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Goals: We aimed to assess outcomes of patients with liver cirrhosis who underwent therapeutic or diagnostic endoscopic retrograde cholangiopancreatography (ERCP) to determine whether these patients had different outcomes relative to patients without cirrhosis., Background: ERCP is an important procedure for treatment of biliary and pancreatic disease. However, ERCP is relatively technically difficult to perform when compared with procedures such as esophagogastroduodenoscopy or colonoscopy. Little is known about how ERCP use affects patients with liver cirrhosis., Study: Using patient records from the National Inpatient Sample (NIS) database, we identified adult patients who underwent ERCP between 2009 and 2014 using International Classification of Disease, Ninth Revision coding and stratified data into 2 groups: patients with liver cirrhosis and those without liver cirrhosis. We compared baseline characteristics and multiple outcomes between groups and compared outcomes of diagnostic versus therapeutic ERCP in patients with cirrhosis. A multivariate regression model was used to estimate the association of cirrhosis with ERCP outcomes., Results: A total of 1,038,258 hospitalizations of patients who underwent ERCP between 2009 and 2014 were identified, of which 31,294 had cirrhosis and 994,681 did not have cirrhosis. Of the patients with cirrhosis, 21,835 (69.8%) received therapeutic ERCP and 9459 (30.2%) received diagnostic ERCP. Patients with cirrhosis had more ERCP-associated hemorrhages (2.5% vs. 1.2%; P <0.0001) compared with noncirrhosis patients but had lower incidence of perforations (0.1% vs. 0.2%; P <0.0001) and post-ERCP pancreatitis (8.6% vs. 7%; P <0.0001). Cholecystitis was the same between groups (2.3% vs. 2.3%; P <0.0001). In patients with cirrhosis, those who received therapeutic ERCP had higher post-ERCP pancreatitis (7.9% vs. 5.1%; P <0.0001) and ERCP-associated hemorrhage (2.7% vs. 2.1%; P <0.0001) but lower incidences of perforation and cholecystitis (0.1% vs. 0.3%; P <0.0001) and cholecystitis (1.9 vs. 3.1%; P <0.0001) compared with those who received diagnostic ERCP., Conclusions: Use of therapeutic ERCP in patients with liver cirrhosis may lead to higher risk of complications such as pancreatitis and postprocedure hemorrhage, whereas diagnostic ERCP may increase the risk of pancreatitis and cholecystitis in patients with cirrhosis. Comorbidities in cirrhosis patients may increase the risk of post-ERCP complications and mortality; therefore, use of ERCP in cirrhosis patients should be carefully considered, and further studies on this patient population are needed., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Adrenal cortical carcinoma is a rare and aggressive cancer with poor prognosis. Cases usually present with signs and symptoms of excessive hormone production. Hyperglycemia and Cushing syndrome are common, but tumor-associated hypoglycemia due to paraneoplastic secretion of insulin-like growth factor-2 (termed Anderson's syndrome) is uncommon. Given the rarity of adrenal cortical carcinoma, diagnosis and management of associated complications is challenging. In this study, we present a case of metastatic adrenal cortical carcinoma with a myriad of hormonal abnormalities. We will also briefly review literature regarding genetic association, pathophysiology, treatment options, and prognosis.

Peg3 (Paternally expressed gene 3) is an imprinted gene encoding a DNA-binding protein that is a well-known transcriptional repressor. Previous studies have shown that the mutant phenotypes of Peg3 are associated with the over-expression of genes involved in lipid metabolism. In the current study, we investigated four potential downstream genes of Peg3, which were identified through ChIP-seq data: Acly, Fasn, Idh1, and Hmgcr. In vivo binding of PEG3 to the promoter region of these key genes involved in lipogenesis was subsequently confirmed through individual ChIP experiments. We observed the opposite response of Acly expression levels against the variable gene dosages of Peg3, involving 0x, 1x, and 2x Peg3. This suggests the transcriptional repressor role of Peg3 in the expression levels of Acly. Another set of analyses showed a sex-biased response in the expression levels of Acly, Fasn, and Idh1 against 0x Peg3 with higher levels in female and lower levels in male mammary glands. These results overall highlight that Peg3 may be involved in regulating the expression levels of several key genes in adipogenesis., Competing Interests: The authors have declared that no competing interests exist.

