Prevalence and spectrum of germline pathogenic variants in cancer susceptibility genes among mexican patients with exocrine pancreatic cancer.

Background: Although universal germline genetic testing is recommended for patients with exocrine pancreatic cancer (PC), access to genetic testing remains limited in low- and middle-income countries. This study aims to narrow the gap in our understanding of the spectrum of germline pathogenic and likely pathogenic variants (PVs) in cancer susceptibility genes in the Mexican population.

Methods: The landscape of PVs in cancer susceptibility genes was identified by next-generation sequencing multigene panel assays among patients with PC who were enrolled in the Clinical Cancer Genomics Community Research Network prospective registry in Mexico City.

Hedgehog pathway inhibitors for locally advanced and metastatic basal cell carcinoma: A real-world single-center retrospective review.

Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50-60% response rate.

The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium.

A single center case series of immune checkpoint inhibitor-induced type 1 diabetes mellitus, patterns of disease onset and long-term clinical outcome.

Background: Type 1 diabetes mellitus (T1DM) is a rare, but serious immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs). Our goal was to characterize treatment outcomes associated with ICI-induced T1DM through analysis of clinical, immunological and proteomic data.

Methods: This was a single-center case series of patients with solid tumors who received ICIs and subsequently had a new diagnosis of T1DM.

Response to high dose ipilimumab plus temozolomide after progression on standard or low dose ipilimumab in advanced melanoma: a retrospective analysis.

Background: Despite advancements in checkpoint inhibitor-based immunotherapy, patients with advanced melanoma who have progressed on standard dose ipilimumab (Ipi) + nivolumab continue to have poor prognosis. Several studies support a dose-response activity of Ipi, and one promising combination is Ipi 10mg/kg (Ipi10) + temozolomide (TMZ).

Methods: We performed a retrospective cohort analysis of patients with advanced melanoma treated with Ipi10+TMZ in the immunotherapy refractory/resistant setting (n = 6), using similar patients treated with Ipi3+TMZ (n = 6) as comparison.

Current chemoprevention approaches in Lynch syndrome and Familial adenomatous polyposis: a global clinical practice survey.

Background: International chemoprevention preferences and approaches in Lynch syndrome (LS) and associated polyposis, including Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) have not been previously explored.

Aim: To describe current chemoprevention strategies for patients with LS or FAP/AFAP (referred to collectively as FAP) practiced by members of four international hereditary cancer societies through administration of a survey.

Results: Ninety-six participants across four hereditary gastrointestinal cancer societies responded to the survey.

Dermatologic Implications of Sleep Deprivation in the US Military.

Short sleep duration is common among US adults and is even more common among people working in protective services and the military. Military service predisposes members to disordered sleep due to the rigors of deployments and field training. In this article, we explore possible mechanisms by which sleep deprivation may affect the skin.

Vaccination uptake for pertussis and influenza vaccines in pregnancy among different practices at a single institution.

Objective: The authors investigated tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccination during pregnancy following Advisory Committee on Immunization Practices' (ACIP's) recommendation for antenatal pertussis vaccination.

Methods: A retrospective chart review was performed in 2019 of women receiving prenatal care at our institution between January 1, 2014 and December 31, 2018. Receipt of ACIP-recommended vaccines were examined using Current Procedural Terminology codes to identify initiation of prenatal care, then administration of Tdap and influenza vaccines.

Change in Pediatric Adenotonsillectomy Postoperative Visit Patterns After Opioid Food and Drug Administration Warning.

Study Objective: This study aimed to determine the association between opioid prescriptions given after tonsillectomy with adenoidectomy (T + A) and pain-related return visit rates in pediatric patients. Determine association between Food and Drug Administration (FDA) black box warning against opioid use in this population and pain-related return visit rates.

Methods: This was a single-institution retrospective cohort study of pediatric patients who underwent T + A between April 2012 and December 2015 and had return visits to the emergency department or urgent care center.

A searchable image resource of GAL4 driver expression patterns with single neuron resolution.

Precise, repeatable genetic access to specific neurons via GAL4/UAS and related methods is a key advantage of neuroscience. Neuronal targeting is typically documented using light microscopy of full GAL4 expression patterns, which generally lack the single-cell resolution required for reliable cell type identification. Here, we use stochastic GAL4 labeling with the MultiColor FlpOut approach to generate cellular resolution confocal images at large scale.

Developing and Validating a Novel Tool to Enhance Functional Status Assessment: The Tennessee Functional Status Questionnaire (TFSQ).

Purpose: Functional status is a major contributor to overall health and reflects both daily activity level (performance) and maximum attainable activity level (capacity). Existing assessment tools evaluate only 1 domain of function and do not provide insight into contributors to functional decline. We addressed these deficiencies by developing the Tennessee Functional Status Questionnaire (TFSQ), which reports activity levels in metabolic equivalents (METs) and evaluates 5 key areas: performance, capacity, activity, pain, and acute care.

The economic value of knowing BRCA status: testing for optimizing treatment in recurrent epithelial ovarian cancer.

