Characteristics of Long-Term Survivors With EGFR-Mutant Metastatic NSCLC.

Introduction: Characteristics of long-term survivors in EGFR-mutant (EGFRm) NSCLC are not fully understood. This retrospective analysis evaluated a multi-institution cohort of patients with EGFRm NSCLC treated in the pre-osimertinib era and sought to describe characteristics of long-term survivors. Methods: Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with EGFRm metastatic NSCLC who started first-line therapy before 2015. Demographics and comutations were compared between greater than or equal to 5-year survivors and less than 5-year survivors. Multivariable Cox proportional hazard and logistic regression models were used to evaluate factors associated with survival and the odds of death within 5 years, respectively. Results: Overall, 133 patients were greater than or equal to 5-year survivors; 127 were less than 5-year survivors. Burden of pathogenic comutations including TP53 and PIK3CA was similar between greater than or equal to 5-year survivors and less than 5-year survivors. Receipt of first-line chemotherapy rather than EGFR tyrosine kinase inhibitor was similar between the groups (22% of <5-y versus 31% of ≥5-y). Baseline brain metastasis and history of smoking were associated with higher odds of death within 5 years (odds ratio = 2.16, p = 0.029 and odds ratio = 1.90, p = 0.046, respectively). Among patients without baseline brain metastases, cumulative incidence of brain metastases at 5 years was 42.3%. Both baseline and post-baseline brain metastasis were associated with worse overall survival compared with no brain metastasis (hazard ratio = 3.26, p < 0.001 and hazard ratio = 4.99, p < 0.001, respectively). Conclusions: Within patients treated for EGFRm metastatic NSCLC before 2015, absence of brain metastasis and nonsmoking status were predictive of 5-year survival. Our findings help to define a subset of patients with EGFRm NSCLC with excellent survival outcomes who may not require intensification of initial therapy.

Disparities in the Use of Preoperative Breast Magnetic Resonance Imaging After Breast Cancer Diagnosis.

PURPOSE: Preoperative magnetic resonance imaging (MRI) after breast cancer diagnosis is increasingly used to improve locoregional staging, particularly among women with dense breasts, extensive ductal carcinoma in situ, and lobular histology. The goals of this study were to (1) assess whether use of preoperative MRI varies by race and insurance type; and (2) determine whether preoperative MRI is associated with downstream surgical management. MATERIALS AND METHODS: We performed a retrospective cohort study of women with stage 0-III breast cancer who were treated with surgical resection within our academic health system (2016-2019). Patients were categorized by race and insurance type. The primary outcome was receipt of preoperative MRI. Secondary outcomes included surgery extent (lumpectomy v mastectomy) and receipt of a second operation. RESULTS: A total of 1,410 women (27% Black, 73% White; 67% private insurance, 26% Medicare, 6% Medicaid) were included. Black patients were significantly less likely to undergo preoperative MRI than White patients (odds ratio [OR], 0.54 [95% CI, 0.38 to 0.76]; P < .001). There was no association between insurance type and preoperative MRI (Medicare v private: OR, 0.77 [95% CI, 0.52 to 1.15]; P = .208; Medicaid v private: OR, 0.67 [95% CI, 0.36 to 1.25]; P = .210). White patients who underwent preoperative MRI were less likely to undergo lumpectomy versus those who did not (OR, 0.53 [95% CI, 0.37 to 0.76]; P < .001). Likelihood of re-excision was lower for Black women who had undergone MRI versus those who had not (OR, 0.43 [95% CI, 0.20 to 0.93]; P = .031). CONCLUSION: Black patients were less likely than White patients to undergo preoperative MRI, yet Black women who underwent MRI were less likely to require re-excision. Standardizing preoperative MRI use may mitigate provider- and system-level biases and promote more equitable care.

Racial Disparities and Strategies for Improving Equity in Diagnostic Follow-Up for Abnormal Screening Mammograms.

