Successful treatment of severe passenger lymphocyte syndrome with efgartigimod synergy.

INTRODUCTION: This case describes passenger lymphocyte syndrome (PLS) generating human platelet antigen 1a (HPA-1a) alloantibodies against the recipient's platelets after liver transplant. Given the rarity of PLS, especially in liver transplant with HPA-1a alloantibodies, disease course and management options are poorly described. METHODS: The patient had cirrhosis secondary to nonalcoholic steatohepatitis complicated by hepatocellular carcinoma, encephalopathy, and severe ascites. The model for end-stage liver disease (MELD) score was 15 at presentation. The patient developed hepatic artery thrombosis after an orthotopic liver transplant and was relisted for transplant with a MELD score of 40. The patient received a hepatitis C virus antibody positive, hepatitis C virus nucleic amplification test positive donor liver on postoperative day (POD) 7 after first transplant. On POD 7 after the second transplant, the patient developed profound thrombocytopenia refractory to platelet infusion. They were found to have serum antibody to HPA-1a based upon serum platelet alloantibody testing. The donor was later found to be negative for HPA-1a by genetic testing. However, the patient's native platelets were HPA-1a positive. The patient was diagnosed with PLS. RESULTS: The patient's treatment course included 57 units of platelets transfused, emergency splenectomy, rituximab, plasma exchange, intravenous immunoglobulin (IVIG), eltrombopag, romiplostim, and efgartigimod. DISCUSSION: The synergistic effect of efgartigimod with eltrombopag and romiplostim most likely resolved the patient's thrombocytopenia. This case represents a novel use of efgartigimod in the treatment of passenger lymphocyte syndrome following liver transplant.

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.

Incidence and risk factors of graft-versus-host disease after liver transplantation: A national study 2010-2020.

BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of hematopoietic cell transplantation, and its incidence is low in liver transplantation (LT). Estimating the incidence of GVHD after LT is challenging due to the paucity of available data from the United Network for Organ Sharing. This is the first national analysis of the incidence and risk factors of GVHD after LT. METHODS: This retrospective cohort study used the National Readmission Database to calculate the incidence rate of GVHD within 1 year of LT using survival analysis. The predictors of GVHD were identified using univariate and multivariate Cox regression analyses. RESULTS: From 2010 to 2020, of 88,433 LTs, 383 cases of GVHD occurred within 1 year after LT, resulting in an incidence rate of 1.0% (95% CI: 0.8%-1.3%). We observed no statistically significant change in the incidence of GVHD after LT from 2010 to 2020 (beta-coefficient, -0.07%; 95% CI: -0.17% to 0.04%, p = 0.188). Interestingly, alcohol-associated liver disease was associated with a lower risk of GVHD (adjusted HR, 0.57; 95% CI: 0.36-0.91, p = 0.018), whereas a higher risk was found to be related to a secondary diagnosis of COVID-19 on index admission. CONCLUSION: Our study found that the incidence rate of GVHD within 1 year of LT in the United States was 1.0% and remained stable from 2010 to 2020. The predictors associated with GVHD include alcohol-associated liver disease and COVID-19. Our study provides valuable insights into the incidence, risk factors, and outcomes of GVHD after LT.

Association of serum IgG4 and disease outcomes in patients with inflammatory bowel disease.

Background: The etiology of inflammatory bowel disease (IBD) is multifactorial and thought to be influenced by inappropriate activation of the gut mucosal immune system. As the only immunoglobulin G (IgG) subclass unable to activate the classical complement cascade, the role of IgG4 in IBD pathophysiology as an immunomodulator is controversial. This study aimed to determine the association of low, normal and high IgG4 levels with the outcomes of IBD patients. Methods: This was a retrospective study of a multisite tertiary care center database evaluating patients with IBD who had an IgG4 level drawn between 2014 and 2021. Subjects were divided into low, normal, and high IgG4 level groups for evaluation of demographic and clinical indicators of IBD activity and severity. Results: Of 284 patients with IBD, 22 had low (7.7%), 16 high (5.6%), and 246 (86.6%) normal IgG4 levels. There was no difference in IBD subtype, mean age, age at IBD diagnosis, or smoking between the 3 groups. There was no difference in number of hospitalizations (P=0.20), C-reactive protein levels, need for intestinal resection (P=0.85), or presence of primary sclerosing cholangitis (P=0.15), pancreatitis (P=0.70), or perianal disease (P=0.68) between the groups. Significantly more patients in the low IgG4 group had previous exposure to vedolizumab compared to the other groups and more patients in the low IgG4 group received vedolizumab (P=0.04), azathioprine (P=0.04) and prednisone (P=0.03) during the 5-year follow up. Conclusion: In this study, a low serum IgG4 level was associated with higher rates of vedolizumab, azathioprine, and steroid use.

