Utility of a Third Heplisav-B Dose in Patients With Inflammatory Bowel Disease Without Immunity After 2-Dose Heplisav-B Vaccination.

INTRODUCTION: Hepatitis B virus (HBV) vaccination is recommended in patients with inflammatory bowel disease (IBD). Although the 2-dose Heplisav-B vaccine has proven effective, more than 20% of patients with IBD do not seroconvert. We prospectively evaluated the effectiveness of a third Heplisav-B dose in patients with IBD lacking HBV immunity despite 2-dose vaccination. METHODS: Adults with IBD who had received 2-dose Heplisav-B vaccination between 2018 and 2023 were identified. Seroconversion was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L measured at ≥4 weeks after vaccination. Patients who did not seroconvert were prospectively offered a third Heplisav-B dose, followed by repeat HBsAb measurement. Demographic, clinical, medication, and vaccination data were compared between those who did and did not seroconvert. RESULTS: Of 192 patients identified, 71.9% (138/192) seroconverted after 2-dose Heplisav-B vaccination. The 54 patients (28.1%) who did not seroconvert were more likely to be male, have diabetes, chronic kidney disease, or elevated Charlson Comorbidity Index. Of the 54 patients, 30 (55.6%) elected to receive a third Heplisav-B dose, with 56.7% (17/30) achieving seroconversion (median HBsAb titer 376 IU/L, IQR 47-1,000 IU/L) despite a median intervaccination time of 416 days (IQR 90.8-667.8). No differences were noted between patients who did vs did not seroconvert after third-dose vaccination. DISCUSSION: In patients with IBD lacking HBV immunity despite 2-dose Heplisav-B vaccination, administration of a third dose resulted in a 56.7% seroconversion rate. Our results suggest that administration of an additional Heplisav-B dose may be an effective strategy in patients lacking immunity despite primary 2-dose vaccination.

In Patients With Inflammatory Bowel Disease, Racial Disparities Exist in Burden of Vaccine-preventable Disease Hospitalizations and Outcomes.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) are at increased risk of vaccine-preventable diseases (VPDs). Despite the increasing prevalence of IBD in non-white populations, little is known regarding racial disparities in VPD burden. METHODS: Retrospectively analyzing the 2016 to 2020 National Inpatient Sample, we identified adults with IBD hospitalized for a principal diagnosis of VPD. The primary outcome investigated was hospitalization for VPD stratified by patient-reported race. Secondary outcomes were in-hospital morbidity, mortality, length of stay, and health care utilization. Multivariable regression analysis was performed to adjust for patient and hospital characteristics. RESULTS: The search identified 554,114 hospitalizations for VPD, including 4170 hospitalizations in patients with IBD. Patients with IBD had significantly greater odds of hospitalization from herpes zoster virus (adjusted odds ratio [aOR]: 1.73) and varicella zoster virus (aOR: 2.31). Comparing white and non-white patients with IBD, significant racial disparities were noted. Non-white patients were at greater odds of hospitalization from influenza (aOR: 1.74), herpes zoster virus (aOR: 1.77), and varicella zoster virus (aOR: 1.62). In-hospital morbidity was greater in non-white patients, including greater odds of requiring intensive care unit stay (aOR: 1.18). Morbidity was elevated in African Americans, with greater odds of acute kidney injury (aOR: 1.25), venous thromboembolism (aOR: 1.17), respiratory failure (aOR: 1.16), and intensive care unit stay (aOR: 1.18). No differences were found in mortality, length of stay, and health care utilization. CONCLUSIONS: Significant racial disparities in VPD hospitalization and in-hospital morbidity were found among adults with IBD in the United States. With the increasing prevalence of IBD in non-white populations, targeted efforts are needed to improve health equity.

Improved Outcomes Associated With Teduglutide Use in Patients With Both Short Bowel Syndrome and Crohn's Disease.

