Impact of solid organ transplant status on outcomes of hospitalized patients with COVID-19 infection.

BACKGROUND: The COVID-19 pandemic has caused significant morbidity and mortality in solid organ transplant (SOT) recipients. However, it remains unclear whether the risk factor for SOT patients is the immunosuppression inherent to transplantation versus patient comorbidities. METHODS: We reviewed outcomes in a cohort of SOT (n = 129) and non-SOT (NSOT) patients (n = 708) admitted to the University of California, Los Angeles for COVID-19 infection. Data analyses utilized multivariate logistic regression to evaluate the impact of patient demographics, comorbidities, and transplant status on outcomes. SOT patients were analyzed by kidney SOT (KSOT) versus nonkidney SOT (NKSOT) groups. RESULTS: SOT and NSOT patients with COVID-19 infection differed in terms of patient age, ethnicity, and comorbidities. NKSOT patients were the most likely to experience death, with a mortality rate of 16.2% compared with 1.8% for KSOT and 8.3% for NSOT patients (p = .013). Multivariable analysis of hospitalized patients revealed that patient age (odds ratio [OR] 2.79, p = .001) and neurologic condition (OR 2.66, p < .001) were significantly associated with mortality. Analysis of ICU patients revealed a 2.98-fold increased odds of death in NKSOT compared with NSOT patients (p = .013). CONCLUSIONS: This study demonstrates the importance of transplant status in predicting adverse clinical outcomes in patients hospitalized or admitted to the ICU with COVID-19, especially for NKSOT patients. Transplant status and comorbidities, including age, could be used to risk stratify patients with COVID-19. This data suggests that immunosuppression contributes to COVID-19 disease severity and mortality and may have implications for managing immunosuppression, especially for critically ill patients admitted to the ICU.

Sirolimus-Based Immunosuppression Is Associated with Decreased Incidence of Post-Transplant Lymphoproliferative Disorder after Heart Transplantation: A Double-Center Study.

Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein-Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8-26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04-0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03-0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk.

Outcomes of Obese Patients Bridged to Heart Transplantation with a Left Ventricular Assist Device.

The current study aims to investigate the impact of left ventricular assist device (LVAD) implantation on weight loss and functional status in obese patients bridged to transplantation (BTT). The United Network for Organ Sharing (UNOS) database was queried to identify patients with body mass index (BMI) ≥ 30 who underwent LVAD implantation as BTT from 2008 to 2018. Patients were divided into three groups based the World Health Organization classification of obesity: obesity class I (BMI, 30.0-34.9 kg/m2), obesity class II (BMI, 35-39.9 kg/m2), and obesity class III (BMI, >40 kg/m2). Patients with incomplete data on BMI were excluded. The primary outcome was a change in BMI while listed. Secondary outcomes included a change in functional status after LVAD implantation and posttransplant morbidity and survival. Out of 14,191 patients who had an LVAD while listed within the study period, 5,354 (37.7%) had a BMI ≥30 kg/m2. Obesity was classified as class I in 3,909 (73%), class II in 1,275 (23.8%), and class III in 170 (3.2%) patients. Among patients with complete data on BMI, 18.9% (n = 394) reported a change in BMI, leading to an improvement in their obesity class, and this was similar for all obesity classes (22% [n = 331], 50% [n = 111], and 60% [n = 43] for classes I, II, and III, respectively). All groups reported an improvement in functional status (65% vs. 62% and 61% for classes I, II, and III, respectively). Posttransplant survival was not significantly different between obese groups (p = 0.787). Compared with classes I and II, the incidence of thrombosis (p = 0.0006) and device malfunction (p = 0.036) was significantly higher in the class III group. About one out of every five obese patients listed for heart transplantation with an LVAD loses weight, leading to a change in their BMI class. Most patients reported a significant improvement in their functional status. Among those successfully BTT, posttransplant survival was similar.

Heart transplantation in the early phase of the COVID-19 pandemic: A single-center case series.

The infectious disease coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID-19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re-evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID-19 screening scrutiny and recipient waiting list management in anticipation of COVID-19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end-stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020.

Current indications for transplantation: stratification of severe heart failure and shared decision-making.

