Angiotensin Receptor Blocker-Related Sprue-like Enteropathy: Review of Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Sprue-like enteropathy (SE) related to olmesartan use was first reported in 2012. In 2017, the manufacturer of Benicar paid $300 million for 2300 claims for olmesartan-related SE. OBJECTIVE: A study in 2019 suggested that SE was related to olmesartan and with the possibility of angiotensin receptor blocker (ARB) class effect. To further characterize this condition, our group examined reports of ARB-related SE to Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: All reports of ARB-related SE from January 2017 to December 2021 were downloaded from the FAERS database. Gastrointestinal adverse events including SE were reviewed. Reporter categories included physicians, pharmacists, other health care professionals, consumers, and attorneys. RESULTS: A total of 106 590 reports of ARB-related adverse effects were analyzed. Sprue-like enteropathy was identified in 4337 cases (4.1% of total reports). Of these, 4240 cases (98.0%) of ARB-related SE were reported in patients using products with olmesartan, and 97 cases of SE were reported for all other ARBs (eprosartan, losartan, telmisartan, irbesartan, valsartan, and candesartan). Reports of olmesartan-related SE increased rapidly in 2017, continued at a high rate in 2018 and 2019, and essentially stopped in 2020 and 2021. CONCLUSIONS AND RELEVANCE: Reports to FAERS for ARB-related SE are mostly related to olmesartan. There was a steep decline in reports of olmesartan-related SE following the lawsuit with potential of lawyer interference. There are reports of SE related to ARBs other than olmesartan, with increased physician awareness and the potential to discover a class effect with future studies.

A Summary of the Rare Reports of Osteonecrosis of the Jaw Associated With Tumor Necrosis-α Inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System Database.

PURPOSE: Recent case reports highlight an association between osteonecrosis of the jaw (ONJ) and antitumor necrosis factor (anti-TNF) medications. Our study reviewed and described reports of anti-TNF associated ONJ reported to the United States of America's Food and Drug Administration Adverse Event Reporting System to explore this potential adverse drug reaction further. METHODS: Using the Food and Drug Administration Adverse Event Reporting System database, we identified reported cases of ONJ between 2010 and 2021. Cases were included in our study if they reported any prior or concomitant anti-TNF medication use. Additionally, only adults (age 18+) and reports from health-care professionals were included. Cases lacking subject age or gender were excluded. After duplicates were removed, a dataset was created and demographics were described including age, gender, and indication for use. Naranjo scoring was conducted to assess adverse drug reaction probability. Subject demographics were then separately described for cases without reported denosumab or bisphosphonate therapy history and compared to those with reported history or concomitant denosumab or bisphosphonate therapy. RESULTS: Over twenty thousand cases of ONJ were reported. Forty-four potential cases (0.22%) of anti-TNF medication-associated ONJ were identified and reviewed. Of these, female gender comprised 77.3% (35 cases) and there was an average age of 61.3 years ± 13.7 years. Twenty cases (45.5%) had no prior/concomitant bisphosphonate or denosumab therapy. Of these, 55% (11 cases) were female and the average age was 54.5 ± 17.3 years. Rheumatoid arthritis was the most frequent indication for use (5 cases, 25%) followed by inflammatory bowel disease (IBD) and psoriatic arthritis (4 cases each, 20%) in this cohort. CONCLUSIONS: Twenty potential cases of anti-TNF-associated ONJ without prior or concomitant medications known to be associated with ONJ were identified and described. Interestingly, male gender was more frequent and subjects were younger in these cases compared to those with prior/concomitant bisphosphonates or denosumab therapy. Naranjo scoring indicated a probable interaction for three cases. Further studies are needed to clarify the association of ONJ and anti-TNF therapy, including investigating potential mechanisms and reporting future cases with sufficient detail to assess possible confounding factors.

Medication-induced osteonecrosis of the jaw: a review of cases from the Food and Drug Administration Adverse Event Reporting System (FAERS).

