Clinical outcomes of lung transplant recipients with pre-transplant Mycobacterium avium complex infection.

BACKGROUND: Lung transplant recipients (LTRs) are at risk for Mycobacterium avium complex (MAC) infections, in part due to the presence of structural lung disease pre-transplant and relatively higher levels of immunosuppression post-transplant. There is a lack of data regarding outcomes of LTR with MAC infections pre-transplant. METHODS: This is a single-center retrospective analysis of patients who received lung transplants (LTs) from 2013 to 2020 with 1) evidence of MAC on culture or polymerase chain reaction before or at the time of transplant or 2) granulomas on explant pathology and positive acid-fast bacillus stains with no other mycobacteria identified. Patients were deemed to have MAC pulmonary disease (MAC-PD) if they met the American Thoracic Society/Infectious Disease Society of America criteria. RESULTS: Fourteen patients (14/882, 2%) met inclusion criteria. Seven patients (7/14, 50%) had pre-transplant MAC-PD, four of whom had cavitary disease. None of the 14 patients had smear-positive cultures at the time of transplant. Two patients in our cohort received treatment for MAC before transplant. Thirteen patients were bilateral LTR (13/14, 93%). One single LTR was the sole patient to receive MAC treatment post-transplant. No patients developed MAC-PD after transplant. CONCLUSION: The bilateral LTR in our cohort did not develop MAC-PD despite not receiving MAC treatment post-transplant. It is possible source control was achieved with native lung explantation. Our observations suggest patients may not uniformly require pre- or post-transplant MAC treatment if they are smear-negative and undergo bilateral LT.

Impact of Mandatory Infectious Disease Specialist Approval on Hospital-Onset Clostridioides difficile Infection Rates and Testing Appropriateness.

BACKGROUND: Inappropriate Clostridioides difficile testing is common in the hospital setting, leading to potential overdiagnosis of infection when single-step nucleic acid amplification testing is used. The potential role of infectious diseases (ID) specialists in enforcing appropriate C. difficile testing is unclear. METHODS: At a single 697-bed academic hospital, we performed a retrospective study from 1 March 2012 to 31 December 2019 comparing hospital-onset C. difficile infection (HO-CDI) rates during 3 consecutive time periods: baseline 1 (37 months, no decision support), baseline 2 (32 months, computer decision support), and intervention period (25 months, mandatory ID specialist approval for all C. difficile testing on hospital day 4 or later). We used a discontinuous growth model to assess the impact of the intervention on HO-CDI rates. RESULTS: During the study period, we evaluated C. difficile infections across 331 180 admission and 1 172 015 patient-days. During the intervention period, a median of 1 HO-CDI test approval request per day (range, 0-6 alerts/day) was observed; adherence by providers with obtaining approval was 85%. The HO-CDI rate was 10.2, 10.4, and 4.3 events per 10 000 patient-days for each consecutive time period, respectively. In adjusted analysis, the HO-CDI rate did not differ significantly between the 2 baseline periods (P = .14) but did differ between the baseline 2 period and intervention period (P < .001). CONCLUSIONS: An ID-led C. difficile testing approval process was feasible and was associated with a >50% decrease in HO-CDI rates, due to enforcement of appropriate testing.

Neither Race nor Ethnicity Impact the Mortality of Residents of Veterans Affairs Community Living Center With COVID-19.

OBJECTIVES: COVID-19 disproportionately affected nursing home residents and people from racial and ethnic minorities in the United States. Nursing homes in the Veterans Affairs (VA) system, termed Community Living Centers (CLCs), belong to a national managed care system. In the period prior to the availability of vaccines, we examined whether residents from racial and ethnic minorities experienced disparities in COVID-19 related mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Residents at 134 VA CLCs from April 14 to December 10, 2020. METHODS: We used the VA Corporate Data Warehouse to identify VA CLC residents with a positive SARS-CoV-2 polymerase chain reaction test during or 2 days prior to their admission and without a prior case of COVID-19. We assessed age, self-reported race/ethnicity, frailty, chronic medical conditions, Charlson comorbidity index, the annual quarter of the infection, and all-cause 30-day mortality. We estimated odds ratios and 95% confidence intervals of all-cause 30-day mortality using a mixed-effects multivariable logistic regression model. RESULTS: During the study period, 1133 CLC residents had an index positive SARS-CoV-2 test. Mortality at 30 days was 23% for White non-Hispanic residents, 15% for Black non-Hispanic residents, 10% for Hispanic residents, and 16% for other residents. Factors associated with increased 30-day mortality were age ≥70 years, Charlson comorbidity index ≥6, and a positive SARS-CoV-2 test between April 14 and June 30, 2020. Frailty, Black race, and Hispanic ethnicity were not independently associated with an increased risk of 30-day mortality. CONCLUSIONS AND IMPLICATIONS: Among a national cohort of VA CLC residents with COVID-19, neither Black race nor Hispanic ethnicity had a negative impact on survival. Further research is needed to determine factors within the VA health care system that mitigate the influence of systemic racism on COVID-19 outcomes in US nursing homes.