PURPOSE: Black and White women undergo screening mammography at similar rates, but racial disparities in breast cancer outcomes persist. To assess potential contributors, we investigated delays in follow-up after abnormal imaging by race/ethnicity. METHODS: Women who underwent screening mammography at our urban academic center from January 2015 to February 2018 and received a Breast Imaging Reporting and Data System 0 assessment were included. Kaplan-Meier estimates described distributions of time between diagnostic events from (1) screening to diagnostic imaging and (2) diagnostic imaging to biopsy. Multivariable logistic regression models estimated the associations between race/ethnicity and receipt of follow-up within 15 and 30 days. RESULTS: Two thousand five hundred and fifty-four women were included (48.6% non-Hispanic [NH] Black, 38.2% NH White, 13.1% other/unknown). Median time between screening and diagnostic imaging varied by race/ethnicity (White: 7 days [IQR, 2-14]; Black: 12 days [IQR, 7-23]; other/unknown: 9 days [IQR, 5-21]). There were similar disparities in days between diagnostic imaging and biopsy (White: 12 [IQR, 7-24]; Black: 21 [IQR, 13-37]; other/unknown: 16 [IQR, 9-30]) and between screening and biopsy (White: 20 [IQR, 11-41]; Black: 35 [IQR, 22-63]; other/unknown: 27.5 [IQR, 17-42]). After adjustment, odds of diagnostic imaging follow-up within 15 days of screening were lower for Black versus White women (odds ratio, 0.59 [95% CI, 0.44 to 0.80]; P < .001). CONCLUSION: In this diverse cohort, disparities in timely diagnostic follow-up after abnormal breast screening were observed, with Black women waiting 1.75 times as long as White women to obtain a tissue diagnosis. National guidelines for time to diagnostic follow-up may facilitate more timely breast cancer care and potentially affect outcomes.

New species and new combinations in the genus Paraisaria (Hypocreales, Ophiocordycipitaceae) from the U.S.A., supported by polyphasic analysis.

Molecular phylogenetic and chemical analyses, and morphological characterization of collections of North American Paraisaria specimens support the description of two new species and two new combinations for known species. P.cascadensissp. nov. is a pathogen of Cyphoderris (Orthoptera) from the Pacific Northwest USA and P.pseudoheteropodasp. nov. is a pathogen of cicadae (Hemiptera) from the Southeast USA. New combinations are made for Ophiocordycepsinsignis and O.monticola based on morphological, ecological, and chemical study. A new cyclopeptide family proved indispensable in providing chemotaxonomic markers for resolving species in degraded herbarium specimens for which DNA sequencing is intractable. This approach enabled the critical linkage of a 142-year-old type specimen to a phylogenetic clade. The diversity of Paraisaria in North America and the utility of chemotaxonomy for the genus are discussed.

Temporal Trends and Factors Associated with Receipt of Post-mastectomy Radiation After Neoadjuvant Chemotherapy in Women with cT3 Breast Cancer.

INTRODUCTION: Given the potential impact of increasingly effective neoadjuvant chemotherapy (NACT) on post-mastectomy radiotherapy (PMRT) recommendations, we examined temporal trends in post-NACT PMRT for cT3 breast cancer. METHODS: We identified women ≥ 18 years in the National Cancer Database (NCDB) diagnosed 2004-2019 with cT3N0-1M0 breast cancer treated with chemotherapy and mastectomy. Multivariable logistic regression and Cox proportional hazards models were used to estimate associations between pathologic NACT response [complete response (CR), partial response (PR), or no response (NR); or disease progression (DP)] and PMRT and between PMRT and overall survival (OS), respectively. RESULTS: We identified 39,901 women (Asian/Pacific Islander 1731, Black 5875, Hispanic 3265, White 27,303). Among cN0 patients with CR, PMRT rates declined from 67% in 2004 to 35% in 2019 but remained unchanged for patients with DP. Relative to NR, CR [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.29-0.46] and PR (OR 0.44, 95% CI 0.36-0.55) in cN0 patients were associated with lower odds of PMRT while DP (OR 1.33, 95% CI 1.05-1.69) was associated with higher odds. Among cN1 patients, PMRT rates decreased from 90% to 73% for CR between 2005 and 2019 and increased from 76% to 82% for DP between 2004 and 2019. Relative to NR, CR (OR 0.78, 95% CI 0.63-0.95) was associated with lower odds of PMRT while DP (OR 1.93, 95% CI 1.58-2.37) was associated with higher odds. PMRT was associated with improved OS among cN1 patients (hazard ratio (HR) 0.77, 95% CI 0.67-0.88). CONCLUSION: CR was associated with decreased PMRT receipt over time, while temporal trends following PR and DP differed by cN status, suggesting that nodal involvement guided PMRT receipt more than in-breast disease.

