Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility.

ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar yet diminished pattern of reduced susceptibility was observed with the long-tailed triazoles posaconazole and itraconazole for the V125A/F126L, F126L, Y132F, and K143R alleles.

Understanding Variations in the Management of Displaced Distal Radius Fractures With Satisfactory Reduction.

BACKGROUND: The American Academy of Orthopaedic Surgeons has set forth Clinical Practice Guidelines (CPGs) to help guide management of closed, displaced distal radius fractures (DRFs). There still exists variation in practice regarding operative vs nonoperative decision-making. This study aims to identify which factors influence the decision to treat DRFs not indicated for surgery by the CPGs after initial closed reduction. METHODS: Fifteen sets of DRFs and clinical vignettes were distributed via email to over 75 orthopedic residency programs, Orthopaedic Trauma Association, and New York Society for Surgery of the Hand membership. A Qualtrics survey collected respondent demographics, choice of treatment, and rationale. RESULTS: Responses were received from 106 surgeons and resident trainees. The odds of selecting operative management for fractures with 5 or more radiographic instability signs versus 3 or 4 was 3.11 (P < .05). Age over 65, higher patient activity level, and dominant-hand injury were associated with greater odds of operative management (3.4, 30.28, and 2.54, respectively). In addition, surgeons with more years in practice and high-volume surgeons had greater odds of selecting operative management (2.43 and 2.11, respectively). CONCLUSIONS: Assessment of instability at the time of injury, patient age and activity level, as well as surgeon volume and time in practice independently affect the decision to manage well-reduced DRF with surgical or nonsurgical treatment. The source of heterogeneity in the treatment of these fractures is borne at least in part from a lack of formal direction on the importance of prereduction instability from the CPGs.

Evaluation of Patient Expectations and Outcomes after Distal Radius Fractures.

BACKGROUND: Patient expectations influence patient-reported outcomes after musculoskeletal injuries. The goal of this study is to determine how pretreatment expectations correlate with outcomes in patients with distal radius fractures. METHODS: Seventy-five patients with an isolated distal radius fracture were prospectively enrolled into nonoperative and operative cohorts. The Trauma Expectation Factor-Trauma Outcome Measure (TEF-TOM) score was the primary outcome measure. Trauma Expectation Factor scores were recorded at the time of enrollment, and TOM scores were recorded at 3, 6, and 12 months. Quick Disabilities of the Arm, Shoulder, and Hand (qDASH) and Patient-Rated Wrist Evaluation (PRWE) scores were also recorded. RESULTS: Trauma Outcome Measure scores at all time points were worse than expected (P < .01). Expectations were higher for patients younger than 65 years than for the 65+ group (P = .02). In patients aged 65+ years, mean TOM at 3 months was not significantly different than expected (P = .11) but decreased by 6 (P = .04) and 12 months (P < .01). Baseline TEF and TEF-TOM scores were not significantly different between operative and nonoperative groups (P = .37). Quick Disabilities of the Arm, Shoulder, and Hand and PRWE scores were not significantly different between age or treatment groups at the final follow-up. CONCLUSIONS: The overall treatment of distal radial injuries in our study did not meet patient expectations. Patients aged 65 years or older had lower expectations but were not able to predict their outcomes better than patients aged <65 years. There were no differences in TEF or TOM by treatment method. Patients demonstrated improved functional outcomes (qDASH/PRWE) at all time points regardless of age and treatment method.

Antifungal Drug Susceptibility and Genetic Characterization of Fungi Recovered from COVID-19 Patients.

Fungal infections are common complications of respiratory viral infections and are associated with the increased need for intensive care and elevated mortality. Data regarding microbiological and molecular characteristics of such infections in COVID-19 patients are scarce. Here, we performed a comprehensive analysis, including species identification, antifungal susceptibility testing, molecular resistance determinants analysis, typing, and retrospective clinical data review, of fungal isolates recovered from 19 COVID-19 patients, who were hospitalized at the Hackensack University Medical Center (HUMC) in Hackensack, New Jersey, USA, in the initial phase of the pandemic from April-May 2020. In total, 17 Candida albicans, two C. parapsilosis, and two Aspergillus fumigatus were analyzed. All Candida spp. isolates were susceptible to micafungin and azole drugs (fluconazole, voriconazole, posaconazole, itraconazole, isavuconazole). A. fumigatus isolates were susceptible to micafungin and all triazole drugs except fluconazole (intrinsic resistance). Multilocus sequence typing (MLST) of C. albicans isolates revealed 15 different sequence types (STs), which clustered below the clade-defining limit of p-distance < 0.04. Pulsed-field gel electrophoresis (PFGE) karyotyping revealed no chromosomal rearrangements in these isolates. A. fumigatus isolates were of different, non-related genotypes. We speculate that virus- and drug-induced immunosuppression (94.7% of the patients received corticosteroids), together with prolonged hospital stay (median duration of 29 days) and mechanical ventilation (median duration of 24 days) likely increased the susceptibility to secondary respiratory and bloodstream infections in the studied patient population. The presence of fungi in blood or respiratory tract fluid was a prognosticator for poor clinical outcome, which presented as an 89.5% 30-day mortality in our patient cohort.