The treatment of functional dyspepsia: present and future.

INTRODUCTION: Functional dyspepsia (FD) is a prevalent, but frequently overlooked and/or under diagnosed disorder of gut-brain interaction (DGBI). Functional dyspepsia frequently co-exists with other DGBIs, and persistent symptoms have a significant impact on patients' quality of life. A variety of therapies (e.g. diet, probiotics, antibiotics, acid suppressants, neuromodulators, prokinetics) are employed to treat the multiple symptoms of FD, although none are uniformly effective. AREAS COVERED: This review covers currently available therapies for the treatment of FD in addition to novel and emerging therapies that may change the treatment paradigm in the near future. PubMed, Embase and the Cochrane data bank were searched from 1990 to October 2022 for relevant articles. EXPERT OPINION: Dietary intervention, eradication of H. pylori, and/or a trial of acid suppression are reasonable initial treatment options for patients with FD. Neuromodulators and fundic accommodation agents are underemployed and should be used more routinely by healthcare providers, especially for patients with moderate-severe symptoms. Alternative therapies, such as cognitive behavioral therapy and hypnotherapy, are gaining recognition as safe and effective treatments for FD and can be used alone or in combination with medications. Virtual reality has the potential to significantly improve global FD symptoms.

EphrinA1-Fc Attenuates Ventricular Remodeling and Dysfunction in Chronically Nonreperfused WT but not EphA2-R-M mice.

BACKGROUND: EphrinA1-Fc abolishes acute I/R injury and attenuates nonreperfused cardiac injury 4 days after permanent occlusion in mice. The goal of this study was to assess the capacity of a single intramyocardial administration of ephrinA1-Fc at the time of coronary artery ligation, to determine the degree to which early salvage effects translate to reduced adverse remodeling after 4 weeks of nonreperfused myocardial infarction (MI) in wild-type B6 and EphA2-R-M (EphA2 receptor null) mice. METHODS: At 4 weeks post-MI, echocardiography, histologic and immunohistochemical analyses of B6 mouse hearts were performed. Primary mouse cardiac fibroblasts (FBs) isolated from B6 mice cultured in the presence of low and high dose ephrinA1-Fc, both with and without pro-fibrotic TGF-ß stimulation and Western blots, were probed for relative expression of remodeling proteins MMP-2, MMP-9 and TIMP-1, in addition to DDR2 and (p)SMAD2/3/totalSMAD2/3. RESULTS: EphrinA1-Fc preserved a significant degree of contractile function, decreased adverse left ventricular remodeling, attenuated excessive compensatory hypertrophy, and decreased interstitial fibrosis in wild-type (WT) B6 mouse hearts. In contrast, most of these parameters were poorer in ephrinA1-Fc-treated EphA2-R-M mice. Of note, fibrosis was proportionately decreased, implying that other EphA receptor(s) are more important in regulating the pro-fibrotic response. Primary FBs showed disparate alteration of MMP-2, MMP-9 and TIMP-1, as well as DDR2 and p-SMAD2/3/totalSMAD2/3, which indicates that matrix remodeling and cardiac fibrosis in the injured heart are influenced by ephrinA1-Fc. CONCLUSION: This study demonstrates the capacity of a single administration of ephrinA1-Fc at the onset of injury to attenuate long-term nonreperfused post-MI ventricular remodeling that results in progressive heart failure, and the important role of EphA2 in mitigating the deleterious effects.