Clinical approach to indeterminate biliary strictures: Clinical presentation, diagnosis, and workup.

Despite advances in cross-sectional imaging and endoscopic technology, bile duct strictures remain a challenging clinical entity. It is crucial to make an early determination of benign or malignant nature of biliary strictures. Early diagnosis not only helps with further management but also minimizes mortality and morbidity associated with delayed diagnosis. Conventional imaging and endoscopic techniques, particularly endoscopic retrograde cholangiopancreatography (ERCP) and tissue sampling techniques play a key in establishing a diagnosis. Indeterminate biliary strictures (IDBSs) have no definite mass on imaging or absolute histopathological diagnosis and often warrant utilization of multiple diagnostics to ascertain an etiology. In this review, we discuss possible etiologies, clinical presentation, diagnosis, and management of IDBSs. Based on available data and expert opinion, we depict an evidence based diagnostic algorithm for management of IDBSs. Areas of focus include use of traditional tissue sampling techniques such as ERCP with brush cytology, intraductal biopsies, fluorescence in situ hybridization and flow cytometry. We also describe the role of endoscopic ultrasound (EUS)-guided fine needle aspiration and biopsies, cholangioscopy, confocal laser endomicroscopy, and intraductal EUS in management of IDBSs.

COVID-19 related biliary injury: A review of recent literature.

Since its emergence in 2019, it has become apparent that coronavirus 2019 (COVID-19) infection can result in multi systemic involvement. In addition to pulmonary symptoms, hepatobiliary involvement has been widely reported. Extent of hepatic involvement ranges from minor elevation in liver function tests (LFTs) to significant hepatocellular or cholestatic injury. In majority of cases, resolution of hepatic injury or improvement in LFTs is noted as patients recover from COVID-19 infection. However, severe biliary tract injury progressing to liver failure has been reported in patients requiring prolonged intensive care unit stay or mechanical ventilation. Due to the timing of its presentation, this form of progressive cholestatic injury has been referred to as COVID-19 cholangiopathy or post-COVID-19 cholangiopathy, and can result in devastating consequences for patients. COVID-19 cholangiopathy is recognized by dramatic elevation in serum alkaline phosphatase and bilirubin and radiologic evidence of bile duct injury. Cholangiopathy in COVID-19 occurs weeks to months after the initial infection and during the recovery phase. Imaging findings and pathology often resemble bile duct injury associated with primary or secondary sclerosing cholangitis. Etiology of COVID-19 cholangiopathy is unclear. Several mechanisms have been proposed, including direct cholangiocyte injury, vascular compromise, and cytokine release syndromes. This review summarizes existing data on COVID-19 cholangiopathy, including reported cases in the literature, proposed pathophysiology, diagnostic testing, and long-term implications.

Fatty Liver Disease and Food Insecurity: Excess in Scarcity.

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is widely prevalent in the U.S and is the primary cause of chronic liver disease. Existing evidence shows that food insecurity may be an independent risk factor for fatty liver disease and is associated with poor health outcomes. Understanding the role of food insecurity in these patients can help develop mitigation strategies to address the growing prevalence of NAFLD. RECENT FINDINGS: Food insecurity is associated with increased overall mortality and health care utilization among patients with NAFLD and advanced fibrosis. Individuals from low-income households with diabetes and obesity are particularly susceptible. Trends in prevalence of NAFLD mirror that of obesity and other cardiometabolic risk factors. Several studies in both adult and adolescent population have described an independent association between food insecurity and NAFLD. Concentrated efforts to lessen food insecurity may improve health outcomes in this group of patients. High-risk patients with NAFLD should be linked with local and federal supplemental food assistance programs. Programs directed at addressing NAFLD-related mortality and morbidity should focus on improving food quality, access to these foods, and promote healthy eating habits.

Prevailing patterns of liver enzymes in patients with COVID-19 infection and association with clinical outcomes.

