Immune-mediated statin myopathy

Statin-induced necrotizing autoimmune myopathy (SINAM) is associated with a unique clinical 5 phenotype of severe proximal muscle weakness during or after exposure to statins in patients with high creatine kinase (CK) levels. Electromyography (EMG) and muscle biopsy reveal features of a necrotizing myopathy and the anti-HMGCR autoantibody is frequently detected. Treatment requires a combination of statin discontinuation as well as immunomodulatory or immunosuppressive therapy. HLA typing (HLADRB1*1101) is strongly associated with anti-10 HMGCR autoantibody positivity in statin-exposed patients. It is well documented that statin triggers autoimmune disease in those with a genetic susceptibility. With the commercial availability of an accurate ELISA test, the natural history of the disease and its phenotypic features are becoming increasingly understood.     

Entomopathogenic marine actinomycetes as potential and low-cost biocontrol agents against bloodsucking arthropods

A novel approach to control strategies for integrated blood-feeding parasite management is in high demand, including the use of biological control agents. The present study aims to determine the efficacy of optimized crude extract of actinomycetes strain LK1 as biological control agent against the fourth-instar larvae of Anopheles stephensi and Culex tritaeniorhynchus (Diptera: Culicidae) and adults of Haemaphysalis bispinosa, Rhipicephalus (Boophilus) microplus (Acari: Ixodidae), and Hippobosca maculata (Diptera: Hippoboscidae). Antiparasitic activity was optimized using the Plackett–Burman method, and the design was developed using the software Design-Expert version 8.0.7.1. The production of the optimized crude actinomycetes LK1 strain extract was performed using response surface methodology to optimize the process parameters of protease inhibitor activity of marine actinobacteria for the independent variables like pH, temperature, glucose, casein, and NaCl at two levels (?1 and +1). The potential actinomycetes strain was identified as Saccharomonas spp., and the metamodeling surface simulation procedure was followed. It was studied using a computer-generated experimental design, automatic control of simulation experiments, and sequential optimization of the metamodels fitted to a simulation response surface function. The central composite design (CCD) used for the analysis of treatment showed that a second-order polynomial regression model was in good agreement with the experimental results at R ²?=?0.9829 (p?<?0.05). The optimized values of the variables for antioxidant production were pH 6.00, glucose 1.3 %, casein 0.09 %, temperature 31.23 °C, and NaCl 0.10 %. The LK1 strain-optimized crude extract was purified using reversed-phase high-pressure liquid chromatography, and the isolated protease inhibitor showed antiparasitic activity. The antiparasitic activity of optimized crude extract of LK1 was tested against larvae of A. stephensi (LC₅₀?=?31.82 ppm; r ²?=?0.818) and C. tritaeniorhynchus (LC₅₀?=?26.62 ppm; r ²?=?0.790) and adults of H. bispinosa (LC₅₀?=?106.58 ppm; r ²?=?0.871), R. (B.) microplus (LC₅₀?=?92.96 ppm; r ²?=?0.913), and H. maculata (LC₅₀?=?84.90 ppm; r ²?=?0.857).     

Preoperative biliary drainage in hilar cholangiocarcinoma: When and how?

Hilar cholangiocarcinoma is a tumor of the extrahepatic bile duct involving the left main hepatic duct, the right main hepatic duct, or their confluence. Biliary drainage in hilar cholangiocarcinoma is sometimes clinically challenging because of complexities associated with the level of biliary obstruction. This may result in some adverse events, especially acute cholangitis. Hence the decision on the indication and methods of biliary drainage in patients with hilar cholangiocarcinoma should be carefully evaluated. This review focuses on the optimal method and duration of preoperative biliary drainage(PBD) in resectable hilar cholangiocarcinoma. Under certain special indications such as right lobectomy for Bismuth type ⅢA or Ⅳ hilar cholangiocarcinoma, or preoperative portal vein embolization with chemoradiation therapy, PBD should be strongly recommended. Generally, selective biliary drainage is enough before surgery, however, in the cases of development of cholangitis after unilateral drainage or slow resolving hyperbilirubinemia, total biliary drainage may be considered. Although the optimal preoperative bilirubin level is still a matter of debate, the shortest possible duration of PBD is recommended. Endoscopic nasobiliary drainage seems to be the most appropriate method of PBD in terms of minimizing the risks of tract seeding and inflammatory reactions.     