BACKGROUND: Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug reaction (ADR) commonly associated with bisphosphonate and denosumab therapy. Prior research utilized an online, public FDA Adverse Event Reporting System (FAERS) Database to explore this ADR. This data identified and described several novel medications associated with ONJ. Our study aims to build upon the prior findings, reporting trends of medication induced ONJ over time and identifying newly described medications. METHODS: We searched the FAERS database for all reported cases of medication related osteonecrosis of the jaw (MRONJ) from 2010 to 2021. Cases lacking patient age or gender were excluded. Only adults (18 +) and reports from Healthcare Professions were included. Duplicate cases were removed. The top 20 medications were identified and described for April 2010-December 2014 and April 2015-January 2021. RESULTS: Nineteen thousand six hundred sixty-eight cases of ONJ were reported to the FAERS database from 2010-2021. 8,908 cases met inclusion criteria. 3,132 cases were from 2010-2014 and 5,776 cases from 2015-2021. Within the cases from 2010-2014, 64.7% were female and 35.3% were male, and the average age was 66.1 ± 11.1 years. Between 2015-2021, 64.3% were female and 35.7% were male, and the average age was 69.2 ± 11.5 years. Review of the 2010-2014 data identified several medications and drug classes associated with ONJ not previously described. They include lenalidomide, corticosteroids (prednisolone and dexamethasone), docetaxel and paclitaxel, letrozole, methotrexate, imatinib, and teriparatide. Novel drugs and classes described between 2015-2021 include palbociclib, pomalidomide, radium 223, nivolumab, and cabozantinib. DISCUSSION: While stricter inclusion criteria and removal of duplicate cases led to fewer overall identified cases of MRONJ when compared to prior research, our data represents a more reliable analysis of MRONJ reports to the FAERS database. Denosumab was the most frequently reported medication associated with ONJ. While unable to imply incidence rates from our data due to the nature of the FAERS database, our findings provide further description of the various medications associated with ONJ and elucidate patient demographics associated with the ADR. Additionally, our study identifies cases of several newly described drugs and drug classes that have not been previously described in literature.

A Case Report of Diffuse Alveolar Hemorrhage Coexisting With Immunoglobulin A (IgA) Nephropathy.

Immunoglobulin A (IgA) nephropathy is the most common cause of primary glomerulonephritis worldwide. IgA vasculitis (formerly known as Henoch-Schonlein purpura) typically presents with IgA nephropathy on renal biopsy in addition to extrarenal symptoms like purpura, abdominal pain, and arthritis. Diffuse alveolar hemorrhage (DAH) is the most common pulmonary complication, but this is rarely seen. In this case report, we describe a 35-year-old male with chronic untreated hepatitis B infection who presented with pulmonary-renal syndrome. He was found to have clinical findings of DAH and concomitant IgA nephropathy on renal biopsy, without having any other typical manifestations of IgA vasculitis. This shows that IgA nephropathy should be considered in the differential diagnosis of DAH and emphasizes the importance of a renal biopsy in patients presenting with pulmonary-renal syndrome.

Cost Analysis of Implementing an Exercise Program for Fall and Fracture Prevention in Older Adults on Proton Pump Inhibitor Therapy.

Purpose: Falls have significant financial impact. Proton pump inhibitor (PPI) therapy is associated with an increased risk of falls and fractures. Exercise programs have been shown to decrease risk of falls in the elderly population and are recommended by the U.S. Preventive Services Task Force for patients over age 65 to reduce falls. Our study aimed to explore the potential financial benefit of implementing three different Centers for Disease Control and Prevention-recommended exercise-based interventions for fall prevention (Tai Chi, Stepping On, and Otago Exercise Program) in ≥65-year-old patients on PPI therapy. Methods: A Markov model was developed to predict the financial implications of fall-related outcomes in the study population. Net cost of the intervention was deducted from the financial savings predicted for fall avoidance relative to the fall reduction conferred by the intervention. Sensitivity analysis was performed on a range of odds ratios between falling and PPI use. Results: Exercise-based interventions were found to offer financial savings when fall reduction rates exceeded 5%, irrespective of variable odds ratios between PPI use and fall rate. Hypothetical implementation of an exercise-based intervention for PPI users ≥65 years of age was estimated to result in annual fall- and fracture-related savings ranging from $10,317.35 to $18,766.28 per individual. Findings suggested an estimated annual reduction in U.S. health care costs of $18 billion to $85 billion. Conclusions: Implementing an exercise-based fall prevention program for elderly PPI users represents a possible strategy to mitigate health care costs in the United States. Future prospective studies are recommended.