Sepsis is a global health burden that needs intensive medical care. Thrombocytopenia in sepsis is well known to increase morbidity as well as mortality. Several studies have been performed both in animal models and in humans to understand the mechanism by which sepsis causes thrombocytopenia. Recent studies have shown that inhibiting thrombocytopenia improves outcomes in sepsis patients. Understanding these mechanisms to identify targets in use of newer treatment modalities besides using resuscitation measures, antibiotics and removal of thrombocytopenia inducing agent could potentially help us improve outcomes in sepsis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

COVID-19 has become a pandemic since its emergence in Wuhan, China. The disease process was initially defined by presence of respiratory symptoms; however, it is now well studied and shown in evidence that this is a multisystem process. Involvement of gastrointestinal (GI) system has been identified, and GI symptoms can be the only presenting symptoms in some patients. Hence, it is important to identify and understand the GI symptoms associated with COVID-19 for appropriate care of patient. We conducted a systematic review and metaanalysis to identify the GI symptoms of COVID-19 and identify association of diarrhea with severity of COVID-19. We performed extensive search of Medline and Embase from December 2019 to May 2020 to identify articles reporting GI symptoms in COVID-19 patients. The primary outcome was prevalence of GI symptoms in COVID-19 patients, and secondary outcome was the association of diarrhea with disease severity. A total of 38 studies with 8407 patients were included. Of the total patients, 15.47% patients had at least one GI symptom. The pooled prevalence of nausea/vomiting was 7.53% and diarrhea was 11.52%. On metaanalysis, patients with diarrhea as one of the presenting symptoms were more likely to have severe disease (OR 1.63, 95% CI: 1.11-3.38, p  = 0.01). Our systematic review and metaanalysis demonstrated that GI symptoms are common in COVID-19. Presence of diarrhea as a presenting symptom is associated with increased disease severity and likely worse prognosis. Early recognition of patients is needed for prompt management of this at-risk population., Supplementary Information: The online version contains supplementary material available at 10.1007/s42399-020-00662-w., Competing Interests: Conflict of InterestNone. A statement specifying whether or not the authors have a conflict of interest should be included. Further details on Disclosure of Potential Conflicts of Interest can be found below., (© Springer Nature Switzerland AG 2021.)

Introduction: Primary malignant mesothelioma of the liver is an extremely rare cancer, with only 16 cases reported in the literature so far. Diagnosis is challenging due to morphological similarity with common liver cancers and the extreme rarity of the condition., Case Description: We present the case of a 70-year-old man who was found to have an incidental liver mass which was diagnosed as primary malignant mesothelioma of the liver., Conclusion: Our report describes the presentation of this rare liver malignancy and the challenges associated with diagnosis and treatment., Learning Points: Primary malignant mesothelioma of the liver is an extremely rare condition.This diagnosis should be considered during the evaluation and treatment of a liver mass., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Introduction: Recurrent deliberate sharp foreign body ingestion is associated with frequent hospitalizations and a high risk of complications, including perforation and peritonitis. These patients require urgent care. In addition, removal of foreign bodies can be challenging., Case Description: We describe the case of a patient with borderline personality disorder who was admitted multiple times with sharps ingestion and presented challenges with her care., Conclusion: Our case highlights the cause of recurrent sharps ingestion and provides recommendations on the retrieval of sharp foreign bodies and prevention., Learning Points: Recurrent sharps ingestion is associated with psychiatric illness.Ingested sharps can cause perforation and peritonitis, so urgent care is required.A multidisciplinary approach is necessary to care for these patients and prevent sharps ingestion in future., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

