Mapping health-related quality of life of children and families receiving pediatric invasive home mechanical ventilation: a scoping review protocol.

BACKGROUND: Children utilizing invasive home mechanical ventilation (administered via tracheostomy tube) receive intensive care at home without the support of trained staff typically present in an intensive care unit; within the context of worsening home nursing shortages, much of the 24/7 care burden falls to families which are likely under supported. Prior reviews have explored the quality of life of children receiving various forms of mechanical ventilation, without addressing the impact on the family. Additionally, the literature inconsistently differentiates the unique experience of families with children using invasive home mechanical ventilation from non-invasive, which has lower morbidity and mortality and requires less nursing care in the home. Therefore, our study aims to explore and map the existing literature regarding the impact of invasive home mechanical ventilation on the child and family's quality of life. Identified gaps will inform future research focused on improving the family quality of life of children with invasive home mechanical ventilation. METHODS: Five databases will be searched using keywords and controlled vocabulary to identify relevant studies: Ovid Medline, Embase, Scopus, and Cochrane Library. English language studies will meet inclusion criteria if they include primary research studies of children or families of children utilizing invasive home mechanical ventilation at home and assess quality of life. Children and young adults aged 0-25 years will be included. We exclude studies of hospitalized children, studies focused solely on healthcare professional experiences or clinical outcomes, and those focused on the period surrounding discharge from admission for tracheostomy placement. Two independent reviewers will screen studies at the title/abstract and full-text levels. Two independent reviewers will extract data from relevant studies. Disagreements will be resolved by an independent third reviewer. A targeted grey literature search will be performed utilizing ProQuest, clinicaltrials.gov, WHO trial registry, Google Scholar, and professional societies. Findings will be presented in tables and figures along with a narrative summary. DISCUSSION: This scoping review seeks to map the literature and provide a descriptive report of the health-related quality of life of children using invasive home mechanical ventilation and their families. REGISTRATION: Open Science Framework https://doi.org/10.17605/OSF.IO/6GB84 Date of Registration: November 29, 2023.

The HER2 flip-HER2 amplification of tumor cells in the cerebrospinal fluid of breast cancer patients with leptomeningeal disease: implications for treating the LM tumor with anti-HER2 therapy.

Introduction: CNSide is a platform that detects and characterizes tumor cells in the cerebrospinal fluid (CSF) of patients with leptomeningeal disease (LMD). The platform was validated per College of American Pathologists (CAP) and Clinical Laboratories Improvement Amendment (CLIA) guidelines and run as a commercial Laboratory Developed Test (LDT) at Biocept in San Diego, CA. The platform allows CSF tumor cell (CSF-TC) enumeration and biomarker characterization by fluorescent in situ hybridization (FISH). Methods: We performed a multicenter retrospective chart review of HER2 FISH CNSide test results that were commercially ordered on 26 patients by physicians for LMD breast cancer patients between April 2020 and October 2022. Results: We show that HER2 is amplified on CSF tumor cells in 62% (16/26) of LMD breast cancer patients. 10/26 (38%) patients had discordant HER2-positivity between the primary tumor tissue and CSF-TC; of these, 35% (9/26) of the patients displayed HER2 amplification on the CSF-TCs, however were categorized as HER2 negative on the primary tumor. Of the 27% (7/26) patients with a HER2 positive primary tumor, one patient showed a HER2 negative LMD tumor. Two patients, 8% (2/26) had a HER2 equivocal primary tumor; of these, one demonstrated a HER2 negative, and one a HER2 positive LMD tumor. Serial analysis (at least 4 longitudinal tests) of HER2 status of the CSF-TC throughout therapy was available for 14 patients and demonstrated that HER2 status of the LMD changed in 29% (4/14) during their treatment course and impacted care decisions. Conclusions: Our data suggests that CSF-TC HER2 FISH analysis in LMD breast cancer patients may be discordant to the primary tumor sample and the discovery of HER2 positivity in the CSF may open doors to anti-HER2 targeted therapy options for LMD patients.

The Population-Level Prevalence of Exocrine Pancreas Insufficiency and the Subsequent Risk of Pancreatic Cancer.