Mesenteric Panniculitis, Sclerosing Mesenteritis and Mesenteric Lipodystrophy: Descriptive Review of a Rare Condition.

Mesenteric panniculitis (MP) is the preferred nomenclature for a continuum of inflammatory diseases of the mesentery. The diagnosis of MP is often based on the appearance of a mass-like structure at the root of the mesentery. Characteristic histology includes focal fat necrosis, chronic inflammation, and sometimes mesenteric fibrosis. At present, robust literature related to diagnosis and management of MP are limited. MP is postulated to be an immune-mediated chronic inflammatory and/or a paraneoplastic disease. A personal or family history of other autoimmune diseases is commonly apparent. Several inciting events have been identified that possibly act as triggers in the development of the disease. Trauma, abdominal surgery, infection, and various cancers have been associated with mesenteric panniculitis. There are several diagnostic and histologic criteria that aid in making the diagnosis of MP. The differential diagnosis for a mesenteric mass includes neoplastic disease, and a biopsy may be indicated to rule out other conditions. While cases of MP with a short duration of symptoms, or spontaneously regression may occur, some patients experience prolonged periods of pain, fever, and alterations in bowel habit, causing significant morbidity. A variety of medical therapies have been suggested for MP. Only two, thalidomide and low-dose naltrexone, have been prospectively evaluated. For patients with chronic MP, good responses to prolonged corticosteroid treatment have been reported. Novel therapies include thalidomide and low-dose naltrexone. Hormonal and immunomodulatory therapies are also used based on small case series, but these treatments may have significant side effects. Surgical intervention is not curative and is avoided except for relief of focal bowel obstruction secondary to fibrotic forms of the disease.

Menstrual Cycle Variation in MRI-Based Quantification of Intraluminal Gas in Women With and Without Dysmenorrhea.

Women frequently report increased bloating, flatulence, and pain during the perimenstrual period. However, it is unknown whether women have more intraluminal gas during menses. To evaluate whether pain-free women or women with dysmenorrhea have different amounts of intraluminal bowel gas during the menses, we utilized magnetic resonance imaging (MRI) to determine colonic gas volumes throughout the menstrual cycle. To avoid dietary influence, the participants were instructed to avoid gas-producing foods before their scheduled MRI. We verified the measurement repeatability across the reviewers and obtained an intraclass correlation coefficient of 0.92. There were no significant differences in intraluminal gas volume between menses and non-menses scans (p = 0.679). Even among the women with dysmenorrhea, there was no significant difference in the intraluminal gas volume between menses and non-menses (p = 0.753). During menstruation, the participants with dysmenorrhea had less intraluminal gas than participants without dysmenorrhea (p = 0.044). However, the correlation between the bowel gas volume and the pain symptoms were not significant (p > 0.05). Although increased bowel symptoms and bloating are reported in the women with dysmenorrhea during menses, our results do not support the hypothesis that increased intraluminal gas is a contributing factor. Although dietary treatment has been shown in other studies to improve menstrual pain, the mechanism responsible for abdominal symptoms requires further investigation. Our findings demonstrate that the intraluminal bowel gas volume measurements are feasible and are unaffected by menses under a controlled diet. The method described might prove helpful in future mechanistic studies in clarifying the role of intraluminal bowel gas in other conditions.

A Prospective, Longitudinal Evaluation of SARS-CoV-2 COVID-19 Exposure, Use of Protective Equipment and Social Distancing in a Group of Community Physicians.