Clinical Outcomes Associated With Pembrolizumab Monotherapy Among Adults With Diffuse Malignant Peritoneal Mesothelioma.

Importance: Diffuse malignant peritoneal mesothelioma (DMPM) represents a rare and clinically distinct entity among malignant mesotheliomas. Pembrolizumab has activity in diffuse pleural mesothelioma but limited data are available for DMPM; thus, DMPM-specific outcome data are needed. Objective: To evaluate outcomes after the initiation of pembrolizumab monotherapy in the treatment of adults with DMPM. Design, Setting, and Participants: This retrospective cohort study was conducted in 2 tertiary care academic cancer centers (University of Pennsylvania Hospital Abramson Cancer Center and Memorial Sloan Kettering Cancer Center). All patients with DMPM treated between January 1, 2015, and September 1, 2019, were retrospectively identified and followed until January 1, 2021. Statistical analysis was performed between September 2021 and February 2022. Exposures: Pembrolizumab (200 mg or 2 mg/kg every 21 days). Main Outcomes and Measures: Median progression-free survival (PFS) and median overall survival (OS) were assessed using Kaplan-Meier estimates. The best overall response was determined using RECIST (Response Evaluation Criteria in Solid Tumors) criteria, version 1.1. The association of disease characteristics with partial response was evaluated using the Fisher exact test. Results: This study included 24 patients with DMPM who received pembrolizumab monotherapy. Patients had a median age of 62 years (IQR, 52.4-70.6 years); 14 (58.3%) were women, 18 (75.0%) had epithelioid histology, and most (19 [79.2%]) were White. A total of 23 patients (95.8%) received systemic chemotherapy prior to pembrolizumab, and the median number of lines of prior therapy was 2 (range, 0-6 lines). Of the 17 patients who underwent programmed death ligand 1 (PD-L1) testing, 6 (35.3%) had positive tumor PD-L1 expression (range, 1.0%-80.0%). Of the 19 evaluable patients, 4 (21.0%) had a partial response (overall response rate, 21.1% [95% CI, 6.1%-46.6%]), 10 (52.6%) had stable disease, and 5 (26.3%) had progressive disease (5 of 24 patients [20.8%] were lost to follow-up). There was no association between a partial response and the presence of a BAP1 alteration, PD-L1 positivity, or nonepithelioid histology. With a median follow-up of 29.2 (95% CI, 19.3 to not available [NA]) months, the median PFS was 4.9 (95% CI, 2.8-13.3) months and the median OS was 20.9 (95% CI, 10.0 to NA) months from pembrolizumab initiation. Three patients (12.5%) experienced PFS of more than 2 years. Among patients with nonepithelioid vs epithelioid histology, there was a numeric advantage in median PFS (11.5 [95% CI, 2.8 to NA] vs 4.0 [95% CI, 2.8-8.8] months) and median OS (31.8 [95% CI, 8.3 to NA] vs 17.5 [95% CI, 10.0 to NA] months); however, this did not reach statistical significance. Conclusions and Relevance: The results of this retrospective dual-center cohort study of patients with DMPM suggest that pembrolizumab had clinical activity regardless of PD-L1 status or histology, although patients with nonepithelioid histology may have experienced additional clinical benefit. The partial response rate of 21.0% and median OS of 20.9 months in this cohort with 75.0% epithelioid histology warrants further investigation to identify those most likely to respond to immunotherapy.

