A KLHL40 3' UTR splice-altering variant causes milder NEM8, an under-appreciated disease mechanism.

Nemaline myopathy 8 (NEM8) is typically a severe autosomal recessive disorder associated with variants in the kelch-like family member 40 gene (KLHL40). Common features include fetal akinesia, fractures, contractures, dysphagia, respiratory failure and neonatal death. Here, we describe a 26-year-old man with relatively mild NEM8. He presented with hypotonia and bilateral femur fractures at birth, later developing bilateral Achilles' contractures, scoliosis, and elbow and knee contractures. He had walking difficulties throughout childhood and became wheelchair bound from age 13 after prolonged immobilization. Muscle magnetic resonance imaging at age 13 indicated prominent fat replacement in his pelvic girdle, posterior compartments of thighs and vastus intermedius. Muscle biopsy revealed nemaline bodies and intranuclear rods. RNA sequencing and western blotting of patient skeletal muscle indicated significant reduction in KLHL40 mRNA and protein, respectively. Using gene panel screening, exome sequencing and RNA sequencing, we identified compound heterozygous variants in KLHL40; a truncating 10.9 kb deletion in trans with a likely pathogenic variant (c.*152G > T) in the 3' untranslated region (UTR). Computational tools SpliceAI and Introme predicted the c.*152G > T variant created a cryptic donor splice site. RNA-seq and in vitro analyses indicated that the c.*152G > T variant induces multiple de novo splicing events that likely provoke nonsense mediated decay of KLHL40 mRNA explaining the loss of mRNA expression and protein abundance in the patient. Analysis of 3' UTR variants in ClinVar suggests variants that introduce aberrant 3' UTR splicing may be underrecognized in Mendelian disease. We encourage consideration of this mechanism during variant curation.

Systemic AAV8-mediated delivery of a functional copy of muscle glycogen phosphorylase (Pygm) ameliorates disease in a murine model of McArdle disease.

McArdle disease is a disorder of carbohydrate metabolism that causes painful skeletal muscle cramps and skeletal muscle damage leading to transient myoglobinuria and increased risk of kidney failure. McArdle disease is caused by recessive mutations in the muscle glycogen phosphorylase (PYGM) gene leading to absence of PYGM enzyme in skeletal muscle and preventing access to energy from muscle glycogen stores. There is currently no cure for McArdle disease. Using a preclinical animal model, we aimed to identify a clinically translatable and relevant therapy for McArdle disease. We evaluated the safety and efficacy of recombinant adeno-associated virus serotype 8 (rAAV8) to treat a murine model of McArdle disease via delivery of a functional copy of the disease-causing gene, Pygm. Intraperitoneal injection of rAAV8-Pygm at post-natal day 1-3 resulted in Pygm expression at 8 weeks of age, accompanied by improved skeletal muscle architecture, reduced accumulation of glycogen and restoration of voluntary running wheel activity to wild-type levels. We did not observe any adverse reaction to the treatment at 8 weeks post-injection. Thus, we have investigated a highly promising gene therapy for McArdle disease with a clear path to the ovine large animal model endemic to Western Australia and subsequently to patients.

Neurogenetic fetal akinesia and arthrogryposis: genetics, expanding genotype-phenotypes and functional genomics.

BACKGROUND: Fetal akinesia and arthrogryposis are clinically and genetically heterogeneous and have traditionally been refractive to genetic diagnosis. The widespread availability of affordable genome-wide sequencing has facilitated accurate genetic diagnosis and gene discovery in these conditions. METHODS: We performed next generation sequencing (NGS) in 190 probands with a diagnosis of arthrogryposis multiplex congenita, distal arthrogryposis, fetal akinesia deformation sequence or multiple pterygium syndrome. This sequencing was a combination of bespoke neurogenetic disease gene panels and whole exome sequencing. Only class 4 and 5 variants were reported, except for two cases where the identified variants of unknown significance (VUS) are most likely to be causative for the observed phenotype. Co-segregation studies and confirmation of variants identified by NGS were performed where possible. Functional genomics was performed as required. RESULTS: Of the 190 probands, 81 received an accurate genetic diagnosis. All except two of these cases harboured class 4 and/or 5 variants based on the American College of Medical Genetics and Genomics guidelines. We identified phenotypic expansions associated with CACNA1S, CHRNB1, GMPPB and STAC3. We describe a total of 50 novel variants, including a novel missense variant in the recently identified gene for arthrogryposis with brain malformations-SMPD4. CONCLUSIONS: Comprehensive gene panels give a diagnosis for a substantial proportion (42%) of fetal akinesia and arthrogryposis cases, even in an unselected cohort. Recently identified genes account for a relatively large proportion, 32%, of the diagnoses. Diagnostic-research collaboration was critical to the diagnosis and variant interpretation in many cases, facilitated genotype-phenotype expansions and reclassified VUS through functional genomics.