INTRODUCTION: Healthcare workers experience a significant risk of exposure to and infection from SARS-CoV-2, COVID-19. Nonetheless, little research has focused on physicians' use of personal protective equipment (PPE), their concerns about becoming infected and their social distancing maneuvers. METHODS: All staff physicians at Advocate Lutheran General Hospital were invited to participate. Their COVID-19 IgG antibody level was measured and an online questionnaire was completed. The questionnaire assessed the risk of COVID-19 exposure, PPE usage, concern for contracting COVID-19, the performance of high-risk procedures, work in high-risk settings, and social distancing practices. Testing was performed in September (T0), and December 2020 (T1) at the height of the global pandemic. RESULTS: A total of 481 (26.7%) of 1800 AGLH physicians were enrolled at T0 and 458 (95% of the original group) at T1. A total of 21 (4.3%) and 39 (8.5%) participants had antibodies at T0 and T1. A total of 63 (13.8%) worked in high-risk settings and 111 (24.2%) performed high-risk procedures. Participants working in high-risk settings had increased exposure to COVID-19 infected patients (OR = 4.464 CI = 2.522-8.459, p < 0.001). Participants were highly adherent to the use of PPE and social distancing practices including mask-wearing in public (86%, 82.1%), avoiding crowds (85.1%, 85.6%), six feet distancing (83.8%, 83.4%), and avoiding public transportation (78%, 83.8%). A total of 251 (55.4%) participants expressed moderate to extreme concern about becoming infected with COVID-19. CONCLUSIONS AND RELEVANCE: Among a group of community physicians, consistent PPE use and social distancing practices were common. These practices were associated with a low level of initial acquisition of COVID-19 infections and a relatively low longitudinal risk of infection.

A Historical Perspective of Healthcare Disparity and Infectious Disease in the Native American Population.

The incidence and severity of COVID-19 infections have been disproportionately high in Native American populations. Native Americans are a high-risk group for COVID-19 because of a variety of healthcare disparities. Historically, these populations suffered excessively during previous epidemics in the United States (US). Several epidemics occurred when disease-naïve indigenous peoples were exposed to European settlers with herd immunity. Native American populations had four times higher mortality in the 1918 Spanish flu epidemic. Deaths from H1N1 infections were higher in Native Americans and most cases and deaths from the Hantavirus pulmonary syndrome (HPS) occurred in Native Americans. Other infectious diseases, including HIV, hepatitis A and hepatitis C are more also common. Diabetes, alcoholism and cardiovascular diseases, all risk factors for severity and mortality in COVID-19 infection, are also more common in this group. Addressing the root causes of enhanced risk in Native American populations will improve outcomes from COVID-19 and future pandemics.

State of the art review: coronary artery disease in patients with inflammatory bowel disease: mechanisms, prevalence, and outcomes.

Extraintestinal disease manifestations of inflammatory bowel disease (IBD), such as arthritis and uveitis, have been well described in the medical literature. However, there has been growing evidence suggesting an association between IBD and both coronary artery disease (CAD) and acute myocardial infarctions (AMI). In this critical review, the pathogenesis of proatherogenic inflammatory markers (CD40-CD40L, IL-6, and TNF-α) are summarised along with clinical evidence that supports the association of these makers with CAD. Moreover, clinical data are examined that suggest an increased risk of AMI and CAD in IBD patients along with recent analyses of in-hospital and post-MI outcomes of AMI in IBD patients. This comprehensive review summarises and expands upon our understanding of the growing association between both CAD and AMI in IBD patients that potentially identifies IBD as a risk factor for developing CAD.

