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1.
N Engl J Med ; 388(23): 2159-2170, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-36972022

RESUMO

BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. RESULTS: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. CONCLUSIONS: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Feminino , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Reparo de Erro de Pareamento de DNA , Método Duplo-Cego , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
2.
J Nutr ; 154(1): 26-40, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37918675

RESUMO

BACKGROUND: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds that may provide cardiometabolic benefits. OBJECTIVES: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored. METHODS: For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with 2 servings of salmon per week for 2 5-wk periods. CHIs were assessed, and fasting plasma was collected pre- and postintervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to postintervention and associations with changes in CHIs. RESULTS: Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (false discovery rate <0.05). Increases in 2 annotated salmon FSCs and 2 metabolites were associated with improvements in CHIs, including total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. CONCLUSIONS: A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for the discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health. The trials supporting this work were registered at NCT02573129 (Mediterranean-style diet intervention) and NCT05500976 (ongoing clinical trial).


Assuntos
Doenças Cardiovasculares , Dieta Mediterrânea , Humanos , Animais , Salmão , Alimentos Marinhos , Colesterol , Biomarcadores , Doenças Cardiovasculares/prevenção & controle , Dieta
3.
Dig Dis Sci ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850506

RESUMO

BACKGROUND: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped. AIMS: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data. METHODS: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample. RESULTS: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively. CONCLUSIONS: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.

4.
Am J Emerg Med ; 80: 230.e3-230.e4, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677910

RESUMO

Acute abdominal pain is a very common chief complaint in the pediatric population, accounting for 5-10% of emergency department (ED) visits. Etiology differentiation is determined by complete history and physical examination, basic laboratory studies, and a variety of imaging study options. In this case report, we present an 8-year-old female with an unusual etiology of acute lower abdominal pain. She presented with tachycardia, hypertension, and bilateral lower quadrant abdominal tenderness without peritonitis. Laboratory studies were unremarkable and appendix ultrasound was indeterminate. CT with contrast revealed right ovarian vein thrombosis. Hematology evaluation did not reveal hypercoagulability. She was discharged on rivaroxaban, which was discontinued after a 3 month course and negative follow-up MRI. Ovarian vein thrombosis (OVT) most commonly develops in the peripartum time frame, with an estimated 20%-40% of cases not related to pregnancies. However, patients with nonpregnancy related OVT were determined to be significantly older than patients with pregnancy related OVT. This case report demonstrates the youngest documented case of OVT. This patient was not in the peripartum period and did not have any identifiable risk factors. Given this unprovoked OVT in a pediatric patient, in patients presenting with abdominal pain with unspecified etiology, advanced imaging studies may be helpful in establishing a diagnosis.


Assuntos
Dor Abdominal , Ovário , Trombose Venosa , Humanos , Feminino , Criança , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico , Ovário/irrigação sanguínea , Ovário/diagnóstico por imagem , Dor Abdominal/etiologia , Tomografia Computadorizada por Raios X , Rivaroxabana/uso terapêutico , Inibidores do Fator Xa/uso terapêutico
5.
Ann Neurol ; 91(3): 424-435, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34984729

RESUMO

OBJECTIVE: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. METHODS: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. RESULTS: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36-60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = -2.35 to -1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = -2.14 to -1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = -1.80 to -1.18). INTERPRETATION: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424-435.


Assuntos
Cognição/fisiologia , Estimulação Encefálica Profunda/métodos , Glucosilceramidase/genética , Heterozigoto , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos , Doença de Parkinson/genética , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia
6.
Am J Emerg Med ; 69: 219.e1-219.e2, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37164785

RESUMO

Alcohol intoxication is a common ingestion in pediatrics with close to 10,000 reports to poison control centers annually. Hypoglycemia, neurological depression (ataxia, coma, nystagmus, etc.) and unstable vitals (hypothermia, hypotension, bradycardia, and respiratory depression) are common presentations. The patient is a 3 month old female who was brought into the Emergency Department (ED) for one day of decreased oral intake and inconsolability. Vital signs were reassuring. Physical exam revealed gaze preference to the right with inability to look left, dysconjugate gaze, and hypotonia. Work-up including CT of the head, and urinalysis was unremarkable. Urine drug screen was found to be positive for ethanol with follow up serum ethanol at 162 mg/dL. With conservative management the patient returned to her baseline. On follow-up with her pediatrician, it was elicited that the mother inadvertently used a water bottle of vodka to mix the patient's formula. This case adds to the paucity of literature of abnormal presentations of alcohol intoxication in an infant.