Failure Rates After Anterior Cruciate Ligament Repair With Suture Tape Augmentation in an Active-Duty Military Population.

Background: Anterior cruciate ligament (ACL) repair had previously been considered the standard of care for a ruptured ACL; however, ACL reconstruction has became the standard of care because of poor midterm outcomes after ACL repair. Recently, studies have suggested that the treatment paradigm should shift back to ACL repair. Purpose/Hypothesis: The purpose of this study was to evaluate the outcomes of ACL repair augmented with suture tape in a high-demand military population. We hypothesized that for proximal ACL avulsions, ACL repair with suture tape augmentation would lead to acceptable failure rates, satisfactory knee stability, excellent functional outcomes, and high rates of return to preinjury activity levels. Study Design: Case series; Level of evidence, 2. Methods: Patients who were treated with ACL repair by a single surgeon between March 2017 and June 2019 and who had a minimum of 2 years of follow-up were included. Intraoperatively, all patients first underwent an arthroscopic examination. If an ACL avulsion of the proximal insertion with adequate remaining tissue was visualized, then ACL repair was performed. The primary outcome assessed was ACL repair failure, defined as reruptures or clinical instability requiring revision to ACL reconstruction. Analysis of the risk factors for ACL repair failure was conducted, with age at surgery, sex, body mass index, level of competition, and tobacco use evaluated. Results: Included were 46 patients (32 male and 14 female; mean age, 28.3 ± 8.4 years) who underwent ACL repair with suture tape augmentation. There were 12 cases of failure (26.1%; 8 male and 4 female). The mean time from injury to surgery in the failure group was 164.1 ± 59.4 days compared to 107.3 ± 98.0 days in the nonfailure group (P = .02). According to multivariate regression analysis, patients aged ≤17 and ≥35 years, elite/competitive/operational patients, and current smokers had a higher chance of ACL repair failure. The mean time to pass a military physical fitness test was 5.0 months. There were no complications other than ACL repair failure. Conclusion: Primary arthroscopic ACL repair with suture tape augmentation resulted in unacceptably high failure rates at a minimum of 2 years of follow-up in a highly active military population. Age ≤17 and ≥35 years, elite level of competition, time from injury to surgery, and active tobacco use were independent risk factors for ACL repair failure.

Mechanistic Investigation of Site-specific DNA Methylating Agents Targeting Breast Cancer Cells.

We previously described the development of a DNA-alkylating compound that showed selective toxicity in breast cancer cells. This compound contained an estrogen receptor α (ERα)-binding ligand and a DNA-binding/methylating component that could selectively methylate the N3-position of adenines at adenine-thymine rich regions of DNA. Herein, we describe mechanistic investigations that demonstrate that this class of compounds facilitate the translocation of the ERα-compound complex to the nucleus and induce the expression of ERα target genes. We confirm that the compounds show selective toxicity in ERα-expressing cells, induce ERα localization in the nucleus, and verify the essential role of ERα in modulating the toxicity. Minor alterations in the compound structure significantly affects the DNA binding ability, which correlates to the DNA-methylating ability. These studies demonstrate the utility of DNA-alkylating compounds to accomplish targeted inhibition of the growth of specific cancer cells; an approach that may overcome shortcomings of currently used chemotherapy agents.

Sox9EGFP Defines Biliary Epithelial Heterogeneity Downstream of Yap Activity.