The parental allele specificity of mammalian imprinted genes has been evolutionarily well conserved, although its functional constraints and associated mechanisms are not fully understood. In the current study, we generated a mouse mutant with switched active alleles driving the switch from paternal-to-maternal expression for Peg3 and the maternal-to-paternal expression for Zim1. The expression levels of Peg3 and Zim1, but not the spatial expression patterns, within the brain showed clear differences between wild type and mutant animals. We identified putative enhancers localized upstream of Peg3 that displayed allele-biased DNA methylation, and that also participate in allele-biased chromosomal conformations with regional promoters. Most importantly, these data suggest for the first time that long-distance enhancers may contribute to allelic expression within imprinted domains through allele-biased interactions with regional promoters., Competing Interests: The authors have declared that no competing interests exist.

In the current study, we characterized the expression and histone modification profiles of the alternative promoters found within imprinted Igf2r, Mest, Zac1, Peg3, Snrpn and non-imprinted Myc loci. In terms of expression pattern, the alternative promoters are highly tissue-specific, which is in a stark contrast to the ubiquitous expression of the corresponding main promoters. The alternative promoters are associated with the histone modification mark H3K4me1, but not with H3K4me3, which is frequently associated with the main promoters. Phylogenetic analyses also indicated that the majority of the alternative promoters are unique to the mammalian lineage, further suggesting the recent formation of these promoters during mammalian evolution. Overall, this study suggests that the alternative promoters of imprinted loci may have been derived from enhancers in recent evolutionary times and co-evolved with the genomic imprinting mechanism., Competing Interests: The authors have declared that no competing interests exist.

Circular RNA is a newly discovered class of non-coding RNA generated through the back-splicing of linear pre-mRNA. In the current study, we characterized two circular RNAs that had been identified through NGS-based 5'RACE experiments. According to the results, the Peg3 locus contains a 214-nucleotide-long circular RNA, circPeg3, that is detected in low abundance from the neonatal brain, lung and ovary. In contrast, the Igf2r locus contains a group of highly abundant circular RNAs, circIgf2r, showing multiple forms with various exon combinations. In both cases, the expression patterns of circPeg3 and circIgf2r among individual tissues are quite different from their linear mRNA counterparts. This suggests potential unique roles played by the identified circular RNAs. Overall, this study reports the identification of novel circular RNAs specific to mammalian imprinted loci, suggesting that circular RNAs are likely involved in the function and regulation of imprinted genes., Competing Interests: The authors have declared that no competing interests exist.

Lenvatinib, an oral multikinase inhibitor, was approved by the US Food and Drug Administration in February 2015. In a pivotal phase III study of 392 patients with progressive radioiodine-refractory thyroid cancer, the overall response rate of patients receiving lenvatinib was 64.8%, with complete response in four patients. The median progression-free survival was 18.3 months in the lenvatinib arm versus 3.6 months in patients receiving placebo. Median overall survival was not reached in either arm. Lenvatinib is a promising new treatment for patients with radioiodine (iodine-131)-refractory differentiated thyroid cancer.

The evidence to support implantable cardioverter defibrillator (ICD) in subjects with nonischemic cardiomyopathy (NICM) for primary prevention of sudden cardiac death (SCD) is not robust. This meta-analysis intends to assess the impact of routine ICD implantation for primary prevention of mortality due to SCD in NICM based on all the published randomized clinical trials (RCTs). Six RCTs were selected using PubMed/Medline, EMBASE, and CENTRAL from inception to December 2016. Outcomes were calculated as random-effects relative risk (RR) and risk difference (RD) with 95% confidence interval (CI). Patients were randomized to ICD arm and control arm (usual care, medical treatment, and anti-arrhythmic drugs). ICD significantly reduced all-cause mortality in NICM patients (RR, 0.74, 95% CI, 0.56-0.97, P  = .03, I 2 = 40). Mortality benefit was achieved due to a significant reduction in sudden cardiac death (SCD) (RR, 0.47, 95% CI, 0.30-0.73, P  < .001, I 2 = 0). There were no statistical differences between two groups with regard to risk of noncardiac mortality, non-SCD, cardiac arrest, cardiac transplant, sustained ventricular tachycardia (VT), and VT requiring medical treatment. Our results support efficacy of ICDs at reducing all-cause mortality due to a reduction in SCD.