Impact of fever thresholds in detection of COVID-19 in Department of Veterans Affairs Community Living Center residents.

BACKGROUND: Among nursing home residents, for whom age and frailty can blunt febrile responses to illness, the temperature used to define fever can influence the clinical recognition of COVID-19 symptoms. To assess the potential for differences in the definition of fever to characterize nursing home residents with COVID-19 infections as symptomatic, pre-symptomatic, or asymptomatic, we conducted a retrospective study on a national cohort of Department of Veterans Affairs (VA) Community Living Center (CLC) residents tested for SARS-CoV-2. METHODS: Residents with positive SARS-CoV-2 tests were classified as asymptomatic if they did not experience any symptoms, and as symptomatic or pre-symptomatic if the experienced a fever (>100.4°F) before or following a positive SARS-CoV-2 test, respectively. All-cause 30-day mortality was assessed as was the influence of a lower temperature threshold (>99.0°F) on classification of residents with positive SARS-CoV-2 tests. RESULTS: From March 2020 through November 2020, VA CLCs tested 11,908 residents for SARS-CoV-2 using RT-PCR, with a positivity of rate of 13% (1557). Among residents with positive tests and using >100.4°F, 321 (21%) were symptomatic, 425 (27%) were pre-symptomatic, and 811 (52%) were asymptomatic. All-cause 30-day mortality among residents with symptomatic and pre-symptomatic COVID-19 infections was 24% and 26%, respectively, while those with an asymptomatic infection had mortality rates similar to residents with negative SAR-CoV-2 tests (10% and 5%, respectively). Using >99.0°F would have increased the number of residents categorized as symptomatic at the time of testing from 321 to 773. CONCLUSIONS: All-cause 30-day mortality was similar among VA CLC residents with symptomatic or pre-symptomatic COVID-19 infection, and lower than rates reported in non-VA nursing homes. A lower temperature threshold would increase the number of residents recognized as having symptomatic infection, potentially leading to earlier detection and more rapid implementation of therapeutic interventions and infection prevention and control measures.

Photoactivated phytochromes interact with HEMERA and promote its accumulation to establish photomorphogenesis in Arabidopsis.

Plant development is profoundly regulated by ambient light cues through the red/far-red photoreceptors, the phytochromes. Early phytochrome signaling events include the translocation of phytochromes from the cytoplasm to subnuclear domains called photobodies and the degradation of antagonistically acting phytochrome-interacting factors (PIFs). We recently identified a key phytochrome signaling component, HEMERA (HMR), that is essential for both phytochrome B (phyB) localization to photobodies and PIF degradation. However, the signaling mechanism linking phytochromes and HMR is unknown. Here we show that phytochromes directly interact with HMR to promote HMR protein accumulation in the light. HMR binds more strongly to the active form of phytochromes. This interaction is mediated by the photosensory domains of phytochromes and two phytochrome-interacting regions in HMR. Missense mutations in either HMR or phyB that alter the phytochrome/HMR interaction can also change HMR levels and photomorphogenetic responses. HMR accumulation in a constitutively active phyB mutant (YHB) is required for YHB-dependent PIF3 degradation in the dark. Our genetic and biochemical studies strongly support a novel phytochrome signaling mechanism in which photoactivated phytochromes directly interact with HMR and promote HMR accumulation, which in turn mediates the formation of photobodies and the degradation of PIFs to establish photomorphogenesis.