Cancer of Ileostomy: a Late Complication of Colectomy for Ulcerative Colitis

Cancer arising at an ileostomy site represents a rare late complication of total colectomy performed for ulcerative colitis. There are no more than 36 published cases in the literature. We describe a case of adenocarcinoma of the mucocutaneous junction at the ileostomy site, occurring 31 years after total colectomy for ulcerative colitis. Wide excision of the moderately differentiated adenocarcinoma was performed with refashioning of the ileostomy. Polypoid adenomas or adenocarcinomas of the ileostomy after colectomy performed for non-neoplastic conditions are extremely uncommon. Biopsies of polypoid lesions at the stoma site are recommended.     

Characteristics of patients with chronic hepatitis-B virus infection in an urban hospital

BACKGROUND: In the United States, among patients with hepatocellular carcinoma (HCC) and portal hypertension from chronic hepatitis-B virus infection, 44% were Hispanic and 28% were African American. Because our institution (Bronx Lebanon Hospital Center, Bronx, NY) predominantly serves these populations, we studied retrospectively the characteristics of patients with chronic hepatitis-B virus infection. METHODS: We reviewed the medical records of all patients aged > 18 years with chronic hepatitis-B virus infection who had been evaluated at our institution between January 1, 2002 and May 31, 2005. RESULTS: We identified 167 patients with chronic hepatitis-B virus infection. Only 12 (7%) patients underwent chronic hepatitis-B virus treatment. One-hundred-forty-six (87%) patients without decompensated liver cirrhosis were not treated owing to the following reasons: normal alanine aminotransferase level (86%), active injection drug or heavy alcohol use (9%), lack of health insurance coverage (3%) and noncompliance with visits during the evaluation period (2%). HCC screening was performed in 78 patients (47%). Lack of insurance coverage and compliance issues were predictors for HCC screening (p = 0.04 and p < 0.001, respectively). CONCLUSIONS: In the South Bronx, 87% patients were not considered candidates for hepatitis-B virus treatment because of normal alanine aminotransferase levels and the interference of potentially modifiable social factors. Only 47% of our patients with chronic hepatitis-B virus infection underwent HCC screening because of lack of insurance coverage and compliance issues.     

Brain‐dead donor heart conservation with a preservation solution supplemented by a conditioned medium from mesenchymal stem cells improves graft contractility after transplantation

Hearts are usually procured from brain‐dead (BD) donors. However, brain death may induce hemodynamic instability, which may contribute to posttransplant graft dysfunction. We hypothesized that BD‐donor heart preservation with a conditioned medium (CM) from mesenchymal stem cells (MSCs) would improve graft function after transplantation. Additionally, we explored the PI3K pathway's potential role. Rat MSCs‐derived CM was used for conservation purposes. Donor rats were either exposed to sham operation or brain death by inflation of a subdural balloon‐catheter for 5.5 hours. Then, the hearts were explanted, stored in cardioplegic solution‐supplemented with either a medium vehicle (BD and sham), CM (BD + CM), or LY294002, an inhibitor of PI3K (BD + CM + LY), and finally transplanted. Systolic performance and relaxation parameters were significantly reduced in BD‐donors compared to sham. After transplantation, systolic and diastolic functions were significantly decreased, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL)‐positive cells and endonuclease G positive cells were increased in the BD‐group compared to sham. Preservation of BD‐donor hearts with CM resulted in a recovery of systolic graft function (dP/dt_max: BD + CM: 3148 ± 178 vs BD: 2192 ± 94 mm Hg/s at 110 µL, P < .05) and reduced apoptosis. LY294002 partially lowered graft protection afforded by CM in the BD group. Our data suggest that PI3K/Akt pathway is not the primary mechanism of action of CM in improving posttransplant cardiac contractility and preventing caspase‐independent apoptosis.