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Management of Graft versus Host Disease Involving the Bone Marrow: Interventions and Outcomes
No full textPurpose: Cytopenias can significantly impact patient outcomes in the immediate post-solid organ transplant period, and they can result from acute graft-versus-host disease (GVHD), though this is less frequent. This study aims to detail our single-center experience with GVHD with bone marrow involvement in patients who underwent liver transplantation (LT) over 10 years. Methods: We reviewed medical charts for patients who underwent LTs at Henry Ford Hospital Transplant Center from January 2014 to December 2023. We recorded all confirmed cases of GVHD with bone marrow involvement after LT. We collected information on their demographics, details of the liver transplant, and how GVHD was presented, diagnosed, and treated. Results: Out of 1,045 LTs performed at our center, 17 patients (1.6%) developed GVHD after transplantation. Of them, 8 had bone marrow involvement that presented in all patients as pancytopenia. Most of them were male (75%) and white (50%). The mean age at presentation was 67 ± 5. The most common indication for transplant was metabolic dysregulation associated steatotic liver disease (MASLD) in 50% of patients. All patients received liver from deceased donor. The average time from transplantation to first symptom reported was 34 days (± 16.4 SD). 7 out of the 8 patients also had skin involvement that presented as a rash (87.5%). Gastrointestinal tract involvement was seen in 62.5% of them and presented as diarrhea in all cases. One patient also had involvement of their central nervous system, which presented as altered mental status and diagnosed with a lumbar puncture. At presentation, a short tandem repeat (STR) test on patients’ peripheral blood demonstrated the presence of a mean of 20.9% (± 31.1%) donor DNA. All patients received high-dose steroids as part of their treatment. 87.5% of them also received Etanercept as part of the treatment regimen, and half of them also received Photopheresis. Only one patient (12.5%) survived for more than 1 year after initial presentation, compared to 78% of patients with GVHD post LT who did not have bone marrow involvement. Conclusions: GVHD after solid organ transplantation typically presents with rash, diarrhea, fever, and pancytopenia 2 to 8 weeks after transplantation. Cytopenia has been described to confer a worse outcome. The lack of clinical trials for GVHD treatment limits an effective therapeutic strategy, and treatment outcomes of GVHD post liver transplant tend to be poor, with \u3e85% mortality rate. [Formula presented] CITATION INFORMATION: Aburumman R., Tahmazian S., Nimri F., Jafri S. Management of Graft versus Host Disease Involving the Bone Marrow: Interventions and Outcomes AJT, Volume 25, Issue 8 Supplement 1 DISCLOSURES: R. Aburumman: None
Cardiovascular disease and gastrointestinal cancers: Mortality trends and persistent disparities in the U.S
No full textBackground: Cardiovascular disease (CVD) is a significant contributor to mortality among patients with gastrointestinal tract (GIT) cancers. This study analyses changes in age-adjusted mortality rates (AAMRs) for CVD in GIT cancer patients in the U.S. from 1999 to 2020, focusing on demographic and geographic disparities. Methods: CVD-related deaths in GIT cancer patients aged ≥25 years were examined using CDC WONDER data. AAMRs per 100,000 individuals were calculated, and trends were assessed via annual percentage changes (APCs) and average annual percentage changes (AAPCs). Results: Between 1999 and 2020, 921,107 CVD deaths occurred among GIT cancer patients. The overall AAMRdecreased from 230.0 in 1999 to 190.7 in 2020, with an AAPC of -0.97∗ (p\u3c 0.000001). Men had higher AAMRs (255.3) than women (144.4), though women experienced a greater decline (AAPC: -1.44∗, p\u3c 0.000001) compared to men (AAPC: -0.88∗, p\u3c 0.000001). Black individuals exhibited the highest AAMR (273.03), followed by Hispanics (199.3), Asians Pacific Islanders (190.0), American Indians (182.75), and Whites (180.87). Asians Pacific Islanders showed the steepest decline (AAPC: -2.56∗, p\u3c 0.000001). Geographically, New York had the highest AAMR (318.73), while Utah recorded the lowest (98.05). Nonmetropolitan areas showed higher AAMRs than metropolitan areas but smaller declines (AAPC: -0.15∗, p = 0.003 vs. -1.13∗, p\u3c0.000001). Conclusions: Despite overall declines in CVD mortality among GIT cancer patients, significant disparities persist by gender, race, and geography. Targeted interventions are needed to address these inequalities and further reduce the burden of CVD among this vulnerable population
