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1.
BMJ Case Rep ; 17(5)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729658

RESUMO

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.


Assuntos
Neoplasias Ósseas , Ependimoma , Neoplasias Pulmonares , Neoplasias Pleurais , Humanos , Masculino , Ependimoma/secundário , Ependimoma/patologia , Ependimoma/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pleurais/secundário , Neoplasias Pleurais/patologia , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Ósseas/secundário , Metástase Linfática/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/diagnóstico por imagem
2.
Pancreas ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696443

RESUMO

OBJECTIVES: To study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC). 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, pancreas enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching of patients with EPI vs. patients without an EPI diagnosis. Adjusted odds ratio (aOR) and hazard ratios (aHR) with 95% confidence intervals were reported. RESULTS: The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years at diagnosis. After propensity score matching, PDAC risk among patients with EPI was twice as high compared to patients without EPI (AHR 1.97, 95% confidence interval [CI] 1.66-2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (aOR: 4.25, 95% CI 2.99-6.04). Only 58% (n = 13, 390) of patients with EPI received PERT with a mean treatment duration of 921 days. No difference was observed in PDAC risk between patients with EPI treated with PERT vs. those that did not receive 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 many of these patients with EPI were not on PERT. PERT did not appear to impact incident PDAC risk after an EPI diagnosis.

3.
J Crohns Colitis ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647194

RESUMO

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 5,131.09 euros/patient/year. Only two thirds of IBD patients were employed and 1 in 3 patients 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.

4.
Surg Endosc ; 38(5): 2817-2825, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38594364

RESUMO

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.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Recidiva Local de Neoplasia , Humanos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Ressecção Endoscópica de Mucosa/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/epidemiologia , Resultado do Tratamento , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais , Intervalo Livre de Doença
5.
Inflamm Bowel Dis ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439613

RESUMO

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.

6.
Inflamm Bowel Dis ; 30(1): 125-131, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36753516

RESUMO

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.


Assuntos
Ácido Aminossalicílico , Produtos Biológicos , Colite Ulcerativa , Adulto , Humanos , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Ácido Aminossalicílico/uso terapêutico , Produtos Biológicos/uso terapêutico , Indução de Remissão
7.
Adolesc Health Med Ther ; 14: 175-193, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37790916

RESUMO

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.

8.
Am J Gastroenterol ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37787427

RESUMO

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.

9.
Healthc Q ; 26(2): 17-23, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37572067

RESUMO

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.


Assuntos
Equidade em Saúde , Neoplasias , Humanos , Detecção Precoce de Câncer , Educação em Saúde , Grupos Focais
10.
Saudi Med J ; 44(6): 570-579, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37343983

RESUMO

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.


Assuntos
Síndrome Coronariana Aguda , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Resultado do Tratamento , Estudos Retrospectivos , Síndrome Coronariana Aguda/tratamento farmacológico , LDL-Colesterol , Arábia Saudita
11.
J Migr Health ; 7: 100188, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37007284

RESUMO

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.

12.
J Gastroenterol Hepatol ; 38(7): 1148-1157, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36882309

RESUMO

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.


Assuntos
COVID-19 , Hepatopatias Alcoólicas , Humanos , Estados Unidos/epidemiologia , Pandemias , COVID-19/epidemiologia , COVID-19/complicações , Hospitalização , Cirrose Hepática/complicações , Hepatopatias Alcoólicas/complicações
13.
ACG Case Rep J ; 10(2): e00986, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36788786

RESUMO

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.

14.
Clin Gastroenterol Hepatol ; 21(6): 1617-1626.e9, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36202347

RESUMO

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.


Assuntos
Água Potável , Dispepsia , Poluentes Ambientais , Doenças Inflamatórias Intestinais , Síndrome do Intestino Irritável , Adulto , Humanos , Poluentes Ambientais/toxicidade , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/etiologia , Exposição Ambiental/efeitos adversos , Material Particulado , Doenças Inflamatórias Intestinais/epidemiologia , California/epidemiologia
15.
Discov Oncol ; 13(1): 126, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380219

RESUMO

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.

16.
Front Oncol ; 12: 1000280, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158642

RESUMO

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.

17.
Nat Cell Biol ; 24(8): 1291-1305, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35915159

RESUMO

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.


Assuntos
Glioblastoma , Proteínas dos Microfilamentos/metabolismo , Linhagem Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glioblastoma/metabolismo , Humanos , Ligantes , Oncogenes/genética , Regulação para Cima
18.
Case Rep Hematol ; 2022: 8271069, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360458

RESUMO

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.

19.
Clin Neurol Neurosurg ; 209: 106909, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34500342

RESUMO

BACKGROUND: Previous studies have shown improved post-surgical outcomes in patients who travel farther for glioblastoma treatment. This study investigates socioeconomic and facility factors that may influence this relationship. METHODS: Overall survival was calculated and compared by distance to treatment facility using univariate and multivariate survival models. The analysis was stratified by facility type, income quartile and insurance status and the association re-evaluated. Kaplan-Meier survival curves were created to analyze the relationship between overall survival and distance group. RESULTS: Individuals who traveled less than 5 miles to treatment had the shortest overall survival (11.8 months), while those who traveled greater than 50 miles had the longest survival (12.9 months). Stratification by income quartile failed to demonstrate an association between distance traveled and survival for those making less than $63,000 (adjusted hazard ratio range: 0.94-1.01). There was no association between survival and distance traveled for patients treated at a community cancer center, comprehensive community cancer center or an integrated network cancer program (adjusted hazard ratio range: 0.86-1.04). CONCLUSION: Financial strain, rather than distance traveled to treatment, may be associated with glioblastoma survival.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Acessibilidade aos Serviços de Saúde , Classe Social , Idoso , Feminino , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Socioeconômicos , Fatores de Tempo , Viagem
20.
J Neurol Sci ; 427: 117538, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34146775

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a very common adverse event for astrocytoma patients, but validation of proposed risk biomarkers has been elusive. We examine whether the status of the isocitrate dehydrogenase (IDH) gene is a risk factor for the development of venous thromboembolism (VTE) in astrocytoma patients. METHODS: We conducted a retrospective chart review of 282 astrocytoma patients enrolled in the PROACTIVE (Prospective Assessment of Correlative Biomarker) study at MD Anderson Cancer Center (MDACC) from 9/1/2000 until 12/31/2013. RESULTS: We identified 282 astrocytoma patients consisting of 49 IDH mutant astrocytomas and 233 IDH wildtype astrocytomas. Glioblastoma was the initial histopathologic diagnosis in 30 (61.2%) of the IDH mutated astrocytomas compared to 227(97.4%) of the IDH wild type astrocytomas. VTE was identified in 52 (18.4%) of patients. VTE was diagnosed in 7 (14.3%) of the IDH mutated astrocytomas compared to 45(19.3%) of the IDH wild type astrocytoma s (p = 0.4094). Median time to VTE from diagnosis was 2.71 months. Median time to VTE from diagnosis was 2.6 months for IDH mutated astrocytomas compared to 3.06 months for the IDH wild type astrocytomas (p = 0.8663). CONCLUSIONS: IDH gene status did not appear as a significant risk factor for the development of venous thromboembolism (VTE) in our cohort of astrocytoma patients. Further research into potential biomarkers for VTE may be warranted.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Isocitrato Desidrogenase , Tromboembolia Venosa , Astrocitoma/complicações , Astrocitoma/genética , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/genética , Humanos , Isocitrato Desidrogenase/genética , Mutação , Estudos Prospectivos , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/genética
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