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.

Hyperbilirubinemia in hospitalized patients: Etiology and outcomes.

There is little information on the differential diagnosis and prognosis of hospitalized patients with hyperbilirubinemia. Here, we hypothesized that hyperbilirubinemia in hospitalized patients is associated with specific diseases and outcomes. This retrospective cohort analysis included patients admitted to the Medical University of South Carolina with a total bilirubin >3 mg/dL from January 9, 2015 to August 25, 2017. Collected clinical data included demographics, primary diagnosis, Charlson Comorbidity Index (CCI), laboratory data, and clinical outcomes. We separated and analyzed the cohort into seven primary diagnostic groups. We identified 1693 patients with a bilirubin level >3 mg/dL. The cohort was 42% female, had an average age of 54, average CCI of 4.8, and average length of stay of 13 days. The causes of hyperbilirubinemia included the following: primary liver disease (868/1693; 51%) with cirrhosis being most common (385/1693; 23%), benign biliary obstruction (252/1693; 15%), hemolytic anemia (149/1693; 9%), malignant biliary obstruction (121/1693; 7%), unknown etiology (108/1693; 6%), primary liver cancer (74/1693; 4%), and metastatic cancer to the liver (57/1693; 3%). Overall, the mortality/discharge to hospice rate in patients with a bilirubin >3 mg/dL was 30%, and was proportional to the severity of hyperbilirubinemia, including when controlling for the underlying severity of illness. Mortality was highest in patients with primary liver disease and malignancy and was lowest in patients with non-cancerous obstruction or hemolytic jaundice. Hyperbilirubinemia in hospitalized patients is most often due to primary liver disease, and identifies patients with a poor prognosis, particularly when caused by primary liver disease or cancer.

A Quality Improvement Approach to Decrease the Utilization of Docusate in Hospitalized Patients.

BACKGROUND AND OBJECTIVES: Docusate sodium is a commonly prescribed medication to relieve constipation, but several studies have demonstrated its ineffectiveness. Its continued use in the hospital setting adds unnecessary cost and risk to patients. At the Mayo Clinic Florida campus, docusate was ordered for 9.7% of patients admitted to the internal medicine resident (IMED) teaching services during the month of January 2020, and the average hospital length of stay (LOS) was 3.1 days. METHODS: A multidisciplinary team of internal medicine resident physicians and pharmacists collaborated to address this quality gap through a quality improvement project. It sought to reduce the number of patients admitted to the IMED teaching services who had an order placed for docusate by 50% in less than 6 months without adversely impacting hospital LOS. Two separate interventions were devised using Six Sigma methodology and implemented to reduce the frequency of docusate orders, which involved educating internal medicine residents and hospital pharmacists, and creating an additional process-related barrier to docusate orders. RESULTS: The percentage of docusate orders decreased from 9.7% to 2.4% ( P = .004) with a grossly unchanged LOS of 3.1 days to 2.7 days ( P = .12) after 5 weeks. CONCLUSION: The implementation of a dual-pronged intervention successfully decreased the use of an ineffective medication in hospitalized patients without impacting the balancing measure, and serves as a model that can be adopted at other institutions with the hope of promoting evidence-based medical care.

Efficacy of a two-dose hepatitis B vaccination with a novel immunostimulatory sequence adjuvant (Heplisav-B) on patients with chronic liver disease: a retrospective study.

Background: Patients with chronic liver disease (CLD) are more likely to have severe morbidity and mortality due to superimposed acute or chronic hepatitis B virus (HBV) infection and should receive routine vaccination against the virus. Heplisav-B is a two-dose, inactivated, yeast-derived vaccine that uses a novel immunostimulatory adjuvant. Our primary objective was to determine the efficacy of hepatitis B vaccination with Heplisav-B in patients with CLD. Methods: This retrospective cohort analysis included patients ≥18 years old with CLD who received Heplisav-B from January 2018 to January 2021. All patients had anti-HBs <10 IU/L prior to vaccination and received two doses of Heplisav-B. Post-vaccination anti-HBs of ≥10 IU/L was considered successful vaccination. Basic demographic information, laboratory markers, and medical history were collected from the electronic health record. Results: A total of 120 patients were included in analysis. The average age of patients was 59 years, 37% were female, and the most common etiology of liver disease was nonalcoholic fatty liver disease. Median days from 2nd vaccination to post-vaccination HBsAb levels was 121 days. 81/120 (67.5%) of patients had evidence of active immunity after receipt of Heplisav-B. On multivariable analysis, age >50 was associated with reduced odds of successful vaccination (OR =0.19, 95% CI: 0.03-0.76). Conclusions: In patients with CLD, Heplisav-B's overall efficacy (67.5%) is greater than reports of Engerix-B (33-45%), and thus is an effective hepatitis B vaccine in this patient population, particularly in cirrhotic patients. Further studies regarding this vaccine are needed in patients with CLD and after liver transplantation.

Efficacy of Hepatitis B Vaccination with a Novel Immunostimulatory Sequence Adjuvant (Heplisav-B) in Patients With Inflammatory Bowel Disease.

