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Background and Aims: Arthroscopic orthopaedic surgery may lead to significant postoperative pain. Interscalene block (ISB) is associated with undesirable effects like phrenic nerve palsy. Shoulder block (ShB) is a relatively recent diaphragm sparing alternative for analgesia in these cases. Methods: This prospective randomised trial was conducted in 70 adult patients posted for arthroscopic Bankart repair surgery. Patients were randomly assigned into two groups: interscalene block [Group ISB (n = 35): 0.5% bupivacaine 10 ml] or shoulder block [Group ShB (n = 35): 0.5% bupivacaine (suprascapular block 10 ml and axillary block 10 ml)] using ultrasound and nerve stimulator. The primary aim of our study was to compare the ISB with ShB for visual analogue score (VAS) in recovery area (zero hour). Time for block performance, VAS, time to first rescue analgesia, total analgesic requirement, patient satisfaction and complications were recorded. Results: VAS was significantly higher in ShB group at 2 and 4 h (P = 0.001 and 0.000) while it was significantly higher in ISB group at 12 h (P = 0.013). The time to first analgesic request was significantly prolonged in ISB group as compared to ShB group (8.22 h vs. 4.69 h; P = 0.002) but total analgesic requirement and patient satisfaction at 24 h were similar. Complications like dyspnoea, ptosis and motor weakness were seen only with ISB group. Conclusion: Both ShB and ISB blocks have similar efficacy in terms of postoperative pain scores, cumulative analgesic requirements and patient satisfaction. However, considering the various undesirable effects associated with ISB, like phrenic nerve blockade, prolonged upper limb weakness and the occurrence of rebound pain, shoulder block may be preferred for arthroscopic shoulder surgeries.

Pediatric-type of diffuse high-grade gliomas (HGG) are classified as a distinct group in the current fifth edition of WHO classification. This group of high-grade tumors is no more called as glioblastoma (GBM), which has been reserved for adult isocitrate dehydrogenase (IDH)-wild type HGG. These tumors are uncommon as compared to embryonal tumors and low-grade gliomas (LGG). Pediatric-type of diffuse HGG biologically differs from their adult counterparts in that they are therapeutically less sensitive to alkylating chemotherapies. They comprise a heterogeneous group of molecularly defined tumors - predominantly histone gene altered, less common receptor tyrosine kinase (RTK)-mediated, and syndrome-associated. This review provides an overview of these uncommon tumors and discusses the diagnostic approach of this heterogeneous group of tumors.

Ewing Sarcoma is a common round cell sarcoma of pediatric patients arising in bone. Extraskeletal location is uncommon and small bowel wall is one of the rarer sites. Twenty-seven cases have been reported in published literature, exclusively arising from the small intestinal wall excluding the ones reported within the mesentery. We report a 45-year-old-man who presented with transient intussusception. After confirmation of a mass, right hemicolectomy was performed. The tumor identified in the ileum, infiltrated the wall through the submucosa, extending through muscularis propria into the subserosa. One of the regional nodes showed metastasis. On immunohistochemistry, the tumor cells were diffusely positive for CD99, CK 8/18 and NKX 2.2. The immunohistochemistry markers highlighted significant overlap between neuroendocrine neoplasm and Ewing Sarcoma. Molecular evaluation revealed the hallmark EWSR1-FLI1 fusion confirming the diagnosis. Extraskeletal Ewing Sarcoma of small intestines is rare and associated with overall poor prognosis. Immunohistochemistry shows considerable overlap with neuroendocrine carcinomas and molecular evaluation is prudent.