Heart failure (HF) is a complex clinical syndrome that results from structural or functional cardiovascular disorders causing a mismatch between demand and supply of oxygenated blood and consecutive failure of the body's organs. For those patients with stage D HF, advanced therapies, such as mechanical circulatory support (MCS) or heart transplantation (HTx), are potentially life-saving options. The role of risk stratification of patients with stage D HF in a value-based healthcare framework is to predict which subset might benefit from advanced HF (AdHF) therapies, to improve outcomes related to the individual patient including mortality, morbidity and patient experience as well as to optimize health care delivery system outcomes such as cost-effectiveness. Risk stratification and subsequent outcome prediction as well as therapeutic recommendation-making need to be based on the comparative survival benefit rationale. A robust model needs to (I) have the power to discriminate (i.e., to correctly risk stratify patients); (II) calibrate (i.e., to show agreement between the predicted and observed risk); (III) to be applicable to the general population; and (IV) provide good external validation. The Seattle Heart Failure Model (SHFM) and the Heart Failure Survival Score (HFSS) are two of the most widely utilized scores. However, outcomes for patients with HF are highly variable which make clinical predictions challenging. Despite our clinical expertise and current prediction tools, the best short- and long-term survival for the individual patient, particularly the sickest patient, is not easy to identify because among the most severely ill, elderly and frail patients, most preoperative prediction tools have the tendency to be imprecise in estimating risk. They should be used as a guide in a clinical encounter grounded in a culture of shared decision-making, with the expert healthcare professional team as consultants and the patient as an empowered decision-maker in a trustful safe therapeutic relationship.

Real-world incidence of efficacy and safety outcomes in patients on direct oral anticoagulants with left ventricular systolic dysfunction at a tertiary referral center.

BACKGROUND: Patients with heart failure (HF) have increased risk for thromboembolic events. Real-world incidences of efficacy and safety outcomes of direct oral anticoagulants (DOACs) in patients with left ventricular systolic dysfunction (LVSD) are of growing clinical interest. HYPOTHESIS: Real-world efficacy and safety outcomes of DOACs in patients with LVSD will be similar to those of LVSD or HF subgroups in the RE-LY, ROCKET-AF, and ARISTOTLE trials. METHODS: We performed a retrospective review of adult patients with LVSD (left ventricular ejection fraction ≤40%) on DOAC therapy between 2010 and 2016. Incidences of safety and efficacy outcomes of anticoagulation with DOACs were extracted from primary and secondary hospital discharge diagnoses. RESULTS: DOACs were prescribed to 287 patients with LVSD over a mean follow-up of 313.3 ± 52.3 days. Many patients had moderate and severe chronic kidney disease (28.9% and 10.1%, respectively) and indications for anticoagulation therapy other than atrial fibrillation (19.9%). For efficacy outcomes, the calculated incidence rates of ischemic stroke and systemic embolism were 1.2 (95% confidence interval [CI]: 0.25-3.56) and 0.81 (95% CI: 0.10-2.94) events per 100 person-years, respectively. For the safety outcomes, incidence rates of GI bleeding and intracranial hemorrhage were 2.4 (95% CI: 0.8-5.3) and 0.41 (95% CI: 0.1-2.2) events per 100 patient-years, respectively. CONCLUSIONS: Our findings are largely compatible with the results of LVSD or HF subgroups in RE-LY, ROCKET-AF, and ARISTOTLE trials and add to increasing confidence that DOACs can be safely used for stroke and systemic embolism prevention in patients with LVSD.

Single-center experience of antifungal prophylaxis for coccidioidomycosis in heart transplant recipients within an endemic area.

In endemic regions, coccidioidomycosis causes substantial morbidity and mortality for patients receiving solid organ transplants. We aimed to demonstrate the effect of antifungal coccidioidal prophylaxis in heart transplant (HT) recipients. We retrospectively reviewed the electronic health records of all patients who received HTs between October 19, 2005, and December 13, 2014. We collected information regarding antifungal regimens and determined whether patients subsequently developed infections. Our 174-person cohort all received antifungal prophylaxis for at least 6 months (mean follow-up, 53.8 months). One proven and one probable coccidioidal infection (each, 0.6%) occurred during the study period. The incidence of coccidioidomycosis was 0.6% at 1 year and 2.3% at 5 years. No cases of proven coccidioidomycosis occurred within 2 years after transplantation. No patients developed disseminated disease, and no sentinel events were attributed to coccidioidomycosis. Both fluconazole and voriconazole were well tolerated. In the absence of intolerance or contraindication, we suggest continuing a universal antifungal prophylactic regimen with fluconazole for at least 6-12 months in HT recipients residing in a coccidioidomycosis-endemic area.

The Incremental Value of Magnetic Resonance Imaging for Identification of Apical Pouch in Patients with Apical Variant of Hypertrophic Cardiomyopathy.