Vaccine Breakthrough Cases in South Dakota: Impact of SARS-CoV-2 Variants in a Rural State.

BACKGROUND: Emergence of the SARS-CoV-2 Delta variant raised concern for greater transmissibility and severity of illness compared to the Alpha variant. Our objective was to compare SARS-CoV-2 vaccine breakthrough cases in South Dakota during the time periods where the Alpha and Delta variants of SARS-CoV-2 predominated. METHODS: Data were obtained from the South Dakota Department of Health's electronic disease surveillance system and South Dakota's Health Information Exchange. SARS-CoV-2 cases were matched with the immunization system data to verify vaccination status of vaccine breakthrough cases (VBC). The Alpha variant time-period (ATP) was defined as April 15-May 10, 2021 and the Delta variant time-period (DTP) as July 18-31, 2021. Case rates, demographics, risk factors, symptomology, and outcomes were compared for VBC during these periods. RESULTS: A total of 155 VBC were reported during the ATP and 153 during the DTP. The rate of SARS-CoV-2 VBC was 1.88 times higher for the DTP than the ATP. VBC during the ATP were more likely to present with no symptoms and during the DTP were more likely to present with subjective fever, cough, headache, loss or altered smell/taste, congestion, or postnasal drip. The average hospital length of stay was 6 days for the ATP and 4 days for the DTP. A total of 5 deaths were reported during the ATP compared to 1 death during the DTP. The non-statistically significant relation of the ATP and the DTP for hospital length of stay and number of deaths indicated a similar severity of disease. CONCLUSIONS: In fully vaccinated South Dakotans, the SARS-CoV-2 Delta variant was shown to cause 1.88 times higher breakthrough cases but resulted in similar severity of illness compared to the Alpha variant.

Biallelic hypomorphic variants in ALDH1A2 cause a novel lethal human multiple congenital anomaly syndrome encompassing diaphragmatic, pulmonary, and cardiovascular defects.

This study shows a causal association between ALDH1A2 variants and a novel, severe multiple congenital anomaly syndrome in humans that is neonatally lethal due to associated pulmonary hypoplasia and respiratory failure. In two families, exome sequencing identified compound heterozygous missense variants in ALDH1A2. ALDH1A2 is involved in the conversion of retinol (vitamin A) into retinoic acid (RA), which is an essential regulator of diaphragm and cardiovascular formation during embryogenesis. Reduced RA causes cardiovascular, diaphragmatic, and associated pulmonary defects in several animal models, matching the phenotype observed in our patients. In silico protein modeling showed probable impairment of ALDH1A2 for three of the four substitutions. In vitro studies show a reduction of RA. Few pathogenic variants in genes encoding components of the retinoic signaling pathway have been described to date, likely due to embryonic lethality. Thus, this study contributes significantly to knowledge of the role of this pathway in human diaphragm and cardiovascular development and disease. Some clinical features in our patients are also observed in Fryns syndrome (MIM# 229850), syndromic microphthalmia 9 (MIM# 601186), and DiGeorge syndrome (MIM# 188400). Patients with similar clinical features who are genetically undiagnosed should be tested for recessive ALDH1A2-deficient malformation syndrome.

Widespread Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Among Attendees at a Large Motorcycle Rally and their Contacts, 30 US Jurisdictions, August-September, 2020.

The 2020 Sturgis motorcycle rally resulted in widespread transmission of severe acute respiratory syndrome coronavirus 2 across the United States. At least 649 coronavirus disease 2019 cases were identified, including secondary and tertiary spread to close contacts. To limit transmission, persons attending events should be vaccinated or wear masks and practice physical distancing if unvaccinated. Persons with a known exposure should be managed according to their coronavirus disease 2019 vaccination or prior infection status and may include quarantine and coronavirus disease 2019 testing.