Introduction: Crohn's disease (CD) with short bowel syndrome (SBS) can present as chronic intestinal failure (CIF) often requiring nutritional support. Teduglutide is a treatment option for these patients. We investigated clinical outcomes of CD-CIF patients with SBS treated with teduglutide. Methods: Adults with CD-CIF and SBS who received teduglutide were identified at a tertiary care academic center between 2012 and 2023. Data was collected retrospectively. Primary outcome measured was reduction in parenteral support (PS) by ≥20% volume, with PS defined as utilization of parenteral nutrition (PN) or intravenous fluids (IVF). Several secondary outcomes included immunosuppressive medication changes, subjective symptom improvement, and stool output. Results: We identified 32 patients with CD-CIF and SBS receiving teduglutide. Comparing clinical outcomes before and after teduglutide, 26 of 32 patients achieved the primary outcome of ≥20% PS reduction. A decrease was seen in patients requiring PN + IVF, with corresponding increases in patients requiring PN only and IVF only. Among all 3 groups, a total of 23 patients received PN prior to teduglutide, which decreased to 14 following teduglutide. Weekly PN volume reduced from 7.00 to 3.55 L and weekly frequency decreased from 7.00 to 3.00 instances (P < .01). Reductions in weekly volume and frequency were observed among all patients receiving IVF support (25 vs 15). Secondary outcomes showed improvement in patient reported subjective symptoms (84.4%), stool output (90.6%), patients meeting criteria for diarrhea/high ostomy output (27 vs 14), and use of unique antidiarrheal medications (3.0 vs 2.0). Conclusions: This retrospective case series demonstrated improved clinical outcomes in patients with CD-CIF and SBS treated with teduglutide resulting in decreased PS requirements, antidiarrheal medications requirement, and stool output without significant effects on immunosuppressive therapy.

Nintedanib-Induced Colitis Can Mimic Inflammatory Bowel Disease.

Nintedanib is a medication that has been increasingly used for treatment of idiopathic and progressive pulmonary fibrosis. In this case series, we describe 3 patients with colitis symptoms associated with nintedanib use. Nintedanib discontinuation resulted in symptomatic resolution in all patients. Budesonide decreased symptoms in 1 patient. Clinicians should be vigilant in taking a thorough medication history and include nintedanib as a cause for gastrointestinal symptoms including colitis.

Cholestatic Drug-Induced Liver Injury in a Patient Taking High-Dose Niacin for Hyperlipidemia.

Niacin, an important component of a balanced diet, is central to lipid metabolism. Occasionally used to treat hyperlipidemia, niacin is widely available without a prescription, making its use often unknown to treating physicians. Severe hepatotoxicity has been reported with niacin use. In the following report, we describe a case of hospitalization for acute decompensated cirrhosis with cholestatic morphology in a patient taking self-initiated large quantities of extended-release niacin. Despite medical management and support, the patient unfortunately expired on day 16 of hospitalization. Given ease of access and unclear long-term benefit in hyperlipidemia, the current case serves to raise awareness of niacin's potential hepatotoxicity through highlighting a severe outcome. Although mode of liver injury remains unknown, the use of extended-release niacin formulations and prolonged high-dose supplementation is associated with enhanced hepatotoxicity. Careful review and counseling of commonly available supplements remains an important task of both hospital and primary care physicians.

The Effect of Renin-Angiotensin-Aldosterone System Blocking Agents on the Long-term Disease Course of Patients With Crohn's Disease.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. STUDY: Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. RESULTS: Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. CONCLUSIONS: Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

Use of Immune Checkpoint Inhibitors in Patients With Inflammatory Bowel Disease After Ileal Pouch-Anal Anastomosis.

It is unknown if immune checkpoint inhibitor therapy increases risk of pouch-related complications in patients with inflammatory bowel disease after ileal-pouch anal anastomosis. In our study, pembrolizumab therapy was not associated with significant gastrointestinal immune-related adverse events or pouch-related complications.

Validation of prediction tools for GI bleeding in patients on dual anti-platelet therapy after percutaneous coronary intervention.