OBJECTIVES: The aim of this study was to study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Using TriNetX (a database of over 79 million US residents), we included patients ≥18 years with EPI (identified via ICD-10 codes) and continuous follow-up from 2016-2022. Patients with prior pancreas resection and PDAC before an EPI diagnosis were excluded. The primary outcome was EPI prevalence. Secondary outcomes included imaging utilization, PDAC risk, and pancreatic enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching (PSM) of patients with EPI versus patients without an EPI diagnosis. RESULTS: The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years. After PSM, PDAC risk among patients with EPI was twice as high compared with patients without EPI (aHR, 1.97; 95% CI, 1.66-2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (adjusted odds ratio, 4.25; 95% CI, 2.99-6.04). Only 58% (n = 13, 390) of patients with EPI received PERT. No difference was observed in PDAC risk between patients with EPI on PERT and those not on PERT (aHR, 1.10; 95% CI, 0.95-1.26; P = 0.17). CONCLUSIONS: Despite a low prevalence, patients with EPI may have a higher risk of PDAC, and majority with EPI were not on PERT. PERT did not impact incident PDAC risk after an EPI diagnosis.

Extraneural metastatic ependymoma: distant metastasis to the pleura, lungs, lymph nodes and bone.

Ependymomas are neuroepithelial tumours arising from ependymal cells surrounding the cerebral ventricles that rarely metastasise to extraneural structures. This spread has been reported to occur to the lungs, lymph nodes, liver and bone. We describe the case of a patient with recurrent CNS WHO grade 3 ependymoma with extraneural metastatic disease. He was treated with multiple surgical resections, radiation therapy and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space and lymph nodes.

Endoscopic submucosal dissection (ESD) outcomes in T1B esophageal cancer: a retrospective study.

BACKGROUND AND AIMS: The role of submucosal endoscopic dissection (ESD) in management of invasive esophageal cancer (EC) remains unclear. In this case series, we evaluate the clinical and technical outcomes of patients who underwent ESD with pathologically staged T1b EC. METHODS: This retrospective study included patients who underwent ESD between December 2016 and April 2023 with pathologically staged T1b EC. Patient demographics, tumor characteristics, and ESD technical outcomes were analyzed. Patients were followed to determine disease-free survival and tumor recurrence rates. RESULTS: Sixteen patients with a total of 17 pathologically staged T1b ECs were included in this case series with a median follow-up time of 28 months [range 3-75]. ESD had high en-bloc (100%) and R0 (82.3%) resection rates. 16/17 patients (94.1%) were discharged the same day, and there were no immediate perioperative complications. 4/17 patients (23.5%) had curative ESD resections with no tumor recurrence. Among those with non-curative resections (n = 13), 5 patients had ESD only, 6 had ESD + surgery, and 2 underwent ESD + chemoradiation. In the ESD only group, 2/5 patients (40%) had tumor recurrence. In the ESD + surgery group, one patient died from a surgical complication, and 1/5 (20%) had tumor recurrence at follow-up. There was no tumor recurrence among patients who had ESD + chemoradiation. CONCLUSION: ESD is safe with high en-bloc and R0 resection rates in T1b EC. Recurrence rates are low but patients need close monitoring. Larger-scale studies are needed to determine the long-term clinical efficacy of ESD in T1b EC.

Work Productivity Impairment in Persons with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The impact of inflammatory bowel disease [IBD] on work productivity remains unclear. In this systematic review and meta-analysis, we quantify work-related outcomes and employment data among persons with IBD. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, the Cochrane library, Scopus, ProQuest, and clinicaltrials.gov from inception to February 2023, to identify studies on work productivity in persons with IBD aged > 18 years. Work productivity was defined primarily by the Work Productivity and Activity Impairment [WPAI] questionnaire which includes absenteeism, presenteeism, overall work impairment, and non-work activity impairment. In addition, we included data on employment, sick leaves, disability pensions, and indirect costs due to productivity loss. Pooled effect analysis was conducted using a random-effects model for pooled estimates of continuous and proportional data with 95% confidence intervals. RESULTS: Among all patients with IBD, the pooled estimates were 16.4% for absenteeism, 35.9% for presenteeism, 39.4% for overall work impairment, and 46.0% for non-work activity impairment. Indirect costs from overall work impairment were 5131.09 euros/patient/year. Only two-thirds of IBD patients were employed, and one in three lost their jobs due to IBD. Among those employed, 39.5% report sick days, 21.3% report work disability, and 12.3% receive disability pensions. Most studies demonstrate clinically meaningful improvements in work productivity with medical and/or surgical therapies. CONCLUSION: Persons with IBD experience significant work impairment and associated indirect costs. This highlights the need for appropriate workplace accommodations and timely medical therapy to alleviate the burden of disease and improve work outcomes.