Outcomes of Intestinal Biopsies Which Are Indeterminate for Rejection Following Intestine Transplant
No full textPurpose: We evaluated the impact of “indeterminate for rejection” (IFR) biopsy results and subsequent clinical outcomes. We aim to evaluate whether changes in immunosuppressive medications and cytomegalovirus (CMV) status at the time of IFR biopsy influence the likelihood of a subsequent biopsy also being classified as IFR or showing a definitive rejection outcome. Methods: Retrospective analysis of adult patients who underwent intestinal transplantation, including those who received multi-organ transplants with intestine with at least one biopsy classified as IFR. Data collected includes immunosuppressive changes, subsequent biopsy results, and infection status. Results: We evaluated 31 patients with long term follow-up following IFR biopsy. 17 (55%) were female. Mean age at time of transplant was 48 years (22-68). 18 (57.9%) patients had intestine transplant only, 13 had multiorgan transplant. There were 84 recorded instances of IFR biopsy results. 54 instances (64%) led to immunosuppression changes, while 30 (36%) did not. 4% of patients in the immunosuppression change group (ICG) and 7% in the no-change group (NCG) had positive CMV PCR at the time of biopsy. In ICG, 69% of cases were negative for rejection on follow-up biopsy. In NCG, 60% were negative for rejection on follow-up biopsy. Persistent indeterminate classification was observed in 9.3% of ICG cases and 20% of NCG. Mild rejection occurred in 20% of ICG cases and 17% of NCG cases. Moderate rejection was seen in 1.9% of ICG cases and 0% of NCG cases. Severe rejection was seen in 0% of ICG cases and 3.3% of NCG cases. There were no statistically significant differences between the two groups (Odds Ratio [OR] = 1.27, 95% Confidence Interval [CI]: 0.47-3.38, p = 0.6). A secondary analysis focused on only the first instance of an IFR biopsy for each patient. 71% of these cases were ICG. 77% of these ICG cases showed subsequent results negative for rejection. 44% of NCG cases showed negative subsequent results for rejection. Persistent IFR occurred in 4.5% of ICG cases and 22% of NCG. Mild rejection occurred in 14% of ICG cases and 22% of NCG. Moderate rejection occurred in 4.5% of ICG and 0% of NCG. Severe rejection occurred in 0% of ICG and 11% of NCG. Conclusions: While medication adjustments were frequently implemented following IFR biopsy, their effect on subsequent biopsy results was not statistically significant. The majority of patients who underwent immunosuppression changes had negative subsequent biopsy outcomes, similar to those without immunosuppression changes. The study highlights the complexity of managing IFR biopsy results in transplant recipients and underscores the need for further research to better understand the appropriate response to IFR biopsy. CITATION INFORMATION: Malick A., Tepe G., Nagai S., Muszkat Y., Beltran N., Pietrowsky T., Jafri S. Outcomes of Intestinal Biopsies Which Are Indeterminate for Rejection Following Intestine Transplant AJT, Volume 25, Issue 8 Supplement 1 DISCLOSURES: A. Malick: None
Outcomes and Risk Factors for Post-Operative Rejection and Transaminitis Following Dual Liver-Lung Transplantation: A Retrospective Cohort Study
No full textPurpose: Dual liver-lung transplantation (DLLT) is a rare and complex procedure, with limited data on post-operative rejection and liver function abnormalities. Understanding risk factors for acute cellular rejection and transaminitis is critical for optimizing immunosuppressive management. This study evaluates post-transplant outcomes in DLLT recipients and explores associations with recipient demographics, transplant indication, and underlying liver lung disease etiology. Methods: A retrospective analysis was conducted on patients at our center who underwent DLLT between 2013 and 2024. Data collected included demographics, transplant indications, length of stay, incidence of acute rejection, and subsequent infections. Post-operative liver function tests (LFTs) beyond one month post-transplant were analyzed, and their relationship with age at transplant, liver disease etiology, and lung disease etiology was assessed. Results: A total of 10 patients (5 males, 5 females, mean age 53.7 years) underwent DLLT between 2013 and 2024. Liver disease etiologies were ethanol-related cirrhosis (n=2), hepatitis C (n=1), cryptogenic cirrhosis (n=1), autoimmune hepatitis (n=1), cystic fibrosis (n=1), and other unspecified causes (n=4). Lung transplant indications included idiopathic pulmonary fibrosis (n=5), pulmonary hypertension (n=2), other forms of interstitial lung disease (n=2), and cystic fibrosis (n=1).Post-operatively, 4 of 10 patients developed transaminitis beyond one month