Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma - A Systematic Review and Meta-analysis.

BACKGROUND: Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias. RESULTS: We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved. CONCLUSION: CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.

Management of Alcohol-Associated liver disease and alcohol use disorder in liver transplant candidates and recipients: Challenges and opportunities.

Alcohol-associated liver disease (ALD) poses a significant global health burden, with rising alcohol consumption and prevalence of alcohol use disorder (AUD) contributing to increased morbidity and mortality. This review examines the challenges and opportunities in the care of liver transplant (LT) candidates and recipients with AUD. Despite advancements in post-transplant patient survival, the risk of disease recurrence and alcohol relapse remains substantial. Several challenges have been identified, including (1) rising disease burden of ALD, variable transplant practices, and systemic barriers; (2) disparities in mental health therapy access and the impact on transplant; (3) variable definitions, underdiagnosis, and stigma affecting access to care; and (4) post-LT relapse, its risk factors, and consequential harm. The review focusses on the opportunities to improve AUD care for LT candidates and recipients through effective biochemical monitoring, behavioral and pharmacologic approaches, creating Centers of Excellence for post-LT AUD care, advocating for policy reforms, and ensuring insurance coverage for necessary services as essential steps toward improving patient outcomes. The review also highlights unmet needs, such as the scarcity of addiction specialists, and calls for further research on personalized behavioral treatments, digital health, and value-based care models to optimize AUD care in the LT setting.

Gonadal androgens are associated with decreased type I interferon production by plasmacytoid dendritic cells and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents.

mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Type I interferon (IFN-I) is an integral part of this early innate response that primes several components of the adaptive immune response. Women are widely reported to respond better than men to tri- and quadrivalent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production, and female pDCs produce more IFN-I than male pDCs since the upstream pattern recognition receptor Toll-like receptor 7 (TLR7) is encoded by X chromosome and is biallelically expressed by up to 30% of female immune cells. Additionally, the TLR7 promoter contains several putative androgen response elements, and androgens have been reported to suppress pDC IFN-I in vitro. Unexpectedly, therefore, we recently observed that male adolescents mount stronger antibody responses to the Pfizer BNT162b2 mRNA vaccine than female adolescents after controlling for natural SARS-CoV-2 infection. We here examined pDC behaviour in this same cohort to determine the impact of IFN-I on anti-spike and anti-receptor-binding domain IgG titres to BNT162b2. Through flow cytometry and least absolute shrinkage and selection operator (LASSO) modelling, we determined that serum-free testosterone was associated with reduced pDC IFN-I, but contrary to the well-described immunosuppressive role for androgens, the most bioactive androgen dihydrotestosterone was associated with increased IgG titres to BNT162b2. Also unexpectedly, we observed that co-vaccination with live attenuated influenza vaccine boosted the magnitude of IgG responses to BNT162b2. Together, these data support a model where systemic IFN-I increases vaccine-mediated immune responses, yet for vaccines with intracellular stages, modulation of the local IFN-I response may alter antigen longevity and consequently improve vaccine-driven immunity.

Macrophage activation syndrome with acute hepatitis in a patient with adult-onset immunodeficiency with anti-interferon gamma antibodies: a case report.

BACKGROUND: Macrophage activation syndrome is a rare disorder leading to unregulated immune activity manifesting with nonspecific constitutional symptoms, laboratory abnormalities, and multiorgan involvement. We report the case of a patient who presented with acute hepatitis secondary to macrophage activation syndrome diagnosed by liver biopsy and successfully treated with intravenous immune globulin, anakinra, and rituximab. CASE PRESENTATION: A 42-year-old Laotian woman with adult-onset immunodeficiency with anti-interferon gamma antibodies presented with a fever, headache, generalized myalgia, dark urine, and reduced appetite in the setting of family members at home with similar symptoms. Her laboratory workup was notable for evidence of acute hepatitis without acute liver failure. After an unrevealing comprehensive infectious and noninvasive rheumatologic workup was completed, a liver biopsy was performed ultimately revealing the diagnosis of macrophage activation syndrome. She was successfully treated with intravenous immune globulin, anakinra, and rituximab. CONCLUSION: This case highlights the importance of maintaining macrophage activation syndrome on the differential of a patient with acute hepatitis of unknown etiology in the correct clinical context and the value of a liver biopsy in making a diagnosis when noninvasive testing is unrevealing.