BACKGROUND & AIMS: Defining the genetic heterogeneity of intrahepatic biliary epithelial cells (BECs) is challenging, and tools for identifying BEC subpopulations are limited. Here, we characterize the expression of a Sox9EGFP transgene in the liver and demonstrate that green fluorescent protein (GFP) expression levels are associated with distinct cell types. METHODS: Sox9EGFP BAC transgenic mice were assayed by immunofluorescence, flow cytometry, and gene expression profiling to characterize in vivo characteristics of GFP populations. Single BECs from distinct GFP populations were isolated by fluorescence-activated cell sorting, and functional analysis was conducted in organoid forming assays. Intrahepatic ductal epithelium was grown as organoids and treated with a Yes-associated protein (Yap) inhibitor or bile acids to determine upstream regulation of Sox9 in BECs. Sox9EGFP mice were subjected to bile duct ligation, and GFP expression was assessed by immunofluorescence. RESULTS: BECs express low or high levels of GFP, whereas periportal hepatocytes express sublow GFP. Sox9EGFP+ BECs are differentially distributed by duct size and demonstrate distinct gene expression signatures, with enrichment of Cyr61 and Hes1 in GFPhigh BECs. Single Sox9EGFP+ cells form organoids that exhibit heterogeneous survival, growth, and HNF4A activation dependent on culture conditions, suggesting that exogenous signaling impacts BEC heterogeneity. Yap is required to maintain Sox9 expression in biliary organoids, but bile acids are insufficient to induce BEC Yap activity or Sox9 in vivo and in vitro. Sox9EGFP remains restricted to BECs and periportal hepatocytes after bile duct ligation. CONCLUSIONS: Our data demonstrate that Sox9EGFP levels provide readout of Yap activity and delineate BEC heterogeneity, providing a tool for assaying subpopulation-specific cellular function in the liver.

Referral, Assessment and Use of Screening Measures Related to Autism Spectrum Disorder at a Tertiary Hospital Setting.

Children with developmental concerns in Australia continue to experience inequitable healthcare and service-related delays, even when diagnostic risk is identified. This study sought to explore service and demographic pathway factors leading up to autism spectrum disorder (ASD) assessment, including value of screening measures applied at triage. Following a trial of centralised intake for referred young children with suspected ASD, observational, retrospective pathway data was explored using bivariate and regression analyses. The mean age of 159 children referred with autism symptoms was 3.6 years, and 64% were diagnosed with ASD. Service allocation was associated with diagnosis, whilst screening tool results were not. Improved pathways are needed to limit wasted waiting times and direct each child to needs-based services.

Occurrence and determinants of Klebsiella species bloodstream infection in the western interior of British Columbia, Canada.

BACKGROUND: Klebsiella species are among the most common causes of bloodstream infection (BSI). However, few studies have evaluated their epidemiology in non-selected populations. The objective was to define the incidence of, risk factors for, and outcomes from Klebsiella species BSI among residents of the western interior of British Columbia, Canada. METHODS: Population-based surveillance was conducted between April 1, 2010 and March 31, 2017. RESULTS: 151 episodes were identified for an incidence of 12.1 per 100,000 population per year; the incidences of K. pneumoniae and K. oxytoca were 9.1 and 2.9 per 100,000 per year, respectively. Overall 24 (16%) were hospital-onset, 90 (60%) were healthcare-associated, and 37 (25%) were community-associated. The median patient age was 71.4 (interquartile range, 58.8-80.9) years and 88 (58%) cases were males. Episodes were uncommon among patients aged < 40 years old and no cases were observed among those aged < 10 years. A number of co-morbid medical illnesses were identified as significant risks and included (incidence rate ratio; 95% confidence interval) cerebrovascular accident (5.9; 3.3-9.9), renal disease 4.3; 2.5-7.0), cancer (3.8; 2.6-5.5), congestive heart failure (3.5; 1.6-6.6), dementia (2.9; 1.5-5.2), diabetes mellitus (2.6; 1.7-3.9), and chronic obstructive pulmonary disease (2.3; 1.5-3.5). Of the 141 (93%) patients admitted to hospital, the median hospital length stay was 8 days (interquartile range, 4-17). The in-hospital and 30-day all cause case-fatality rates were 24/141 (17%) and 27/151 (18%), respectively. CONCLUSIONS: Klebsiella species BSI is associated with a significant burden of illness particularly among those with chronic co-morbid illnesses.

Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection.