post-transplant, with liver biopsy confirming acute cellular rejection. Three patients received IV solumedrol, while one was managed with an oral steroid taper. Transaminitis resolved in all four cases after steroid treatment. Within three months, two patients treated with IV solumedrol developed infections from Candida and Aspergillus, though none developed CMV viremia. Two deaths occurred in the cohort. One patient passed away four years after transplant due to multifocal pneumonia, while the second patient passed away nine years post-transplant due to septic shock secondary to pneumonia in the setting of a new diagnosis of angiosarcoma. Neither patient had experienced rejection. Rejection and transaminitis were not significantly associated with age at transplant, liver disease etiology, or lung disease etiology. Conclusions: This study provides one of the first detailed assessments of rejection and liver function abnormalities following DLLT. While transaminitis and acute cellular rejection occurred in 40% of patients, no clear predisposing factors were identified. IV solumedrol use for rejection was associated with increased infection risk, emphasizing the need for careful immunosuppressive management in this population. Further research with larger cohorts is essential to improve risk stratification and post-transplant care in DLLT recipients. CITATION INFORMATION: Saleem A., Obri M., Ilyas O., Alomari A., Faisal M., Abusuliman M., Chaudhary A., Rehman S., Franco-Palacios D., Nagai S., Venkat D., Jafri S. Outcomes and Risk Factors for Post-Operative Rejection and Transaminitis Following Dual Liver-Lung Transplantation: A Retrospective Cohort Study AJT, Volume 25, Issue 8 Supplement 1 DISCLOSURES: A. Saleem: None
Characterization and Risk Factors for Readmission and Emergency Department Presentations in Dual Liver-Lung Transplantation Patients
No full textPurpose: Dual liver-lung transplantation (DLLT) is a rare procedure, with limited data characterizing patient demographics, risk factors, and post-transplant outcomes, particularly regarding hospital readmissions and emergency department (ED) presentations. This study aims to assess the rates of hospital readmission, ED presentations, and associated risk factors in DLLT recipients. Methods: A retrospective analysis was conducted on patients at our center who underwent DLLT between 2013 and 2024. Demographics, transplant indications, length of stay, acute rejection, causes of readmission, and ED presentations were analyzed. Readmission rates were categorized as occurring within 0-3 months and between 3 months and 1 year post-transplant. Mortality outcomes were also assessed. Results: Ten patients (5 male, 5 female) with a mean age of 53.7 years underwent DLLT. Liver disease etiologies were ethanol-related cirrhosis (n=2), hepatitis C (n=1), cryptogenic cirrhosis (n=1), autoimmune hepatitis (n=1), cystic fibrosis (n=1), and other unspecified causes (n=4). Lung transplant indications included idiopathic pulmonary fibrosis (n=5), pulmonary hypertension (n=2), interstitial lung disease (n=2), and cystic fibrosis (n=1). All patients (100%) were readmitted within 3 months, and 40% experienced additional readmissions within the first year. The most common causes of early readmissions (0-3 months) included infections (40%), diarrhea (20%), critical illness myopathy (20%), rejection (10%), and biliary stricture (10%). ED presentations within 1 year occurred in 50% of patients, with leading causes including melena (n=2), tachycardia (n=1), fever (n=1), and gastrostomy tube dysfunction (n=1). Initial length of stay, lung transplant etiology, liver disease etiology, and age at transplantation were not associated with readmission or ED presentation rates (p\u3e0.05). Two patients (20%) died within 10 years post-transplant, one at 4 years and one at 8 years. Readmission within 1 year was not significantly associated with mortality at 5 or 10 years. Conclusions: DLLT recipients experience high rates of early readmission, with infections being the leading cause. ED presentations are common, with gastrointestinal and infectious concerns predominating. No significant associations were found between transplant etiology, initial hospital stay, or age at transplantation and readmission or ED presentation rates. Long-term mortality was not associated with early readmission. These findings underscore the need for enhanced post-transplant surveillance and targeted interventions to mitigate early complications. CITATION INFORMATION: Saleem A., Obri M., Ilyas O., Alomari A., Faisal M., Omeish H., Chaudhary A., Nagai S., Franco-Palacios D., Venkat D., Jafri S. Characterization and Risk Factors for Readmission and Emergency Department Presentations in Dual Liver-Lung Transplantation Patients AJT, Volume 25, Issue 8 Supplement 1 DISCLOSURES: A. Saleem: None