BACKGROUND: COVID-19 is now a critical threat to global public health. Although the majority of patients present with respiratory illness, several studies have described multiorgan involvement. This study evaluated the prevailing patterns of liver enzymes in COVID-19 patients on admission and their association with clinical outcomes. METHODS: This was a single-center retrospective analysis of all inpatients with COVID-19. Demographic and clinical factors, and liver enzyme tests, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were noted on admission. The association of liver enzyme elevation with outcomes such as inpatient death, need for intubation, and vasopressor use was determined using the chi-square test and multivariate regression analysis. RESULTS: Among 200 patients, AST and ALT elevation was seen in 55% and 20%, respectively. Alkaline phosphatase elevation was seen in 28%. AST elevation was associated with inpatient death (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05; P=0.035), need for vasopressors (OR 1.034, 95%CI 1.015-1.055; P=0.001), and intubation (OR 1.03, 95%CI 1.01-1.05; P=0.002). An AST/ALT ratio of 2 or more was seen in 34% of patients and was associated with need for intubation (OR 2.678, 95%CI 1.202-5.963; P=0.016), and need for vasopressors (OR 3.352, 95%CI 1.495-7.514; P=0.003). CONCLUSION: Serum aminotransferase levels are useful markers of hepatocellular injury. Patients with elevated AST or AST/ALT ratio are at higher risk of severe disease, as evidenced by intubation, vasopressor use, and inpatient death. These patients should be monitored closely given their propensity for severe disease.

Examining the Rate of Clostridioides (Formerly Clostridium) Difficile Infection Pre- and Post-COVID-19 Pandemic: An Institutional Review.

Background/ Rationale Clostridioides difficile infection (CDI) is transmitted via the fecal-oral route and is implicated in antibiotic-associated colitis. Similar to CDI, patients with coronavirus disease 2019 (COVID-19) require early identification and isolation, appropriate personal protective equipment, and environmental disinfection to prevent further transmission. In light of this similarity between isolation and protective requirements to prevent transmission of these diseases, we aim to investigate whether there was a decrease in the incidence of CDI during the peak periods of the COVID-19 pandemic compared to historical rates. Methods This is a single-center retrospective analysis of the rates of CDI in our institution. COVID-19 time periods were identified from March 2020 to January 2021 and peak periods (with >50 active patients per day) were defined. The non-COVID-19 periods were July 2017 to February 2020. Rates of CDI were also directly compared across the yearly time period. CDI rates were presented in a per 1000 patient days format. Rates were analyzed per year and during the COVID-19 peaks at our institution. Mann-Whitney U test was used to compare rates between two time periods, while differences across multiple time intervals were analyzed using the Kruskal-Wallis test. Results The median (interquartile range [IQR]) of CDI rates of infection per 1000 patient days for the non-COVID time period from July 2017 to February 2020 was 0.34 (0.23-0.45) while COVID time periods had higher 0.44 (0.25-0.51) rates of CDI although this was not statistically significant (p=0.224). However, there was a statistically significant difference (p=0.036) with COVID peak periods having higher rates of CDI 0.49(0.39-0.74) vs 0.34(0.23-0.44). Overall, there was no statistically significant difference in the rates of CDI across years or time periods (p=0.396). Discussion/Conclusion There was no difference in the rates of hospital-acquired CDI between COVID-19 and non-COVID-19 time periods at our institution.

Risk of Hepatobiliary-Gastrointestinal Malignancies and Appropriate Cancer Surveillance in Patients With Primary Sclerosing Cholangitis.

Patients with primary sclerosing cholangitis (PSC) are at risk of hepatobiliary and gastrointestinal cancers. Increased risk of cancer is a result of the chronic, progressive fibro-inflammatory state which ultimately results in the destruction of biliary ducts. PSC is often associated with inflammatory bowel disease (IBD). Patients with PSC are at significant risk of cholangiocarcinoma (CCA), gall bladder malignancy and those with IBD are at increased risk of colorectal cancer. It is important to implement cancer surveillance protocols in these patients. The aim of these protocols is the prevention or early detection of cancerous or pre-cancerous lesions. Given that PSC is rare, large prospective studies evaluating the risk of malignancy in these patients are not available. A great deal of uncertainty exists regarding how to best implement cancer surveillance in these patients. About 50% of deaths in PSC patients are due to malignancy and many patients eventually progress to end-stage liver disease and succumb to hepatic failure. In this review, we cover cancer surveillance strategies in PSC patients based on existing literature and expert opinions.