Gastrointestinal (GI) mucosal dysfunction predicts and likely contributes to non-infectious comorbidities and mortality in HIV infection and persists despite antiretroviral therapy. However, the mechanisms underlying this dysfunction remain incompletely understood. Neutrophils are important for containment of pathogens but can also contribute to tissue damage due to their release of reactive oxygen species and other potentially harmful effector molecules. Here we used a flow cytometry approach to investigate increased neutrophil lifespan as a mechanism for GI neutrophil accumulation in chronic, treated HIV infection and a potential role for gastrointestinal dysbiosis. We report that increased neutrophil survival contributes to neutrophil accumulation in colorectal biopsy tissue, thus implicating neutrophil lifespan as a new therapeutic target for mucosal inflammation in HIV infection. Additionally, we characterized the intestinal microbiome of colorectal biopsies using 16S rRNA sequencing. We found that a reduced Lactobacillus: Prevotella ratio associated with neutrophil survival, suggesting that intestinal bacteria may contribute to GI neutrophil accumulation in treated HIV infection. Finally, we provide evidence that Lactobacillus species uniquely decrease neutrophil survival and neutrophil frequency in vitro, which could have important therapeutic implications for reducing neutrophil-driven inflammation in HIV and other chronic inflammatory conditions.

Penile Stretching as a Treatment for Peyronie's Disease: A Review.

INTRODUCTION: Peyronie's disease (PD) is a debilitating condition that affects a sizable number of men worldwide. Current treatment options consist of oral therapy, intralesional injections, and surgery. Penile stretching has been used as a treatment for PD, including penile traction therapy (PTT) and vacuum erection devices (VEDs), with numerous trials completed or underway. AIM: To present and summarize the current literature on penile stretching for the treatment of PD. METHODS: Using PubMed, we performed a literature review of studies from January 1990 through July 2018 that focused on penile stretching for PD management. PTT and VED were included in the search criteria. MAIN OUTCOME METHODS: Penile curvature correction was effective, and stretched penile length was improved. RESULTS: PD therapies that use penile stretching as a mechanical intervention to alter tissue characteristics were studied. PTT has been successful in primary penile lengthening and curvature correction in the acute phase of PD. PTT also improved length retention in men undergoing plication and incision/grafting procedures. Combination of PTT and intralesional injection therapy for PD treatment requires further investigation. There are fewer studies investigating VEDs and their role in PD management, but initial small trials suggest a role in curvature correction and penile lengthening. CONCLUSIONS: Penile stretching is an effective therapy for PD. Data from limited trials suggest a role for PTT and VEDs in the management of PD, although further research is needed. Cowper MG, Burkett CB, Le TV et al. Penile Stretching as a Treatment for Peyronie's Disease: A Review. Sex Med Rev 2019;7:508-515.

Clinical utility of portable electrophysiology to measure fatigue in treatment-naïve non-small cell lung cancer.

PURPOSE: Cancer-related fatigue (CRF) biology remains poorly understood. Responsible mechanisms may be central or peripheral and originate anywhere from the brain to muscle fiber. Objective measurement is complex and previously limited to specialized laboratories. Portable electroencephalography (EEG) and electromyography (EMG) may enhance objective measurement. This study evaluated the feasibility and acceptability of portable EMG-EEG in CRF assessment. METHODS: A prospective observational feasibility study compared ten outpatients with inoperable, treatment-naïve non-small cell lung cancer and CRF to ten healthy volunteers. All completed a sustained isometric hand-grip contraction at 30% maximal level until self-perceived exhaustion. 128-channel EEG and 2-channel EMG signals of forearm muscles were recorded. Device acceptability was evaluated by questionnaire. RESULTS: The task was evaluated in two stages; first and last 20 s. CRF cohort perceived exhaustion earlier than volunteers (mean 137 ± 76 s vs 208 ± 51 s). As fatigue progressed, EMG amplitude increased significantly (CRF p = 0.02; volunteers: p = 0.04) in both groups as did EMG beta band power (CRF p = 0.008; volunteers: p = 0.006). The increase was significantly less in CRF (amplitude p = 0.032; beta power: p = 0.014). EEG beta band power in the contralateral motor cortex increased significantly (CRF p = 0.03; volunteers: p = 0.019) in both cohorts but to greater extent (p = 0.024) in CRF. One hundred percent device acceptability was reported. CONCLUSIONS: A laboratory-based evaluation was successfully adapted to the outpatient setting during routine visits. High acceptability supports clinical utility. In CRF, a higher degree of cortical activation was required to drive a much lower level of muscle performance. This suggests impairment of both central and peripheral mechanisms in CRF.

