Can Machine Learning Assist in Diagnosis of Primary Immune Thrombocytopenia? A Feasibility Study.

Primary Immune Thrombocytopenia (ITP) is a rare autoimmune disease characterised by the immune-mediated destruction of peripheral blood platelets in patients leading to low platelet counts and bleeding. The diagnosis and effective management of ITP are challenging because there is no established test to confirm the disease and no biomarker with which one can predict the response to treatment and outcome. In this work, we conduct a feasibility study to check if machine learning can be applied effectively for the diagnosis of ITP using routine blood tests and demographic data in a non-acute outpatient setting. Various ML models, including Logistic Regression, Support Vector Machine, k-Nearest Neighbor, Decision Tree and Random Forest, were applied to data from the UK Adult ITP Registry and a general haematology clinic. Two different approaches were investigated: a demographic-unaware and a demographic-aware one. We conduct extensive experiments to evaluate the predictive performance of these models and approaches, as well as their bias. The results revealed that Decision Tree and Random Forest models were both superior and fair, achieving nearly perfect predictive and fairness scores, with platelet count identified as the most significant variable. Models not provided with demographic information performed better in terms of predictive accuracy but showed lower fairness scores, illustrating a trade-off between predictive performance and fairness.

Donor Age More Than 20 Years Greater Than Recipient Age Is Associated With Worse 5 Year Survival in Young Adult Heart Transplantation.

Prior studies indicate donor age-recipient age (DA-RA) difference may be of prognostic value in adolescents, although not adults. We aim to analyze the relationship between DA-RA difference and long-term survival of young adult heart transplantation (HTx) recipients. First-time, single-organ HTx recipients aged 18-30 who underwent HTx between 2010 and 2020 were analyzed from the United Network for Organ Sharing (UNOS) registry. Four cohorts were created based on DA-RA difference. The primary outcome was 5 year post-HTx survival. Secondary outcome was post-HTx complications. One thousand eight hundred three donor-recipient pairs were divided into four groups: DA-RA < 0, 0 ≤ DA-RA < 10, 10 ≤ DA-RA < 20, and DA-RA ≥ 20 with 682 (37.8%), 651 (36.1%), 356 (19.7%), 114 (6.3%) pairs in each cohort, respectively. The estimated 5 year survival of the DA-RA ≥ 20 cohort was 66.5% compared to the other three groups at ~75%. After adjustment, DA-RA ≥ 20 was independently associated with worse survival compared to DA-RA < 0 (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.06-2.27; log-rank p = 0.008). There was no significant difference in complication incidence across cohorts. Among young adults, accepting a donor heart more than 20 years older than the recipient was associated with worse 5 year survival. We did not detect a significant difference up to 20 years. This information may help guide appropriate donor selection in the young adult population.

The Impact of Pre-Heart Transplantation Blood Transfusion Varies Based on Recipient MELD-XI Score.

Prior studies reveal adverse effects of transfusion on cardiac surgery, but little is known of transfusion impact on heart transplantation. First-time, single-organ adult heart transplant recipients between January 1, 2010, and December 31, 2020, were included, stratified above or below a model for end-stage liver disease excluding international normalized ratio (MELD-XI) score of 9.4, and propensity score matched to their nearest neighbor. A 90 day landmark analysis within each cohort was also performed. Unadjusted analysis showed transfusion recipients, MELD-XI ≥9.4, were more likely to experience post-heart transplantation mortality (Hazard Ratio (HR), 1.352 [95% Confidence Interval (CI), 1.239-1.477], p < 0.001), persisting after adjustment for potential confounders (adjusted HR, 1.211 [95% CI, 1.100-1.335], p < 0.001) and after propensity-score matching (HR, 1.174 [95% CI, 1.045-1.319], p = 0.007). Post-transplant length of stay was longer (25.9 vs. 23.2 days, p < 0.001). Post-transplant dialysis was more common (18.7 vs. 15.9%, p = 0.009). There was no survival difference on 90 day landmarked analysis (p = 0.108). With MELD-XI <9.4, there was slight survival detriment among transfusion recipients on univariable analysis (HR, 1.111 [95% CI, 1.001-1.234], p = 0.049) but not on multivariable analysis (adjusted HR, 1.061 [95% CI, 0.952-1.181], p = 0.285). There was similar survival after propensity-score matching (HR, 1.032 [95% CI, 0.903-1.180], p = 0.642) and on landmark analysis (p = 0.581). Ultimately, transfusion was associated with worse post-heart transplantation outcomes among recipients with a MELD-XI ≥9.4.

