Asthma deaths during sports: report of a 7-year experience

BACKGROUND: Asthma mortality and the mortality of athletes during sports have been described separately in detail in the medical literature. However, asthma has not been reported as a cause of death in competitive athletes. OBJECTIVE: The object of this study was to raise the awareness of physicians, coaches, trainers, and parents that children and adults can have fatal asthma exacerbations during and immediately after participating in sports. METHODS: The Temple Sports Asthma Research Center identified athletes from 1993 until 2000 who died during or after sporting activity by using the nationwide Burrell's Information Service. Once a possible asthma-related sports death was identified, the autopsy report was requested from the coroner or medical examiner, and an attempt was made to contact the family. Contact with the family was limited to information about the death, medical history, sports involvement, and any medication usage by the person who had died. Secondary sources, including news reports, were used to confirm whether the subject died of asthma during or immediately after a sporting activity. RESULTS: Two hundred sixty-three possible cases were identified. Sixty-one deaths met the criteria for study inclusion. White deaths outnumbered black deaths by 2 to 1. Deaths among male subjects predominated. Most subjects were younger than the age of 20 years, with the most prevalent age group being between 10 to 14 years old. Fifty-one percent (18 of 35) of the competitive athletes had their fatal event while participating in organized sport, 14 in a practice situation and 4 deaths during a game or meet setting. Basketball and track were the 2 most frequent activities performed at the time of the fatal event. CONCLUSION: The subjects who had fatal asthma exacerbations were usually white male subjects between the ages of 10 and 20 years. Mild intermittent or persistent asthma by history was commonly identified. Sudden fatal asthma exacerbations occur in both competitive and recreational athletes and can be precipitated by sporting activity.     

Bilateral periorbital and cervicofacial emphysema following retinal surgery and fluid gas exchange in a case of inadvertent globe perforation

Surgical emphysema is defined as gas or air trapped in the subcutaneous tissue plane. Here, we report a rare case of bilateral periorbital and cervicofacial subcutaneous emphysema following a vitreoretinal surgery for inadvertent globe perforation during the administration of peribulbar anesthesia. This condition, although self-resolving when restricted to the subcutaneous plane has the potential to spread into deeper tissue planes such as the retropharyngeal space. The presence of crepitus helps to distinguish it from angioneurotic edema. Ophthalmologists must be sensitive to the fact that surgical emphysema can be a very rare, but possible complication of an intraocular surgery following globe perforation.     

Results of Wagner SL revision stem with impaction bone grafting in revision total hip arthroplasty

Background:

As the number of total hip arthroplasties (THAs) performed increases, so do the number of required revisions. Impaction bone grafting with Wagner SL Revision stem is a good option for managing bone deficiencies arising from aseptic osteolysis. We studied the results of cementless diaphyseal fixation in femoral revision after total hip arthroplasty and whether there was spontaneous regeneration of bone stock in the proximal femur after the use of Wagner SL Revision stem (Zimmer, Warsaw, IN, USA) with impaction bone grafting.

Materials and Methods:

We performed 53 hip revisions using impaction bone grafting and Wagner SL Revision stems in 48 patients; (5 cases were bilateral) for variety of indications ranging from aseptic osteolysis to preiprosthetic fractures. The average age was 59 years (range 44-68 years). There were 42 male and 6 female patients. Four patients died after surgery for reasons unrelated to surgery. 44 patients were available for complete analysis.

Results:

The mean Harris Hip Score was 42 before surgery and improved to 86 by the final followup evaluation at a mean point of 5.5 years. Of the 44 patients, 87% (n=39) had excellent results and 10% (n=5) had good results. The stem survival rate was 98% (n=43).

Conclusion:

Short term results for revision THA with impaction bone grafting and Wagner SL revision stems are encouraging. However, it is necessary to obtain long term results through periodic followup evaluation, as rate of complications may increase in future.     