Low screening rates and high prevalence of osteoporosis in cirrhosis: A real-world retrospective analysis.

BACKGROUND: Patients with cirrhosis are at increased risk for osteoporosis, and those who suffer a fracture are at high risk for mortality. Despite this, osteoporosis is often overlooked and undertreated. This study aimed to evaluate osteoporosis screening, management, and adverse osteoporosis medication events in patients with cirrhosis. METHODS: We performed a retrospective chart review of adult outpatients with compensated and decompensated cirrhosis seen in single health system over a 6-year period. Patient demographics, liver and bone health comorbidities, DEXA scan results, and medications were abstracted. RESULTS: In total, 5398 patients met criteria. The cohort was predominately white (79.1%) and older (age 59). 44.4% were female. 64.6% had decompensated cirrhosis. Median MELD-Na score was 12.8. 23.5% had a DEXA scan ordered, approximately 50% completed this test. Patients who were older, female, white, with more severe liver disease, and other osteoporosis risk factors were more likely to have a DEXA scan ordered. 48.5% of patients had osteopenia and 30.2% had osteoporosis on DEXA scan. Only 22.6% of patients with osteoporosis received treatment, most commonly oral bisphosphonates. Oral bisphosphonate prescription was not associated with variceal bleeding (8.4% without vs. 4.8% with, p = 0.487). CONCLUSION: A minority of patients with cirrhosis were screened for osteoporosis. The majority screened had osteopenia or osteoporosis on DEXA scan. Less than a quarter of patients with osteoporosis were started on treatment. Real-world experience of oral bisphosphonate use did not reveal higher rates of gastrointestinal bleeding. There is room for improvement in all aspects of bone health care in cirrhosis.

Pre-existing Hepatic Encephalopathy: Really a Contraindication to Elective TIPS?

PURPOSE: To evaluate the impact of pre-transjugular intrahepatic portosystemic shunt (TIPS) hepatic encephalopathy (HE) on developing post-TIPS HE. MATERIALS AND METHODS: In this retrospective, single center observational study, all patients who underwent successful TIPS placement between January 2005 and May 2020 with data pertaining to HE in their chart were included. Patient demographics and procedural details were recorded. Clinical outcomes post-TIPS, were collected and compared across patients with and without pre-TIPS HE. RESULTS: Of 326 included patients, 159 (159/326, 48.8%) had a history of pre-TIPS HE. In total those without a history of HE were more likely to develop HE during follow up (136 (136/167, 81.4%) vs 107 (107/159, 67.3%), p = 0.001). When evaluating for predictors of developing HE within 3 months of TIPS placement, no significant variables were found on logistic regression, including prior history of HE (HR 1.16 (95% CI 0.73-1.84), p = 0.529). Univariate and multivariate regression analysis, however, showed that a history of HE was predictive of developing HE at any point in the follow-up period (p = 0.002 and p = 0.008, respectively). However, on Kaplan-Meier analysis no significant difference in the development of HE (p = 0.574) or hospital admission for HE (p = 0.554) post-TIPS was seen between patients with and without pre-TIPS HE. Additionally, there was no difference in 3-month survival (p = 0.412) or overall survival post-TIPS survival (p = 0.798). CONCLUSION: Pre-TIPS HE did not predict the development of HE within 3 months of TIPS. Outcomes such as hospital admission and survivability were not different between patients with and without prior HE.

Laboratory-adapted and wild-type black soldier flies express differential plasticity in bioconversion and nutrition when reared on urban food waste streams.