Background: This study aimed to estimate the incremental lifetime effects, costs, and net monetary benefit (NMB) of knowing information for recurrent ovarian cancer (ROC) patients in a given year and the cumulative savings of yearly hypothetical cohort testing over 16 years. We compared two strategies: (1) 'with information' and (2) 'without information.'

Methods: Incremental NMB (INMB) was calculated as the average net monetized benefit of knowing status.

Economic value of knowing BRCA status: BRCA testing for prostate cancer prevention and optimal treatment.

Background: We aimed to estimate the incremental lifetime effects, costs, and net-monetary-benefit (NMB) of knowing information by testing of patients with low-risk localized prostate cancer (PCa) in the US and guiding subsequent screening and treatment, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1)'with information' and (2)'without information.' We also estimated the expected value of perfect information.

The economic value of knowing BRCA status: universal BRCA testing for breast cancer prevention.

Background: This study aimed to estimate the incremental lifetime effects, costs, and net monetary benefit (NMB) of knowing information by universal genetic testing of all US women without breast cancer turning 40 in a given year, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1) 'with information' and (2) 'without information.'

Methods: Incremental NMB (INMB) was calculated as the monetized benefit per person of knowing status.

A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant.

Pathogenic variants (PVs) in the SDHD gene increase risk for paragangliomas (PGL)/pheochromocytomas, renal cell carcinomas, and gastrointestinal stromal tumors. Penetrance in individuals with SDHD PVs varies in reported research from 40-70%, and there is limited evidence of specific genotype risks. This study aims to characterize a multi-generational family with SDHD p.

Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy.

Introduction: Approximately 40% of patients with uveal melanoma (UM) will develop metastatic disease. Tumors measuring at least 12mm in basal diameter with a class 2 signature, as defined by a widely used gene expression-profiling test, are associated with significantly higher risk of metastasis, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk.

Discrepancies between tumor genomic profiling and germline genetic testing.

Background: Tumor genomic profiling (TGP) often incidentally identifies germline pathogenic variants (PVs) associated with cancer predisposition syndromes. Methods used by somatic testing laboratories, including germline analysis, differ from designated germline laboratories that have optimized the identification of germline PVs. This study evaluated discrepancies between somatic and germline testing results, and their impact on patients.

Mainstreaming germline genetic testing for patients with pancreatic cancer increases uptake.

Germline genetic testing is recommended for all patients with pancreatic cancer (PC) but uptake rates are low. We implemented a mainstreaming program in oncology clinics to increase testing for PC patients. Genetic counselors trained oncology providers to offer a standardized multigene panel and obtain informed consent using an educational video.

Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond and in Breast and Ovarian Cancer Patients.

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in , , and other DNA damage repair (DDR) genes beyond or . We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.

Genetic Evaluation for Hereditary Cancer Syndromes Among African Americans: A Critical Review.

While hereditary cancer syndromes have been described and studied for centuries, the completion of the human genome project fueled accelerated progress in precision medicine due to the introduction of genetic testing in the 1990s, creating avenues for tailored treatments and medical management options. However, genetic testing has not benefited everyone equitably, with nearly all of the published work based on individuals of non-Hispanic White/European ancestry. There remains a gap in knowledge regarding the prevalence, penetrance, and manifestations of common hereditary cancer syndromes in the African-American population due to significant disparities in access and uptake of genetic testing.

Considerations for Germline Testing in Melanoma: Updates in Behavioral Change and Pancreatic Surveillance for Carriers of Pathogenic Variants.

The largest proportion of hereditary melanoma cases are due to pathogenic variants (PVs) in the gene, which account for 20%-40% of familial melanomas and confer up to a 30%-70% lifetime risk for melanoma in individuals with these variants. In addition, PVs in the gene also increase risk for pancreatic cancer (~5-24% lifetime risk). Individuals with PVs in the gene also tend to have an earlier onset of cancer.

Non-Melanoma Skin Cancers and Other Cutaneous Manifestations in Bone Marrow Failure Syndromes and Rare DNA Repair Disorders.

Although most non-melanoma skin cancers are felt to be sporadic in origin, these tumors do play a role in several cancer predisposition syndromes. The manifestations of skin cancers in these hereditary populations can include diagnosis at extremely early ages and/or multiple primary cancers, as well as tumors at less common sites. Awareness of baseline skin cancer risks for these individuals is important, particularly in the setting of treatments that may compromise the immune system and further increase risk of cutaneous malignancies.

Poor Perception and Knowledge of Electronic Cigarettes Among Adolescents and Their Parents.

Objectives: Electronic cigarettes (e-cigs) and vaping are a popular form of substance abuse among adolescents. Studies have shown that adolescents have a poor understanding of e-cigs but little is known about parental understanding. The primary objective was to assess if a discrepancy in perception and knowledge regarding the content and safety profile of e-cigs between adolescents and their parents exists.

Cutaneous Cold Weather Injuries in the US Military.

Service members of the US Military are at risk for cutaneous cold weather injuries due to the demands of military training, combat operations, and peacekeeping missions. In this article, we review common cutaneous cold weather injuries likely to be encountered in the military, including frostbite, immersion foot, pernio, Raynaud phenomenon (RP), and cold urticaria. We aim to bring awareness to these specific injuries to improve diagnostic and treatment outcomes, both in service members and civilians.