Bevacizumab and gastrointestinal perforations: a review from the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND: Bevacizumab is used in the treatment of advanced malignancies and has a "black box" warning for gastrointestinal perforations. Despite this known side effect, there are no large descriptive series of patients who experience bevacizumab-induced gastrointestinal perforations. AIM: To review and describe post-market cases of bevacizumab-induced gastrointestinal perforation reported by healthcare professionals to the United States Food and Drug Association Adverse Event Reporting System (FAERS) database. METHODS: In total, 74 025 cases of bevacizumab-induced adverse drug reaction were reported to FAERS from January 1 2004 to July 6 2021. We identified 2874 cases of bevacizumab-induced gastrointestinal perforation. A total of 1375 cases were determined to contain complete patient demographic data after the removal of duplicates and were reviewed. Subgroup analysis was completed on gastro-oesophageal perforations given the lack of prior data. RESULTS: The average patient age was 61.9 ± 11.4 years. A total of 698 cases included descriptive locations of perforations with most occurring in the large intestine (385 cases, 55.2% of specifically described cases). Colorectal cancer was the most common indication for bevacizumab (691 cases, 50.3%) followed by ovarian cancer (197 cases, 14.3%) and non-small cell lung cancer (182 cases, 13.2%). Death was reported in 554 patients (40.3% of cases). Sixty-two cases of gastro-oesophageal perforation were identified. CONCLUSIONS: This is the largest collective descriptive study of bevacizumab-induced gastrointestinal perforations, and sheds light on this often fatal complication. We additionally identified and described a rare subgroup of patients experiencing bevacizumab-induced gastro-oesophageal perforation not previously described.

Secondary Amyloidosis Presenting as Ischemic Proctitis.

A 49-year-old man presented with abdominal pain and rectal bleeding for two days associated with a 50-pound unintentional weight loss. History was notable for hypertension, chronic kidney disease, obesity, gout, and acute cholecystitis status post cholecystectomy. Computed tomography (CT) of the abdomen and pelvis showed rectal wall thickening. Colonoscopy showed proctitis with superficial ulcerations. In the setting of renal insufficiency, malabsorption, and low-voltage QRS complexes on electrocardiogram (ECG), amyloidosis was considered in the differential diagnosis. Rectal and renal biopsies with subsequent retrospective staining of gallbladder tissue confirmed amyloid deposition. Gastrointestinal involvement of amyloidosis is relatively uncommon. Particularly, amyloid deposition in the gallbladder and rectum is very rare. The development of AA amyloidosis in our patient may have been related to gout, obesity, and the presence of a heterozygous complex variant for the MEFV (familial Mediterranean fever) gene. Awareness of this atypical presentation of amyloidosis is important, as additional staining of biopsy samples is necessary, and diagnosis allows for directed treatment.

Complications and Management of Eptifibatide-Induced Thrombocytopenia.

BACKGROUND: Eptifibatide is used in acute coronary syndromes to reversibly block platelet aggregation by inhibiting the platelet glycoprotein IIb/IIIa receptor. A serious adverse effect of eptifibatide is a profound drop in platelet count, termed eptifibatide-induced thrombocytopenia (EIT). OBJECTIVE: To provide insight into the types of complications and management of EIT. METHODS: Cases of EIT submitted to the Food and Drug Administration adverse event reporting system were evaluated. Data analyses included management of EIT, complications of thrombocytopenia, initial platelets, and platelet nadir following eptifibatide. RESULTS: 103 cases of EIT were reported from January 2010 to 2019; 57 cases met the Naranjo scale and were included. Only 37 of those cases contained information on how EIT was managed. Eptifibatide administration was withheld in all 37 of those cases. Platelet transfusions were administered in 20 cases (54%). Two cases were managed with steroids (5.4%), and 1 case used intravenous immunoglobulin G to reverse EIT (2%). The median initial platelet count prior to administration of eptifibatide was 207 000 cells/mm3 (SD = 69 000; n = 27), and median platelet nadir was 9000 cells/mm3 (SD = 19 000; n = 35) The majority of complications of EIT included bleeding events (16/28, 57%). Delayed procedures, prolonged stay, allergic reactions, and thrombosis were each reported in 3 patients (10.75%). CONCLUSION AND RELEVANCE: Most cases of EIT were managed by withholding eptifibatide with platelet transfusion if necessary. The majority of complications included bleeding. However, significant procedure delays, prolonged hospital stay, thrombosis, and allergic reactions were also reported.

