Validation of the NCCN/Yale criteria for the identification of pathogenic variant carriers.

Background: Diffuse gastric and lobular breast cancer (LBC) syndrome is an autosomal-dominant syndrome characterised by early-onset diffuse gastric cancer and LBC most often caused by germline pathogenic variants (PVs) in . We previously showed the International Gastric Cancer Linkage Consortium (IGCLC) criteria for genetic testing to have poor sensitivity for PV and proposed our own simpler and more sensitive Yale criteria. The European Reference Network on Genetic Tumour Risk Syndromes subsequently proposed expanding the IGCLC criteria and showed its LBC-expanded criteria to be more sensitive than the IGCLC criteria in a European cohort of PV carriers.

Simplified and more sensitive criteria for identifying individuals with pathogenic variants.

Background: Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant syndrome most often caused by pathogenic variants in . The International Gastric Cancer Linkage Consortium (IGCLC) recently updated its criteria for genetic testing. The purpose of this study was to estimate the sensitivity of IGCLC's 2020 criteria for identifying carriers of pathogenic variants and to formulate a new set of criteria that is simpler and more sensitive.

Genetic Gastric Cancer Risk Syndromes.

Purpose Of Review: Gastric cancer is a leading cause of cancer death in the world. Between 1% and 3% of cases are associated with specific genetic cancer risk syndromes. The purpose of this article is to review the latest insights, as well as gaps in knowledge, regarding some of the most common hereditary gastric cancer syndromes: hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), Lynch syndrome, the adenomatous polyposis syndromes, and the hamartomatous polyposis syndromes.

Incidental Otolaryngologic Pathology Noted Upon Esophagogastroduodenoscopy: Case Series and Review of Literature.

Objectives: We report and analyze eight cases in which patients were referred from gastroenterology (GI) to otolaryngology following esophagogastroduodenoscopy (EGD). We aim to provide specific examples of head and neck pathology encountered by gastroenterologists during upper endoscopy.

Methods: A series of eight cases between 2016 and 2019 were analyzed by chart review.

Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS.

Objective: To identify coinhibitory immune pathways important in the brain, we hypothesized that comparison of T cells in lesions from patients with MS with tumor-infiltrating T cells (TILs) from patients with glioblastoma multiforme may reveal novel targets for immunotherapy.

Methods: We collected fresh surgical resections and matched blood from patients with glioblastoma, blood and unmatched postmortem CNS tissue from patients with MS, and blood from healthy donors. The expression of TIGIT, CD226, and their shared ligand CD155 as well as PD-1 and PDL1 was assessed by both immunohistochemistry and flow cytometry.

Examining Referral Patterns between Otolaryngology and Gastroenterology: A Window into Potential Inter-Specialty Knowledge Gaps.

Objective: The objective of this study was to examine referral patterns between otolaryngology and gastroenterology in order to delineate areas of clinical overlap, as well as to identify areas that might benefit from improved inter-specialty communication and collaboration.

Methods: Montefiore's tool was used to define parameters for electronic medical record data extraction from 2015 to 2018. Two cohorts were generated, one representing referrals placed by and a second representing referrals placed by .

Going Against the Grains: Gluten-Free Diets in Patients Without Celiac Disease-Worthwhile or Not?

While the gluten-free diet (GFD) is the only known effective therapy for celiac disease, in recent years it has become increasingly popular in the USA and worldwide, with many believing it to be more "healthful" and others claiming that it has beneficial effects for health conditions, many extraintestinal, other than celiac disease. This review examines the evidence for use of the GFD in patients without celiac disease who self-report intestinal and/or extraintestinal symptoms (non-celiac gluten sensitivity), as well as for enhancement of athletic performance and treatment of autism, rheumatoid arthritis, and psychiatric disorders. Overall, the evidence for use of GFDs in conditions other than celiac disease is poor.

Detection of Gluten in Gluten-Free Labeled Restaurant Food: Analysis of Crowd-Sourced Data.

Introduction: Adherence to a gluten-free (GF) diet is the mainstay of therapy for celiac disease. Until now, those wishing to avoid gluten in restaurants had to rely on menu labels, word of mouth, intuition, and restaurant workers' advice, with a relative dearth of supporting data. We used crowd-sourced data from users of a portable gluten detection device to estimate rates of, and identify risk factors for, gluten contamination of supposed GF restaurant foods.

Mucosal Melanoma: New Insights and Therapeutic Options for a Unique and Aggressive Disease.

Mucosal melanoma is a rare disease that is distinct from melanomas arising at other sites in the body. While melanocytes are most abundant in the skin, they can be found in smaller numbers in the mucous membranes, as well as in the eye. There are epidemiologic, genetic, and other physiologic differences between melanomas arising from melanocytes at these various sites, and these differences have important implications for both disease prognosis and treatment.

Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme.

Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) have been highly successful in the treatment of cancer. While PD-1 expression has been widely investigated, its role in CD4+ effector T cells in the setting of health and cancer remains unclear, particularly in the setting of glioblastoma multiforme (GBM), the most aggressive and common form of brain cancer. We examined the functional and molecular features of PD-1+CD4+CD25-CD127+Foxp3-effector cells in healthy subjects and in patients with GBM.

Gender differences in onabotulinum toxin A dosing for adductor spasmodic dysphonia.

Objectives/hypothesis: The objective of this study was to determine the influence of gender on onabotulinum toxin A dosing for the treatment of adductor spasmodic dysphonia symptoms.

Study Design: Retrospective review.

Methods: A chart review of the senior author's database of botulinum toxin injections was performed.

PD-1 marks dysfunctional regulatory T cells in malignant gliomas.

Immunotherapies targeting the immune checkpoint receptor programmed cell death protein 1 (PD-1) have shown remarkable efficacy in treating cancer. CD4CD25FoxP3 Tregs are critical regulators of immune responses in autoimmunity and malignancies, but the functional status of human Tregs expressing PD-1 remains unclear. We examined functional and molecular features of PD-1 Tregs in healthy subjects and patients with glioblastoma multiforme (GBM), combining functional assays, RNA sequencing, and cytometry by time of flight (CyTOF).

Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology.

Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed cortical function during focal seizures may depend on decreased subcortical cholinergic arousal, which leads to a sleep-like state of cortical slow-wave activity. To test this hypothesis, we sought to directly activate subcortical cholinergic neurons during focal limbic seizures to determine the effects on cortical function.