PURPOSE. Substitutions of aspartate-47 (D47) of Connexin50 (Cx50) have been linked to autosomal dominant congenital cataracts in several human pedigrees. To elucidate the lens abnormalities caused by a substitution at this position, we studied No2 mice, which carry the Cx50D47A mutation and parallel the human pathology. METHODS.Lenses from mice of different ages (neonatal to 4 months) were examined by darkfield and immunofluorescence microscopy. Protein levels were determined by immunoblotting using primary antibodies directed against connexins, other membrane proteins, crystallins, and proteins residing in different organelles. RESULTS.Lenses of both heterozygous and homozygous Cx50D47A mice had cataracts and were smaller than those of wild-type littermates. Levels of Cx50 were severely reduced in mutant animals as compared with those in wild-type mice (<20% in heterozygotes and 3% in homozygotes). Levels of Cx46 and aquaporin0 were also decreased, but to a lesser extent. The immunostaining pattern of lens connexins was altered in mutant animals. The lenses of Cx50D47A mice showed persistence of nuclear remnants in deep regions of the lens and elevated levels of H3 histone and the mitochondrial protein, Tom20. c-Crystallin levels were decreased in lenses of all mutant mice, and b-crystallins were reduced in homozygotes.CONCLUSIONS. These data suggest that mice expressing Cx50D47A develop cataracts due to a severe decrease in the abundance of functional connexin channels. They also implicate Cx50 in fiber cell differentiation, since mutant lenses showed impaired degradation of organelles and decreased levels of some crystallins.

Major decreases in connexin levels precede the development of cataracts. These mice represent a useful model for elucidation of the progression of lens abnormalities during cataractogenesis especially as caused by a mutant connexin.

Objective To determine factors associated with post-tracheotomy hospital readmission within 30 days of discharge. Methods Children 18 years and younger who underwent tracheotomy at Children’s Hospital Los Angeles (CHLA) between 1/1/2005 and 12/31/2013 with at least 30 days of follow-up at CHLA were identified through ICD-9 procedure codes. Patient characteristics and covariates were obtained by linking manual chart review and administrative data. We used multivariate logistic regression to identify the independent association between risk factors and the primary outcome of 30-day all-cause same-hospital readmission. Results Of the 273 patients included, the median age at admission was 6 months [interquartile range (IQR): 1–51 months]. Among this primarily male (60.8%) and Hispanic (66.3%) cohort with a high proportion of discharge on positive pressure ventilation (47.1%), the 30-day readmission rate was 22% (n=60). Of the readmissions, 92% (n=55) were unplanned and 64% (n=35) were associated with acute respiratory illnesses. Multivariate regression analysis demonstrated that, among patients ≤ 12 months, discharge on positive pressure ventilation [adjusted odds ratio (aOR)=2.88, 95% confidence interval (CI)=1.19–6.97] was associated with increased odds of readmission, while gastrostomy tube placement during the tracheotomy hospitalization (aOR=0.42, 95% CI=0.19–0.96) and prematurity (aOR=0.35, 95% CI=0.15–0.83) were associated with decreased odds of readmission. In patients > 1 year of age, increased length of hospitalization (aOR=1.01 per hospital day, 95% CI=1–1.02) and presence of comorbid malignancy (aOR=6.03, 95% CI=1.25–29.16) were associated with increased odds of readmission. Conclusions Over one-fifth of children undergoing tracheotomy had an unplanned hospital readmission within 30 days after discharge. Because the majority of readmissions were unplanned and due to acute respiratory illnesses, future research should investigate how discharge procedures and improved care coordination may lower readmission rates in high-risk patients (e.g., patients discharged on positive pressure ventilation).

Management of refractory pain in pediatric sickle cell disease (SCD) and oncology is reliant on opioids though high opioid dosing increases side effects and tachyphylaxis. We introduced low-dose ketamine infusion (LDKI) to our inpatient unit to determine if LDKI was tolerable. We subsequently hypothesized that LDKI would improve pain scores. We reviewed inpatients from LDKI initiation in March 2014 through October 2017, with the day before LDKI initiation compared with the day of LDKI initiation and 2 subsequent days. For patients with SCD, the LDKI admission was compared with up to 3 admissions in the prior year for a vaso-occlusive event. Nineteen patients (12 oncology, 7 SCD) with a median age of 14.6 years received LDKI for a median of 6 days at a median initial dose of 0.06 mg/kg/h (1.1 µg/kg/min). There was no change in pain scores or opioid utilization when comparing the day before LDKI initiation with subsequent days. No patient discontinued LDKI because of intolerability. For patients with SCD, there was a median 32% reduction in cumulative pain scores when comparing the LDKI admission with prior admissions. LDKI is well tolerated for refractory pediatric cancer-related and sickle cell-related pain.

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