Background: Previous reports have been inconsistent in generating a consensus for optimal treatment strategy for patients with percutaneous coronary intervention (PCI) who also require oral anticoagulation (OAC). We conducted a traditional and network meta-analysis to evaluate the safety and efficacy of anti-thrombotic regimens in this subset of patients., Methods: 30 articles were recovered through preferred reporting items for systematic reviews and meta-analyses (PRISMA) using MEDLINE, EMBASE and Cochrane Central Register of Controlled Clinical Trials (CENTRAL) from inception to December 2016., Results: Dual antiplatelet therapy (DAPT) was found to be the safest treatment modality when compared to triple therapy (TT) or combination of OAC and single antiplatelet agent (OAC+SAP) [Major bleeding: (DAPT vs OAC+SAP: odds ratio (OR), 0.53; 95% credible interval (CrI), 0.30-0.91) (DAPT vs TT: OR, 0.45; 95% CrI, 0.31-0.64)]. There were no significant differences in major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular (CV) or total survival, stent thrombosis or target vessel revascularization (TVR) amongst the three treatment arms. TT was ranked superior for stroke reduction (SUCRA, 69%) followed by OAC+SAP and DAPT. When traditional analysis was adjusted for randomized data, OAC+SAP was equivalent to TT with regards to stroke (OR, 0.74; 95% confidence interval (CI), 0.38-1.46; p=0.39) and showed significant reduction in MACE and total mortality., Conclusion: DAPT was found to be the safest and equally effective regimen when compared to TT and OAC+SAP. However this strategy bears considerable risk to patients with high thromboembolic risk. This issue can be encountered by using OAC+SAP as an alternative of TT in patients with intermediate to high stroke risk and intermediate to high bleeding propensity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cocaine is one of the most commonly abused drugs in the United States. Ingestion of cocaine may result in a wide array of disease processes due to its stimulant properties, contaminants, or to downstream effects, such as myo- cardial infarction, stroke, or cardiac arrest. Pulmonary complaints are common in patients seeking treatment for cocaine-associated medical problems and include acute eosinophilic pneumonia, pneumothorax, pneumomediastium, diffuse alveolar hemorrhage (DAH), pulmonary hypertension and granulomatosis. We present a case of DAH due to cocaine abuse and rapid resolution with mechanical ventilation and supportive care. [Full article available at http://rimed.org/rimedicaljournal-2016-08.asp, free with no login].

Introduction: Deliberate self-harm (DSH) is one of the common psychiatric emergencies in medical practice. It has become a global health problem with rates increasing over time. Very few studies have been conducted on this important health issue in Nepal. We conducted a hospital based study to evaluate the cause, mode and psychiatric comorbidities present in patients of DSH., Methods: This cross sectional study was performed on 200 cases of deliberate self-harm in a tertiary referral centre in Eastern Nepal from April 2012 to July 2012 by the data collected from the medical records of these patients. Various sociodemographic data and psychiatric comorbidities prevalent in them were studied., Results: Most of the patients (77%) were below the age of 35. The female-to-male ratio was 1.35:1. 76% of the patients had received formal education. Majority (73.5%) were married. By occupation, 38% were housewives and 25.5% were students. 72.5% of cases had consumed organophosphates/-chlorides. Interpersonal conflict (72%) was the major cause for DSH. Psychiatric disorders according to ICD-10 criteria were found in 37% of cases and premorbid personality problems were found in 20% of cases. The most prevalent psychiatric disorder was adjustment disorder (13.5%) followed by mood disorder (11%)., Conclusion: Majority of DSH cases were of younger generation. Psychiatric disorders and comorbid personality problems were commonly seen in DSH patients. This has significance for proper evaluation and management.