BACKGROUND: Owing to the use of immunosuppressive agents, patients with inflammatory bowel disease (IBD) have an increased risk of vaccine preventable diseases, including infection with hepatitis B virus (HBV). Heplisav-B, an FDA-approved vaccine, is more effective (90% to 100%) than Engerix-B (70.5% to 90.2%) at inducing immunity to HBV in clinical studies. Available data on efficacy of Heplisav-B vaccine in patients with IBD are limited. METHODS: This retrospective observational study included patients age 18 years and older with ulcerative colitis (UC) or Crohn's disease (CD) who received 1 or 2 doses of Heplisav-B vaccine and had postvaccination serologic testing. Prior to immunization, all participants were seronegative for HBsAb antibodies (HBsAb) measured as <10 IU/mL. Postvaccination HBsAb of ≥10 IU/mL was considered successful vaccination. Patient demographics, disease characteristics, and medications were abstracted. RESULTS: One hundred six patients were included in the analysis. Median age was 43 years, and 44 (42%) were female. Thirty-nine patients (37%) had UC, whereas 67 (63%) had CD. Eighty-three patients (78.3%) had active immunity after vaccination with Heplisav-B, with median postvaccination HBsAb levels of 114 IU/L. Patients with chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, immunomodulator use, or those on 2 or more of immunosuppressive medications were less likely to respond to Heplisav-B, though these findings were not statistically significant on a multivariate analysis aside from chronic kidney disease. CONCLUSIONS: Heplisav-B, a 2-dose vaccine, is an effective vaccine for HBV in patients with IBD. In our study, its overall efficacy (78.3%) is greater than that reported for the presently available 3-dose vaccination (Engerix) in patients with IBD.

Heplisav-B, a 2-dose vaccine, is an effective vaccine for HBV in patients with IBD. In our study, it had an overall efficacy of 78.3%. Patients on an immunomodulator and/or 2 or more immunosuppressants had decreased response rate to vaccination.

Exocrine pancreatic insufficiency after bariatric surgery.

BACKGROUND: Exocrine pancreatic insufficiency (EPI) is a known complication of upper gastrointestinal surgery and has recently been associated with bariatric surgery. Our objectives were to determine the incidence of EPI in patients who underwent bariatric surgery and to identify the type of bariatric procedure most associated with EPI. METHODS: This retrospective cohort analysis included patients age ≥18 years who underwent bariatric surgery at Mayo Clinic between 2010 and 2020. Patients with a history of other gastrointestinal or hepatobiliary resection, revision of bariatric surgery, EPI prior to surgery, and surgery greater than >10 years earlier were excluded from the study. Characteristics were compared between two groups based on type of bariatric surgery including Roux-en-Y gastric bypass (RYGB) or gastric sleeve (GS). Characteristics were also analyzed between patients with RYGB who developed post-operative steatorrhea and those who did not. RESULTS: Of 150 patients, 126 underwent RYGB while 24 patients had GS. Thirty-one (20.6%) patients developed post-operative steatorrhea and 14 (9.3%) were diagnosed with EPI. Mean pancreatic elastase level was 287 ± 156 mcg/g and fecal fat level 31 ± 22 g/d. There was a significantly higher proportion of post-operative steatorrhea in patients who underwent RYGB compared to gastric sleeve surgery (p = 0.029). CONCLUSION: The incidence of EPI after bariatric surgery in our cohort was 9.3%. Overall, patients who underwent RYGB had higher rates of EPI (10.3%) than those who had GS (4.2%). Clinicians should be aware of EPI as a cause for steatorrhea in patients who underwent bariatric surgery and consider treatment with enzyme replacement therapy.

Overwhelming cryptococcosis complicated by cryptococcal endocarditis.

Cryptococcal species endocarditis is infrequently described, carries high mortality and nearly always occurs in immunocompromised states or on prosthetic valves. We report the case of a man in his 70s with multiple recent hospitalisations for pneumonia, hypercalcaemia and septic tank exposure who presented with intermittent fevers, progressive weakness,and worsening encephalopathy, manifested as confusion and word-finding difficulties for 3 weeks. Workup revealed cryptococcal species on blood serum gram stain, native aortic valve endocarditis and meningitis. Cerebrospinal fluid analysis demonstrated lymphocytosis, ultimately found to be secondary to chronic lymphocytic leukaemia. Surgical valve replacement was deemed medically contraindicated and antifungal therapy was initiated. Though poorly understood with very few documented cases, management of cryptococcal endocarditis relies on prompt diagnosis, early surgery when indicated, long-term antifungal therapy and treatment of underlying immunocompromising states where possible.

Comparison of idiopathic recurrent acute pancreatitis [IRAP] and recurrent acute pancreatitis with genetic mutations.

