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Gene fusions involving the neurotrophic receptor tyrosine kinase genes NTRK1, NTRK2, and NTRK3, are well established oncogenic drivers in a broad range of pediatric and adult tumors. These fusions are also important actionable markers, predicting often dramatic response to FDA approved kinase inhibitors. Accurate interpretation of the clinical significance of NTRK fusions is a high priority for diagnostic laboratories, but remains challenging and time consuming given the rapid pace of new data accumulation, the diversity of fusion partners and tumor types, and heterogeneous and incomplete information in variant databases and knowledgebases. The ClinGen NTRK Fusions Somatic Cancer Variant Curation Expert Panel (SC-VCEP) was formed to systematically address these challenges and create an expert-curated resource to support clinicians, researchers, patients and their families in making accurate interpretations and informed treatment decisions for NTRK fusion-driven tumors. We describe a system for NTRK fusion interpretation (including compilation of key elements and annotations) developed by the NTRK fusions SC-VCEP. We illustrate this stepwise process on examples of LMNA::NTRK1 and KANK1::NTRK2 fusions. Finally, we provide detailed analysis of current representation of NTRK fusions in public fusion databases and the CIViC knowledgebase, performed by the NTRK fusions SC-VCEP to determine existing gaps and prioritize future curation activities.

ObjectivesScalable informatics solutions that provide molecularly tailored treatment recommendations to clinicians are needed to streamline precision oncology in care settings.Materials and methodsWe developed a cloud-based virtual molecular tumor board (VMTB) platform that included a knowledgebase, scoring model, rules engine, an asynchronous virtual chat room and a reporting tool that generated a treatment plan for each of the 1725 patients based on their molecular profile, previous treatment history, structured trial eligibility criteria, clinically relevant cancer gene-variant assertions, biomarker-treatment associations, and current treatment guidelines. The VMTB systematically allows clinician users to combine expert-curated data and structured data from clinical charts along with molecular testing data to develop consensus on treatments, especially those that require off-label and clinical trial considerations.ResultsThe VMTB was used as part of the cancer care process for a focused subset of 1725 patients referred by advocacy organizations wherein resultant personalized reports were successfully delivered to treating oncologists. Median turnaround time from data receipt to report delivery decreased from 14 days to 4 days over 4 years while the volume of cases increased nearly 2-fold each year. Using a novel scoring model for ranking therapy options, oncologists chose to implement the VMTB-derived therapies over others, except when pursuing immunotherapy options without molecular support.DiscussionVMTBs will play an increasingly critical role in precision oncology as the compendium of biomarkers and associated therapy options available to a patient continues to expand.ConclusionFurther development of such clinical augmentation tools that systematically combine patient-derived molecular data, real-world evidence from electronic health records and expert curated knowledgebases on biomarkers with computational tools for ranking best treatments can support care pathways at point of care.

BACKGROUND Perioperative shivering is the most common problem encountered after subarachnoid block in 40-60% of the patients. Shivering can lead to psychological stress and slow down the recovery process. This study was performed to compare the effects of prophylactic intravenous granisetron and intravenous tramadol against perioperative shivering after subarachnoid block in lscs. METHODS After obtaining ethical committee clearance and parturient consent, sixty parturients posted for lscs under subarachnoid anaesthesia were divided into 2 groups of 30 each. Group G(n=30) received granisetron 40µg/kg intravenously and Group T(n=30) received tramadol 1mg/kg intravenously 5 minute a before the subarachnoid block. Perioperatively, vitals, shivering and sedation score was assessed using 5 point scale in intervals of 5 minutes for first 30 minutes and every 30 minutes till the return of modified bromage scale of 6 postoperatively. RESULTS Intraoperatively and postoperatively heart rate, blood pressure, mean arterial pressure, oxygen saturation and electrocardiography had no significant variation in both the groups. 20% of the parturients who received granisetron and 27% of the parturients who received tramadol had various grades of shivering, though the grade of shivering observed was low in tramadol group. 33% of the parturients who had received tramadol had nausea and vomiting perioperatively. CONCLUSION Granisetron and tramadol are both equally effects against prophylaxis of perioperative shivering after subarachnoid block in lscs. However, Granisetron seems to be the most suitable drug as it also helps in preventing the side effects to like sedation, nausea and vomiting caused by tramadol. [ABSTRACT FROM AUTHOR]