Inflammatory Bowel Disease and Breastfeeding: A Narrative Review.

Inflammatory bowel disease (IBD) frequently affects women of childbearing age who may consider breastfeeding. Although breastfeeding has numerous benefits, there remain concerns regarding the safety of breastfeeding among women with IBD. Breastfeeding is important in developing the immune system of infants and has been shown to protect against the development of IBD. The risk of developing an increase in disease activity postpartum is the same regardless of breastfeeding status. Most IBD medications are also considered safe in breastfeeding and have no major risks to infants. Despite this, breastfeeding rates remain low among women with IBD, mostly due to concerns about the safety of IBD therapy with breastfeeding. Many women self-discontinue their IBD medications to breastfeed, and there is often uncertainty among health professionals to make recommendations about therapy. Dedicated IBD clinics can greatly support mothers during pregnancy and breastfeeding periods to enhance their knowledge, optimize their medication adherence, and improve their postpartum outcomes. This review aims to provide the most recent evidence-based literature regarding the safety of breastfeeding in women with IBD and the current recommendations about medical therapies with breastfeeding.

The literature supports breastfeeding as a generally safe and beneficial practice for mothers with inflammatory bowel disease, though misconceptions around the safety of this practice persist. Multidisciplinary care models are essential for improving outcomes for women with inflammatory bowel disease who are breastfeeding.

Histological Remission Placebo Rates in Ulcerative Colitis Trials: A Systematic Review and Meta-analysis.

BACKGROUND: High histologic remission rates have been reported with placebos in randomized controlled trials (RCTs) evaluating ulcerative colitis (UC) therapies and have varied based on trial designs. We performed a systematic review and meta-analysis to quantify placebo histological remission rates and identify factors influencing those rates. METHODS: MEDLINE, EMBASE, and the Cochrane library were searched from inception of the databases until December 2021. We included placebo-controlled RCTs of adult patients with UC treated with aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. We pooled estimates using a random-effects model and performed subgroup analysis and meta-regression to evaluate the effect of different covariates on placebo rates. RESULTS: Thirty-three studies (30 induction and 3 maintenance) were included. The overall placebo histological remission rate was 15.7% (95% confidence interval, 12.9%-19%) across all 33 studies. High heterogeneity was observed among studies with I2 = 62.10%. The pooled estimate of histological remission was 15.8% in induction studies and 14.5% in maintenance studies. Subgroup analysis revealed statistically significant differences in placebo rates when accounting for background medications, the intervention drug class, and disease severity (P = .041, .025, and .025, respectively). There was no statistical difference between induction vs maintenance studies or between different histological scales (P = .771, and .075, respectively). CONCLUSIONS: Placebo histological remission rates range from 13% to 19% in UC RCTs, but studies are highly heterogeneous. Factors found to influence placebo rates include presence of background medications, the drug used, and the disease severity. These observations inform future trial designs to minimize placebo rates and reduce heterogeneity.

High histological remission rates have been reported with placebos in ulcerative colitis randomized control trials. This review aims to quantify placebo histological remission rates and identify factors influencing those rates to improve future trial designs.

The Effectiveness of Indigenous Knowledge-Based Lifestyle Interventions in Preventing Obesity and Type 2 Diabetes Mellitus in Indigenous Children in Canada: A Systematic Review.