BACKGROUND AND AIMS: The management of dual anti-platelet therapy after percutaneous coronary intervention (PCI) and GI bleeding (GIB) remains a clinical dilemma. We sought to identify predictors of GIB and recurrent bleeding and to determine whether recurrent bleeding increases the risk of major adverse cardiovascular events (MACEs). METHODS: In this single-center retrospective study, patients undergoing PCI were identified. The primary and secondary endpoints were GIB at 180 days and recurrent bleeding or MACE at 365 days. Logistic regression was used to identify predictors of GIB and recurrent bleeding. Cox proportional hazards modeling was used to determine whether recurrent bleeding can predict a MACE. RESULTS: Five hundred thirty-six patients were included. On multivariable analysis, PCI for acute coronary syndrome was associated with a 95% increased odds of GIB (P < .001). The P2Y12 inhibitor was continued in >90% of patients, which trended toward significance for recurrent bleeding (P < .10). The HAS-BLED score (Hypertension, Abnormal renal and liver function, Stroke, Bleeding tendency or predisposition, Labile INRs, Elderly, Drugs), including a labile international normalized ratio and prior major bleeding, was strongly associated with recurrent bleeding (P ≤ .009). Recurrent bleeding was associated with a 115% increased risk of MACEs (P = .02). We derived a novel risk score, named the SIGE score ([S]TEMI at PCI, having a labile [I]NR at PCI, index [G]IB within 180 days of PCI, and previous precatheterization [E]ndoscopy within 6 months), to predict recurrent bleeding at 365 days with a high predictive accuracy (area under the curve, .773; 95% confidence interval, .702-.845). CONCLUSIONS: The SIGE score may help to predict recurrent bleeding, which was shown to be associated with an increased risk of MACEs. Further external validation is needed.

Improving management of hyponatraemia by increasing urine testing in the emergency department.

Hyponatraemia on hospital admission is associated with increased length of stay, healthcare expenditures and mortality. Urine studies collected before fluid or diuretic administration are essential to diagnose the underlying cause of hyponatraemia, thereby empowering admitting teams to employ the appropriate treatment. A multidisciplinary quality improvement (QI) team led by internal medicine residents performed a QI project from July 2020 through June 2021 to increase the rate of urine studies collected before fluid or diuretic administration in the emergency department (ED) in patients admitted with moderate to severe hyponatraemia. We implemented two plan-do-study-act (PDSA) cycles to address this goal. In PDSA Cycle #1, we displayed an educational poster in employee areas of the ED and met with nursing staff at their monthly meetings to communicate the project and answer questions. We also obtained agreement from ED attending physicians and nursing leaders to support the project. In PDSA Cycle #2, we implemented a structural change in the nursing triage process to issue every patient who qualified for bloodwork with a urine specimen container labelled with a medical record number on registration so that the patient could provide a sample at any point, including while in the waiting area. After PDSA Cycle #1, urine specimen collection increased from 34.5% to 57.5%. After PDSA Cycle #2, this increased further to 59%. We conclude that a combination of educational and structural changes led to a significant increase in urine specimen collection before fluid or diuretic administration among patients presenting with moderate-to-severe hyponatraemia in the ED.

Targeting leukemia inhibitory factor in pancreatic adenocarcinoma.

INTRODUCTION: The Leukemia Inhibitory Factor (LIF) is a member of the interleukin-6 (IL-6) cytokine family. Known to induce differentiation of myeloid leukemia cells, evidence has accumulated supporting its role in cancer evolution through regulating cell differentiation, renewal, and survival. LIF has recently emerged as a biomarker and therapeutic target for pancreatic ductal adenocarcinoma (PDAC). The first in-human clinical trial has shown promising safety profile and has suggested a potential role for LIF inhibitor in combination regimen. AREAS COVERED: Herein, we summarize, discuss, and give an expert opinion on the role of LIF in PDAC promotion, and its potential role as a biomarker and target of anti-cancer therapy. We conducted an exhaustive PubMed search for English-language articles published from 1 January 1970, to 1 August 2022. EXPERT OPINION: PDAC carries a devastating prognosis for patients, highlighting the need for advancing drug development. The results of the phase 1 trial with MSC-1 demonstrated tolerability and safety but modest efficacy. Future research should focus on investigating LIF targets in combination with current standard-of-care chemotherapy, and immunotherapy can be a promising approach. Further, larger multicenter clinical trials are needed to define the use of LIF as a new biomarker in PDAC patients.