BACKGROUND: The development of a left ventricular (LV) apical pouch in patients with apical hypertrophic cardiomyopathy (aHCM) has been thought to be the transition point that can become an apical aneurysm, which is linked to higher risk of adverse events. In our study, we sought to compare the ability of transthoracic echocardiography (echo) and cardiac magnetic resonance imaging (cMRI) to accurately identify the presence of an apical pouch or aneurysm in patients with aHCM. METHODS: We retrospectively reviewed the charts of all consecutive patients that had features of aHCM on imaging. Data from cMRI and echo examinations were abstracted, and the ability of these diagnostic modalities to identify the presence of a LV apical pouch and aneurysm was analyzed. RESULTS: Of 31 patients with aHCM, 17 (54.8%) had an apical pouch and 2 were found to have apical aneurysm (6.5%) on cMRI. Echo with and without perflutren contrast was able to accurately identify both aneurysms, but only 47.1% (8/17) of apical pouches seen by cMRI. Two patients had apical thrombus that was identified by cMRI, but not by echo. CONCLUSION: Our findings indicate that cMRI is superior to echo in identifying apical pouches in patients with aHCM. Our results also suggest that in patients undergoing echo, the use of perflutren contrast for LV opacification increases the diagnostic yield. Further study is necessary to delineate whether earlier identification of an apical pouch will be of clinical benefit for patients with aHCM by altering clinical management and avoiding adverse cardiovascular events.

The impact of 2011 ACGME duty hour restrictions on internal medicine resident workload and education.

The Accreditation Council for Graduate Medical Education (ACGME) implemented work hour restrictions for physicians in training in 2003 that were revised July 1, 2011. Current published data are insufficient to assess whether such work hour restrictions will have long-term impact on residents' education. We searched computer-generated reports of hospital in-patient census, continuity clinic census, in-training exam scores and first-year resident attendance at educational conferences for the academic years 2010-2011 (August 1, 2010-May 31, 2011) and 2011-2013 (August 1, 2011-May 31, 2013). During the first year of the study period, the residents' inpatient internal medicine services admitted 1,754 patients; during this same period for academic years 2011-2012 and 2012-2013, the teaching services admitted 1,539 and 1,428 patients respectively, yielding a decrease of 16.4%. Monthly, these services cared for a mean of 27.1 (27.1/175.4 [15.4%]) fewer patients and 9.7 (9.7/34.4 [28.2%]) fewer patients per intern than in the previous year. No statistical difference was observed regarding continuity clinic attendance and in-training exam scores. Residents in the years following work hours restrictions attended more educational conferences. Implementation of 2011 ACGME work hour regulations resulted in fewer patients seen by first-year residents in hospital, but did not affect in-training exam scores. Whether these findings will translate into differences in patient outcomes, and quality of care remains to be seen.

Trastuzumab-induced hepatotoxicity: a case report.

BACKGROUND: Trastuzumab is a humanized monoclonal antibody approved for the treatment of breast cancer with HER2 amplification and/or overexpression. There are only 2 prior cases of trastuzumab-related hepatotoxicity reported in the literature. CASE REPORT: We report the case of a 60-year-old woman who was treated with trastuzumab for stage I invasive ductal carcinoma of the right breast. She successfully completed 6 months of therapy when an increase in liver transaminases was noted on routine examination. A full work-up for causes of acute and chronic liver disease was negative. After review of the patient's medication list, trastuzumab was thought to be the most likely culprit for the liver injury, based on timing of administration and rise in liver enzymes.

The utility of Coccidioides polymerase chain reaction testing in the clinical setting.

Coccidioidomycosis, the fungal infection caused by dimorphic Coccidioides sp., is typically diagnosed by histopathologic identification of spherules in affected secretions and tissues or by culture. These tests are reliable but time-intensive, delaying diagnosis and treatment. To evaluate a polymerase chain reaction (PCR) test developed to detect Coccidioides sp. in clinical specimens, we conducted a retrospective chart review of all patients (N = 145) who underwent Coccidioides PCR at our institution between April 27, 2007, and May 6, 2008, abstracting clinical, microbiologic, serologic, radiographic, treatment, and follow-up data. One hundred fifty-eight PCR tests (153 respiratory; 5 cerebrospinal fluid) produced 5 positive and 153 negative findings. Five of nine patients (56%) with confirmed or highly probable pulmonary coccidioidomycosis had a positive PCR on respiratory specimens, and four of nine (44%) had a positive culture. Among two patients with coccidioidal meningitis, none had a positive PCR, whereas Coccidioides sp. in fungal culture grew for one of two. Among six asymptomatic patients with probable coccidioidomycosis, none had a positive culture or PCR. Compared with culture of respiratory specimens, PCR demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 75, 99, 60, and 99%, respectively. Coccidioides PCR appears accurate in identifying negative results, and its sensitivity is similar to that of fungal culture.