Coccidioidomycosis is an infection caused by Coccidioides species, which are endemic for the Southwestern United States and parts of Central America and South America. Most infected individuals are asymptomatic or have mild-to-moderate respiratory illness. Coccidioidomycosis is more severe in patients with depressed cellular immunity, such as organ transplant recipients. We retrospectively reviewed charts of 391 liver transplant recipients (mean follow-up, 38.7 months; range, 2-105 months). Before transplantation, 12 patients had a history of coccidioidomycosis and 13 patients had asymptomatic seropositivity. Of these 25 patients, 23 had no active coccidioidomycosis posttransplantation and 2 had reactivated infection. One of 5 patients with indeterminate serology before transplantation died of disseminated coccidioidomycosis shortly after transplantation. De novo coccidioidomycosis developed in 12 patients (3%) who had no evidence of coccidioidomycosis pretransplantation. Of 15 total episodes of posttransplantation coccidioidomycosis, 10 (66%) occurred during the first year. Dissemination was noted in 33% of active coccidioidomycosis after transplantation; two patients (13%) died of coccidioidomycosis. Because most coccidioidal infections occurred in the first posttransplantation year despite targeted antifungal prophylaxis, we recommend a new strategy of universal antifungal prophylaxis for 6-12 months for liver transplant recipients who reside in the endemic area.
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.
On February 26, 2020, the first case of community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States (US) was confirmed. 1 SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), and on March 11, the World Health Organization declared COVID-19 a global pandemic. By May 27, 2020, SARS-CoV-2 had infected over 1.6 million people in the United States, resulting in over 100 000 deaths. 2 The ongoing pandemic has presented a challenging predicament for organ transplantation programs. The combination of a protracted asymptomatic incubation period of SARS-CoV-2 and the lack of capacity for rapid testing of potential donors to avoid transmission of SARS-CoV-2 were challenges to transplant programs. 3 Further, the effects of SARS-CoV-2 in highly immunosuppressed patients in the early post-transplant period are currently unclear. Nonetheless, it has been assumed that any significant viral infection in this patient cohort would be detrimental, which has been demonstrated in early reports. 4 In addition, cardiovascular disease has emerged as a risk factor for mortality with COVID-19. 5 Indeed, the number of patients inactivated on the heart transplant waitlist more than doubled between the weeks of March 8 and
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.
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.
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.
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 costeffectiveness. Risk stratification and subsequent outcome prediction as well as therapeutic recommendationmaking 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.
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