Background: Indigenous children in Canada have high rates of obesity and type 2 diabetes mellitus (T2DM). Culturally appropriate interventions, guided by an Indigenous knowledge-based view of health, are crucial to target these conditions. The objective of this systematic review was to assess the impact of indigenous Knowledge-based lifestyle interventions on the prevention of obesity and T2DM in Indigenous children in Canada. Methods: Database searches were conducted from inception until February 22, 2022. The main outcomes were changes in Body Mass Index (BMI) z-score and the development of T2DM. The other outcomes included adiposity, metabolic, and lifestyle determinants of health. The GRADE approach was used to assess confidence in the evidence. Results: Four non-randomized controlled trials (non-RCTs) and six uncontrolled studies were identified. Peer-led interventions led to a reduction in BMI z-score and waist circumference. GRADE assessment revealed very low quality of evidence due to a lack of randomization and small sample sizes. There were no diabetes-specific reported programs. Conclusion: Limited evidence from non-randomized studies suggest that peer-led indigenous Knowledge-based lifestyle interventions improve BMI z-score and central adiposity. There is a need for community-owned and adequately powered randomized studies for interventions that aim to treat and prevent obesity and T2DM in Indigenous children in Canada. Systematic Review Registration: PROSPERO CRD42017072781.

The Impact of Patients' Primary Language on Inpatient Gastrointestinal Bleeding Outcomes.

BACKGROUND: The impact of English proficiency on gastrointestinal bleeding (GIB) outcomes remains unclear. In this analysis, we compare inpatient GIB outcomes between patients with English as their primary language (EPL) and those with a primary language other than English (PLOE). METHODS: Using the 2019 State Inpatient Databases for New Jersey, Maryland, and Michigan, we created an analysis cohort of GIB hospitalizations using International Classification of Diseases, 10th Revision codes. Patients were stratified by primary language (EPL vs PLOE) and type of bleeding (variceal upper GI bleeding [VUGIB], nonvariceal upper GI bleeding [NVUGIB], and lower GI bleeding (LGIB)]. Regression analyses were used to compare mortality, 30-day readmissions, and length of stay. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported. P < 0.05 was considered statistically significant. RESULTS: In the cohort, 5.5%-10% of the patients spoke a primary language other than English. Endoscopy utilization was lower among patients with PLOE vs EPL for NVUGIB (17.2% vs 21.2%, P < 0.001) and LGIB (26.3% vs 29.2%, P = 0.027). Patients with PLOE had higher odds of dying of VUGIB (aOR 1.45, 95% CI 1.16-2.48) and LGIB (aOR 1.71, 95% CI 1.22-2.12). Patients with PLOE were also more likely to be readmitted after NVUGIB (aOR 1.75, 95% CI 1.64-1.81). However, after controlling for the percentage of patients with PLOE discharged from each hospital, the disparities in mortality and readmissions were no longer detected. DISCUSSION: Disparities exist in GIB outcomes among patients with PLOE, but these gaps narrow at hospitals with higher percentages of patients with PLOE. Cultural and linguistic competence may improve outcomes in this vulnerable group.

Creating Health Equity in Cancer Screening: Developing Outreach Strategies for Under-Screened Populations through Community Engagement.

Inequities in cancer screening were identified in Calgary, AB, by correlating low screening participation with higher material deprivation. This initiative sought to understand awareness of and barriers to breast, cervical and colorectal cancer screening to inform the co-design and implementation of an outreach strategy to increase screening awareness. Online focus groups with community members (n = 69) identified five themes, and interviews with community health workers (n = 21) identified four themes. The engagement phase led to a multi-component outreach strategy including a multilingual video series, a media campaign leveraging partner channels and a health worker information package with resources to assist with hosting community-based education sessions.

Prospective evaluation of lipid management following acute coronary syndrome in Saudi Arabia.

OBJECTIVES: To evaluate LDL-C control in patients within 6 months after hospitalization for ACS in Saudi Arabia. METHODS: This multicenter, prospective, observational registry evaluates LDL-C control in patients within 6 months after hospitalization for ACS in Saudi Arabia between December 2017 and October 2019. The study aimed at recruiting 170 patients and data were collected retrospectively at baseline and prospectively at 2 subsequent visits. RESULTS: 201 patients were included at baseline, 193 completed the 3-month visit and 186 completed the 6-month visit. Post-ACS, virtually all patients were prescribed high-intensity statins and LDL-C levels decreased consistently. However, at LDL-C target assessment, 57.1% of patients still had LDL-C levels >55 mg/dL, while 62.6% of patients had achieved LDL-C level decrease >50%. The composite milestone of LDL-C decrease >50% and LDL-C levels <55 mg/dL was met by 20.6% of study patients. Importantly, 37% of patients did not have LDL-C reading post-ACS and the primary outcome was only valuable for 126 out of 201 patients (63%). CONCLUSION: Levels and decrease of LDL-C from baseline achieved in this study are suboptimal, according to updated 2019 ESC/EAS guidelines. While statins were prescribed to all patients post-ACS, the recommended add-on treatments were largely overlooked. Gaps in dyslipidemia management linger, despite clear updated guidelines.