Coronavirus Disease among Workers in Food Processing, Food Manufacturing, and Agriculture Workplaces.

We describe coronavirus disease (COVID-19) among US food manufacturing and agriculture workers and provide updated information on meat and poultry processing workers. Among 742 food and agriculture workplaces in 30 states, 8,978 workers had confirmed COVID-19; 55 workers died. Racial and ethnic minority workers could be disproportionately affected by COVID-19.

Autosomal recessive cardiomyopathy and sudden cardiac death associated with variants in MYL3.

PURPOSE: Variants in genes encoding sarcomeric proteins are the most common cause of inherited cardiomyopathies. However, the underlying genetic cause remains unknown in many cases. We used exome sequencing to reveal the genetic etiology in patients with recessive familial cardiomyopathy. METHODS: Exome sequencing was carried out in three consanguineous families. Functional assessment of the variants was performed. RESULTS: Affected individuals presented with hypertrophic or dilated cardiomyopathy of variable severity from infantile- to early adulthood-onset and sudden cardiac death. We identified a homozygous missense substitution (c.170C>A, p.[Ala57Asp]), a homozygous translation stop codon variant (c.106G>T, p.[Glu36Ter]), and a presumable homozygous essential splice acceptor variant (c.482-1G>A, predicted to result in skipping of exon 5). Morpholino knockdown of the MYL3 orthologue in zebrafish, cmlc1, resulted in compromised cardiac function, which could not be rescued by reintroduction of MYL3 carrying either the nonsense c.106G>T or the missense c.170C>A variants. Minigene assay of the c.482-1G>A variant indicated a splicing defect likely resulting in disruption of the EF-hand Ca2+ binding domains. CONCLUSIONS: Our data demonstrate that homozygous MYL3 loss-of-function variants can cause of recessive cardiomyopathy and occurrence of sudden cardiac death, most likely due to impaired or loss of myosin essential light chain function.

A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, a pentanucleotide expansion in intron 2 of RFC1 was identified as the genetic cause of CANVAS. We screened an Asian-Pacific cohort for CANVAS and identified a novel RFC1 repeat expansion motif, (ACAGG)exp, in three affected individuals. This motif was associated with additional clinical features including fasciculations and elevated serum creatine kinase. These features have not previously been described in individuals with genetically-confirmed CANVAS. Haplotype analysis showed our patients shared the same core haplotype as previously published, supporting the possibility of a single origin of the RFC1 disease allele. We analysed data from >26 000 genetically diverse individuals in gnomAD to show enrichment of (ACAGG) in non-European populations.

Assessing County-Level Vulnerability for Opioid Overdose and Rapid Spread of Human Immunodeficiency Virus and Hepatitis C Infection in South Dakota.

BACKGROUND: Key indicators of vulnerability for the syndemic of opioid overdose, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) due to injection drug use (IDU) in rural reservation and frontier counties are unknown. We examined county-level vulnerability for this syndemic in South Dakota. METHODS: Informed by prior methodology from the Centers for Disease Control and Prevention, we used acute and chronic HCV infections among persons aged ≤40 years as a proxy measure of IDU. Twenty-nine county-level indicators potentially associated with HCV infection rates were identified. Using these indicators, we examined relationships through bivariate and multivariate analysis and calculated a composite index score to identify the most vulnerable counties (top 20%) to this syndemic. RESULTS: Of the most vulnerable counties, 69% are reservation counties and 62% are rural. The county-level HCV infection rate is 4 times higher in minority counties than nonminority counties, and almost all significant indicators of opioid-related vulnerability in our analysis are structural and potentially modifiable through public health interventions and policies. CONCLUSIONS: Our assessment gives context to the magnitude of this syndemic in rural reservation and frontier counties and should inform the strategic allocation of prevention and intervention services.

Multistate Mumps Outbreak Originating from Asymptomatic Transmission at a Nebraska Wedding - Six States, August-October 2019.

In August 2019, 30 attendees at a Nebraska wedding developed mumps after being exposed to one asymptomatic index patient who was fully vaccinated according to Advisory Committee on Immunization Practices (ACIP) recommendations (1), resulting in a multistate outbreak. A public health investigation and response revealed epidemiologic links that extended from the index patient through secondary, tertiary, and quaternary patients and culminated in a measles-mumps-rubella (MMR) booster vaccination campaign in the local community where approximately half of the patients resided.