Blood type O heart transplant candidates have longer waitlist time and higher delisting under the new allocation system.

OBJECTIVE: Prior studies have examined the effect of blood type on heart transplantation (HTx) waitlist outcomes in cohorts through 2015. We aim to analyze the effect of blood type on contemporary waitlist outcomes with a new allocation system focus. METHODS: Adults listed for HTx between April 2015 and December 2020 were included. Survival to HTx and waitlist death/deterioration was compared between type O and non-type O candidates using competing risks regression. Donor/recipient ABO compatibility trends were further investigated. RESULTS: Candidates with blood type O (n = 7509) underwent HTx less frequently than candidates with blood type other than type O (n = 9699) (subhazard ratio [sHR], 0.56; 95% CI, 0.53-0.58) with higher rates of waitlist death/deterioration (sHR, 1.18; 95% CI, 1.04-1.34). Subgroup analyses demonstrated persistence of this trend under the new donor heart allocation system (HTx: sHR, 0.58; 95% CI, 0.54-0.62; death/clinical deterioration: sHR, 1.27; 95% CI, 1.02-1.60), especially among those listed at high status (1, 2, or 3) (HTx: sHR, 0.69; 95% CI, 0.63-0.75; death/deterioration: sHR, 1.61; 95% CI, 1.16-2.22). Among those listed at status 3, waitlist death/deterioration was modified by presence of a durable left ventricular assist device (left ventricular assist device: sHR, 1.57; 95% CI, 0.58-4.29; no left ventricular assist device: sHR, 3.79; 95% CI, 1.28-11.2). Type O donor heart allocation to secondary ABO candidates increased in the new system (14.5% vs 12.0%; P < .01); post-HTx survival remained comparable between recipients with blood type O and non-type O (log-rank P = .07). CONCLUSIONS: Further logistical considerations are warranted to minimize allocation inequity regarding blood type under the new allocation system.

The Use of Impella 5.5 for Donor-Heart Hemodynamic Support in Heart Transplantation.

Primary graft dysfunction is a feared complication and cause of mortality post-heart transplant. Primary graft dysfunction may require mechanical circulatory support, such as venoarterial extracorporeal membrane oxygenation, which carries its own risk for complications. We developed a new mechanical circulatory support method for patients who underwent heart transplant bridged with Impella 5.5, which was then placed into the donor heart. Among 12 heart transplants, four required Impella 5.5 support. The average age was 55.8 years. The mean duration for postoperative mechanical circulatory support was 3.8 days, ranging from 2 to 5 days. No patients developed severe right ventricular dysfunction. In our limited study, complications and mortality associated with the replanted Impella 5.5 were both 0%.

Heart Transplant Waitlist Outcomes and Wait Time by Center Volume in the Pre-2018 Allocation Change Era.

Although the transplant outcomes of centers are heavily monitored and compared, with a particular link between posttransplant outcomes and center volume demonstrated, little data exist comparing waitlist outcomes. Here, we explored waitlist outcomes by transplant center volume. We performed a retrospective analysis of adults listed for primary heart transplantation (HTx) from 2008 to 2018 using the United Network for Organ Sharing database. Transplant centers were split into low (<10 HTx/year), medium (10-30 HTx/year), and high (>30 HTx/year) volume, and waitlist outcomes were compared. Of the 35,190 patients included in our study, 23,726 (67.4%) underwent HTx, 4,915 (14.0%) died or deteriorated before receiving HTx, 1,356 (3.9%) were delisted due to recovery, and 1,336 (3.8%) underwent left ventricular assist device (LVAD) implantation. High-volume centers had higher rates of survival to transplant (71.3% vs. 60.6% for low-volume centers and 64.9% for medium-volume centers), and low rates of death or deterioration (12.6% vs. 14.6% for low-volume centers and 15.1% for medium-volume centers). Listing at a low-volume center was independently associated with death or delisting before HTx (HR 1.18, p = 0.007), whereas listing at a high-volume center (HR 0.86; p < 0.001) and prelisting LVAD (HR 0.67, p < 0.001) were protective. Death or delisting before HTx was lowest for patients listed in higher volume centers.

Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.

PURPOSE: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.

Improved 3 Year Heart Transplant Survival in Black Recipients Following the Affordable Care Act.

To improve healthcare access, the US government implemented the Affordable Care Act (ACA) in 2014. Previous studies investigating its impact on healthcare inequities showed significant improvement in Black transplant recipient outcomes. Our objective is to determine the ACA's impact on Black heart transplant (HTx) recipients. Using the United Network for Organ Sharing database, we analyzed 3,462 Black HTx recipients pre- and post-ACA (January 2009 to December 2012, and January 2014 to December 2017). Black recipient numbers and rates of overall HTx, insurance effects on survival, geographic changes in HTx, and post-HTx survival were compared pre- and post-ACA. Black recipients increased from 1,046 (15.3%) to 2,056 (22.2%) post-ACA ( p < 0.001). Three year survival increased among Black recipients (85.8-91.9%, p = 0.01; 79.4-87.7%, p < 0.01; 78.3-84.6%, p < 0.01). Affordable Care Act implementation was protective for survival (hazard ratio [HR] = 0.64 [95% confidence interval [CI], 0.51-0.81], p < 0.01). Publicly insured patient survival increased post-ACA to match that of privately insured (87.3-91.8%, p = 0.001). United Network for Organ Sharing (UNOS) Regions 2, 8, and 11 experienced improved survival post-ACA ( p = 0.047, p = 0.02, and p < 0.01, respectively). The post-ACA era showed improved HTx access and survival in Black recipients, indicating that national medical policy may play a strong role in eliminating racial disparities. Further attention is required to improve inequities in medical care. http://links.lww.com/ASAIO/B2.

Autoimmune hemolytic anemia during pregnancy and puerperium: an international multicenter experience.

Relapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33 women evaluated at 12 centers from 1997 to 2022. Among the 20 women diagnosed with AIHA before pregnancy, 10 had a relapse. An additional 13 patients developed de novo AIHA during gestation/puerperium (2 patients had AIHA relapse during a second pregnancy). Among 24 hemolytic events, anemia was uniformly severe (median Hb, 6.4 g/dL; range, 3.1-8.7) and required treatment in all cases (96% steroids ± intravenous immunoglobulin, IVIG, 58% transfusions). Response was achieved in all patients and was complete in 65% of the cases. Antithrombotic prophylaxis was administered to 8 patients (33%). After delivery, rituximab was administered to 4 patients, and cyclosporine was added to 1 patient. The rate of maternal complications, including premature rupture of membranes, placental detachment, and preeclampsia, was 15%. Early miscarriages occurred in 13% of the pregnancies. Fetal adverse events (22% of cases) included respiratory distress, fetal growth restriction, preterm birth, AIHA of the newborn, and 2 perinatal deaths. In conclusion, the occurrence of AIHA does not preclude the ability to carry out a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.

Supplemental Offer and Acceptance Program Outcomes in a Family Medicine Residency Network.

BACKGROUND AND OBJECTIVE: The National Resident Matching Program's (NRMP) Supplemental Offer and Acceptance Program (SOAP) places unmatched applicants in residency programs. We examined the outcomes and experience of family medicine residency programs that matched with residents through SOAP. METHODS: In 2020, all program directors in a regional family medicine residency network whose programs had participated in SOAP (n=23) completed a survey on their experience with SOAP and characteristics of residents who were matched via SOAP (n=52) anytime between 2012 and 2020. Resident outcome measures included graduation, remediation, leadership, fit, and comparisons of Milestones areas. Experiences with the SOAP process included factors that may have led the program to SOAP and advice for other programs participating. RESULTS: Eighty-seven percent of residents matched via the SOAP graduated, and the majority compared favorably to other residents. Two-thirds of program directors were very likely to hire their residents matched via the SOAP. Rural programs had similar outcomes, although rural-track positions represented 30% of all residents matched via the SOAP in the study. More than half of all responding program directors reported being underprepared for the SOAP process. Program directors recommend getting familiar with the NRMP resources and setting aside time for key personnel in case a program needs to participate in SOAP. CONCLUSIONS: The vast majority of residents matched via the SOAP are well prepared for training, contribute to their programs, and perform as well as other residents. Rural programs are more likely to place residents via SOAP than nonrural programs.

