Skeletal muscle fibrosis and stiffness increase after rotator cuff tendon injury and neuromuscular compromise in a rat model

Rotator cuff tears can cause irreversible changes (e.g., fibrosis) to the structure and function of the injured muscle(s). Fibrosis leads to increased muscle stiffness resulting in increased tension at the rotator cuff repair site. This tension influences repairability and healing potential in the clinical setting. However, the micro‐ and meso‐scale structural and molecular sources of these whole‐muscle mechanical changes are poorly understood. Here, single muscle fiber and fiber bundle passive mechanical testing was performed on rat supraspinatus and infraspinatus muscles with experimentally induced massive rotator cuff tears (Tenotomy) as well as massive tears with chemical denervation (Tenotomy + BTX) at 8 and 16 weeks post‐injury. Titin molecular weight, collagen content, and myosin heavy chain profiles were measured and correlated with mechanical variables. Single fiber stiffness was not different between controls and experimental groups. However, fiber bundle stiffness was significantly increased at 8 weeks in the Tenotomy + BTX group compared to Tenotomy or control groups. Many of the changes were resolved by 16 weeks. Only fiber bundle passive mechanics was weakly correlated with collagen content. These data suggest that tendon injury with concomitant neuromuscular compromise results in extra‐cellular matrix production and increases in stiffness of the muscle, potentially complicating subsequent attempts for surgical repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1111–1116, 2014.     

Dermal scarification versus intramuscular diclofenac sodium injection for the treatment of renal colic: a prospective randomized clinical trial

The aim of the study is to determine whether dermal scarification is equally effective for treating acute renal colic compared to diclofenac sodium intramuscular therapy. A prospective, randomized controlled study was conducted with methodologic rigor based on CONSORT criteria. A total of 291 patients, aged ≥18 years, suffering from acute renal colic were included in this trial and randomly assigned in two groups. Patients in the first group (A) received endodermal injection (dermal scarification) of 1 ml normal saline at the area of intensity of pain. The second group (B) received 75 mg diclofenac sodium by intramuscular injection. The success of each method defined the primary end point. Pain intensity before and after treatment was assessed using a visual analog scale. The time onset and the duration of analgesia were also recorded. There was no significant difference between the two groups regarding hematuria (p = 0.158), stone identification at KUB (p = 0.751) and mean pain intensity (p = 0.609) before treatment initiation. The method was successful in 75.5 % of patients in group A and 74.3 % of patients in group B (p = 0.812). Mean pain reduction was comparable, 5.65 ± 3.05 in group A and 5.34 ± 2.99 in group B (p = 0.379), with dermal scarification eliciting its effect considerably faster, whereas the duration of analgesia was longer in the diclofenac group (p < 0.05). In conclusion, dermal scarification could constitute an alternative method for treating renal colic as it is equally effective compared to the standard treatment of diclofenac sodium.     

Understanding the biology of reactive oxygen species and their link to cancer: NADPH oxidases as novel pharmacological targets

Reactive oxygen species (ROS), the cellular products of myriad physiological processes, have long been understood to lead to cellular damage if produced in excess and to be a causative factor in cancer through the oxidation and nitration of various macromolecules. Reactive oxygen species influence various hallmarks of cancer, such as cellular proliferation and angiogenesis, through the promotion of cell signalling pathways intrinsic to these processes and can also regulate the function of key immune cells, such as macrophages and regulatory T cells, which promote angiogenesis in the tumour environment. Herein we emphasize the family of NADPH oxidase enzymes as the most likely source of ROS, which promote angiogenesis and tumourigenesis through signalling pathways within endothelial, immune and tumour cells. In this review we focus on the pharmacological inhibitors of NADPH oxidases and suggest that, compared with traditional anti‐oxidants, they are likely to offer better alternatives for suppression of tumour angiogenesis. Despite the emerging enthusiasm towards the use of NADPH oxidase inhibitors for cancer therapy, this field is still in its infancy; in particular, there is a glaring lack of knowledge of the roles of NADPH oxidases in in vivo animal models and in human cancers. Certainly a clearer understanding of the relevant signalling pathways influenced by NADPH oxidases during angiogenesis in cancer is likely to yield novel therapeutic approaches.     