Vaccines for all: A formative evaluation of a multistakeholder community-engaged COVID-19 vaccine outreach clinic for migrant communities.

Background: Racialized, low-income, and migrant populations experience persistent barriers to vaccines against COVID-19. These communities in East and Northeast Calgary were disproportionately impacted by COVID-19, yet faced vaccine access barriers. Diverse multi-stakeholder coalitions and community partnerships can improve vaccine outreach strategies, but how stakeholders perceive these models is unknown. Methods: We conducted a formative evaluation of a low-barrier, community-engaged vaccine outreach clinic in Calgary, Alberta, Canada, on June 5-6, 2021. We delivered an online post-clinic survey to clinic stakeholders, to assess whether the clinic achieved its collectively derived pre-specified goals (effective, efficient, patient-centered, and safe), to asses whether the clinic model was scalable, and to solicit improvement recommendations. Survey responses were analyzed using descriptive statistics and thematic analysis. Results: Overall, 166/195 (85%) stakeholders responded. The majority were from non-healthcare positions (59%), between 30 and 49 years of age (87/136; 64%), and self-identified as racialized individuals (96/136; 71%). Respondents felt the clinic was effective (99.2%), efficient (96.9%), patient-centered (92.3%), and safe (90.8%), and that the outreach model was scalable 94.6% (123/130). There were no differences across stakeholder categories. The open-ended survey responses supported the scale responses. Improvement suggestions describe increased time for clinic planning and promotion, more multilingual staff, and further efforts to reduce accessibility barriers, such as priority check-in for people with disabilities. Conclusion: Diverse stakeholders almost universally felt that this community-engaged COVID-19 vaccine outreach clinic achieved its goals and was scalable. These findings support the value of community-engaged outreach to improve vaccine equity among other marginalized newcomer communities.

A nationwide study of liver disease hospitalizations during the coronavirus pandemic in the United States.

BACKGROUND AND AIM: The impact of the Coronavirus disease-2019 (COVID-19) pandemic on patients with liver disease is not well described at the population level in the United States. We used the largest, nationwide inpatient dataset to describe inpatient liver disease outcomes in the United States during the first year of the pandemic (2020) using 2018 and 2019 as comparator years. METHODS: Using the National Inpatient Sample (2018-2020), we explored year-to-year and 2020 month-to-month trends in hospitalizations, length of stay, and inpatient mortality for liver-related complications including cirrhosis, alcohol-associated liver disease (ALD) and alcoholic hepatitis using regression modeling. We reported relative change (RC) in the study period. RESULTS: Decompensated cirrhosis hospitalizations decreased in 2020 compared with 2019 (RC: -2.7%, P < 0.001) while all-cause mortality increased by 15.5% (P < 0.001). Hospitalizations for ALD increased compared with pre-pandemic years (RC: 9.2%, P < 0.001) with a corresponding increase in mortality in 2020 (RC 25.2%, P = 0.002). We observed an increase in liver transplant surgery mortality during the peak months of the pandemic. Importantly, mortality from COVID-19 was higher among patients with decompensated cirrhosis (adjusted odds ratio [OR] 1.72, 95% confidence interval [CI] [1.53-1.94]), Native Americans (OR 1.76, 95% CI [1.53-2.02]), and patients from lower socioeconomic groups. CONCLUSIONS: Cirrhosis hospitalizations decreased in 2020 compared with pre-pandemic years but were associated with higher all-cause mortality rates particularly in the peak months of the COVID-19 pandemic. In-hospital COVID-19 mortality was higher among Native Americans, patients with decompensated cirrhosis, chronic illnesses, and those from lower socioeconomic groups.