Outcomes Following Graft Enterectomy After Intestinal and Multivisceral Transplantation: A Multicenter Analysis
No full textPurpose: Graft enterectomy following intestinal transplantation (IT) or multivisceral transplantation (MVT) is a critical event that significantly impacts patient morbidity, survival, and long-term nutritional dependence. Data on IT failure requiring enterectomy and outcomes following enterectomy remain poorly defined. This study aims to describe the clinical outcomes of patients who underwent enterectomy after IT or MVT, providing insights into the post-enterectomy course. Methods: Retrospective analysis of 20 patients who underwent IT or MVT and subsequently required graft enterectomy from four transplant centers between 2012 and 2024. The primary outcome was patient survival analyzed by Kaplan-Meijer analysis. Secondary outcomes included retransplantation and infection within 3 months. Results: Among the 20 patients who underwent graft enterectomy following IT or MVT, there were 10 men and 10 women, with 55% receiving their transplants before the age of 18. The average age of the cohort at the time of enterectomy was 21 years, with a median age of 7 years. The average age of the pediatric patients was 4, and adult patients was 45. IT alone accounted for 75% of transplants, while 25% were MVT. Rejection was the primary indication for enterectomy in 100% of cases. MVT recipients were significantly more likely to undergo re-transplantation compared to IT recipients (p=0.01) and showed a trend toward improved survival (p=0.40). At 6 months and 1-year post-enterectomy, survival rates were 73% and 67% for IT recipients and 80% and 80% for MVT recipients, respectively. The pediatric transplant recipients had significantly increased survival compared to the adults (p=\u3c0.01). There was no significant difference between IT and MVT recipients in their development of PTLD or infection within 3 months of enterectomy. Conclusions: Graft enterectomy remains a significant event following IT and MVT, with rejection being its most common indication. MVT demonstrated a trend of higher survival and significantly higher re-transplantation rates compared to IT alone after enterectomy. Pediatric transplant recipients had higher survival rates than adult transplant recipients. Our findings highlight the need for improved immunosuppressive protocols and post-transplant monitoring to mitigate the risk of graft failure. Further research is warranted to enhance long-term survival and quality of life in this complex population. CITATION INFORMATION: Toiv A., Justus H., Sarowar A., Lee V., Marquez J., Altamura-Murgia G., Horslen S., Weiner J., Schiano T., Segovia M., Jafri S. Outcomes Following Graft Enterectomy After Intestinal and Multivisceral Transplantation: A Multicenter Analysis AJT, Volume 25, Issue 8 Supplement 1 DISCLOSURES: A. Toiv: None
The Society of Thoracic Surgeons National Intermacs Database Risk Model for Durable Left Ventricular Assist Device Implantation
No full textBACKGROUND: Statistical risk models for durable left ventricular assist device (LVAD) implantation inform candidate selection, quality improvement, and evaluation of provider performance. This study developed a 90-day mortality risk model using The Society of Thoracic Surgeons National Intermacs Database (STS Intermacs).
METHODS: STS Intermacs was queried for primary durable LVAD implants from January 2019 to September 2023. Multivariable logistic regression was used to derive a model based on preimplant risk factors by using derivation (2019-2021 implants) and validation (2022-2023 implants) cohorts. Model performance (derivation and validation cohorts) was assessed using C-statistics, Brier scores, and calibration plots. A refined model (all patients) was generated to calculate observed-to-expected (O/E; 95% CI) ratios for each center.
RESULTS: The study population consisted of 11,342 patients from 2019 to 2023 who were sequentially divided in time into derivation (n = 6775) and validation (n = 4567) cohorts. Ninety-day mortality was 8.0% (9.2% in the derivation cohort vs 7.4% in the validation cohort; P = .001). Logistic regression applied to derivation and validation cohorts produced similar discrimination (area under the curve [AUC], 0.714 [95% CI, 0.69-0.74]; and AUC, 0.707; [95% CI, 0.67-0.72], respectively) and calibration (Brier score, .08 vs .07), with overestimation of risk among patients with a predicted risk \u3e0.4. The O/E analysis identified 22 (12.5%) centers with worse than expected mortality with a 95% CI \u3e1.0 and 14 centers (8.0%) with better than expected mortality with a 95% CI \u3c1.0 (all P \u3c .05).