BACKGROUND: Idiopathic recurrent acute pancreatitis (IRAP) describes frequent episodes of pancreatitis without an etiology found using current testing. We compared the natural history of IRAP with recurrent acute pancreatitis with genetic mutations. METHODS: Retrospective cohort of patients with recurrent acute pancreatitis (≥2 episodes) and negative conventional testing. All patients had ≥1 episode after cholecystectomy and completed genetic testing. Primary outcomes were chronic pancreatitis incidence, pancreatic cancer, and mortality. Secondary outcomes included opioid and ERCP utilization. RESULTS: 128 patients met criteria for presumed IRAP. 35 patients met criteria for true IRAP. 12 patients had recurrent acute pancreatitis with gene mutations. Chronic pancreatitis developed in 27 (77.1%) IRAP patients over a median of 6 years. Chronic pancreatitis incidence was similar in IRAP and CFTR mutation carriers; but developed later in SPINK1 carriers. No patients developed pancreatic cancer or died from pancreatic-related causes. Patients were frequently treated with oral opioids and ERCP, without significant differences within or between groups. CONCLUSION: IRAP and pancreatitis in mutation carriers is associated with chronic pancreatitis. Important differences in natural history were observed, but no association was found with cancer or pancreas-related mortality. Efforts to understand the genetic contributions to IRAP, minimize opioids and unnecessary ERCPs are encouraged.

Hiatal Hernia Associated with Higher Odds of Dysplasia in Patients with Barrett's Esophagus.

BACKGROUND: Patients with Barrett's esophagus (BE) are more likely to have associated hiatal hernia (HH) compared to the general population. Studies show that HH are typically longer and wider in patients with BE. AIMS: To determine whether patients with HH have associated increased odds of coexistence of BE by examining inpatient prevalence, as well as determining other inpatient outcomes. METHODS: This was a case-control study using the NIS 2016, the largest public inpatient database in the USA. All patients with ICD10CM codes for BE were included. None were excluded. The primary outcome was determining the association between BE and HH in hospitalized patients, stratified by grade of dysplasia. Secondary outcomes included measuring use of endoscopic ablation in patients with BE and HH compared to patients with BE and no HH, determining the degree of association between HH and esophagitis in patients with or without BE, as well as the association between esophagitis and dysplasia in patients with BE and HH. RESULTS: A total of 118,750 patients with BE were identified, of which 24,030 had associated HH. Adjusted odds of having associated BE in patients with HH was 10.9 (p < 0.01) compared to patients without HH. Patients with HH also displayed significantly higher odds of both low-grade dysplasia (aOR 34.5, p < 0.01) and high-grade dysplasia (aOR 14.7, p < 0.01). For secondary outcomes, the odds of undergoing ablation for BE was higher 4.77 (p < 0.01) in patients with HH. CONCLUSIONS: Patients with HH have significantly higher odds of having associated BE, regardless of the level of dysplasia. Furthermore, the odds of undergoing ablation are much higher, likely reflecting higher odds of dysplasia. This highlights the importance of BE in patients with HH, and potentially consider these patients as higher risk.

Cost-Effectiveness of an Adjuvanted Hepatitis B Vaccine (HEPLISAV-B) in Patients With Inflammatory Bowel Disease.

Background: Compare the cost-effectiveness of 2 recombinant hepatitis B virus (HBV) vaccines in patients with inflammatory bowel disease (IBD). Methods: Markov models were developed for 2 IBD cohorts: (1) 40-year-old patients prior to starting IBD treatment and (2) 40-year-old patients already receiving therapy. Cohort A received full vaccination series, cohort B had primary vaccine failure and received a vaccine booster. Two vaccines were compared: adjuvanted HEPLISAV-B and nonadjuvanted Engerix-B. Clinical probabilities of acute hepatitis, chronic hepatitis, cirrhosis, fulminant hepatic failure and death, treatment costs, and effectiveness estimates were obtained from published literature. A lifetime analysis and a US payer perspective were used. Probabilistic sensitivity analyses were performed for different hypothetical scenarios. Results: Analysis of cohort A showed moderate cost-effectiveness of HEPLISAV-B ($88,114 per quality-adjusted life year). Analysis of cohort B showed increased cost-effectiveness ($35,563 per quality-adjusted life year). Changing Engerix-B to HEPLISAV-B in a hypothetical group of 100,000 patients prevented 6 and 30 cases of acute hepatitis; and 4 and 5 cases of chronic hepatitis annually for cohorts A and B, respectively. It also prevented 1 and 2 cases of cirrhosis, and 1 and 2 deaths over 20 years for each cohort. Cost-effectiveness was determined by vaccination costs, patient age, and progression rate from chronic hepatitis to cirrhosis. Conclusions: HEPLISAV-B is cost-effective over Engerix-B in patients receiving immunosuppressive therapy for IBD. Benefits increase with population aging and lower costs of vaccines. We advocate measuring levels of HBV antibodies in patients with IBD and favor adjuvanted vaccines when vaccination is needed.

The conformational signature of ß-arrestin2 predicts its trafficking and signalling functions.

Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based 'signalsomes'. Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters to monitor conformational changes in ß-arrestin2, here we show that GPCRs impose distinctive arrestin 'conformational signatures' that reflect the stability of the receptor-arrestin complex and role of ß-arrestin2 in activating or dampening downstream signalling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in ß-arrestin2 conformation. Our findings demonstrate that information about ligand-receptor conformation is encoded within the population average ß-arrestin2 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands and in identifying factors that dictate arrestin conformation and function.