Total ventricular mass oversizing +50% or greater was a predictor of worse 1-year survival after heart transplantation.

OBJECTIVES: Current donor-recipient size matching guidelines rely primarily on body weight, with no specified oversizing cutoff values. Recent literature has explored predicted total ventricular mass matching over body weight matching. We aim to explore the impact of total ventricular mass oversizing on heart transplant outcomes. METHODS: The United Network for Organ Sharing database was queried for adults who underwent primary heart transplant from 1997 to 2017. By using validated equations, donor-recipient total ventricular mass mismatch was calculated. Donor-recipient pairs were divided into 3 groups by total ventricular mass mismatch. Post-heart transplant 1-year survival was analyzed using the Kaplan-Meier method and Cox proportional hazards models. We also investigated post-heart transplant complications, independent predictors for mortality, donor-recipient sex mismatch, and donor-recipient body habitus in total ventricular mass mismatch greater than +50%. RESULTS: A total of 34,455 donor-recipient pairs were included. Fractional polynomial regression demonstrated increased the risk of mortality with higher total ventricular mass mismatch. Total ventricular mass mismatch of +48.3% maximized the Youden Index. Donor-recipient pairs were subsequently grouped by total ventricular mass mismatch as -20% to +30%, +30% to +50%, and greater than +50%. Total ventricular mass mismatch greater than +50% was an independent risk factor for 1-year mortality (hazard ratio, 1.40, P = .004) and was associated with increased postoperative stroke (P = .002). Some 80.3% of these recipients were smaller female patients with male donors. Total ventricular mass mismatch from +30% to +50% was not associated with worse survival (P = .17). CONCLUSIONS: Total ventricular mass mismatch greater than +50% is associated with worse 1-year survival, although this group comprises a small portion of heart transplant. total ventricular mass mismatch from +30% to +50% is not associated with worse survival. These outcomes should be considered in selecting donors and in efforts to expand the potential donor pool.

Impella 5.5 Support Beyond 50 Days as Bridge to Heart Transplant in End-Stage Heart Failure Patients.

Prolonged mechanical circulatory support (MCS) for severe left ventricular dysfunction in cardiogenic shock as a bridge to heart transplantation (HTx) generally requires a surgical procedure. Typically, a surgically implanted temporary extracorporeal left ventricular assist device (LVAD) is chosen because of superior flow and durability compared with a percutaneously delivered endovascular LVAD (pVAD). However, compared with its predecessors, the Impella 5.5 trans-valvular pVAD provides higher hemodynamic support and features improved durability. Here, we present four successful cases with prolonged Impella 5.5 support as a bridge to HTx, with a mean support duration of 70 days (maximum 83 days). These cases highlight several potential benefits of Impella 5.5. The minimally invasive implantation procedure of the device reduces bleeding, decreases the postoperative recovery period, and enables early patient ambulation to reduce physical deconditioning before HTx surgery. Furthermore, Impella 5.5 adequately unloads the left ventricle and provides hemodynamic support to maintain end-organ function to further optimize hemodynamics before HTx. The evolution of Impella 5.5 technology may provide an alternative bridging strategy to traditional surgically implanted temporary MCS in select cases.

Use of Mechanical Circulatory Support to Demonstrate Pulmonary Hypertension Reversibility in Mitral Stenosis.

A 56 year old female with a history of rheumatic mitral stenosis (MS) presented with severe pulmonary edema. Transthoracic echocardiogram demonstrated severe MS (mean valve area 0.5 cm 2 , mean gradient of 16 mm Hg) with preserved left ventricular ejection fraction. Right heart catheterization demonstrated elevated pulmonary artery (PA) pressures of 110/80 mm Hg and a wedge pressure of 40 mm Hg. Mechanical circulatory support (MCS) was initiated with extracorporeal left atrial to femoral artery bypass. MCS allowed preoperative unloading of the left atrium. The volume status and lung congestion were optimized before surgery. In addition, pulmonary hypertension reversibility was demonstrated with significantly lower PA pressures after initiation of MCS. Intraoperatively, the MCS left atrial inflow cannula was pulled back into the right heart and used as a venous cannula for cardiopulmonary bypass. Successful mitral valve replacement was performed. Postoperatively, the mitral valve mean gradient was 3 mm Hg.

