Single incision technique using an interference screw for the repair of distal biceps tendon ruptures

Various techniques throughout the years have been published on surgical repair of the distal biceps tendon foracute ruptures or for recalcitrant biceps tendinosis. The first report of a single incision technique to repair this tendon was in 1897 by S. Johnson in the New York Medical Journal. Since that time many different approaches and techniques have been developed. Interference screw fixation has been a reliable and well-tested method of tendon/ligament to bone attachment. There is a large body of literature concerning the various aspects of interference fit in the anterior cruciate ligament and proximal biceps tendon literature. Anatomic measurements, osteological analysis, and radiographic examination have provided information for the design of an interference screw that can be safely used in the proximal radius. We describe a technique using an interference screw through a single incision. We present two techniques for open tenodesis of the long head of the biceps.     

Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia: a case–control study

The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition （P=0.002）, duration of mucositis （P= 0.003） and the average grade of mucositis （P= 0.03）. The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering： from leukaemia.     

Evaluating the contribution of the gene TARDBP in Italian patients with amyotrophic lateral sclerosis

Background and objectives

Genetic variants in the gene TARDBP, encoding TDP-43 protein, are associated with amyotrophic lateral sclerosis (ALS) in familial (fALS) and sporadic (sALS) cases. Objectives of this study were to assess the contribution of TARDBP in a large cohort of Italian ALS patients, to determine the TARDBP-associated clinical features and to look for genotype–phenotype correlation and penetrance of the mutations.

Methods

A total of 1992 Italian ALS patients (193 fALS and 1799 sALS) were enrolled in this study. Sanger sequencing of TARDBP gene was performed in patients and, when available, in patients' relatives.

Results

In total, 13 different rare variants were identified in 43 index cases (10 fALS and 33 sALS) with a cumulative mutational frequency of 2.2% (5.2% of fALS, 1.8% of sALS). The most prevalent variant was the p.A382T followed by the p.G294V. Cognitive impairment was detected in almost 30% of patients. While some variants, including the p.G294V and the p.G376D, were associated with restricted phenotypes, the p.A382T showed a marked clinical heterogeneity regarding age of onset, survival and association with cognitive impairment. Investigations in parents, when possible, showed that the variants were inherited from healthy carriers and never occurred de novo.

Conclusions

In our cohort, TARDBP variants have a relevant frequency in Italian ALS patients and they are significantly associated with cognitive impairment. Clinical presentation is heterogeneous. Consistent genotype–phenotype correlations are limited to some mutations. A marked phenotypic variability characterizes the p.A382T variant, suggesting a multifactorial/oligogenic pathogenic mechanism.     

Left atrial appendage closure: a balanced management of the thromboembolic risk in patients with hemophilia and atrial fibrillation

Journal of Thrombosis and Thrombolysis - Atrial fibrillation is the most common cardiac arrhythmia and is a major cause of embolic stroke. In patients at high bleeding risk such as those with...     

T cells in severe childhood asthma

Severe asthma in children is a debilitating condition that accounts for a disproportionately large health and economic burden of asthma. Reasons for the lack of a response to standard anti‐inflammatory therapies remain enigmatic. Work in the last decade has shed new light on the heterogeneous nature of asthma, and the varied immunopathologies of severe disease, which are leading to new treatment approaches for the individual patient. However, most studies to date that explored the immune landscape of the inflamed lower airways have focused on adults. T cells are pivotal to the inception and persistence of inflammatory processes in the diseased lungs, despite a contemporary shift in focus to immune events at the epithelial barrier. This article outlines current knowledge on the types of T cells and related cell types that are implicated in severe asthma. The potential for environmental exposures and other inflammatory cues to condition the immune environment of the lung in early life to favour pathogenic T cells and steroid resistance is discussed. The contributions of T cells and their cytokines to inflammatory processes and treatment resistance are also considered, with an emphasis on new observations in children that argue against conventional type 1 and type 2 T cell paradigms. Finally, the ability for new technologies to revolutionize our understanding of T cells in severe childhood asthma, and to guide future treatment strategies that could mitigate this disease, is highlighted.     

19-Hydroxylase inhibition of adrenal mitochondrial P450 11 beta/18/19-hydroxylase by a suicide inhibitor

19-Nor-deoxycorticosterone (19-nor-DOC) is a mineralocorticoid that is increased in some forms of experimental and human hypertension. The pivotal step in 19-nor-DOC biosynthesis is adrenal P450 19-hydroxylase, but this enzyme has not been clearly distinguished from P450 11 beta/18-hydroxylase. This study attempted to specifically inhibit adrenal 19-hydroxylation of deoxycorticosterone (DOC) using a suicide aromatase inhibitor, 19-acetylenic androstenedione (19-AA). Purified bovine P450 11 beta/18/19-hydroxylase was incubated with excess substrate DOC, adrenodoxin, and adrenodoxin reductase in the presence of increasing doses of the inhibitor, 19AA. 11 beta-, 18-, and 19-hydroxylation were measured by quantification of corticosterone, 18-OH-DOC, and 19-OH-DOC respectively. Measurements of these products demonstrated that 11 beta- and 18-hydroxylation was not inhibited whereas 19-hydroxylation was inhibited as manifested by decreased 19-OH-DOC formation (p less than .05). The IC50 of 19-AA was approximately 10(-12) M. The specific inhibition of 19-hydroxylation suggests that the 19-hydroxylase may be an enzyme distinct from the P450 11 beta/18-hydroxylase. This further suggests that 19-nor-DOC biosynthesis may be under independent regulation and may be amendable to specific in vivo inhibition.