Gastric Cancer in BRCA1 Germline Mutation Carriers: Results of Endoscopic Screening and Molecular Analysis of Tumor Tissues.

INTRODUCTION: There is some evidence suggesting a link between BRCA1/2 germline mutations and increased risk of gastric cancer. METHODS: Endoscopic screening for stomach malignancies was performed in 120 BRCA1 mutation carriers in order to evaluate the probability of detecting the tumor disease. RESULTS: No instances of gastric cancer were revealed at the first visit. The analysis of atrophic changes performed by OLGA (Operative Link for Gastritis Assessment) criteria revealed that OLGA stages I-IV alterations were observed in 26 of 41 (63%) subjects aged >50 years as compared to 29 of 79 (37%) in younger subjects (p = 0.007, χ2 test). One BRCA1 mutation carrier developed gastric cancer 4 years after the first visit for endoscopic examination. We performed next-generation sequencing analysis for this tumor and additional 4 archival gastric cancers obtained from BRCA1/2 mutation carriers. Somatic loss of the remaining BRCA1/2 allele was observed in 3 out of 5 tumors analyzed; all of these carcinomas, but none of the malignancies with the retained BRCA1/2 copy, showed chromosomal instability. CONCLUSION: Taken together, these data justify further studies on the relationships between the BRCA1/2 and gastric cancer.

Evaluation of misrepresented findings in the abstracts of acute respiratory distress syndrome randomized trials with nonsignificant primary endpoints.

OBJECTIVE: We investigated the randomized controlled trials (RCTs) related to acute respiratory distress syndrome (ARDS) to assess the presentation and frequency of misrepresented research findings, also known as spin. METHODS: We searched PubMed (MEDLINE) for studies published from January 1, 2011 to December 31, 2019. We included randomized controlled trials with an ARDS intervention and a nonsignificant primary endpoint. Trial screening and data extraction was performed on all studies independently and in duplicate. The primary endpoint was to investigate the frequency and manifestation of spin in RCT abstracts. Our secondary endpoint was to investigate associations between funding source and spin. RESULTS: Our PubMed search returned 766 articles with 37 meeting inclusion criteria. Spin was present in 14 (14/37, 37.8%; 95% CI 22.5%-55.2%) abstracts. The most common manifestations of spin were claiming benefit based on a significant secondary endpoint (6/14, 42.9%), followed by the use of 'trend' statements, such as 'trend toward significance' (2/14, 14.3%; 95% CI 1.8%-42.8%). The most common spin in abstract conclusions was in the form of claiming benefit due to a significant secondary endpoint (3/4, 75%; 95% CI 19.4%-99.4%). Our secondary endpoint did not identify a significant difference in the prevalence of spin in publicly funded (5/19, 26.3%; 95% CI 9.1%-51.2%) compared to privately funded (4/12, 33.3%; 95% CI 9.9%-65.1%) studies (p>.05). CONCLUSIONS: RCTs of ARDS interventions with nonsignificant primary endpoints often included spin in the abstract. Spin in the abstract may influence clinician appraisal and interpretation of diagnostic or treatment modalities.

Endemic North American Plants as Potentially Suitable Agents for Wound Cleaning Under Resource Scarce Conditions.

INTRODUCTION: Skin and subcutaneous infections are dangerous sequelae of soft tissue injuries, especially in austere situations where medical technology is not available. Numerous plant species endemic to North America have been described as having antibacterial properties. Of these, St. John's wort (Hypericum perforatum), chamomile (Matricaria chamomilla), and white oak (Quercus alba) were selected for testing against Staphylococcus aureus. Our objective was to assess the suitability of all 3 plants as potential antiseptic agents using methods easily replicated in a resource-scarce environment. METHODS: Water-soluble natural products were extracted from different concentrations of each plant part using either mechanical agitation at ambient temperature or boiling in unsterilized tap water. Antibacterial activity of each extract against S aureus was assessed using a conventional agar well diffusion bioassay. Zones of inhibition were measured using electronic calipers and were compared to tap water as the negative control. RESULTS: Aqueous extracts of St. John's wort and white oak bark displayed antibacterial effects against S aureus, with St. John's wort being more potent. Chamomile displayed no inhibitory properties at the concentrations examined. CONCLUSIONS: These data suggest that both St. John's wort and white oak are potential candidates for infection prophylaxis and therapy in austere wilderness scenarios, with St. John's wort being the more potent agent. White oak may be more logistically feasible because the larger surface area of a white oak tree allows for harvesting a larger quantity of bark compared to the smaller surface area of the St. John's wort plant.

Exome-based search for recurrent disease-causing alleles in Russian population.

Exomes of 27 Russian subjects were analyzed for the presence of medically relevant alleles, such as protein-truncating variants (PTVs) in known recessive disease-associated genes and pathogenic missense mutations included in the ClinVar database. 36 variants (24 PTVs and 12 amino acid substitutions) were identified and then subjected to the analysis in 897 population controls. 9/36 mutations were novel, however only two of them (POLH c.490delG associated with xeroderma pigmentosum variant (XPV) and CATSPER1 c.859_860delCA responsible for spermatogenic failure) were shown to be recurrent. 27 out of 36 pathogenic alleles were already described in prior genetic studies; seven of them occurred only in the index cases, while 20 demonstrated evidence for persistence in Russian population. In particular, non-random occurrence was revealed for SERPINA1 c.1096G > A (alpha-1 antitrypsin deficiency), C8B c.1282C > T and c.1653G > A (complement component 8B deficiency), ATP7B c.3207C > A (Wilson disease), PROP1 c.301_302delAG (combined pituitary hormone deficiency), CYP21A2 c.844G > T (non-classical form of adrenogenital syndrome), EYS c.1155T > A (retinitis pigmentosa), HADHA c.1528G > C (LCHAD deficiency), SCO2 c.418G > A (cytochrome c oxidase deficiency), OTOA c.2359G > T (sensorineural deafness), C2 c.839_866del (complement component 2 deficiency), ACADVL c.848T > C (VLCAD deficiency), TGM5 c.337G > T (acral peeling skin syndrome) and VWF c.2561 G > A (von Willebrand disease, type 2N). These data deserve to be considered in future medical genetic activities.