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Outcomes of Simultaneous Liver and Kidney Transplant vs. Liver Transplant Alone: Insights from a Midwest Transplant Center
No full textPurpose: We aimed to evaluate long-term renal and survival outcomes in patients with chronic kidney disease (CKD) undergoing liver transplantation alone (LTA) versus simultaneous simultaneous liver and kidney transplant (SLK). Methods: A retrospective study included adult CKD patients (GFR \u3c60 for ≥3 months pre-transplant) who underwent LTA or SLK at our center (2015-2022). Data collected covered demographics, comorbidities, liver disease, and dialysis status. The primary outcome was GFR at 3 months pre-transplant and 3, 6, 12, and 36 months post-transplant. Secondary outcomes included LOS, 1-year readmission, rejection, retransplantation, and mortality at 1, 3, and 5 years. Results: Our study included 231 patients: 67 underwent SLK, and 164 received LTA. Patient characteristics are in Table 1. Cirrhosis was the primary transplant indication in 193 patients (97%), mostly due to alcohol. The SLK group had higher creatinine on transplant day, pre-transplant HRS, and significantly lower pre-transplant GFR (22.1 ± 11.7 vs. 47.8 ± 15.6, p \u3c 0.001). Both groups showed GFR improvement (p \u3c 0.01), but SLK had consistently higher post-transplant GFR, especially at 3 months (65.8 ± 24.5 vs. 52.3 ± 19.0, p \u3c 0.01) (Figure 1). GFR decline was greater in LTA (p \u3c 0.01). Mortality (28% vs. 20%, p = 0.14) and LOS (13 days, p = 0.3) were similar. Pre- or emergent post-transplant dialysis prolonged hospital stay (p \u3c 0.01, p \u3c 0.027). No significant differences were found in readmission (68% SLK vs. 63% LTA, p = 0.4) or re-transplantation (6.7% vs. 9.4%, p = 0.9). Graft rejection was higher in SLK (23% vs. 17%) but not significant (p = 0.3). Conclusions: Our study shows that SLK transplant provided better long-term renal preservation in patients with CKD. Mortality,LOS,readmission, and re-transplant rates were similar between groups,suggesting that SLK does not significantly increase perioperative risk or resource use. [Formula presented] CITATION INFORMATION: Abusuliman M., Kadouh A., Aburumman R., Rosario A., Pradeep A., Cox T., Rehman S., Klutke J., Saleem A., Alomari A., Abusuliman A., Amreia M., Arwani R., Dababneh Y., Khan M., Jafri S. Outcomes of Simultaneous Liver and Kidney Transplant vs. Liver Transplant Alone: Insights from a Midwest Transplant Center AJT, Volume 25, Issue 8 Supplement 1 DISCLOSURES: M. Abusuliman: None
Intestinal Transplantation for Short Bowel Syndrome from Gun Shot Wounds: A Case Series
No full textPurpose: Short bowel syndrome (SBS) is a malabsorption disorder leading to nutritional deficiencies and high morbidity. Gunshot wounds (GSWs) and other abdominal traumas are known causes of SBS. Intestinal transplantation offers a unique therapeutic option for this patient population; however, outcomes are not well elucidated. We present two cases of patients who developed SBS secondary to GSWs, underwent intestinal transplantation, and subsequently required transplant enterectomy. Methods: We evaluated patients with SBS due to GSW receiving an intestinal transplant at a single center for outcomes including rejection, infection, graft survival, and patient survival. Results: Two males sustained GSWs necessitating small bowel and colon resection, leading to SBS that became dependent on parenteral nutrition with multiple line-related complications. Both patients underwent isolated small bowel transplantation. Patient 1: A 21-year-old underwent transplant with post operative course remaining largely unremarkable for 102 months until he presented with abdominal pain and found to be in cellular and humoral rejection. He developed septic shock due to bacteremia and adenovirus enteritis and did not respond to medical management, necessitating eventual transplant enterectomy. Afterwards, he was managed with parenteral nutrition, however clinical course was complicated by multiple infections and opioid misuse. Patient ultimately expired 12 months post-transplant enterectomy. Patient 2: A 37-year-old underwent transplant and remained hospitalized for 41 days afterwards. Three weeks post-transplant he was noted to have cellular and humoral rejection requiring plasmapheresis and immunoglobulin. Approximately 12 months post-transplant, he presented with septic shock and multiorgan failure. Endoscopy revealed ulcerated and friable mucosa, leading to transplant enterectomy. Despite surgical intervention, his clinical status deteriorated, and he expired shortly thereafter. Conclusions: Patients undergoing intestinal transplantation for SBS secondary to GSW represent a unique and understudied population. These cases highlight the significant risks of rejection, transplant enterectomy, and morbidity. Despite these risks, outcomes are robust as illustrated with the first patient who had many years of normal bowel function, post-transplant. Further research is warranted to optimize management strategies and improve survival rates for this vulnerable population as advancements in transplantation continue. CITATION INFORMATION: Nabaty R., Muszkat Y., Nagai S., Beltran N., Pietrowsky T., Jafri S. Intestinal Transplantation for Short Bowel Syndrome from Gun Shot Wounds: A Case Series AJT, Volume 25, Issue 8 Supplement 1 DISCLOSURES: R. Nabaty: None