Rapid Review: Nonsteroidal Anti-inflammatory Agents and Aminosalicylates in COVID-19 Infections.

In the current COVID-19 pandemic, there has been concern regarding the use of ibuprofen and other nonsteroidal anti-inflammatory agents by COVID-19 infected patients. Aminosalicylates (5-ASAs) are structurally similar and have anti-inflammatory functions that resemble those of nonsteroidal anti-inflammatory agents. Since 5-ASAs are a mainstay treatment for inflammatory bowel disease, the authors review the pharmacology of both classes of drugs and discuss the potential relevance of 5-ASAs in the ongoing discussion of medication use in patients infected with COVID-19.

Prevalence of Bloodstream Infections in Children With Short-Bowel Syndrome With a Central Line Presenting to Emergency Department With Fever.

BACKGROUND: Children with short-bowel syndrome (SBS) have significant morbidity and mortality from bloodstream infections (BSIs). We studied the prevalence of BSI in children with SBS and identified possible predictors of BSI. METHODS: This retrospective cohort study included patients with SBS who presented to Holtz Children's Hospital from April 1, 2009, to June 30, 2014, with fever or reported fever. Data including vital signs, white blood cell (WBC) count, C-reactive protein (CRP) levels, and blood and urine cultures were reviewed. We calculated the prevalence of BSI and its confidence level. We also assessed the odds of BSI with increases in WBC and CRP values. RESULTS: A total of 246 encounters were evaluated. The adjusted calculated prevalence rate for BSI in children with SBS and fever was 55% (95% CI, 42.3%-65.4%). There were 114 gram-negative infections (72.6%), 46 gram-positive infections (29.3%), and 17 fungal infections (10.8%). Using the regression model, each additional 10 units above 20 mg/L CRP increased the odds of BSI by 26%. There was no association between WBC count and the presence of BSI. CONCLUSION: Children with fever and SBS are at high risk for BSI with gram-positive and gram-negative organisms as well as fungus. WBC count at presentation is a poor predictor of BSI. Though elevated CRP increased the odds of BSI, its low negative predictive value made it a poor predictor of BSI in these patients. Children with SBS and fever should be treated urgently with broad-spectrum antibiotics.

The waiting game: laparoscopic repair of dual Morgagni and paraesophageal hernias in an elderly, infirm patient.

Morgagni hernias are congenital diaphragmatic disruptions that occur when intra-abdominal organs herniate posterior to the sternum. It is very rare to concomitantly diagnose a paraesophageal hernia (PEH) in a patient with a Morgagni hernia. Here, we describe an elderly female patient presenting with severe chest pain subsequently diagnosed with a non-strangulated Morgagni hernia as well as PEH. She underwent successful robotic laparoscopic surgical repair of the hernias with resolution of her symptoms. This case demonstrates the need for early surgical intervention of Morgagni hernias to prevent sequelae, such as strangulation, and the rising benefits of laparoscopic repairs in adult patients.

The Mesentery, Systemic Inflammation, and Crohn's Disease.

Initially thought to be a structure that only provided support to the abdominal contents, the mesentery has now gained special attention in the scientific community. The new approach of studying the mesentery as an individual organ has highlighted its importance in the development of local and systemic inflammatory diseases and its potential role in Crohn's disease. Its topographical relationship with the intestine in the setting of active inflammation and "creeping fat" is possibly one of the most important arguments for including the mesentery as an important factor in the pathogenesis of Crohn's disease. In this review, we discuss the importance of the mesentery from the anatomical and embryological standpoints. We also will summarize data on mesenteric inflammation in patients with Crohn's disease. The significance of the mesentery in systemic inflammatory syndromes will be discussed, and we provide an overview of primary inflammatory disorders of the mesentery. Finally, we discuss surgical approaches for patients requiring resection for Crohn's disease that incorporate mesenteric factors, pointing out recent data suggesting that these have the potential for improving outcomes and reducing disease recurrence.10.1093/ibd/izy201_video1izy201.video15794169491001.