CONCLUSIONS: The STS Intermacs risk model demonstrated satisfactory discrimination and calibration. This tool may be used to inform candidate selection, facilitate quality improvement, and assess provider performance
Outcomes of Left Main Chronic Total Occlusion Percutaneous Coronary Interventions
No full textBACKGROUND: Percutaneous coronary intervention (PCI) of left main (LM) chronic total occlusions (CTO) has received limited study.
METHODS: We compared the clinical and procedural characteristics and outcomes of patients who underwent LM versus non-LM CTO PCI at 41 US and non-US centers between 2012 and 2024.
RESULTS: During the study period 85 of 15,254 CTO PCIs (0.6%) performed in 14,969 patients were LM CTO PCIs. LM CTO PCI patients were older, had higher rates of dyslipidemia and heart failure and most (88.8%) had prior coronary artery bypass graft surgery (CABG). They were more likely to have moderately or severely calcified lesions (80.7% vs. 45.7%, p \u3c 0.001) and had higher J-CTO (2.76 ± 1.17 vs. 2.37 ± 1.26, p = 0.008), PROGRESS-CTO MACE (3.56 vs. 2.57, p \u3c 0.001), Mortality (2.45 vs. 1.68, p \u3c 0.001), Pericardiocentesis (2.74 vs. 1.87, p \u3c 0.001), Acute MI (1.72 vs. 0.89, p \u3c 0.001) and Perforation (3.21 vs. 2.19, p \u3c 0.001) scores. There was no difference in technical success (80.5% vs. 87.2%, p = 0.086) or major cardiovascular adverse events (MACE) (2.4% vs. 2.0%, p = 0.700). LM CTO PCI patients with and without prior CABG surgery had similar technical success and MACE. The retrograde approach in prior CABG patients was more likely to be performed through saphenous vein grafts.
CONCLUSIONS: LM CTO PCI is infrequently performed, is associated with high comorbidity burden and angiographic complexity but can be performed with high success and acceptable complication rates
Beyond the Status of Health: A Collection of Stories Representing Diverse Maternal Mental Health Perspectives
No full textA Maximum-Use Trial of Ruxolitinib Cream in Children Aged 2-11 Years with Moderate to Severe Atopic Dermatitis
No full textBACKGROUND: Ruxolitinib cream has demonstrated anti-inflammatory and antipruritic activity and was well tolerated in a phase 3 study in patients aged 2-11 years with mild to moderate atopic dermatitis (AD).
OBJECTIVE: This study examined the safety, tolerability, pharmacokinetics, efficacy, and quality of life (QoL) with ruxolitinib cream under maximum-use conditions and with longer-term use.
METHODS: Eligible patients were aged 2-11 years with moderate to severe AD [Investigator\u27s Global Assessment (IGA) score 3-4], and ≥ 35% affected body surface area (BSA). Patients applied 1.5% ruxolitinib cream twice daily to all baseline-identified lesions during the 4-week maximum-use period, then to active lesions only up to week 52 (patients with ≤ 20% affected BSA from week 8). Safety was assessed by frequency and severity of adverse events. Pharmacokinetic parameters were assessed as secondary endpoints, and efficacy and QoL were exploratory endpoints.
RESULTS: Overall, 29 patients (median age 5 years) were enrolled. Treatment-emergent adverse events were reported in 9/29 patients (31.0%); there were no adverse events of special interest (i.e., no serious infections, malignancies, major adverse cardiovascular events, or thromboses) during the study period. Mean steady-state plasma concentration during the maximum-use period was below the known half-maximal inhibitory concentration of Janus kinase-mediated myelosuppression in adults. Reductions in affected BSA and IGA observed at week 4 were sustained with as-needed use through 52 weeks. Improvements in patient-reported outcomes and QoL measures were consistent with efficacy results.
CONCLUSION: These results support the safety of ruxolitinib cream in children (2-11 years) with AD, including those with extensive disease, and are consistent with previous efficacy findings.
GOV IDENTIFIER: NCT05034822, first registered 30 August 2021