Association Between Coronavirus Disease 2019 and Acute Complicated Diverticulitis.

Background Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized. Through potentially overlapping pathophysiology, co-occurrence of COVID-19 and first-time acute diverticulitis has been reported. Our study aims to further characterize this association in COVID-19-positive patients within a large tertiary care academic center. Methodology Patients diagnosed with COVID-19 who subsequently developed acute diverticulitis within 30 days were identified between 2020 and 2022. COVID-19 and acute diverticulitis were diagnosed by polymerase chain reaction and computed tomography, respectively. Patients with prior history of acute diverticulitis were excluded. Patient characteristics and comorbid conditions were collected. Characterization of the COVID-19 course (treatment setting, medical/ventilatory therapy) and acute diverticulitis (treatment setting, medical/surgical therapy, complications) was performed retrospectively. Subanalysis was performed by COVID-19 vaccination status, the severity of COVID-19, and the timing of acute diverticulitis diagnosis. Results A total of 81 patients were identified, with a median duration between COVID-19 diagnosis and acute diverticulitis of 13 days (interquartile range = 2.5-21.0), with 44.4% of patients requiring hospitalization for COVID-19. The all-cause complication rate of acute diverticulitis was noted to be 59.3%, most commonly intestinal perforation (39.5%), abscess formation (37.0%), and peritonitis (14.8%). Although a trend toward increased all-cause complications (65.9%), intestinal perforation (43.9%), and peritonitis (19.5%) was noted in unvaccinated patients, this did not reach significance. Although all-cause complication rate did not differ in patients diagnosed with acute diverticulitis at the time of COVID-19 presentation, a significantly elevated incidence of intestinal perforation (55.9% vs. 27.7%, p = 0.01), peritonitis (29.4% vs. 4.3%, p < 0.01), and the need for emergent surgical intervention (38.2% vs. 10.6%, p < 0.01) was noted. Conclusions Our study indicates that patients diagnosed with first-time acute diverticulitis within 30 days of COVID-19 infection have a high complication rate, most commonly intestinal perforation. Additionally, patients diagnosed with acute diverticulitis at the same time as COVID-19 detection had a significantly elevated rate of complications and emergent surgical needs. Given the high complication rate, patients who develop diverticulitis within a short timeframe of COVID-19 infection may benefit from increased clinician vigilance and monitoring.

Pharmacotherapeutic options for pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy projected to be the 2nd leading cause of cancer related death in the USA by 2030. This manuscript discusses current and evolving treatment approaches in patients with pancreatic cancer. AREAS COVERED: PDAC is classified as: a) resectable, b) borderline resectable, c) unresectable (locally advanced and metastatic). The standard of care for patients who present with resectable pancreatic adenocarcinoma is six months of adjuvant modified (m) FOLFIRINOX, gemcitabine plus capecitabine, or single agent gemcitabine. For many reasons, there has been a paradigm shift to employing neoadjuvant chemotherapy. For resectable and borderline resectable patients, we generally start with systemic therapy and reevaluate resectability with subsequent scans specifically when the tumor is located in the head or body of the pancreas. Combined chemoradiation therapy can be employed in select patients. The standard of care for metastatic PDAC is FOLFIRINOX or gemcitabine and nab-paclitaxel. Germline and somatic genomic profiling should be obtained in all patients. Patients with a germline BRCA mutation can receive upfront gemcitabine and cisplatin. EXPERT OPINION: Thorough understanding of molecular pathogenesis in PDAC has opened various therapeutic avenues. We remain optimistic that future treatment modalities such as targeted therapies, cellular therapies and immunotherapy will further improve survival in PDAC.

