Universal masking to control healthcare-associated transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

OBJECTIVES: To assess extent of a healthcare-associated outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and to evaluate the effectiveness of infection control measures, including universal masking. DESIGN: Outbreak investigation including 4 large-scale point-prevalence surveys. SETTING: Integrated VA healthcare system with 2 facilities and 330 beds. PARTICIPANTS: Index patient and 250 exposed patients and staff. METHODS: We identified exposed patients and staff and classified them as probable and confirmed cases based on symptoms and testing. We performed a field investigation and an assessment of patient and staff interactions to develop probable transmission routes. Infection prevention interventions included droplet and contact precautions, employee quarantine, and universal masking with medical and cloth face masks. We conducted 4 point-prevalence surveys of patient and staff subsets using real-time reverse-transcriptase polymerase chain reaction for SARS-CoV-2. RESULTS: Among 250 potentially exposed patients and staff, 14 confirmed cases of coronavirus disease 2019 (COVID-19) were identified. Patient roommates and staff with prolonged patient contact were most likely to be infected. The last potential date of transmission from staff to patient was day 22, the day universal masking was implemented. Subsequent point-prevalence surveys in 126 patients and 234 staff identified 0 patient cases and 5 staff cases of COVID-19, without evidence of healthcare-associated transmission. CONCLUSIONS: Universal masking with medical face masks was effective in preventing further spread of SARS-CoV-2 in our facility in conjunction with other traditional infection prevention measures.

A Comparative Analysis of 150 Thumb Polydactyly Cases from the CoULD Registry Using the Wassel-Flatt, Rotterdam, and Chung Classifications.

PURPOSE: Three commonly used classifications for thumb polydactyly are the Wassel-Flatt, Rotterdam, and Chung. The ideal classification system would have high validity and reliability and be descriptive of the thumb anomaly. The purposes of this investigation were to (1) compare the inter- and intrarater reliability of these 3 classifications when applied to a large sample of patients enrolled in the Congenital Upper Limb Differences (CoULD) Registry and (2) determine the prevalence of radial polydactyly types when using the various classifications in a North American population. METHODS: Inter- and intrarater reliability were determined using 150 cases of radial polydactyly presented in a Web-based format to 7 raters in 3 rounds, a preliminary training round and 2 observation rounds. Raters classified each case according to the Wassel-Flatt, Rotterdam, and Chung classifications. Inter- and intrarater reliability were evaluated with the intraclass correlation coefficient (ICC) calculated using 2-way random measures with perfect agreement. RESULTS: For Wassel-Flatt, both the interrater (ICC, 0.93) and the intrarater reliability (ICC, 0.91) were excellent. The Rotterdam classification had excellent reliability for both interrater reliability (ICC, 0.98) and intrarater reliability (ICC, 0.94), when considering type alone. Interrater analysis of the additional subtypes demonstrated a wide range of reliabilities. The Chung classification had good interrater (ICC, 0.88) and intrarater reliability (ICC, 0.77). Within the Wassel-Flatt classification, the most frequent unclassifiable thumb was a type IV hypoplastic thumb as classified by the Rotterdam classification. CONCLUSIONS: The Wassel-Flatt and Rotterdam classifications for radial polydactyly have excellent inter- and intrarater reliability. Despite its simplicity, the Chung classification was less reliable in comparison. The Chung and Rotterdam classification systems capture the hypoplastic subtypes that are unclassifiable in the Wassel-Flatt system. Addition of the hypoplastic subtype to the Wassel-Flatt classification (eg, Wassel-Flatt type IVh) would maintain the highest reliability and classify over 90% of thumbs deemed unclassifiable in the Wassel-Flatt system. CLINICAL RELEVANCE: The Wassel-Flatt and Rotterdam classifications have excellent inter-and intrarater reliability for the hand surgeon treating thumb polydactyly. Addition of a hypoplastic subtype to the Wassel-Flatt (Type 4h) allows classification of most previously unclassifiable thumbs.

Lamin B receptor-related disorder is associated with a spectrum of skeletal dysplasia phenotypes.

LBR (Lamin B Receptor) encodes a bifunctional protein important for cholesterol biosynthesis and heterochromatin organization on the inner nuclear membrane. Pathogenic variants in LBR are associated with marked phenotypic variability, ranging from the benign Pelger-Huët anomaly to lethal Greenberg Dysplasia. We performed trio exome sequencing (ES) on two patients with atypical variants of skeletal dysplasia and their unaffected parents. Patient 1 exhibited frontal bossing, mid-face hypoplasia, short stature with rhizomelic limb shortening, and relative macrocephaly at birth. Although remained short, Patient 1 later showed spontaneous improvement in her skeletal findings. Exome sequencing revealed two novel variants in LBR, c.1504C > G (p.Arg502Gly) in exon 12 and c.1748G > T (p.Arg583Leu) in exon 14, which were inherited from her unaffected father and mother, respectively. Sterol analysis revealed an increased level of cholesta­8,14­dien­3ß­ol to 2.9% of total sterols, consistent with a functional deficiency of 3ß­hydroxysterol Δ14­reductase. Patient 2 presented at birth with short stature and marked rhizomelic limb shortening but later exhibited decreasing severity of shortening of the long bones and improvement in the radiographic skeletal abnormalities although he continued to be significantly short at age 10 years. Exome sequencing revealed that Patient 2 is homozygous for a pathogenic variant c.1534C > T (p.Arg512Trp) in exon 12 of LBR, which was inherited from his unaffected consanguineous parents. This report provides further evidence for a phenotypic spectrum of LBR-associated disorders and expands the genotypic spectrum by describing 3 novel disease-causing variants that have not been previously associated with a disease. Moreover, our data on Patient 1 demonstrate that variants throughout the gene appear to influence both the sterol reductase and nuclear functions of LBR.

The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by inappropriate expression of the double homeodomain protein DUX4. DUX4 has bimodal effects, inhibiting myogenic differentiation and blocking MyoD at low levels of expression, and killing myoblasts at high levels. Pax3 and Pax7, which contain related homeodomains, antagonize the cell death phenotype of DUX4 in C2C12 cells, suggesting some type of competitive interaction. Here, we show that the effects of DUX4 on differentiation and MyoD expression require the homeodomains but do not require the C-terminal activation domain of DUX4. We tested the set of equally related homeodomain proteins (Pax6, Pitx2c, OTX1, Rax, Hesx1, MIXL1 and Tbx1) and found that only Pax3 and Pax7 display phenotypic competition. Domain analysis on Pax3 revealed that the Pax3 homeodomain is necessary for phenotypic competition, but is not sufficient, as competition also requires the paired and transcriptional activation domains of Pax3. Remarkably, substitution mutants in which DUX4 homeodomains are replaced by Pax7 homeodomains retain the ability to inhibit differentiation and to induce cytotoxicity.