IgG4-related disease: a complex under-diagnosed clinical entity.

IgG4-related disease (IgG4-RD) encompasses a spectrum of complex fibro-inflammatory disorders which are often under diagnosed due to unfamiliarity by clinicians. A challenging multitude of clinical manifestations makes the diagnosis cumbersome. The primary clinical feature in IgG4-RD entails a tumor-like presentation coupled with tissue-destructive lesions. Histopathological findings include lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. These findings, in combination with elevated serum immunoglobulin G4 levels, are diagnostic in the setting of single- or multi-organ involvement. A closer understanding of the role of T cells and B cells in the increased production of IgG4 has led to a notion that IgG4 can act as a pathogen, anti-inflammatory agent, or rheumatoid factor. Glucocorticoids are the primary treatment modality; however, relapse is common with prolonged therapy. Alternatively, immunomodulatory agents are being increasingly used as therapy. The aim of this article is to raise awareness of IgG4-RD and review the diagnostic algorithm, as IgG4-RD often mimics a wide array of clinical conditions. In addition, we summarize the pathogenesis and current treatment guidelines of IgG4-RD for clinicians. Awareness and accurate diagnosis are crucial in preventing progression to chronic diseases, thereby diminishing disease-related morbidity and mortality.

Clinical Characteristics, Management, and Outcomes of Suspected Poststroke Acute Coronary Syndrome.

BACKGROUND: Acute coronary syndrome (ACS) can complicate acute ischemic stroke, causing significant morbidity and mortality. To date, literatures that describe poststroke acute coronary syndrome and its morbidity and mortality burden are lacking. METHODS: This is a single center, retrospective study where clinical characteristics, cardiac evaluation, and management of patients with suspected poststroke ACS were compared and analyzed for their association with inpatient mortality and 1-year all-cause mortality. RESULTS: Of the 82 patients, 32% had chest pain and 88% had ischemic ECG changes; mean peak troponin level was 18, and mean ejection fraction was 40%. The medical management group had older individuals (73 versus 67 years, p < 0.05), lower mean peak troponin levels (12 versus 49, p < 0.05), and lower mean length of stay (12 versus 25 days, p < 0.05) compared to those who underwent stent or CABG. Troponin levels were significantly associated with 1-year all-cause mortality. CONCLUSION: Age and troponin level appear to play a role in the current clinical decision making for patient with suspected poststroke ACS. Troponin level appears to significantly correlate with 1-year all-cause mortality. In the management of poststroke acute coronary syndrome, optimal medical therapy had similar inpatient and all-cause mortality compared to PCI and/or CABG.

A Review of Neurogenic Stunned Myocardium.

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective of this review of literature is to enhance physician's awareness of NSM and its features to help tailor management according to the patient's clinical profile.

Impact of end stage kidney disease on costs and outcomes of Clostridium difficile infection.

OBJECTIVES: To assess the impact of end stage kidney disease (ESKD) on the outcomes of Clostridium difficile infection (CDI), including complications of infection, length of hospital stay, overall mortality, and healthcare burden. METHODS: The National Inpatient Sample (NIS) database created by the Agency of Healthcare Research and Quality (AHRQ) was used, covering the years 2009 through 2013. Manufacturer-provided sampling weights were used to produce national estimates. RESULTS: All-cause unadjusted in-hospital mortality was significantly higher for patients with CDI and ESKD than for patients without ESKD (11.6% vs. 7.7%, p<0.001). The in-hospital mortality remained higher even after adjusting for age, sex, race, and Charlson index group using multivariate logistic regression (odds ratio 1.47, confidence interval 1.41-1.53). The median length of stay was found to be longer by 2days in the ESKD group (9 vs. 7 days, p<0.001). The average cost of hospitalization for patients with CDI and ESKD was also significantly higher compared to the non-ESKD group (USD $35 588 vs. $23 505, in terms of the 2013 value of the USD, p<0.001). CONCLUSIONS: The presence of end stage kidney disease in hospitalized patients with Clostridium difficile infection is associated with higher mortality, a longer length of stay, and a higher cost of hospitalization.