A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders

Genetic ataxias are associated with mutations in hundreds of genes with high phenotypic overlap complicating the clinical diagnosis. Whole‐exome sequencing (WES) has increased the overall diagnostic rate considerably. However, the upper limit of this method remains ill‐defined, hindering efforts to address the remaining diagnostic gap. To further assess the role of rare coding variation in ataxic disorders, we reanalyzed our previously published exome cohort of 76 predominantly adult and sporadic‐onset patients, expanded the total number of cases to 260, and introduced analyses for copy number variation and repeat expansion in a representative subset. For new cases (n = 184), our resulting clinically relevant detection rate remained stable at 47% with 24% classified as pathogenic. Reanalysis of the previously sequenced 76 patients modestly improved the pathogenic rate by 7%. For the combined cohort (n = 260), the total observed clinical detection rate was 52% with 25% classified as pathogenic. Published studies of similar neurological phenotypes report comparable rates. This consistency across multiple cohorts suggests that, despite continued technical and analytical advancements, an approximately 50% diagnostic rate marks a relative ceiling for current WES‐based methods and a more comprehensive genome‐wide assessment is needed to identify the missing causative genetic etiologies for cerebellar ataxia and related neurodegenerative diseases.     

Heterozygous CTNNB1 and TBX4 variants in a patient with abnormal lung growth,pulmonary hypertension,microcephaly, and spasticity

The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full-term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.     

Identification of Intellectual Disability Genes in Female Patients with a Skewed X‐Inactivation Pattern

Intellectual disability (ID) is a heterogeneous disorder with an unknown molecular etiology in many cases. Previously, X‐linked ID (XLID) studies focused on males because of the hemizygous state of their X chromosome. Carrier females are generally unaffected because of the presence of a second normal allele, or inactivation of the mutant X chromosome in most of their cells (skewing). However, in female ID patients, we hypothesized that the presence of skewing of X‐inactivation would be an indicator for an X chromosomal ID cause. We analyzed the X‐inactivation patterns of 288 females with ID, and found that 22 (7.6%) had extreme skewing (>90%), which is significantly higher than observed in the general population (3.6%; P = 0.029). Whole‐exome sequencing of 19 females with extreme skewing revealed causal variants in six females in the XLID genes DDX3X, NHS, WDR45, MECP2, and SMC1A. Interestingly, variants in genes escaping X‐inactivation presumably cause both XLID and skewing of X‐inactivation in three of these patients. Moreover, variants likely accounting for skewing only were detected in MED12, HDAC8, and TAF9B. All tested candidate causative variants were de novo events. Hence, extreme skewing is a good indicator for the presence of X‐linked variants in female patients.     

Davidson Trauma Scale (DTS): normative scores in the general population and effect sizes in placebo-controlled SSRI trials

The Davidson Trauma Scale (DTS) was developed as a self-rating for use in diagnosing and measuring symptom severity and treatment outcome in post-traumatic stress disorder (PTSD); 630 subjects were identified by random digit dialing and evaluated for a history of trauma. Prevalence rates of PTSD and subthreshold PTSD with impairment were 2.2 and 4.1%, respectively. In this general population sample, 438 subjects endorsed at least one trauma, and four groups were generated: A) threshold PTSD (n = 13), B) subthreshold PTSD with impairment (n = 26), C) subthreshold PTSD without impairment (n = 78), and D) no PTSD (n = 321). Mean (SD) DTS score in the entire population was 11.0 +/- 18.1. Differences were found in four of the five pairwise between-group contrasts. In a second sample of 447 clinical trial participants from three SSRI vs. placebo studies, we assessed treatment effect size according to different measures. In all three clinical trials, effect size with the DTS was equal to, or better than, those found for the Impact of Event Scale (IES), Clinician Administered PTSD Scale (CAPS), and Structured Interview for PTSD (SIP). These results further affirm the utility of the DTS as a self-rating measure of PTSD symptom severity and in evaluating treatment response.