BACKGROUND: The black soldier fly (BSF) offers a potential solution to address shortages of feed and food sources; however, selecting effective rearing substrates remains a major hurdle in BSF farming. In an urban area like Singapore, current practice is based on rearing BSF on homogeneous waste streams (e.g., spent brewery grains or okara) because heterogeneous food wastes (e.g., mixed kitchen/canteen waste or surplus cooked food) present several operational challenges with respect to the standardization of development, nutritional content, and harvesting. RESULTS: In this study, we compared two genetic strains of BSF larvae (wild-type and laboratory-adapted line) in a bioconversion experiment with diverse types of food waste (homogeneous/heterogeneous; plant/meat) and we quantified the phenotypic plasticity. Our results demonstrate different plasticity in bioconversion performance, larval growth and larval nutrition between the two BSF lines. This difference may be attributed to the selective breeding the laboratory-adapted line has experienced. Notably, larval lipid content displayed little to no genetic variation for plasticity compared with larval protein and carbohydrate content. Despite variation in larval development, heterogeneous food wastes can produce better performance in bioconversion, larval growth, and larval nutrient content than homogeneous food waste. All-meat diets result in high larvae mortality but larval survival could be rescued by mixing meat with plant-based food wastes. CONCLUSION: Overall, we suggest using mixed meals for BSF larvae feeding. Targeted breeding may be a promising strategy for the BSF industry but it is important to consider the selection effects on plasticity in larval nutrition carefully. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Association of Benign Paroxysmal Positional Vertigo with Depression and Anxiety-A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the extent to which Benign Paroxysmal Positional Vertigo (BPPV) is associated with a higher prevalence of depression and anxiety in patients. DATA SOURCES: Three databases including PubMed, Embase, and The Cochrane Library were searched by two independent authors from inception to June 12, 2022 for observational studies and randomized controlled trials investigating the association between BPPV and depression and anxiety. We included studies published as full-length articles in peer-reviewed journals with an adult population aged at least 18 years who have BPPV, detected through validated clinical methods like clinical diagnosis, interview and Dix-Hallpike test. RESULTS: A total of 23 articles met the final inclusion criteria and 19 articles were included in the meta-analysis. BPPV was associated with a 3.19 increased risk of anxiety compared to controls, and 27% (17%-39%) of BPPV patients suffered from anxiety. Furthermore, the weighted average Beck's Anxiety Inventory score was 18.38 (12.57; 24.18), while the weighted average State-Trait Anxiety Index score was 43.08 (37.57; 48.60). CONCLUSION: There appears to be some association between BPPV and anxiety, but further studies are required to confirm these associations. Laryngoscope, 134:526-534, 2024.

Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents.

Introduction: The key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination. Methods: We studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12-16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS-CoV-2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS-CoV-2-specific IgG and neutralising antibodies and cellular immunity specific for SARS-CoV-2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed. Results: Robust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS-CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32-52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV-2 previously infected, 743,691 vs. 269,985; p <0.0001) by the MSD v-plex assay. There was no evidence of a stronger vaccine-induced immunity in females compared than in males. Discussion: These findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.

Cellular immunity to SARS-CoV-2 following intrafamilial exposure in seronegative family members.

