Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study

Background: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. Methods: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. Results: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age \u3e50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections. Conclusions: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes

Miliary Histoplasmosis in a Patient with Rheumatoid Arthritis

Miliary histoplasmosis is a rare presentation that may mimic miliary tuberculosis. We report a case of miliary histoplasmosis in a 52-year-old male who was being treated with hydroxychloroquine, methotrexate, and sulfasalazine for his rheumatoid arthritis and presented to the emergency department with shortness of breath and fevers. Computed tomography (CT) chest revealed miliary pulmonary nodules. Urine Histoplasma antigen and serum Histoplasma antigen were negative; however, Coccidioides immitis complement immunofixation assay and Coccidioides IgM were positive. The patient was initiated on treatment for pulmonary coccidioidomycosis and immunosuppression was held. However, a few days later, Histoplasma capsulatum was isolated from cultures from bronchoscopy. This case highlights the difficulty in diagnosing histoplasmosis in immunocompromised patients and the importance of having a broad differential diagnosis for miliary pulmonary nodules. Tissue culture and histopathology remain the gold standard for the diagnosis of histoplasmosis. Further research needs to be conducted to determine the optimal duration of histoplasmosis treatment in immunocompromised patients

Analysis of temporal changes in HIV-1 CRF01_AE gag genetic variability and CD8 T-cell epitope evolution

Currently, little is known about the time-dependent evolution of human immunodeficiency virus-1 (HIV-1) circulating recombinant forms (CRF) 01_AE, a dominant recombinant form associated with HIV-1 epidemics worldwide. Since gag is a highly immunodominant HIV-1 protein, we performed a comparative analysis of the CRF01_AE gag protein\u27s time-dependent changes and evolution. A total of 3105 HIV-1 CRF01_AE gag sequences representing 17 countries from the timeline 1990-2017 were obtained. The sequences\u27 phylogenetic relationship and epidemic dynamics were analyzed through a Maximum Likelihood tree and Bayesian Skyline plot, respectively. Genomic variability was measured through Shannon entropy and time-dependent immunoevolution was analyzed using changes in proteasomal degradation pattern, cytotoxic T lymphocytes (CTL) epitopes, and Human leukocyte antigens (HLA) restriction profile. The most recent common ancestor of the HIV CRF01_AE epidemic was estimated to be 1974±1. A period of exponential growth in effective population size began in 1982, fluctuated, and then stabilized in 1999. Genetic variability (entropy) consistently increased, however, epitope variability remained comparable; the highest number of novel CTL epitopes were present in 1995-1999, which were lost over time. The spread of the HIV-1 CRF01_AE epidemic is predominant in countries within Asia. Population immunogenetic pressures in the region may have contributed to the initial changes and following adaptation/stabilization of epitope diversity within gag sequences

Reactivation of Pulmonary Tuberculosis following Treatment of Myelofibrosis with Ruxolitinib

Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib

DataSheet_1_Patient years lost due to cytomegalovirus serostatus mismatching in the scientific registry of transplant recipients.docx

BackgroundThe cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty.MethodsWe conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age.ResultsAmong 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (pConclusionThe risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients.</p

Mucormycosis in Patients with Inflammatory Bowel Disease: Case Series and Review of the Literature

Mucormycosis is a rare and often fatal invasive fungal infection mostly seen in immune-compromised individuals. A high index of clinical suspicion is necessary, so that effective preemptive therapy can be started, as timely intervention is crucial. In this series we present three cases of invasive mucormycosis in patients with underlying inflammatory bowel disease that had received therapy with immunomodulators prior to the infection. All three had varied clinical manifestations. We also review the literature of invasive mucormycosis in patients with inflammatory bowel disease

Cognitive impairment burden in older and younger adults across the kidney transplant care continuum

BackgroundYounger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis.MethodsTo quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two- center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1- year post- KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL] < 6 or instrumental activities of daily living [IADL] < 8).ResultsAmong KT candidates, global cognitive impairment (18- 34 years: 11.1%; 35- 49 years: 14.0%; 50- 64 years: 19.5%; - ¥65 years: 22.0%) and severe cognitive impairment burden (18- 34 years: 1.1%; 35- 49 years: 3.0%; 50- 64 years: 6.2%; - ¥65 years: 7.7%) increased linearly with age. Among KT recipients at admission, global cognitive impairment (18- 34 years: 9.1%; 35- 49 years: 6.1%; 50- 64 years: 9.3%; - ¥65 years: 15.7%) and severe cognitive impairment burden (18- 34 years: 1.4%; 35- 49 years: 1.4%; 50- 64 years: 2.2%; - ¥65 years: 4.6%) was lower. Despite lowest burden of cognitive impairment among KT recipients at 1- year post- KT across all ages (18- 34 years: 1.7%; 35- 49 years: 3.4%; 50- 64 years: 4.3%; - ¥65 years: 6.5%), many still exhibited severe cognitive impairment (18- 34 years: .0%; 35- 49 years: 1.9%; 50- 64 years: 2.4%; - ¥65 years: 3.5%).ConclusionFindings were consistent for executive function impairment. While cognitive impairment increases with age, younger KT candidates have a high burden comparable to community- dwelling older adults, with some potentially suffering from severe forms. Transplant centers should consider routinely screening patients during clinical care encounters regardless of age.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171037/1/ctr14425.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171037/2/ctr14425_am.pd