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown compounds at m/z of 357 and 312 while decreased metabolites included creatinine, androgen derivatives and other unknown yet to be identified compounds. Furthermore, the creatine to creatinine ratio is significantly associated with disease progression in DMD patients. This ratio sharply increased with age in DMD patients while it decreased with age in healthy controls. Overall, this study yielded promising metabolic signatures that could prove useful to monitor DMD disease progression and response to therapies in the future.

[This corrects the article DOI: 10.1371/journal.pone.0153461.].

BACKGROUND Postoperative sore throat is one of the most common complications after endotracheal intubation. Both Ketamine and magnesium can block N-methyl-D-aspartic acid (NMDA) receptors and provide central and local analgesia. The study was conducted to compare the effect of magnesium sulfate and ketamine gargle on the incidence and severity of postoperative sore throat. MATERIAL AND METHODS A total of 120 patients' candidate for surgery were enrolled in the study. Patients in ketamine group (K, n=40) received ketamine gargle (30mg in 30 mL of 25% dextrose in saline), Magnesium group (M, n=40) received magnesium sulfate gargle (1.5mg in 30 mL of 25% dextrose in saline) and Dextrose group (D, n=40) received dextrose gargle (30 mL of 25% dextrose) 15 minutes before the operation. Patient complaint of postoperative sore throat, and its severity measured post operatively were recorded at baseline in recovery room, and then 2, 4, and 24 hours after operation using on a 4-point scale (0-3). RESULTS There were no significant differences between age, sex, body mass index (BMI), the Modified Mallampati class distribution and ASA grade between three groups of patients. Hemodynamics of patients, including blood pressure, mean arterial pressure and pulse rate were not significantly different (P > 0.05). Number of patients with sore throat were significantly lower in magnesium group and ketamine group compared to Dextrose group. Dextrose group had significantly higher incidence of sore throat at 2 hr (P = 0.023) and at 4 hr (P = 0,031) compared to Magnesium group after the operation. No patient had severe sore throat in group M and group K. CONCLUSIONS Magnesium at even a low dose decreases incidence of sore throat and pain severity more effectively when compared to ketamine gargles. [ABSTRACT FROM AUTHOR]

The antioxidant L‐Carnosine is reported to improve negative and cognitive symptoms in Schizophrenia. A randomized double‐blind placebo‐controlled study was planned to study the effectiveness of adjuvant L‐Carnosine therapy in patients with Schizophrenia. 100 eligible patients with predominant negative symptoms as measured by scale for assessment of negative symptoms (SANS total score ≥ 60) and Schizophrenia diagnosis (International Classification of Disorder‐Tenth Edition, ICD‐10) were recruited. They were randomly allocated to receive a fixed dose of either 400 mg L‐Carnosine or identical placebo for 3 months and increased to 800 mg from 13th week till completion of study. Primary outcome measures assessed changes in SANS scores with L‐Carnosine at 24 weeks compared to baseline, 4 and 12 weeks. Secondary outcome measures were done to assess the improvement in cognitive symptoms (executive function, attention, and memory) at 24 weeks using subtests of NIMHANS (National Institute for Mental Health and Neurosciences) cognitive battery. Side effects were assessed using adverse events reporting form. The attention scores (p =.023) showed significant differences in patients receiving 800 mg of L‐Carnosine at the end of the study. There were no significant differences in negative symptoms in the two arms at study completion. L‐Carnosine dosing of 800 mg may be a promising agent to enhance executive functions in Schizophrenia. [ABSTRACT FROM AUTHOR]