Introduction: Family studies of antiviral immunity provide an opportunity to assess virus-specific immunity in infected and highly exposed individuals, as well as to examine the dynamics of viral infection within families. Transmission of SARS-CoV-2 between family members represented a major route for viral spread during the early stages of the pandemic, due to the nature of SARS-CoV-2 transmission through close contacts. Methods: Here, humoral and cellular immunity is explored in 264 SARS-CoV-2 infected, exposed or unexposed individuals from 81 families in the United Kingdom sampled in the winter of 2020 before widespread vaccination and infection. Results: We describe robust cellular and humoral immunity into COVID-19 convalescence, albeit with marked heterogeneity between families and between individuals. T-cell response magnitude is associated with male sex and older age by multiple linear regression. SARS-CoV-2-specific T-cell responses in seronegative individuals are widespread, particularly in adults and in individuals exposed to SARS-CoV-2 through an infected family member. The magnitude of this response is associated with the number of seropositive family members, with a greater number of seropositive individuals within a family leading to stronger T-cell immunity in seronegative individuals. Discussion: These results support a model whereby exposure to SARS-CoV-2 promotes T-cell immunity in the absence of an antibody response. The source of these seronegative T-cell responses to SARS-CoV-2 has been suggested as cross-reactive immunity to endemic coronaviruses that is expanded upon SARS-CoV-2 exposure. However, in this study, no association between HCoV-specific immunity and seronegative T-cell immunity to SARS-CoV-2 is identified, suggesting that de novo T-cell immunity may be generated in seronegative SARS-CoV-2 exposed individuals.

Mortality and Cardiovascular Outcomes in Adult Non-Liver Solid Organ Transplant Patients With Nonalcoholic Steatohepatitis.

BACKGROUND: The effect of nonalcoholic steatohepatitis (NASH) on mortality or major adverse cardiovascular events (MACE) in non-liver solid organ transplant recipients (NL-SOT) is unknown. METHODS: Using a retrospective design, adult NL-SOT recipients who had biopsy-proven NASH were compared NL-SOT recipients with normal liver function tests and imaging; propensity matched at a 1:10 ratio on the following: age, sex, race, transplant year, transplant organ, smoking status, and diabetes status. Both deceased and living donor recipients were included; heart and liver transplant patients were excluded. Primary outcome was incidence of all-cause mortality and MACE (a composite outcome of coronary artery disease, ischemic stroke, and peripheral arterial disease). RESULTS: Seven patients (3 kidney and 4 lung transplants) had biopsy-proven NASH and 70 patients without NASH, both groups were predominantly male (53%-57%), White (86%-91%), and overweight (mean body mass index ∼ 26). The majority of patients were on calcineurin inhibitors (≥85%), antimetabolites (≥97%), and prednisone (≥50%). Survival analysis showed that NASH patients had a higher risk of death (hazard ratio [HR], 3.24; 95% confidence interval [CI], 1.26-8.33, P = 0.02). NASH did not affect the risk of death-censored graft failure (HR, 1.08; 95% CI, 0.14-8.67; P = .94) or the risk of MACE (HR, 1.03; 95% CI, 0.23-4.62; P = .97). CONCLUSIONS: In NL-SOT recipients, NASH is significantly associated with mortality but not with MACE.

Impact of Gastroenterology Consultation on the Clinical Outcomes of Patients Admitted With Hepatic Encephalopathy.

Introduction Hepatic encephalopathy (HE) is a common complication of cirrhosis and a common reason for hospital admission. We aimed to determine whether expert consultation from gastroenterology (GI) leads to better clinical outcomes for inpatients with HE. Methods A retrospective review was performed of all adult patients (age ≥ 18) admitted with HE to a tertiary care hospital between January 2013 and April 2018. Patients who received a GI consult were compared to patients who did not receive a GI consult (No consult group). The primary outcome was hospital length of stay (LOS); secondary outcomes were rates of 30-day hospital readmission and 90-day mortality. Multivariate analysis was conducted to adjust for known confounders.  Results Four hundred and twenty-five patients (814 encounters) were included in the study; of these, 236 patients had received a GI consultation for HE. Patients in the GI consult group were younger (mean age 55 vs 58 years, p= 0.02) and had higher Model For End-Stage Liver Disease-sodium (MELD-Na) score (mean MELD-Na 23.5 vs 17.5, p<0.01) compared to patients who did not receive GI consultation. The precipitants of HE were significantly different between the groups: there was more spontaneous bacterial peritonitis (SBP) and GI bleeding (GIB) in the GI consult group and more lactulose non-adherence in the no consult group. There was no difference in the etiology of liver disease between the two groups. Median LOS for the GI consult group was six days vs three days in the no consult group (p<0.01); the incidence rate ratio was 1.79 (95%CI 1.59-2.02, p<0.01) on multivariate analysis. There was no difference in 30-day readmission or 90-day mortality between the two groups.  Conclusion GI consultation for patients with HE admitted to a hospital medicine service may be associated with longer LOS. In selected patients admitted with HE, GI consultation may not be necessary to achieve good clinical outcomes.