Lactobacillus rhamnosus sepsis, endocarditis and septic emboli in a patient with ulcerative colitis taking probiotics.

A man in his 60s presented to the emergency room with fever and fatigue after a 2.5-month course of corticosteroids. His medical history was significant for bioprosthetic aortic valve replacement and moderately severe ulcerative colitis treated with balsalazide and daily lactobacillus-containing probiotics. Initial investigations revealed Lactobacillus rhamnosus bacteraemia without complication. Four days after hospital discharge, the patient experienced acute-onset right-sided paraesthesia and lower-limb paresis. On return to the emergency room, MRI of the brain demonstrated innumerable ring-enhancing lesions with haemorrhagic transformation. Transoesophageal echocardiogram revealed a small mobile density on the bioprosthetic aortic valve, raising the suspicion for L. rhamnosus infective endocarditis with secondary septic emboli to the brain. The patient was subsequently treated with intravenous gentamycin and ampicillin, with transition to indefinite oral amoxicillin suppressive therapy. The current case highlights the potential risk of lactobacilli translocation in an immunosuppressed patient with ulcerative colitis taking probiotics.

Tilsotolimod: an investigational synthetic toll-like receptor 9 (TLR9) agonist for the treatment of refractory solid tumors and melanoma.

INTRODUCTION: Cancer immunotherapy has seen tremendous strides in the past 15 years, with the introduction of several novel immunotherapeutic agents. Nevertheless, as clinical practice has shown, significant challenges remain with a considerable number of patients responding sub-optimally to available therapeutic options. Research has demonstrated the important immunoregulatory role of the tumor microenvironment (TME), with the potential to either hinder or promote an effective anti-tumor immune response. As such, scientific efforts have focused on investigating novel candidate immunomodulatory agents with the potential to alter the TME toward a more immunopotentiating composition. AREAS COVERED: Herein, we discuss the novel investigational toll-like receptor 9 agonist tilsotolimod currently undergoing phase II and III clinical trials for advanced refractory cancer, highlighting its mode of action, efficacy, tolerability, and potential future applications in the treatment of cancer. To this effect, we conducted an exhaustive Web of Science and PubMed search to evaluate available research on tilsotolimod as of August 2021. EXPERT OPINION: With encouraging early clinical results demonstrating extensive TME immunomodulation and abscopal effects on distant tumor lesions, tilsotolimod has emerged as a potential candidate immunomodulatory agent with the possibility to augment currently available immunotherapy and provide novel avenues of treatment for patients with advanced refectory cancer.

Appearance of a "Whip-Like" Rash in a Young Male Undergoing Therapy for Testicular Embryonal Carcinoma.

Bleomycin, a cytotoxic antibiotic commonly used as part of combination chemotherapy regimes in the treatment of germ cell tumors, is well known among clinicians for its potential pulmonary toxicity. Less well known, although postulated to occur through a similar pathomechanism, are the wide spectrum of dermatologic adverse reactions associated with bleomycin therapy. The current case report describes the sudden and distressing appearance of a pruritic erythematous flagellate "whip-like" rash in a 30-year-old Caucasian male undergoing treatment for testicular embryonal carcinoma following the second infusion of bleomycin-containing chemotherapy. Diagnosed as bleomycin-induced flagellate dermatitis, the case describes the dermatologic sequela and therapeutic interventions utilized. While commonly used in testicular cancer, decreasing use of bleomycin-containing chemotherapy regimens has made the appearance of this increasingly rare, yet important and distressing, toxic adverse reaction a diagnostic challenge. Given that patients may present acutely to primary care providers, dermatologists, and nurse practitioners, awareness of this rare adverse reaction is important in order to alleviate patient anxiety, initiate appropriate therapy, set expectations of expected dermal sequela, and initiate an informed collaborative discussion regarding the continuation versus cessation of bleomycin-containing therapy.