Pediatric cholesteatoma and variants in the gene encoding connexin 26

Objectives/Hypothesis:

Connexin 26 is a gap junction protein encoded by the GJB2 gene. It is expressed in cholesteatoma, and mutations cause proliferative skin disorders and sensorineural hearing loss (SNHL). Deletions of GJB6, which encodes connexin 30, cause SNHL in a digenic manner with a heterozygous GJB2 mutation. We hypothesize that GJB2 and GJB6 mutations might influence the development of cholesteatoma.

Study Design:

Prospective observational study to identify GJB mutations in pediatric cholesteatoma.

Methods:

Peripheral blood samples from 98 children with cholesteatoma were screened for mutations in the GJB2 gene by direct sequencing of the coding region (exon 2 and the intron/exon boundary). Deletions of the GJB6 gene were tested using multiple ligation probe amplification methods. GJB status was compared with other populations and patient age and extent of cholesteatoma at presentation.

Results:

Fourteen children had at least one GJB2 variant (14%). Of these, three had two variants. Two of the variants were neutral polymorphisms. One child with the GJB2 genotype 35delG/35delG also had SNHL. No correlation was found between GJB2 status and patient age or cholesteatoma severity at presentation. No GJB6 deletions were found.

Conclusions:

GJB2 gene variants are present in a minority of children with cholesteatoma, but may be more common than in normal populations. It is conceivable that alterations of connexin 26 expression could contribute to the multifactorial disease process in cholesteatoma by modifying the cell‐to‐cell communication that is important in proliferation and migration of keratinocytes. Laryngoscope, 2010     

Myocardial viability on echocardiography predicts long-term survival after revascularization in patients with ischemic congestive heart failure

OBJECTIVES

This study was conducted to evaluate the effect of revascularization on survival in patients with congestive heart failure (CHF) due to ischemic left ventricular (LV) systolic dysfunction based on the presence of myocardial viability (MV).

BACKGROUND

There are insufficient data regarding the survival benefit of revascularization in patients with CHF due to ischemic LV systolic dysfunction.

METHODS

Follow-up was obtained in 87 consecutive patients with CHF due to ischemic LV systolic dysfunction (New York Heart Association [NYHA] class II-IV; LV ejection fraction <0.35) who underwent low-dose dobutamine echocardiography (DE). MV within each of 12 myocardial segments representing the LV was defined as having either: 1) normal function or mild dyssynergy at rest; 2) severe resting dyssynergy that improved on DE, or 3) worsening of function on DE except in the case of akinesia.

RESULTS

At a mean follow-up of 40 ± 17 months, 37 patients had received revascularization on the basis of clinical grounds, and there were 22 (25%) cardiac-related deaths. Multivariate Cox regression analysis revealed that when patients with at least five segments showing MV underwent revascularization, mortality was reduced by an average of 93% (confidence interval of 22% to 99%), which was associated with improvement in NYHA class as well as LV ejection fraction. Patients with less than five segments showing MV who underwent revascularization (and thus, showing mostly scar), and those with at least 5 segments demonstrating MV who were treated medically, had a much higher mortality.

CONCLUSIONS

Revascularization produces a clear survival benefit in patients with CHF due to ischemic LV systolic dysfunction who have a significant region of the LV demonstrating MV. These data may have wide-ranging implications in the management of patients with coronary artery disease whose main clinical presentation is CHF.     

Lobular Neoplasia of the Breast

Abstract: Lobular neoplasia is increasingly being detected, probably due to the widespread screening for breast malignancies. The understanding of lobular neoplasia is undergoing a paradigm shift, from being considered a predictor of recurrence to being considered a pre‐invasive lesion, based on molecular studies suggesting a clonal link with invasive lobular cancer. The management of patients diagnosed to have lobular neoplasia is in evolution, with the increasing need for risk stratification and hence the necessity to identify this entity separately as either lobular carcinoma in‐situ and atypical lobular hyperplasia. The indications for wide local excision for patients diagnosed to have lobular neoplasia on biopsy are being defined. The evidence for preventive strategies like hormonal treatment with Tamoxifen or aromatase inhibitors for high risk patients is increasing, with the results from prospective interventional trials. The role of screening magnetic resonance imaging for surveillance of high risk patients with lobular neoplasia is under evaluation.     

Late dislodgement of left bundle branch pacing lead and successful extraction

A 61-years-old male underwent left bundle branch pacing for nonischemic dilated cardiomyopathy with recurrent heart failure. Left bundle branch pacing (LBBP) resulted in reduction in QRS duration along with improvement in left ventricular ejection fraction (LVEF) to 64% during follow-up. Two years after implantation he had recurrence of symptoms along with decline in LVEF to 51%. Late lead dislodgement was diagnosed and re-do LBBP was planned. The lead was extracted en-masse without complication and a new 3830 lead was positioned deep inside the proximal septum to capture the left bundle. Postprocedure echocardiography showed no ventricular septal defect or damage to tricuspid leaflet.     

A Framework for Adapted Nutritional Therapy for Children With Cancer in Low‐ and Middle‐Income Countries: A Report From the SIOP PODC Nutrition Working Group

The utilization of adapted regimens for the treatment of pediatric malignancies has greatly improved clinical outcomes for children receiving treatment in low‐ and middle‐income countries (LMIC). Nutritional depletion has been associated with poorer outcomes, increased abandonment of therapy, and treatment‐related toxicities. Surveys have found that nutritional intervention is not incorporated routinely into supportive care regimens. Establishing nutritional programs based upon institutional resources may facilitate the incorporation of nutritional therapy into clinical care in a way that is feasible in all settings. We present a framework for establishing and monitoring of nutritional care based on the infrastructure of institutions in LMIC.