalence of history of HCV among patients with COVID-19 and to study the relationship of in-hospital mortality in relation with other predictors of poor outcomes in the presence or absence of COVID-19 induced acute liver injury. METHODS In a retrospective single-center study design, 1193 patients with COVID-19 infection were studied. Patients were then classified into those with and without a history of HCV, 50 (4.1%) and 1157 (95.9%) respectively. RESULTS Multivariate cox-regression models showed that age, HCV, D-Dimer, and ferritin were the only predictors of in-hospital mortality. Acute liver injury and fibrosis score (Fib-4 score) were not different between both groups. Multivariate cox-regression model for liver profile revealed that aspartate aminotransferase/ alanine aminotransferase ratio, Fib-4 score, and HCV were predictors of in-hospital mortality. After propensity score matching HCV was the only predictor of mortality in the multivariate cox-regression model. A model including HCV was found to add predictive value to clinical and laboratory parameters. CONCLUSION In patients with COVID-19, history of HCV infection leads to an accentuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virulence, irrespective of baseline comorbidities, admission laboratory variables, or COVID-19-induced liver injury, which may be related to extrahepatic effects of HCV leading to enhanced ACE-2/TMPRSS mechanisms of SARS-CoV-2 viral entry, baseline cytokine-mediated pro-inflammation, and endothelial dysfunction.

Lee first described the concept of preoperative assessment testing (PAT) clinic in 1949. An efficiently run clinic is associated with increased cost-effectiveness by lowering preoperative admission time and thus reducing the length of stay and the associated costs. The setup of the PAT clinic should be based on the needs, culture, and resources of the institution. Various models for the setup of PAT clinic have been described, including the concept of a perioperative surgical home, which is a patient-centered model designed to improve health and the delivery of health care and to reduce the cost of care. Although there are several constraints in the development of PAT clinics, with increasing awareness about the usefulness of pre-operative risk assessments, growing bodies of literature, and evidence-based guidelines, these clinics are becoming a medical necessity for the improvement of perioperative care.

Cranial nerve palsy could be one of the presenting features of underlying benign or malignant tumors of the head and neck. The tumor can involve the cranial nerves by local compression, direct infiltration or by paraneoplastic process. Cranial nerve involvement depends on the anatomical course of the cranial nerve and the site of the tumor. Patients may present with single or multiple cranial nerve palsies. Multiple cranial nerve involvement could be sequential or discrete, unilateral or bilateral, painless or painful. The presentation could be acute, subacute or recurrent. Anatomic localization is the first step in the evaluation of these patients. The lesion could be in the brain stem, meninges, base of skull, extracranial or systemic disease itself. We present 3 cases of underlying neoplasms presenting as cranial nerve palsies: a case of glomus tumor presenting as cochlear, glossopharyngeal, vagus and hypoglossal nerve palsies, clivus tumor presenting as abducens nerve palsy, and diffuse large B-cell lymphoma presenting as oculomotor, trochlear, trigeminal and abducens nerve palsies due to paraneoplastic involvement. History and physical examination, imaging, autoantibodies and biopsy if feasible are useful for the diagnosis. Management outcomes depend on the treatment of the underlying tumor.

The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 coronavirus, has produced an urgent requirement and search for improved treatments while effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. For arginine residues of the SARS-CoV-2 coronavirus predicted to be in functional domains, we examined which are activated toward modification by MG – residues with predicted or expected low pK a by neighboring group in interactions. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related coronaviridae: SARS-CoV and MERS. Finally, w e identified drugs which increase cellular MG concentration to virucidal levels: antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel. Our findings provide evidence of potential vulnerability of SARS-CoV-2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.

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