Razonable, Raymund R.

AbstractOne of the many challenges that has befallen the Infectious Diseases and Graduate Medical Education communities during the coronavirus disease 2019 (COVID-19) pandemic is the maintenance of continued effective education and training of the future leaders of our field. With the remarkable speed and innovation that has characterized the responses to this pandemic, educators everywhere have adapted existing robust and safe learning environments to meet the needs of our learners. This paper will review distinct aspects of education and training of the Infectious Diseases fellows we believe the COVID-19 pandemic has impacted most, including mentoring, didactics, and wellness. We anticipate that several strategies developed in this context and described herein will help to inform training and best practices during the pandemic and beyond.

Abstract Background Cryptococcus spp is a major cause of opportunistic infections in immunocompromised patients, primarily due to Cryptococcus neoformans and Cryptococcus gattii. There are occasional reports of other Cryptococcus species causing invasive human disease. However, their epidemiology and clinical significance are not fully defined. We sought to describe cases with cultures positive for Cryptococcus species other than C neoformans and C gattii. Methods A retrospective descriptive analysis of clinical and laboratory data of patients with cultures growing Cryptococcus species other than C neoformans and C gattii from November 2011 to February 2019 was performed. Three Mayo Clinic sites in Arizona, Florida, and Minnesota were included. Results From 176 cases with a culture growing Cryptococcus spp, 54 patients (30%) had a culture for Cryptococcus other than C neoformans and C gattii in the study time frame. The most common species were Cryptococcus magnus, Cryptococcus laurentii, and Cryptococcus ater. The organisms were isolated and identified in culture of bronchoalveolar lavage (11), skin (11), urine (7), oral (4), sinus (3), intraoperative soft tissue (3), sputum (2), synovial fluid (2), cerebrospinal fluid (2), and intravenous catheter (2), among others (7). Only 8 (15%) cases were considered to be potentially pathogenic, with 1 case of invasive disease. Antifungal treatment was fluconazole, itraconazole, and griseofulvin, for a mean systemic antifungal duration of 42 days. Conclusions This large series of patients with Cryptococcus spp other than C neoformans and C gattii suggests that these species rarely cause clinically significant infection in humans. Only 1 case of invasive disease was found.

AbstractThe contrasting outcomes of lymphocyte manipulation after solid organ transplantation are allograft rejection and infections, commonly with cytomegalovirus (CMV). Peripheral blood absolute lymphocyte count (ALC) may serve as a predictive marker for these outcomes. Using a retrospective review of clinical and laboratory dataset, we aimed to determine whether a range of ALC (termed “safe ALC corridor”) exists where CMV infection and rejection outcomes are minimal in a cohort of 381 kidney transplant recipients. In an extended Cox model using a time‐dependent covariate for peripheral blood ALC, a value below the cut‐off of 610 cells/uL was associated with the development of CMV infection both in the overall cohort (Hazard Ratio [HR] 2.25 (95% confidence internal [CI] 1.02‐4.96; P = .043) and the subgroup of high‐risk CMV D+/R‐ mismatch patients (HR 2.91 [95% CI 1.09‐7.77]; P = .033). In contrast, a time‐dependent Cox analysis did not show any significant association between ALC and rejection (per IQR decrease, HR 1.2 [95% CI: 0.76‐1.9]; P = .434). Accordingly, a “safe ALC corridor” could not be defined. In conclusion, a low peripheral blood ALC (ie, threshold of 610 cells/uL) can be used to stratify the risk of CMV disease after kidney transplantation.