COVID-19 Outbreak Among Employees at a Meat Processing Facility - South Dakota, March-April 2020.

On March 24, 2020, the South Dakota Department of Health (SDDOH) was notified of a case of coronavirus disease 2019 (COVID-19) in an employee at a meat processing facility (facility A) and initiated an investigation to isolate the employee and identify and quarantine contacts. On April 2, when 19 cases had been confirmed among facility A employees, enhanced testing for SARS-CoV-2, the virus that causes COVID-19, was implemented, so that any employee with a COVID-19-compatible sign or symptom (e.g., fever, cough, or shortness of breath) could receive a test from a local health care facility. By April 11, 369 COVID-19 cases had been confirmed among facility A employees; on April 12, facility A began a phased closure* and did not reopen during the period of investigation (March 16-April 25, 2020). At the request of SDDOH, a CDC team arrived on April 15 to assist with the investigation. During March 16-April 25, a total of 929 (25.6%) laboratory-confirmed COVID-19 cases were diagnosed among 3,635 facility A employees. At the outbreak's peak, an average of 67 cases per day occurred. An additional 210 (8.7%) cases were identified among 2,403 contacts of employees with diagnosed COVID-19. Overall, 48 COVID-19 patients were hospitalized, including 39 employees and nine contacts. Two employees died; no contacts died. Attack rates were highest among department-groups where employees tended to work in proximity (i.e., <6 feet [2 meters]) to one another on the production line. Cases among employees and their contacts declined to approximately 10 per day within 7 days of facility closure. SARS-CoV-2 can spread rapidly in meat processing facilities because of the close proximity of workstations and prolonged contact between employees (1,2). Facilities can reduce this risk by implementing a robust mitigation program, including engineering and administrative controls, consistent with published guidelines (1).

COVID-19 Mortality Among American Indian and Alaska Native Persons - 14 States, January-June 2020.

American Indian/Alaska Native (AI/AN) persons experienced disproportionate mortality during the 2009 influenza A(H1N1) pandemic (1,2). Concerns of a similar trend during the coronavirus disease 2019 (COVID-19) pandemic led to the formation of a workgroup* to assess the prevalence of COVID-19 deaths in the AI/AN population. As of December 2, 2020, CDC has reported 2,689 COVID-19-associated deaths among non-Hispanic AI/AN persons in the United States.† A recent analysis found that the cumulative incidence of laboratory-confirmed COVID-19 cases among AI/AN persons was 3.5 times that among White persons (3). Among 14 participating states, the age-adjusted AI/AN COVID-19 mortality rate (55.8 deaths per 100,000; 95% confidence interval [CI] = 52.5-59.3) was 1.8 (95% CI = 1.7-2.0) times that among White persons (30.3 deaths per 100,000; 95% CI = 29.9-30.7). Although COVID-19 mortality rates increased with age among both AI/AN and White persons, the disparity was largest among those aged 20-49 years. Among persons aged 20-29 years, 30-39 years, and 40-49 years, the COVID-19 mortality rates among AI/AN were 10.5, 11.6, and 8.2 times, respectively, those among White persons. Evidence that AI/AN communities might be at increased risk for COVID-19 illness and death demonstrates the importance of documenting and understanding the reasons for these disparities while developing collaborative approaches with federal, state, municipal, and tribal agencies to minimize the impact of COVID-19 on AI/AN communities. Together, public health partners can plan for medical countermeasures and prevention activities for AI/AN communities.

Update: COVID-19 Among Workers in Meat and Poultry Processing Facilities - United States, April-May 2020.

