Yetmar, Zachary A

ABSTRACT Background Cytomegalovirus (CMV) infection is among the most common infections after solid organ transplantation and leads to high rates of morbidity and mortality. With the proliferation of large, claims‐based datasets, there is a need to assess the validity of ICD‐10‐CM codes in identifying CMV infection. Methods We conducted a retrospective cohort study of solid organ transplant recipients (SOTRs) from a regional health system who underwent first transplantation between January 1, 2016, and June 30, 2025, had at least 30 days of post‐transplant follow‐up, and had known donor/recipient CMV serostatus. We performed cross‐sectional and time‐to‐event analyses comparing the test performance of B25 ICD‐10‐CM codes in identifying CMV infection, clinically significant CMV infection (csCMVi), CMV disease, and CMV DNA reaching various thresholds. Results Of 8169 SOTRs, 3084 (37.8%) had B25 coded during follow‐up. In addition, 4287 (52.5%) developed CMV infection, 2356 (28.8%) csCMVi, 297 (3.6%) CMV disease, and 1669 (20.4%) CMV DNA ≥ 1000 IU/mL. B25 codes were most specific to any CMV infection (88.5%), most sensitive to CMV DNA ≥ 100 000 IU/mL (98.2%), and csCMVi had the highest Youden's Index (0.651; sensitivity 84.1%, specificity 81.0%). Multivariable Cox regression provided similar results but with variations in effect measure between ICD‐10‐CM codes and clinical CMV definitions. Conclusions ICD‐10‐CM codes showed modest performance in identifying CMV infection, most closely resembling csCMVi. ICD‐10‐CM codes poorly reflect CMV severity, however, and may overestimate CMV infection by some clinical definitions. These limitations should be considered when using CMV diagnosis codes for claims‐based studies of SOTRs.

ABSTRACT Background Cytomegalovirus (CMV) infection remains one of the most prevalent and consequential post solid organ transplant (SOT) infections. Treatment is often challenging, especially when dealing with refractory and resistant CMV infections. Methods We performed a retrospective multicenter cohort study of SOT recipients with clinically significant CMV infection (csCMVi) during 2010–2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Analysis was done with Kaplan‐Meier, univariable logistic regression analysis, and multivariable Cox regression. Results We included 145 SOT recipients with csCMVi, majority were liver transplant (49%). Most common induction was an anti‐IL‐2 antibody (43.9%). The majority ( n = 82; 56.5%) were CMV D+/R‐ mismatch and presented asymptomatic infection (50.3%). After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R‐ mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48–0.95, p = 0.029) while lower absolute lymphocyte count (ALC) had a higher risk of early refractory csCMVi (OR 1.54; CI 1.01–2.44, p = 0.048). Drug‐resistant csCMVi occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2.00; CI 1.08–3.93, p = 0.031). 25 patients (17.2%) experienced recurrent csCMVi within 6 months. 30 patients (20.7%) died; refractory, resistant or recurrent CMV infections were not associated with mortality. Conclusion Refractory csCMVi is associated with a low ALC and an earlier onset after transplant. Resistant csCMVi is associated with high initial CMV DNA levels. Recurrence of csCMVi is common and potentially associated with low ALC at the end of antiviral treatment.

ABSTRACT Purpose The purpose of this study was to evaluate the incidence and risk factors for developing recurrent clinically significant cytomegalovirus infections (csCMVi) in heart transplant recipients. Methods We conducted a retrospective cohort study involving adult heart transplant recipients at three large transplant centers in the United States between January 2011 and March 2019. All patients with a history of csCMVi, defined as CMV disease or CMV infection requiring preemptive therapy, were followed from the date of treatment completion for the primary csCMVi episode. Outcomes of interest were recurrent csCMVi and all‐cause mortality. Results Among 98 heart transplant recipients with csCMVi, 22 (22.4%) episodes of recurrent csCMVi occurred. Median time‐to‐recurrent csCMVi was 31.5 (IQR 21.3–59.8) days following treatment completion. A preceding episode of CMV disease (versus infection) was associated with a lower risk of recurrent csCMVi (HR 0.29, 95% CI 0.08–0.98; p = 0.047). Patients with lymphopenia had higher rates of recurrent csCMVi without statistical significance (HR 2.13, 95% CI 0.88–5.13; p = 0.093). Seroconversion by the end‐of‐therapy among CMV D+/R− mismatched patients was associated with a reduced risk of csCMVi recurrence (HR 0.07, 95% CI 0.02–0.30; p < 0.001). Overall, 17 (17.3%) patients died during follow‐up, which was not significantly higher among those with recurrent csCMVi (HR 2.13, 95% CI 0.78–5.79; p = 0.141). Conclusions About one in five heart recipients with csCMVi developed post‐treatment recurrence. A preceding episode of CMV disease and seroconversion was protective against recurrence. Lymphopenia may be a practical biomarker to stratify recurrence risk. Overall, recurrent csCMVi was not significantly associated with mortality.