Trends in Outcomes of Heart Transplants Using Extended Criteria Donors: A United Network for Organ Sharing Database Analysis.

BACKGROUND: Although the use of extended criteria donors (ECDs) is traditionally avoided because of poorer outcomes, management of heart transplant (HTx) recipients has evolved over the past decades. We sought to examine the temporal trends in outcomes of ECDs in HTx. METHODS: We queried the United Network for Organ Sharing database for adult HTx recipients who fit the EXPAND Trial criteria for ECDs: ischemic time ≥ 4 hours, ejection fraction < 50%, age > 55 years, and history of coronary artery disease. Transplant years were stratified into the following 4 periods: (1) 2000 to 2004, (2) 2005 to 2009, (3) 2010 to 2014, and (4) 2014 to 2018. The 2-sample t test, Kaplan-Meier survival analysis, log-rank test, analysis of variance, multivariable Cox proportional hazards, and multinomial logistic regression were used to compare data between periods. RESULTS: Through periods 1 to 4, 39,028 patients were stratified as follows: 9217 (2942 ECDs, 31.9%), 9224 (2730 ECDs, 29.6%), 10,309 (2762 ECDs, 26.8%), and 10,278 (2190 ECDs, 21.3%). Transplants using ECDs in periods 1 and 2 had increased 1-year mortality compared with periods 3 and 4 (16.9% and 15.6% vs 11.9% and 10.9% respectively, P < .001). Later periods also demonstrated improved Karnofsky scores (P < .001). CONCLUSIONS: Although use of ECDs decreased across the periods, we noted significant improvement in 1-year survival rates and postoperative functional status.

A Simple Technique for Reliable Donor Organ Temperature Management With the SherpaPak System.

Here, we present our technique for thermoregulation of cardiac preservation solution with the SherpaPak device before heart transplantation. If it is above the ideal range (5-10°C) to avoid organ injury and ensure proper function, the cardiac preservation solution bag should be placed in ice water to bring down temperature until the ideal range is achieved. SherpaPak has limitation in immediately correcting initial temperatures outside of the normal range, so we believe this simple step should be included into standard SherpaPak procedure to ensure its effectiveness and to preserve the best organ function.

Geographic Variation in Heart Transplant Extended Criteria Donors in the United States.

BACKGROUND: Recent research has explored the use of higher risk extended criteria donors (ECDs) as a means of expanding the donor pool for heart transplantation. Here we sought to explore the current geographic distribution and survival outcomes of ECD utilization in various regions across the United States. METHODS: The United Network for Organ Sharing database was retrospectively queried for adult primary heart transplantation from 2000 to 2019. The EXPAND trial definition of ECD was used: ischemic time ≥ 4 hours, ejection fraction < 50%, age > 55 years, and history of coronary artery disease. Geographic data and 2019 population estimates were obtained from the US Census Bureau. RESULTS: Of the 42 642 transplants included in our analysis, 11 750 (27.6%) used ECDs. Region utilization of ECDs ranged from 18.4% to 46.5% of transplants. Region 6 had the highest utilization rate at 46.5%; this was primarily driven by the number of transplants with ischemic time ≥ 4 hours. Region 6 encompasses the largest total area (1.08 million square miles) and smallest population density (15.6 people per square mile). Region 8 had the lowest marginal donor utilization rate at 18.4%. Regions with high utilization of low ejection fractions, older donors, and donors with coronary artery disease (ie, regions 1 and 2) were able to maintain an average utilization rate of ECDs by maintaining short ischemic times. CONCLUSIONS: Large discrepancies in the use of ECDs exist across the different United Network for Organ Sharing regions. This is primarily driven by longer ischemic times, likely guided by variance in population densities between different regions.