Tumor molecular profiling plays an integral role in identifying genomic anomalies which may help in personalizing cancer treatments, improving patient outcomes and minimizing risks associated with different therapies. However, critical information regarding the evidence of clinical utility of such anomalies is largely buried in biomedical literature. It is becoming prohibitive for biocurators, clinical researchers and oncologists to keep up with the rapidly growing volume and breadth of information, especially those that describe therapeutic implications of biomarkers and therefore relevant for treatment selection. In an effort to improve and speed up the process of manually reviewing and extracting relevant information from literature, we have developed a natural language processing (NLP)-based text mining (TM) system called eGARD (extracting Genomic Anomalies association with Response to Drugs). This system relies on the syntactic nature of sentences coupled with various textual features to extract relations between genomic anomalies and drug response from MEDLINE abstracts. Our system achieved high precision, recall and F-measure of up to 0.95, 0.86 and 0.90, respectively, on annotated evaluation datasets created in-house and obtained externally from PharmGKB. Additionally, the system extracted information that helps determine the confidence level of extraction to support prioritization of curation. Such a system will enable clinical researchers to explore the use of published markers to stratify patients upfront for 'best-fit' therapies and readily generate hypotheses for new clinical trials.

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.

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.

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is an uncommon extranodal lymphoma that accounts for more than 95% of all the CNS lymphomas. Unlike its systemic/nodal counterpart, which is currently subtyped into cell-of origin (COO) subtypes, its feasibility and utility are largely debatable in PCNS-DLBCL. Objectives: To classify PCNS-DLBCL into COO-subtypes based on immunohistochemical algorithms by Hans and Choi and evaluate concordance between the two. A further aim is to investigate the clinicoradiological and histomorphological parameters of the subtypes thus obtained. Materials and Methods: As many as 143 cases of primary CNS lymphoma were evaluated by immunohistochemistry for CD10, BCL6, MUM1, GCET, and FOXP1 and based on which the said 143 cases were further classified into COO subtypes using Hans and Choi algorithms. Results: Mean age was 53.8 years with marginal male preponderance and predominantly centroblastic morphology (75.5%). CD 10 was positive in 8.9% of the cases, BCL6 in 58.6%, MUM1 in 89.9%, GCET in 32.9%, and FOXP1 in 79.5%. As much as 84.9% cases were of non-germinal center B-cell (GCB) subtype and 15.1% cases were of GCB subtype as determined based on Hans algorithm. Furthermore, 90.7% cases were of activated B-cell (ABC) subtype and 9.3% cases were of GCB subtype according to Choi algorithm. A 91.8% concordance was observed between Hans and Choi algorithms. Among the 6 discordant cases, 5 cases were subtyped as GCB by Hans and ABC by Choi and 1 case as ABC by Hans and GCB by Choi. Conclusion: Most of PCNS-DLBCLs are of non-GCB/ABC COO subtype, but inconsistences abound in the utility of IHC algorithms in PCNS-DLBCL COO subtypes.

Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG) of the Clinical Genome Resource (ClinGen), in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD). MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i) reviewing clinical actionability interpretations from institutions participating in the WG, ii) conducting extensive literature search of clinical somatic interpretation schemas, and iii) survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP), can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of somatic variants to ClinVar, all of which will enhance translation to clinical oncology practice.

Manually curated variant knowledgebases and their associated knowledge models are serving an increasingly important role in distributing and interpreting variants in cancer. These knowledgebases vary in their level of public accessibility, and the complexity of the models used to capture clinical knowledge. CIViC (Clinical Interpretation of Variants in Cancer - www.civicdb.org ) is a fully open, free-to-use cancer variant interpretation knowledgebase that incorporates highly detailed curation of evidence obtained from peer-reviewed publications and meeting abstracts, and currently holds over 6300 Evidence Items for over 2300 variants derived from over 400 genes. CIViC has seen increased adoption by, and also undertaken collaboration with, a wide range of users and organizations involved in research. To enhance CIViC’s clinical value, regular submission to the ClinVar database and pursuit of other regulatory approvals is necessary. For this reason, a formal peer reviewed curation guideline and discussion of the underlying principles of curation is needed. We present here the CIViC knowledge model, standard operating procedures (SOP) for variant curation, and detailed examples to support community-driven curation of cancer variants.

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