LONG-TERM SAFETY OF SELADELPAR 10 MG WITH UP TO 5 YEARS OF TREATMENT IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS
No full textIntroduction The Phase 3, placebo-controlled RESPONSE study (NCT04620733) of seladelpar, a first-in-class delpar (selective PPAR-delta agonist), in primary biliary cholangitis (PBC) patients with an inadequate response or intolerance to ursodeoxycholic acid demonstrated significant improvements in cholestatic markers and pruritus with seladelpar over 1 year and similar proportions of adverse events (AEs) and serious AEs (SAEs) between the seladelpar and placebo groups. To assess long-term safety, data from all PBC patients exposed to seladelpar 10 mg in 6 studies with similar entry criteria were pooled. Methods AE data from 2 placebo-controlled and 4 open-label studies were pooled for all patients treated with seladelpar 10 mg as of 31 Jan 2024, beginning with first exposure to seladelpar, including all exposure periods and excluding treatment gaps. Placebo exposure was pooled from the 2 placebo-controlled studies. Exposure-adjusted patient incidences of AEs, SAEs, and AEs of interest (defined as liver-, muscle-, and renal-related AEs) were calculated. Results As of the data cutoff, a total of 486 patients received seladelpar 10 mg: 355 were treated for ≥1 year; 170, ≥2 years; 66, ≥3 years; 36, ≥4 years; and 10, ≥5 years. The exposure-adjusted patient incidence (per 100 patient-years) for seladelpar 10 mg was 48.3 for AEs, 8.0 for SAEs, 9.8 for Grade ≥3 AEs, and 6.1 for liver-related AEs (table 1). There were no treatment-related SAEs. Muscle and renal AEs occurred in \u3c7 patients per 100 patient-years. Placebo exposure included 152 patients: 117 were treated for ≥12 weeks, 84 for ≥6 months, and 57 for 12 months of placebo treatment in RESPONSE. The exposure-adjusted patient incidence (per 100 patient-years) for patients treated with placebo was 132 for AEs (rate reflective of shorter exposure time for placebo patients), 7.8 for SAEs, 12.2 for Grade ≥3 AEs, and 13.3 for liver-related AEs (with other AEs of interest occurring at lower rates). AEs leading to treatment discontinuation occurred in 2.9 patients per 100 patient-years in seladelpar patients and 5.6 per 100 patient-years in placebo patients. Conclusions Analysis of a large safety database for seladelpar in PBC patients with exposure through 5 years indicated that seladelpar was well tolerated with a safety profile similar to placebo
Complications of TPN in cirrhotic population
No full textBackground This retrospective study seeks to illuminate complications in cirrhotic patients receiving TPN. TPN is generally started in patients with cirrhosis due to moderate to severe malnutrition. TPN-associated decompensation can be Serious and even progress to the liver. In our study, we look for complications due to decompensation and its contribution to overall mortality. Methods A retrospective chart review was conducted of all adults (18 years or older) at our center (2014-2024) with a history of Cirrhosis while on TPN. Data on basic patient demographics, indication for TPN, Duration of TPN therapy, changes in TPN formulation, and mortality were collected. Results In the study, a total of 12 107 patients had cirrhosis at the time of TPN initiation. Mortality was seen in 9 12 cirrhotics as compared to 43 95 non-cirrhotics. 4 12 cirrhotics had line infection, 0 12 had line clots, 7 12 had worsening ascite. A statistically significant difference in mortality was not observed. The association between cirrhosis and time from peak LFT to death was significant with p- 0.025 in which cirrhotics had a longer time between peaking LFT with 240 days compared to 70.55 days in non-cirrhotic. Conclusions Our findings suggest that TPN is associated with decompensation with ascites being the most common complication likely in the setting of volume overload. However, mortality is not significantly associated with pre-existing cirrhosis, rather cirrhosis had a larger difference between peak value and death. This can indicate that cirrhotic decompensation generally occurs slowly over time whereas non-cirrhotic generally die of liver failure which has a short course till death. The size of the study is extremely small and the external validity of the data can be questionable. This underscores the need for further research to identify an association between cirrhosis and TPN.