Imaging Artificial Intelligence: A Framework for Radiologists to Address Health Equity, From the AJR Special Series on DEI.

Artificial intelligence (AI) holds promise for helping patients access new and individualized health care pathways while increasing efficiencies for health care practitioners. Radiology has been at the forefront of this technology in medicine; many radiology practices are implementing and trialing AI-focused products. AI also holds great promise for reducing health disparities and promoting health equity. Radiology is ideally positioned to help reduce disparities given its central and critical role in patient care. The purposes of this article are to discuss the potential benefits and pitfalls of deploying AI algorithms in radiology, specifically highlighting the impact of AI on health equity; to explore ways to mitigate drivers of inequity; and to enhance pathways for creating better health care for all individuals, centering on a practical framework that helps radiologists address health equity during deployment of new tools.

Expert consensus on improving iron deficiency anemia management in obstetrics and gynecology in Asia.

Iron deficiency anemia (IDA) is a major health burden among women in Asia. Key issues in IDA management in Asia are under-diagnosis and under-treatment. The lack of Asia-specific guidelines, and suboptimal utilization of treatment compounds the management of IDA. To address these gaps, a panel of 12 experts in obstetrics, gynecology, and hematology from six regions in Asia convened to review current practices and clinical evidence and provide practical guidance on IDA diagnosis and management in Asian women. The Delphi approach was used to obtain objective opinions and attain consensus on statements pertaining to awareness, diagnosis, and management of IDA. In total, 79 statements attained consensus and are summarized to provide guidance on raising awareness of IDA and approaches for improved diagnosis and treatment of IDA among women in various settings: pregnancy, postpartum, heavy menstrual bleeding, gynecologic cancers, and perioperative care. This clinician-led consensus integrates appropriate recommendations based on clinical evidence and best practices and is intended to guide decision making in the management of iron deficiency/IDA in women. The expert panel raises a call for timely diagnosis and utilization of appropriate treatment, including use of high-dose intravenous iron, stringent blood management, and interdisciplinary collaboration, for optimization of IDA management among women in Asia.

Combined heart-liver transplantation practices survey in North America: Evaluation and organ listing practices.

We conducted a web-based survey to characterize liver transplant (LT) evaluation and listing practices for patients being evaluated for combined heart-liver transplantation (CHLT), with a specific emphasis on patients with congenital heart disease (CHD), around transplant centers in North America. Very few protocols for liver evaluation and listing in patients undergoing combined heart-liver transplantation are published, and no guidelines currently exist on this topic. A subject of intense debate in the transplant community is the decision of which patients with CHD and liver disease benefit from CHLT compared with heart transplantation. A focus group from the American Society of Transplantation Liver-Intestine Community of Practice Education Subcommittee developed a web-based survey that included questions (1) respondee demographic information; (2) LT evaluation practices in CHLT; (3) liver organ listing practices in CHLT, and (4) 4 clinical vignettes with case-based scenarios in CHLT liver listings among CHD patients who underwent Fontan palliation. The survey was distributed to medical and surgical LT program directors of 47 centers that had completed at least 1 CHLT up to July 2021 in the US and the University of Toronto, Canada. The survey had an excellent 83% response rate (87% for centers that completed at least 1 CHLT in the past 5 y). Total 66.7% used transjugular liver biopsy with HVPG measurements, 30% used percutaneous liver biopsy with no consensus on the use of a fibrosis staging system, 95% mandated contrasted cross-sectional imaging, and 65% upper endoscopy. The following isolated findings evaluation mandated CHLT listing: isolated elevated HVPG (61.5%); the presence of portosystemic collaterals on imaging (67.5%); the endoscopic presence of esophageal or gastric varices (75%), and the presence of HCC (80%), whereas the majority of centers did not feel that the presence of isolated splenomegaly (100%), thrombocytopenia (81.6%), endoscopic findings of portal hypertensive gastropathy (66.7%), or highly sensitized patients (84.6%) justified CHLT. In our survey of North American centers that had performed at least 1 CHLT in the past 5 years, we observed heterogeneity in practices for both evaluation and listing protocols in these patients.

