A Phase Ib/II,open-label,multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma

Journal of Neuro-Oncology - To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent...     

Rhabdomyolysis: Diagnosis and Treatment in Bariatric Surgery

Background Rhabdomyolysis (RML) and subsequent acute renal failure can be serious problems following bariatric operations. Early diagnosis and treatment are important to avoid the complications of RML. Methods This review was achieved by searching the key words: Rhabdomyolysis, diagnosis, treatment and bariatric surgery.We included prospective, retrospective, case reports and review articles. Results RML diagnosis can be done by: signs and symptoms, physical evaluation, laboratory findings and imaging examinations. Muscle weakness, myalgia, decubitus ulcer, proteinuria and myoglobinuria are the more mentioned findings. Elevation of CPK levels is the most sensitive diagnostic evidence of RML. Treatment is geared toward preserving renal function by avoiding dehydration, hypovolemia, tubular obstruction, aciduria, and free radical release. Early recognition allows the administration of fluids, bicarbonate, and mannitol. Conclusion Prophylactic measures and early diagnosis and treatment of rhabdomyolysis in bariatric surgery are imperative to prevent the potential fatal complications of this condition.     

Gastrointestinal safety of triflusal solution in healthy volunteers: a proof of concept endoscopic study

Purpose  

Triflusal is an antiplatelet agent that irreversibly acetylates cyclooxygenase isoform 1 (COX-1) and therefore inhibits thromboxane biosynthesis. It was initially marketed as capsules containing 300 mg of active substance. In 2006 a new 600 mg (10 ml) oral solution form of triflusal was authorized in Spain. The primary aim of this study was to compare the gastrointestinal safety of the new triflusal oral solution with triflusal capsules in healthy volunteers.     

Closure of the Abdominal Cavity after Severe Peritonitis in Bariatric Surgery Utilizing a Mesh and Plastic Device

The major cause of peritonitis in bariatric surgery is leakage of GI contents, which can have a catastrophic outcome for the bariatric patient. To resolve this serious problem, the surgeon must act quickly. This paper describes a 27-year-old female after gastric bypass with disruption of the gastroenterostomy and severe contamination and peritonitis. Closure of the anastomotic leak, drainage, and gastrostomy in the bypassed stomach were performed, but the abdomen could not be closed, due to dilated bowel and the intra-abdominal edema with the sepsis. Temporary laparostomy closure was performed; a plastic sheet with an overlying mesh was sutured to the fascial margins. Planned multiple reoperations permitted removal of necrotic and infected debris, with progressive approximation and ultimate closure of the fascia. This treatment resulted in a successful outcome for the patient.     

A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib,LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors

Investigational New Drugs - Notch signaling plays an important role in development and tissue homeostasis. Deregulation of Notch signaling has been implicated in multiple malignancies....     

A genotyping system capable of simultaneously analyzing >1000 single nucleotide polymorphisms in a haploid genome

A high-throughput genotyping system for scoring single nucleotide polymorphisms (SNPs) has been developed. With this system, >1000 SNPs can be analyzed in a single assay, with a sensitivity that allows the use of single haploid cells as starting material. In the multiplex polymorphic sequence amplification step, instead of attaching universal sequences to the amplicons, primers that are unlikely to have nonspecific and productive interactions are used. Genotypes of SNPs are then determined by using the widely accessible microarray technology and the simple single-base extension assay. Three SNP panels, each consisting of >1000 SNPs, were incorporated into this system. The system was used to analyze 24 human genomic DNA samples. With 5 ng of human genomic DNA, the average detection rate was 98.22% when single probes were used, and 96.71% could be detected by dual probes in different directions. When single sperm cells were used, 91.88% of the SNPs were detectable, which is comparable to the level that was reached when very few genetic markers were used. By using a dual-probe assay, the average genotyping accuracy was 99.96% for 5 ng of human genomic DNA and 99.95% for single sperm. This system may be used to significantly facilitate large-scale genetic analysis even if the amount of DNA template is very limited or even highly degraded as that obtained from paraffin-embedded cancer specimens, and to make many unpractical research projects highly realistic and affordable.     

Microtransponder-based multiplex assay for genotyping cystic fibrosis

BACKGROUND: We developed and evaluated a genotyping assay for detection of 50 cystic fibrosis (CF) mutations. The assay is based on small (500 microm) electronic chips, radio frequency (RF) microtransponders (MTPs). The chips are analyzed on a unique fluorescence and RF readout instrument. METHODS: We divided the CF assay into 4 panels: core, Hispanic, African-American, and Caucasian. We amplified 18 CF transmembrane regulator (CFTR) DNA fragments covering 50 mutations by use of multiplex PCR using 18 CFTR gene-specific primer pairs. PCR was followed by multiplex allele-specific primer extension (ASPE) reactions and hybridization to capture probes synthesized on MTPs. We used 100 ASPE primers and 100 capture probes. We performed fluorescence measurements of hybridized MTP kits and assay analysis using a custom automated bench-top flow instrument. RESULTS: We validated the system by performing the assay on 23 commercial DNA samples in an internal study and 32 DNA samples in an external study. For internal and external studies, correct calls were 98.8% and 95.7%, false-positive calls 1.1% and 3.9%, and false-negative calls 0.12% and 0.36%, respectively. CONCLUSIONS: The MTP-based multiplex assay and analysis platform can be used for CF genotyping.