Acute Pancreatitis as a First Presentation of Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a rare necrotizing antineutrophil cytoplasmic antibody-associated vasculitis characterized by inflammation in small-sized arteries. Gastrointestinal involvement is exceedingly rare in GPA. Here, we present a case of recurrent acute pancreatitis as the initial presentation of GPA. The diagnosis was made based on radiological and pathological findings of acute pancreatitis in conjunction with positive anti-PR3 antibody which is strongly associated with GPA. Systemic vasculitides are rare but important to consider in cases of idiopathic acute pancreatitis. Early diagnosis and therapy allow for high rates of remission and improved survival rates.

Environmental Pollutants Are Associated With Irritable Bowel Syndrome in a Commercially Insured Cohort of California Residents.

BACKGROUND AND AIMS: Prior studies have linked environmental pollutants with gastrointestinal (GI) diseases. Here, we quantify the relationships between 7 pollutants and the zip code-level incidence of irritable bowel syndrome (IBS), functional dyspepsia, inflammatory bowel diseases (IBDs), and eosinophilic esophagitis (EoE) in California. METHODS: Claims in Optum's Clinformatics Data Mart were linked with environmental exposures in California, derived from CalEnviroScreen 3.0. We identified adult patients with new diagnoses of each GI disease, and estimated claims-derived, zip code-level disease incidence rates. Two study periods were considered: 2009-2014 (International Classification of Diseases-Ninth Revision era) and 2016-2019 (International Classification of Diseases-Tenth Revision [ICD-10] era). Multivariable negative binomial regression models were used to test associations between 7 pollutants (ozone, particulate matter <2.5 µm [PM2.5], diesel emissions, drinking water contaminants, pesticides, toxic releases from industrial facilities, traffic density) and zip code-level incidence of the GI diseases along with a negative control outcome, adjusting for numerous potential confounders. RESULTS: Zip code-level IBS incidence was associated with PM2.5 (P < .001 in both eras) and airborne toxic releases from facilities (P < .001 in both eras). An increase of 1 µg/m3 in PM2.5 or 1% in toxic releases translates to an increase in the IBS incidence rate of about 0.02 cases per 100 person-years. Traffic density and drinking water contaminant exposures were also associated with increasing IBS incidence, but these associations were not significant in both eras. Similarly, exposure to PM2.5, drinking water contaminants and airborne toxic releases from facilities were associated with functional dyspepsia incidence, though not in both eras. No significant associations were noted between pollutants and IBD or EoE incidence. CONCLUSION: Exposure to PM2.5 and airborne toxic releases from facilities are associated with higher IBS incidence among a cohort of commercially insured Californians. Environmental pollutant exposure was not associated with the incidence of IBDs and EoE in this cohort.

Impact of CDKN2A/B, MTAP, and TERT Genetic Alterations on Survival in IDH Wild Type Glioblastomas.

PURPOSE: Poor outcomes in IDH wild-type (IDHwt) glioblastomas indicate the need to determine which genetic alterations can indicate poor survival and guidance of patient specific treatment options. We sought to identify the genetic alterations in these patients that predict for survival when adjusting particularly for treatments and other genetic alterations. METHODS: A cohort of 167 patients with pathologically confirmed IDHwt glioblastomas treated at our institution was retrospectively reviewed. Next generation sequencing was performed for each patient to determine tumor genetic alterations. Multivariable cox proportional hazards analysis for overall survival (OS) was performed to control for patient variables. RESULTS: CDKN2A, CDKN2B, and MTAP deletion predict for worse OS independently of other genetic alterations and patient characteristics (hazard ratio [HR] 2.192, p = 0.0017). Patients with CDKN2A copy loss (HR 2.963, p = 0.0037) or TERT mutated (HR 2.815, p = 0.0008) glioblastomas exhibited significant associations between radiation dose and OS, while CDKN2A and TERT wild type patients did not. CDKN2A deleted patients with NF1 mutations had worse OS (HR 1.990, p = 0.0540), while CDKN2A wild type patients had improved OS (HR 0.229, p = 0.0723). Patients with TERT mutated glioblastomas who were treated with radiation doses < 45 Gy (HR 3.019, p = 0.0010) but not those treated with ≥ 45 Gy exhibited worse OS compared to those without TERT mutations. CONCLUSION: In IDHwt glioblastomas, CDKN2A, CDKN2B, and MTAP predict for poor prognosis. TERT and CDKN2A mutations are associated with worse survival only when treated with lower radiation doses, thus potentially providing a genetic marker that can inform clinicians on proper dose-fractionation schemes.