Safety of Transesophageal Echocardiography in Patients Referred for Tricuspid Valve Disease at a Center for Structural Heart Disease
No full textOBJECTIVES: The aim of this study was to examine safety outcomes in patients referred for transesophageal echocardiograms (TEEs) for tricuspid valve disease.
DESIGN: Retrospective observational study.
SETTING: Single quaternary referral center specializing in structural heart disease.
PARTICIPANTS: One hundred five patients referred for TEE for tricuspid valve disease between July 2022 and June 2023.
INTERVENTIONS: This study was not interventional, but assessed the safety of TEE.
METHODS AND MAIN RESULTS: The primary outcome was a composite of hypotension (mean arterial pressure [MAP] \u3c 60 mmHg); use of epinephrine, norepinephrine, or calcium chloride; aborted studies due to documented clinical instability; emergent intubation; hospitalization or escalation of care post-TEE; oropharyngeal or gastrointestinal injury; or cardiac arrest. Secondary outcomes were 30-day cardiovascular mortality, all vasopressor use, and time spent per TEE. The primary outcome was noted in 32 patients (30.5%). The rate of cardiac arrest was 2.9% (3/105). Hypotension (MAP \u3c 60 mmHg) was noted in 30 patients, with 7 patients needing hospitalization after TEE. No patients had oropharyngeal or gastrointestinal injury. There was a greater prevalence of moderate to severe right ventricular (RV) dilation (77% vs 53%; p = 0.022) and moderately to severely decreased RV function (48% vs 25%; p = 0.023) in patients who met the primary outcome. Both RV fractional area change (37.9% vs 29.8%; p = 0.003) and tricuspid annular plane systolic excursion (1.84 cm vs 1.45 cm; p = 0.002) were lower on baseline transthoracic echocardiogram.
CONCLUSIONS: Patients with severe tricuspid regurgitation had a high prevalence of adverse events when undergoing TEE. Further studies are needed to compare these outcomes with other groups undergoing diagnostic TEE and delineate what risk factors may place these patients at greater risk
Managing Cardiogenic Shock Caused by Acute Myocardial Infarction: Invisible Challenges Revealed in a Statewide Registry
No full textDeucravacitinib: Laboratory Parameters Across Phase 3 Plaque Psoriasis Trials
No full textINTRODUCTION: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the USA and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. In POETYK PSO-1 and PSO-2, deucravacitinib was superior to placebo and apremilast and well tolerated in patients with plaque psoriasis. Patients who completed PSO-1/PSO-2 could enroll in the POETYK long-term extension (LTE) trial. This analysis evaluates the effects of deucravacitinib on laboratory parameters.
METHODS: POETYK PSO-1 and PSO-2 were 52-week, phase 3, double-blinded trials that randomized patients 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At week 52, eligible patients enrolled in POETYK LTE and received open-label deucravacitinib. Mean changes from baseline in laboratory parameters, laboratory adverse events (AEs), and laboratory AEs resulting in discontinuation were evaluated over 3 years.