Late-Onset Rejection in Liver Allograft Biopsies: An Analysis of Process, Pattern, and Clinical Implications.

OBJECTIVES: Both alloimmune and nonalloimmune factors affect the long-term survival of liver allograft recipients. Various patterns of late-onset rejection are recognized, including typical acute cellular rejection (tACR), ductopenic rejection (DuR), nonspecific hepatitis (NSH), isolated central perivenulitis (ICP), and plasma cell-rich rejection (PCRR). This study compares the clinicopathologic features of late-onset rejection (LOR) in a large-cohort context. METHODS: For-cause liver biopsies more than 6 months after transplant were included from the University of Minnesota between 2014 and 2019. Histopathologic, clinical, laboratory, treatment, and other data were analyzed in nonalloimmune and LOR cases. RESULTS: The study consisted of 160 patients (122 adults, 38 pediatric patients), with 233 (53%) biopsies showing LOR: 51 (22%) tACR; 24 (10%) DuR; 23 (10%) NSH; 19 (8%) PCRR; and 3 (1%) ICP. Mean onset of 80 vs 61 months was longer for nonalloimmune injury (P = .04), a difference lost without tACR (mean, 26 months). Graft failure was highest with DuR. Response to treatment, as measured by changes in liver function tests, was similar between tACR and other LORs, and NSH occurred more often in pediatric patients (P = .001); tACR and other LOR incidence was similar. CONCLUSIONS: LORs occur in pediatric and adult patients. Except for tACR, patterns overlap in many ways, with DuR having the greatest risk of graft loss, but other LORs respond well to antirejection treatments.

Lower survival and higher rates of cirrhosis in patients with ROUX-EN-Y gastric bypass hospitalised with alcohol-associated hepatitis.

OBJECTIVE: The incidence of alcohol-associated liver disease (ALD) is increasing, and weight loss surgery is more common due to the obesity epidemic. Roux-en-Y gastric bypass (RYGB) is associated with alcohol use disorder and ALD; however, its impact on outcomes in patients hospitalised for alcohol-associated hepatitis (AH) is unclear. DESIGN: We performed a single-centre, retrospective study of patients with AH from June 2011 to December 2019. Primary exposure was the presence of RYGB. The primary outcome was inpatient mortality. Secondary outcomes included overall mortality, readmissions and cirrhosis progression. RESULTS: 2634 patients with AH met the inclusion criteria; 153 patients had RYGB. Median age of the entire cohort was 47.3 years; median Model for End Stage Liver Disease - Sodium (MELD-Na) was 15.1 in the study group versus 10.9 in the control group. There was no difference in inpatient mortality between the two groups. On logistic regression, increased age, elevated body mass index, MELD-Na >20 and haemodialysis were all associated with higher inpatient mortality. RYGB status was associated with increased 30-day readmission (20.3% vs 11.7%, p<0.01), development of cirrhosis (37.5% vs 20.9%, p<0.01) and overall mortality (31.4% vs 24%, p=0.03). CONCLUSIONS: Patients with RYGB have higher rates of readmissions, cirrhosis and overall mortality after discharge from hospital for AH. Allocation of additional resources on discharge may improve clinical outcomes and reduce healthcare expenditure in this unique patient population.

Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype.

HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ART-naive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.