Abstract Rationale Many lung transplant centers prescribe antifungal medications after transplantation to prevent invasive fungal infections (IFIs); however, the effectiveness of antifungal prophylaxis at reducing the risk of all-cause mortality or IFI has not been established. Objectives We aimed to evaluate the effect of antifungal prophylaxis on all-cause mortality and IFI in lung transplant patients. Methods Using administrative claims data, we identified adult patients who underwent lung transplantation between January 1, 2005, and December 31, 2018. Propensity score analysis using inverse probability treatment–weighting approach was used to balance the differences in baseline characteristics between those receiving antifungal prophylaxis and those not receiving antifungal prophylaxis. Cox proportional hazards regression was used to compare rates of all-cause mortality and IFI in both groups. Results We identified 662 lung transplant recipients (LTRs) (387 received prophylaxis and 275 did not). All-cause mortality was significantly lower in those receiving antifungal prophylaxis compared with those not receiving antifungal prophylaxis (event rate per 100 person-years, 8.36 vs. 19.49; hazard ratio, 0.43; 95% confidence interval, 0.26–0.71; P = 0.003). Patients receiving antifungal prophylaxis had a lower rate of IFI compared with those not receiving prophylaxis (event rate per 100 person-years, 14.94 vs. 22.37; hazard ratio, 0.68; 95% confidence interval, 0.44–1.05; P = 0.079), but did not reach statistical significance. Conclusions In this real-world analysis, antifungal prophylaxis in LTRs was associated with reduced all-cause mortality compared with those not receiving antifungal prophylaxis. Rates of IFI were also lower in those receiving prophylaxis, but this was not statistically significant in our primary analysis.

Abstract Background The risk factors for development of viremia in high-risk donor cytomegalovirus (CMV)-seropositive and recipient CMV-seronegative (D+R−) transplant recipients are incompletely defined. Methods The study population comprised patients in the preemptive therapy (PET) arm of a randomized, controlled trial of PET versus prophylaxis using valganciclovir in D+R− liver transplant recipients. Weekly surveillance monitoring for viremia for 100 days was performed using a sensitive CMV-DNA polymerase chain reaction assays. Risk factors for viremia and time to onset (≤4 vs >4 weeks) of viremia were examined using logistic regression models. Results Viremia developed in 84% (79/94) of recipients and older donor age was the only independent factor associated with viremia (odds ratio, 2.20 for each quartile increase in donor age; 95% confidence interval [CI], 1.07–4.52; P = .031). Recipients who developed early-onset viremia (within 4 weeks) also had significantly older donors than those with later-onset viremia (difference in age 10.1 years; 95% CI, 2–19; P = .03). Conclusions Older donor age was an independent predictor of viremia and earlier-onset of viremia in D+R− liver transplant recipients. Future studies should assess the mechanistic links underlying this novel association. Clinical Trial Registration NCT01552369.

AbstractBackgroundThe relative costs of preemptive therapy (PET) or prophylaxis for the prevention of cytomegalovirus (CMV) disease in high-risk donor CMV-seropositive/recipient-seronegative (D+/R−) liver transplant recipients have not been assessed in the context of a randomized trial.MethodsA decision tree model was constructed based on the probability of outcomes in a randomized controlled trial that compared valganciclovir as PET or prophylaxis for 100 days in 205 D+/R− liver transplant recipients. Itemized costs for each site were obtained from a federal cost transparency database. Total costs included costs of implementation of the strategy and CMV disease treatment-related costs. Net cost per patient was estimated from the decision tree for each strategy.ResultsPET was associated with a 10% lower absolute rate of CMV disease (9% vs 19%). The cost of treating a case of CMV disease in our patients was $88 190. Considering cost of implementation of strategy and treatment-related cost for CMV disease, the net cost-savings per patient associated with PET was $8707 compared to prophylaxis. PET remained cost-effective across a range of assumptions (varying costs of monitoring and treatment, and rates of disease).ConclusionsPET is the dominant CMV prevention strategy in that it was associated with lower rates of CMV disease and lower overall costs compared to prophylaxis in D+/R− liver transplant recipients. Costs were driven primarily by more hospitalizations and higher CMV disease–associated costs due to delayed onset postprophylaxis disease in the prophylaxis group.

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVID pos ; n = 2,317) versus COVID-19-negative (COVID neg ; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVID pos over COVID neg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVID pos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.