Abstract Background There is a lack of comprehensive, large cohort studies investigating the predictors for severity and hospitalization in human granulocytic anaplasmosis (HGA). Methods We conducted a retrospective cohort study including all cases of HGA identified by positive blood Anaplasma polymerase chain reaction (PCR) at the Mayo Clinic Laboratory, Rochester between 2011 and 2021. Multivariable logistic regression was performed to evaluate risk factors associated with hospitalization. Results A total of 465 cases were identified. Of those, 67% (n = 312) were managed in the outpatient setting. Hospitalized patients (n = 153, 33%) were more likely to be older (median age of 71 vs 61; P ≤ .001) and immunocompromised (17% vs 7%; P ≤ .001). The triad of leukopenia, thrombocytopenia, and transaminitis was observed in 24% of the cases, but was associated with risk of hospitalization (odds ratio [OR] 1.78, 95% confidence interval [CI]: 1.05–3.03; P ≤ .033). The presence of a coinfection did not impact mortality or hospitalization. Conclusions The risk factors for hospitalization in patients with HGA include altered mental status, higher absolute neutrophil count (ANC), advanced age, comorbidities, and immunosuppression. The classic hematological and biochemical profile may be absent in the majority of cases. Co-testing may be of higher benefit in select cases.

ABSTRACT Background Multiple outpatient therapies have been developed for COVID‐19 in high‐risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population. Methods We performed a retrospective cohort study using de‐identified administrative claims data from OptumLabs Data Warehouse. Patients were included if they were age ≥ 18 years, diagnosed with COVID‐19 between January 2022 and December 2023, and underwent SOT prior to COVID‐19. The primary outcome was 30‐day hospitalization. Stabilized inverse probability of treatment weighting was used to account for potential confounding variables. Results 4192 SOT recipients with COVID‐19 were identified. 1403 received an outpatient COVID‐19 therapy, including anti‐spike monoclonal antibodies ( N = 748, 53.3%), molnupiravir ( N = 327, 23.3%), ritonavir‐boosted nirmatrelvir ( N = 217, 15.5%), or remdesivir ( N = 141, 10.0%). In weighted analysis compared to no treatment, anti‐spike monoclonal antibodies (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.28–0.55; p < 0.001), molnupiravir (HR 0.56, 95% CI 0.36–0.89; p = 0.013), and nirmatrelvir (HR 0.47, 95% CI 0.25–0.89; p = 0.020) were associated with reduced hospitalization risk, while remdesivir (HR 1.00, 95% CI 0.50–1.98; p = 0.992) was not. Hospitalization rates were similar between the treatment agents, apart from remdesivir showing a higher risk compared to anti‐spike monoclonal antibodies. Conclusions Outpatient COVID‐19 therapies were largely associated with improved outcomes among SOT recipients. These treatment agents showed similar rates of 30‐day hospitalization, except for remdesivir. The choice of outpatient COVID‐19 therapy in SOT recipients should primarily account for patients’ individual circumstances and drug‐drug interactions rather than differential therapeutic efficacy. image

Abstract Nocardiosis is an uncommon yet potentially devastating infection. Nocardia tends to affect individuals with chronic lung disease or immunocompromising conditions, 2 groups increasing in number. Incidence of nocardiosis is likely to increase as well, and it is vital to have an approach to this complex disease. Here, we aim to review the presentation, diagnosis, and management of Nocardia in the modern era. We will also highlight areas of uncertainty in our understanding of nocardiosis and propose a general approach to nocardiosis therapy, accounting for response and tolerance of Nocardia treatment.