Health-Care Utilization and Complications of Endoscopic Esophageal Dilation in a National Population.

BACKGROUND/AIMS: Esophageal stricture is usually managed with outpatient endoscopic dilation. However, patients with food impaction or failure to thrive undergo inpatient dilation. Esophageal perforation is the most feared complication, and its risk in inpatient setting is unknown. METHODS: We used National Inpatient Sample (NIS) database for 2007-2013. International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes were used to identify patients with esophageal strictures. Logistic regression was used to assess association between hospital/patient characteristics and utilization of esophageal dilation. RESULTS: There were 591,187 hospitalizations involving esophageal stricture; 4.2% were malignant. Endoscopic dilation was performed in 28.7% cases. Dilation was more frequently utilized (odds ratio [OR], 1.36; p<0.001), had higher in-hospital mortality (3.1% vs. 1.4%, p<0.001), and resulted in longer hospital stays (5 days vs. 4 days, p=0.01), among cases of malignant strictures. Esophageal perforation was more common in the malignant group (0.9% vs. 0.5%, p=0.007). Patients with malignant compared to benign strictures undergoing dilation were more likely to require percutaneous endoscopic gastrostomy or jejunostomy (PEG/J) tube (14.1% vs. 4.5%, p<0.001). Palliative care services were utilized more frequently in malignant stricture cases not treated with dilation compared to those that were dilated. CONCLUSIONS: Inpatient endoscopic dilation was utilized in 29% cases of esophageal stricture. Esophageal perforation, although infrequent, is more common in malignant strictures.

Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk?

Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren's syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors.

Inadequate response or intolerability to oral methotrexate: Is it optimal to switch to subcutaneous methotrexate prior to considering therapy with biologics?

Methotrexate (MTX) is considered an anchor drug in the treatment of rheumatoid arthritis. It is also the first-line therapy in a multitude of rheumatologic conditions. Low-dose oral MTX is the preliminary modality of treatment for rheumatoid arthritis due to its affordability, favorable outcomes, and limited risks. However, patients refractory to low-dose MTX therapy may require larger doses of oral MTX. Several studies in the past have demonstrated variability in bioavailability of oral MTX at high doses. This warrants a subsequent switch to parenteral MTX. Widely used among the parenteral preparations of MTX is subcutaneous (SC) MTX. SC MTX provides dependable efficacy, predictable bioavailability, sustained clinical outcomes, and minimal GI adverse effects. It is useful either singularly or in combination therapy regimens. Although SC MTX and intramuscular MTX have similar pharmacokinetics, SC MTX may be preferred by most patients. Development of prefilled syringes and auto-injectors have enabled self-administration of the medication providing the patients with a sense of independence and improved general well-being. Hence, SC MTX can prove to be more efficacious in patients refractory to oral MTX therapy or in patients experiencing severe gastrointestinal adverse effects.

Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes.

Cryopyrin-associated periodic syndromes (CAPS) is a rare group of autoinflammatory disorders that includes familial cold autoinflammatory syndrome or FCAS, Muckle-wells syndrome or MWS, and neonatal-onset multisystem inflammatory disease or NOMID. CAPS is caused by a mutation in the NOD-like receptor family, pyrin domain containing 3 (NLRP3) gene. This ultimately leads to increased production of interleukin (IL)-1ß. IL-1ß is a biologically active member of the IL-1 family. It is not only a pro-inflammatory cytokine responsible for features such as fever, rash, and arthritis, but is also a major mediator in the central pathways of fatigue. Fatigue is a major component of CAPS and is associated with severely compromised quality of life. In clinical studies, fatigue was measured using functional assessment of chronic illness therapy-fatigue or FACIT-F and short form-36 or SF-36, physical component score instruments. These questionnaires can also be used to monitor improvement of fatigue following initiation of therapy. IL-1 inhibitors block the IL-1 signaling cascade, thereby preventing systemic inflammation in CAPS. The decrease in systemic inflammation is accompanied by improvement in fatigue.