Meat and poultry processing facilities face distinctive challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1). COVID-19 outbreaks among meat and poultry processing facility workers can rapidly affect large numbers of persons. Assessment of COVID-19 cases among workers in 115 meat and poultry processing facilities through April 27, 2020, documented 4,913 cases and 20 deaths reported by 19 states (1). This report provides updated aggregate data from states regarding the number of meat and poultry processing facilities affected by COVID-19, the number and demographic characteristics of affected workers, and the number of COVID-19-associated deaths among workers, as well as descriptions of interventions and prevention efforts at these facilities. Aggregate data on confirmed COVID-19 cases and deaths among workers identified and reported through May 31, 2020, were obtained from 239 affected facilities (those with a laboratory-confirmed COVID-19 case in one or more workers) in 23 states.* COVID-19 was confirmed in 16,233 workers, including 86 COVID-19-related deaths. Among 14 states reporting the total number of workers in affected meat and poultry processing facilities (112,616), COVID-19 was diagnosed in 9.1% of workers. Among 9,919 (61%) cases in 21 states with reported race/ethnicity, 87% occurred among racial and ethnic minority workers. Commonly reported interventions and prevention efforts at facilities included implementing worker temperature or symptom screening and COVID-19 education, mandating face coverings, adding hand hygiene stations, and adding physical barriers between workers. Targeted workplace interventions and prevention efforts that are appropriately tailored to the groups most affected by COVID-19 are critical to reducing both COVID-19-associated occupational risk and health disparities among vulnerable populations. Implementation of these interventions and prevention efforts† across meat and poultry processing facilities nationally could help protect workers in this critical infrastructure industry.

COVID-19 in Correctional and Detention Facilities - United States, February-April 2020.

An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities† on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.

COVID-19 Among Workers in Meat and Poultry Processing Facilities - 19 States, April 2020.

Congregate work and residential locations are at increased risk for infectious disease transmission including respiratory illness outbreaks. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is primarily spread person to person through respiratory droplets. Nationwide, the meat and poultry processing industry, an essential component of the U.S. food infrastructure, employs approximately 500,000 persons, many of whom work in proximity to other workers (1). Because of reports of initial cases of COVID-19, in some meat processing facilities, states were asked to provide aggregated data concerning the number of meat and poultry processing facilities affected by COVID-19 and the number of workers with COVID-19 in these facilities, including COVID-19-related deaths. Qualitative data gathered by CDC during on-site and remote assessments were analyzed and summarized. During April 9-27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19-related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. Methods to decrease transmission within the facility include worker symptom screening programs, policies to discourage working while experiencing symptoms compatible with COVID-19, and social distancing by workers. Source control measures (e.g., the use of cloth face covers) as well as increased disinfection of high-touch surfaces are also important means of preventing SARS-CoV-2 exposure. Mitigation efforts to reduce transmission in the community should also be considered. Many of these measures might also reduce asymptomatic and presymptomatic transmission (3). Implementation of these public health strategies will help protect workers from COVID-19 in this industry and assist in preserving the critical meat and poultry production infrastructure (4).

CD8+ T-cells negatively regulate inflammation post-myocardial infarction.

The adaptive immune response is key for cardiac wound healing post-myocardial infarction (MI) despite low T-cell numbers. We hypothesized that CD8+ T-cells regulate the inflammatory response, leading to decreased survival and cardiac function post-MI. We performed permanent occlusion of the left anterior descending coronary artery on C57BL/6J and CD8atm1mak mice (deficient in functional CD8+ T-cells). CD8atm1mak mice had increased survival at 7 days post-MI compared with that of the wild-type (WT) and improved cardiac physiology at day 7 post-MI. Despite having less mortality, 100% of the CD8atm1mak group died because of cardiac rupture compared with only 33% of the WT. Picrosirius red staining and collagen immunoblotting indicated an acceleration of fibrosis in the infarct area as well as remote area in the CD8atm1mak mice; however, this increase was due to elevated soluble collagen implicating poor scar formation. Plasma and tissue inflammation were exacerbated as indicated by higher levels of Cxcl1, Ccl11, matrix metalloproteinase (MMP)-2, and MMP-9. Immunohistochemistry and flow cytometry indicated that the CD8atm1mak group had augmented numbers of neutrophils and macrophages at post-MI day 3 and increased mast cell markers at post-MI day 7. Cleavage of tyrosine-protein kinase MER was increased in the CD8atm1mak mice, resulting in delayed removal of necrotic tissue. In conclusion, despite having improved cardiac physiology and overall survival, CD8atm1mak mice had increased innate inflammation and poor scar formation, leading to higher incidence of cardiac rupture. Our data suggest that the role of CD8+ T-cells in post-MI recovery may be both beneficial and detrimental to cardiac remodeling and is mediated via a cell-specific mechanism.NEW & NOTEWORTHY We identified new mechanisms implicating CD8+ T-cells as regulators of the post-myocardial infarction (MI) wound healing process. Mice without functional CD8+ T-cells had improved cardiac physiology and less mortality 7 days post MI compared with wild-type animals. Despite having better overall survival, animals lacking functional CD8+ T-cells had delayed removal of necrotic tissue, leading to poor scar formation and increased cardiac rupture, suggesting that CD8+ T-cells play a dual role in the cardiac remodeling process.