Comparison of the locations where young adults smoke, vape, and eat/drink cannabis: Implications for harm reduction.

BACKGROUND: Cannabis vaping and edible use are increasingly popular methods of cannabis use. These discreet methods could increase risk of cannabis-related problems by facilitating cannabis use in a wider range of settings. METHODS: A sample of 1018 college students were recruited to complete a survey about their health and behavior. Participants who used cannabis in the past year (35.1%, n = 357) answered questions about their cannabis use, including where they were the last time they smoked, vaped, or ate/drank cannabis, and their experience of cannabis-related problems. RESULTS: Compared with cannabis smoking, participants were more likely to have vaped cannabis (15.8% smoked vs. 24.6% vaped; X2 = 4.59, p = .032), and were slightly, but not statistically significantly, more likely to have used cannabis edibles (17.5% smoked vs. 24.2% used edibles; X2 = 3.57, p = .059), in locations other than a private residence. For example, participants were more likely to have vaped cannabis in a car than to have smoked cannabis in a car (8.8% vaped vs. 3.5% smoked; X2 = 4.26, p = .039). More frequent cannabis vaping was associated with driving while high on cannabis, even after accounting for overall frequency of cannabis use and other covariates (OR = 1.22, p = .047). More frequent cannabis vaping and edible use were associated with various cannabis-related problems, but, in general, these associations became statistically non-significant after accounting for overall frequency of cannabis use. CONCLUSIONS: Cannabis vaporizers and edibles facilitate cannabis use in locations that require discretion. Increased availability of cannabis vaporizers and edibles could increase risk of cannabis-related problems by enabling use in more settings.

The pathophysiology of cancer-related fatigue: current controversies.

Fatigue is one of the most common and debilitating cancer symptoms, and is associated with impaired quality of life. The exact pathophysiology of cancer-related fatigue (CRF) is poorly understood, but in any individual, it is likely multifactorial and involves inter-related cytokine, muscular, neurotransmitter, and neuroendocrine changes. Underlying CRF mechanisms proposed include central and peripheral hypotheses. Central mechanisms include hypotheses about cytokine dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm disruption, serotonin, and vagal afferent nerve function while peripheral mechanisms include hypotheses about adenosine triphosphate and muscle contractile properties. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is characteristic. The purpose of this article is to provide a narrative review of the literature and present the current controversies in the pathophysiology of CRF, particularly in relation to central and peripheral hypotheses for CRF. An understanding of pathophysiology may facilitate direct and simple therapeutic interventions for those with cancer.

Subjective and objective taste and smell changes in cancer.

CONTEXT: Malnutrition is highly prevalent in cancer patients and an important predictor of morbidity, mortality, treatment response, and toxicity. Taste and smell changes (TSCs) are common and may contribute to malnutrition. Research has previously focused on patients receiving chemotherapy (CT) or head and neck radiotherapy (RT). However, TSCs may occur pre-treatment, with other treatment modalities, and in cancer survivors. This review evaluates objective and subjective assessment of taste and smell, discusses the prevalence of TSCs in cancer, and reviews the clinical sequelae of TSCs in cancer patients. OBJECTIVES: To critically evaluate objective and subjective assessment of TSCs, and the prevalence and clinical sequelae of TSCs in cancer. METHODS: A literature search was conducted using PubMed, CINAHL and Embase for English-language articles published January 2009-June 2016. Search terms included combinations of the following: chemosensory, taste, smell, cancer, chemotherapy, radiotherapy, hormone therapy, immunotherapy, survivors. Reference lists of articles retrieved were also reviewed. RESULTS: Variation in objective and subjective assessment methodologies has resulted in difficulties interpreting the literature. TSC prevalence varies depending on stage of disease and treatment regimens, from 16% to 70% and 50% to 70% during CT and RT, respectively. TSCs in patients who are treatment-naïve, receiving hormone or immunotherapy treatment, post-treatment and cancer survivors have not been adequately studied. TSCs are associated with impaired nutritional status. The relationship between cancer-associated symptoms and nutritional status is not clearly defined. CONCLUSION: There is no gold standard assessment tool for TSCs. Heterogeneity in study methods hinders conclusive identification of the most appropriate way to measure TSCs. Subjective measures may reflect the patient experience and more reliably predict changes in dietary behaviour. Evaluation of TSCs should form part of all nutritional assessments in cancer patients. The true prevalence and severity of TSCs at all stages of cancer could then be established.