Neutrophilia and post-radiation thrombocytopenia predict for poor prognosis in radiation-treated glioma patients.

Introduction: Poor outcomes in glioma patients indicate a need to determine prognostic indicators of survival to better guide patient specific treatment options. While preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been suggested as prognostic systemic inflammation markers, the impact of post-radiation changes in these cell types is unclear. We sought to identify which hematologic cell measurements before, during, or after radiation predicted for patient survival. Methods: A cohort of 182 patients with pathologically confirmed gliomas treated at our institution was retrospectively reviewed. Patient blood samples were collected within one month before, during, or within 3 months after radiation for quantification of hematologic cell counts, for which failure patterns were evaluated. Multivariable cox proportional hazards analysis for overall survival (OS) and progression-free survival (PFS) was performed to control for patient variables. Results: Multivariable analysis identified pre-radiation NLR > 4.0 (Hazard ratio = 1.847, p = 0.0039) and neutrophilia prior to (Hazard ratio = 1.706, p = 0.0185), during (Hazard ratio = 1.641, p = 0.0277), or after (Hazard ratio = 1.517, p = 0.0879) radiation as significant predictors of worse OS, with similar results for PFS. Post-radiation PLR > 200 (Hazard ratio = 0.587, p = 0.0062) and a percent increase in platelets after radiation (Hazard ratio = 0.387, p = 0.0077) were also associated with improved OS. Patients receiving more than 15 fractions of radiation exhibited greater post-radiation decreases in neutrophil and platelet counts than those receiving fewer. Patients receiving dexamethasone during radiation exhibited greater increases in neutrophil counts than those not receiving steroids. Lymphopenia, changes in lymphocyte counts, monocytosis, MLR, and changes in monocyte counts did not impact patient survival. Conclusion: Neutrophilia at any time interval surrounding radiotherapy, pre-radiation NLR, and post-radiation thrombocytopenia, but not lymphocytes or monocytes, are predictors of poor patient survival in glioma patients.

EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation.

The epidermal growth factor receptor (EGFR) is a prime oncogene that is frequently amplified in glioblastomas. Here we demonstrate a new tumour-suppressive function of EGFR in EGFR-amplified glioblastomas regulated by EGFR ligands. Constitutive EGFR signalling promotes invasion via activation of a TAB1-TAK1-NF-κB-EMP1 pathway, resulting in large tumours and decreased survival in orthotopic models. Ligand-activated EGFR promotes proliferation and surprisingly suppresses invasion by upregulating BIN3, which inhibits a DOCK7-regulated Rho GTPase pathway, resulting in small hyperproliferating non-invasive tumours and improved survival. Data from The Cancer Genome Atlas reveal that in EGFR-amplified glioblastomas, a low level of EGFR ligands confers a worse prognosis, whereas a high level of EGFR ligands confers an improved prognosis. Thus, increased EGFR ligand levels shift the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastomas by suppressing invasion. The tumour-suppressive function of EGFR can be activated therapeutically using tofacitinib, which suppresses invasion by increasing EGFR ligand levels and upregulating BIN3.

Pure White Cell Aplasia and Immune Thrombocytopenia after Thymoma Resection: A Case Report and Review of the Literature.

We report a case of pure white cell aplasia (PWCA) postthymoma resection in a 74-year-old male presenting with a 2-week history of fevers, night sweats, and severe febrile neutropenia. His pure white cell aplasia was treated with intravenous immunoglobulin (IVIg), granulocyte colony-stimulating factor (G-CSF), prednisone, and cyclosporine with a mixed response. He also developed immune thrombocytopenia, which responded well to a short course of eltrombopag. With continued cyclosporine treatment, his platelet counts were stable after stopping eltrombopag. The patient's cyclosporine treatment was complicated by renal failure, resulting in cessation of cyclosporine. His PWCA and immune thrombocytopenia significantly worsened after stopping cyclosporine, and unfortunately, he died from multiorgan failure and sepsis.