Anatomic predictors of recurrence after cryoablation for atrial fibrillation: a computed tomography based composite score

Journal of Interventional Cardiac Electrophysiology - Effective pulmonary vein isolation (PVI) with cryoablation depends on adequate occlusion of pulmonary veins (PV) by the cryoballoon and is...     

The presence of insomnia and depression contributes to the acceptance of an initial treatment trial of continuous positive airway pressure therapy in patients with obstructive sleep apnea

Sleep and Breathing - The presence of comorbid insomnia and sleep apnea (COMISA) reduces the initial acceptance of continuous positive airway pressure (CPAP) therapy in 39–58% of patients...     

Endobiliary biopsy

The differential diagnosis between benign and malignant biliary strictures is challenging and requires a multidisciplinary approach with the use of serum biomarkers, imaging techniques, and several modalities of endoscopic or percutaneous tissue sampling. The diagnosis of biliary strictures consists of laboratory markers, and invasive and non-invasive imaging examinations such as computed tomography (CT), contrast-enhanced magnetic resonance cholangiopancreatography, and endoscopic ultrasonography (EUS). Nevertheless, invasive imaging modalities combined with tissue sampling are usually required to confirm the diagnosis of suspected malignant biliary strictures, while pathological diagnosis is mandatory to decide the optimal therapeutic strategy. Although EUS-guided fine-needle aspiration biopsy is currently the standard procedure for tissue sampling of solid pancreatic mass lesions, its diagnostic value in intraductal infiltrating type of cholangiocarcinoma remains limited. Moreover, the “endobiliary approach” using novel slim biopsy forceps, transpapillary and percutaneous cholangioscopy, and intraductal ultrasound-guided biopsy, is gaining ground on traditional endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography endobiliary forceps biopsy. This review focuses on the available endobiliary techniques currently used to perform biliary strictures biopsy, comparing the diagnostic performance of endoscopic and percutaneous approaches.     

Endoscopic sphincterotomy in patients with "acalculus" cholangitis associated with juxtapapillary diverticula

BACKGROUND/AIMS: The aim of this study was to investigate patients who underwent endoscopic sphincterotomy for "acalculus" cholangitis associated with juxtapapillary diverticula. METHODOLOGY: In a retrospective study we analyzed 87 patients who underwent endoscopic sphincterotomy for cholangitis; the cholangitis considered "acalculus", when outlining the extra- and intrahepatic bile ducts, we could not observe any intraluminal defect or stricture, and during the clearing of the bile ducts with the balloon, after endoscopic sphincterotomy, there was no evidence of stones, fragments of stones or sludge. Patients who had undergone previous endoscopic sphincterotomy, or who had additional pancreatobiliary diseases were excluded from this study. There were 11 patients with "acalculus" cholangitis associated with juxtapapillary diverticula, and sufficient clinical data available for this study. RESULTS: Nine patients presented pain, fever, and jaundice. In two patients diagnosis was established via the test of abnormal liver biochemistry. Seven patients had positive blood cultures and three of them developed confusion and hypotension. Endoscopic sphincterotomy succeeded in all cases; no evidence of stones, fragments of stones or sludge was recorded during the clearing of bile ducts, after endoscopic sphincterotomy, with the balloon. Five patients presented mild post-endoscopic sphincterotomy complications successfully treated. In the follow-up period, from 4 months to 7 years after endoscopic sphincterotomy, none of the patients developed symptoms of cholangitis. CONCLUSIONS: We recommend endoscopic sphincterotomy in patients with "acalculus" cholangitis associated with juxtapapillary diverticula, despite the absence of obvious obstruction, and the possible morbidity which is inherent with an invasive procedure like endoscopic sphincterotomy.