Medical students' understanding of oral and maxillofacial surgery: an Irish perspective.

Oral and Maxillofacial Surgery (OMFS) remains an enigmatic specialty in Irish medicine and many students are unaware of its scope and the unique career pathway involved. We completed a multicentre cross-sectional study to identify their ability to identify the requirements for entry to specialty training year 3 (ST3) in OMFS, to assess their awareness of OMFS surgeons, and their general awareness of, and exposure to, the specialty. Data were collected through an electronic questionnaire. Participants were asked to select the most suitable surgical specialty to treat a number of common conditions in the head and neck, and to choose the requirements they deemed essential for specialist training. Knowledge was measured by the number of correct responses. A total of 443 medical students participated (University College Cork (UCC) n=328, 74%; Royal College of Surgeons in Ireland (RCSI) n=113, 26%). A total of 318/374 (85%) had had no previous experience of OMFS, 38/374 (10%) had had theoretical teaching only, and 18/374 (5%) had had clinical experience. A total of 212/329 (64%) wished for greater exposure as a student, but only 34/329 (9%) would consider a career in the specialty. The median (IQR) number of correct responses for OMFS procedures was 3.0/10 (2.0), with women, direct entrants, and RCSI students scoring highest. Only 11/367 (3%) could identify the minimum entry requirements for a post of specialist registrar. This study has identified a potential gap in the undergraduate curriculum. Although medical students are rarely taught about OMFS, they show an interest in learning more.

Predictors of hepatotoxicity among patients treated with antituberculous medication.

INTRODUCTION: Hepatotoxicity in patients diagnosed with active tuberculosis (TB) is the commonest adverse effect of therapy. We sought to analyse trends in liver function in patients diagnosed with active TB and to determine predictors of hepatotoxicity. METHODS: We studied 275 patients with active TB treated at the Mercy University Hospital (Cork, Ireland) from 2009 to 2014 A retrospective review was undertaken of all patients' laboratory data and patient correspondence to determine predictors of hepatotoxicity. RESULTS: A total of 170 (62%) male and 105 (38%) female patients with active TB with a mean age of 44 years were studied. In total 15 patients (6%) required their medication to be stopped or altered as a consequence of hepatotoxicity. There was a significant difference in age between patients with hepatotoxicity (52.95 years) and those that didn't develop hepatotoxicity (41.33 years) ( P ≤ 0.01). Irish born patients were more likely to develop hepatotoxicity ( P = 0.025). There was no significant association between hepatotoxicity, illicit drug use ( P = 0.211), smoking ( P = 0.95), cavitatory disease ( P = 0.191), site of disease ( p = 0.224), alcohol use ( P = 0.088) or history of alcohol excess ( p = 0.736). Among patients with TB, peak AST values did not occur within the first 2 weeks as widely thought but later (week 10). CONCLUSION: Our study shows hepatotoxicity as a consequence of antituberculous therapy is common. Hepatotoxicity was more common in older patients and Irish born patients, and resulted in drug interruptions and treatment changes. Given the late peak in AST values at week 10 in patients treated with antituberculous therapy, the authors advocate that liver function tests should be monitored regularly throughout the course of treatment.