RESULTS: A total of 1519 patients received one or more doses of deucravacitinib across trials. Total exposure over 3 years was 3294.3 person-years. No clinically relevant mean changes were observed in laboratory parameters. Grade ≥ 3 laboratory AEs were infrequent during the 1-year period, with incidence rates remaining stable in patients treated with deucravacitinib through 3 years. Most laboratory AEs remained at the same grade; shifts to higher grades were infrequent, with most increases being to grade ≤ 2. Discontinuations due to laboratory AEs were rare.
CONCLUSIONS: Deucravacitinib did not result in clinically meaningful changes in laboratory parameters over 3 years, including changes seen with Janus kinase (JAK) 1,2,3 inhibitors. Grade ≥ 3 laboratory AEs and discontinuations were rare.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, POETYK PSO-1 (NCT03624127), POETYK PSO-2 (NCT03611751), POETYK LTE (NCT04036435)
Updating the American Association of Physicists in Medicine (AAPM) Diagnostic Radiology Resident Physics Curriculum: Strategies, Content, and Dissemination
No full textRATIONALE AND OBJECTIVES: The Diagnostic Radiology Resident Physics Curriculum (DRRPC), initiated in 2007 by the American Association of Physicists in Medicine (AAPM) and last updated in 2018, is an essential educational resource for those teaching physics to radiology residents. Regular updates are crucial to ensure the curriculum aligns with evolving technologies and clinical practices, maintaining its relevance and effectiveness in educating the next generation of radiologists. The paper aims to describe the update strategies of the DRRPC, focusing on the current iteration, its structure, and the newest updates.
MATERIALS AND METHODS: The update process, led by the Diagnostic Radiology Resident Physics Curriculum Working Group, commenced with a comprehensive survey targeting AAPM members who contribute to radiology physics teaching. The survey was conducted to assess the curriculum\u27s current applicability and gather feedback for improvements. Subsequent updates were based on extensive stakeholder consultations and detailed analysis of survey data.
RESULTS: The revision process has led to significant enhancements in the curriculum, emphasizing practical clinical applications and the integration of cutting-edge technology. New modules on advanced image processing, artificial intelligence, informatics, and radiopharmaceutical therapy were developed, responding to the evolving needs of radiological education and practice.
CONCLUSION: The updated DRRPC supports educators in providing a dynamic and relevant training experience
Enhancer of zeste homolog 2 (EZH2) in endocrine tumors: current knowledge and future directions
No full textINTRODUCTION: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that orchestrates gene expression via epigenetic and non-epigenetic mechanisms. EZH2 performs epigenetic functions by methylating histones and/or non-histone proteins and suppressing or activating target genes. Moreover, non-epigenetic functions involve dysregulation of target genes independent of histone methylation, thereby impacting multiple signaling pathways.
AREAS COVERED: EZH2 has emerged as a pivotal player in the initiation of various cancers. EZH2 overexpression facilitated by H3K27me3 is the principal driver. However, the consequent dysregulation of target genes resulting from EZH2 overexpression has emerged as a secondary instigator of tumorigenesis, leading to metastasis and poor prognosis. Further complexity arises from somatic mutations in EZH2 and downstream target genes such as BRAF and RASSF1A. However, understanding its effects on endocrine tumors/cancers remains an underexplored with the potential to significantly enhance clinical outcomes and contribute to human health. Therefore, the present review focuses on the multifaceted functions of EZH2 and its pathophysiological mechanisms in tumor proliferation, with a specific emphasis on endocrine tumors.
EXPERT OPINION: Investigating EZH2 mechanisms and targeting with inhibitors and drugs is an active area of research that could offer a promising avenue for treatment and a better understanding of molecular therapeutic interventions
Substance Use Disorders and Interprofessional Management in the Pre and Post Liver Transplant Settings
No full textSubstance use disorders (SUDs) are rising in the general population and also in the transplant population. Alcohol use disorder leading to alcohol-associated liver disease is the most common of all SUDs in the liver transplantation setting. Uncontrolled SUDs and relapse after transplant can lead to graft loss and mortality, as well as reduce quality of life and patient functioning. SUDs can be treated effectively through integrated, interprofessional management by addiction and medical/surgical professional members of the transplant team. Teams should be aware of pitfalls in interprofessional teamwork and communication so that corrective steps could be implemented for improved efficiency