Public Health Response to an Avian Influenza A(H7N8) Virus Outbreak in Commercial Turkey Flocks - Indiana, 2016.

In January 2016, highly pathogenic avian influenza (HPAI) A(H7N8) virus and low pathogenicity avian influenza (LPAI) A(H7N8) virus were detected in commercial turkey flocks in Dubois County, Indiana. The Indiana State Department of Health (ISDH) and the Dubois County Health Department (DCHD) coordinated the public health response to this outbreak, which was the first detection of HPAI A(H7N8) in any species (1). This response was the first to fully implement unpublished public health monitoring procedures for HPAI responders that were developed by the U.S. Department of Agriculture (USDA) and CDC in 2015 (Sonja Olsen, CDC, personal communication, October 2017). No cases of zoonotic avian influenza infection in humans were detected during the outbreak.

CT-Guided Percutaneous Lung Biopsies in Patients With Suspicion for Infection May Yield Clinically Useful Information.

OBJECTIVE: The objective of our study was to assess the frequency and time frame with which CT-guided lung biopsies for suspected infection yield information that can affect patient management. MATERIALS AND METHODS: All CT-guided lung biopsies over a 68-month period performed for the purpose of diagnosing a suspected infection were reviewed to determine the proportion that yielded information affecting patient management. Patients were included if infection was the only consideration causing the pulmonary lesion in question. RESULTS: Twenty-one biopsies were performed to identify a specific organism causing infection in patients with suspected infection; all patients were receiving antibiotics, 20 (95%) were immunocompromised, and 15 (71%) had undergone a prior bronchoscopy. Material collected from the biopsy provided a diagnosis in nine (43%) patients, whereas the biopsy results were nondiagnostic in the remaining 12 (57%). Of the nine patients for whom the biopsy yielded a diagnosis, eight biopsies revealed the species causing an infection (38%) and one biopsy (5%) detected posttransplant lymphoproliferative disease. Of the nine diagnoses, management was changed as a result of the biopsy in six patients (29% of all patients). The organisms identified by CT-guided lung biopsy in eight patients were fungi of the order Mucorales (i.e., mucormycosis) (n = 3), Aspergillus (n = 3), Pseudomonas (n = 1), and Nocardia (n = 1). The mean elapsed time between biopsy and pathologic diagnosis was 4 days (median, 3 days). There was no association between prior bronchoscopy and nondiagnostic biopsy results. CONCLUSION: CT-guided lung biopsies in patients with a high pretest suspicion for infection result in information sufficient to change patient management in 29% of patients. Organisms identified in these patients were most frequently fungi.

Parental Refusal of Vitamin K and Neonatal Preventive Services: A Need for Surveillance.

Objectives Vitamin K deficiency bleeding (VKDB) in infants is a coagulopathy preventable with a single dose of injectable vitamin K at birth. The Tennessee Department of Health (TDH) and Centers for Disease Control and Prevention (CDC) investigated vitamin K refusal among parents in 2013 after learning of four cases of VKDB associated with prophylaxis refusal. Methods Chart reviews were conducted at Nashville-area hospitals for 2011-2013 and Tennessee birthing centers for 2013 to identify parents who had refused injectable vitamin K for their infants. Contact information was obtained for parents, and they were surveyed regarding their reasons for refusing. Results At hospitals, 3.0% of infants did not receive injectable vitamin K due to parental refusal in 2013, a frequency higher than in 2011 and 2012. This percentage was much higher at birthing centers, where 31% of infants did not receive injectable vitamin K. The most common responses for refusal were a belief that the injection was unnecessary (53%) and a desire for a natural birthing process (36%). Refusal of other preventive services was common, with 66% of families refusing vitamin K, newborn eye care with erythromycin, and the neonatal dose of hepatitis B vaccine. Conclusions for Practice Refusal of injectable vitamin K was more common among families choosing to give birth at birthing centers than at hospitals, and was related to refusal of other preventive services in our study. Surveillance of vitamin K refusal rates could assist in further understanding this occurrence and tailoring effective strategies for mitigation.