Assuntos
Intoxicação Alcoólica , Etanol , Humanos , Lactente , Criança , Feminino , Intoxicação Alcoólica/complicações , Intoxicação Alcoólica/diagnóstico , Coma , Bebidas Alcoólicas , Mães
7.
J Emerg Nurs ; 49(2): 210-221, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36411149

RESUMO

INTRODUCTION: To understand the experiences of emergency nurses who have returned to work after parental leave, specifically relating to the return to work transition, work-life balance, work engagement, and opportunities to continue human milk expression. METHODS: Nurses (N = 19) were recruited from 5 emergency departments within 1 hospital system in the United States Midwest. Nurses (n = 11) were eligible to participate in a one-on-one interview if they had returned from parental leave within 6 months of the interview date. Nurses (n = 8) were eligible to participate in a focus group if they had returned from parental leave within 2 years of the interview date. Interviews were structured and data collection concluded when researchers believed data saturation was reached. Interviews were audio recorded and transcribed verbatim. Data were analyzed using Braun and Clarke's qualitative thematic analysis 6-phase framework. RESULTS: Three major themes from the data were identified: (1) work engagement, (2) lactation, and (3) childcare. Work engagement was broken down into the subthemes: lack of communication, perceived engagement expectations, and actual engagement. Lactation was broken down into the subthemes: the act of pumping, lactation breaks, and lactation rooms. The coronavirus disease 2019 pandemic impact on return-to-work is described under each major theme. DISCUSSION: Our findings provide insight into the unique challenges and experiences of nurses navigating parental leave and return-to-work in the emergency department. Strategies such as provision of managerial check-ins, return to work reorientation, lactation break coverage, enhanced supplementary lactation support, and leadership-provided accommodation may lighten the burden of these challenges and improve the returning nurse's job satisfaction.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Feminino , Humanos , Retorno ao Trabalho , Licença Parental , Pais , Pesquisa Qualitativa
8.
Gynecol Oncol ; 166(3): 465-470, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35781163

RESUMO

OBJECTIVE: The objective of this study was to compare the rate of groin recurrence among women undergoing superficial or deep inguinal lymph node dissections in suspected early-stage vulvar carcinoma. Secondary objectives included comparison of overall survival and post-operative morbidity between the study groups. METHODS: A retrospective cohort of 233 patients with squamous cell carcinoma (SCC) of the vulva who underwent an inguinal lymph node dissection at two major academic institutions from 1999 to 2017 were analyzed. Demographic, surgical, recurrence, survival, and post-operative morbidity data were collected for 233 patients, resulting in a total of 400 groin node dissections analyzed. RESULTS: Rates of overall primary recurrence of disease between superficial and deep inguinal LND (42.5 vs. 39.8%, p = 0.70) and rates of inguinal recurrence (3.4 vs. 8.3%, p = 0.16) were similar. Overall rates of postoperative morbidity were significantly higher in the cohort undergoing deep LND (70.3% vs 44.3%, p < 0.01). Rates of lymphedema (42.4 vs 15.9%, p < 0.01), readmission (26.3 vs 6.8%, p < 0.01), and infection (40.7 vs 14.8%, p < 0.01) were all significantly higher among patients undergoing deep LND. There was no significant difference noted in overall survival between the study groups when adjusting for stage and age (HR 1.08, p = 0.84). CONCLUSION: Superficial inguinal LND had no significant difference in rate of recurrence or overall survival when compared to deep inguinal LND in patients with vulvar SCC. Those who received a deep LND had a significant increase in overall morbidity, including lymphedema, readmission, and infection. For patients who cannot undergo or fail sentinel lymph node mapping, a superficial inguinal lymph node dissection may have similar outcomes in recurrence and overall survival with a reduction in overall morbidity as compared to a complete, or deep, lymph node dissection.


Assuntos
Carcinoma de Células Escamosas , Linfedema , Neoplasias Vulvares , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Linfedema/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgia
9.
J Nerv Ment Dis ; 210(7): 486-489, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35766541

RESUMO

ABSTRACT: Leave passes provide authorized leave for hospitalized patients from a psychiatric inpatient unit. Although providing day passes was once a relatively common practice, there are relatively few data describing their safety and efficacy. This descriptive study examines the use of leave passes in an adult inpatient unit at a university hospital between 2017 and 2021, with attention to reasons for granting the day pass, duration, and outcome of the pass. During the study period, 10 patients with primary psychotic or mood disorders received 12 passes for housing coordination, COVID-19 vaccination, or major family events. There were no fatalities or abscondments. One patient experienced severe agitation and engaged in nonsuicidal self-injurious behavior. A second patient showed mild, redirectable psychomotor agitation upon return to the unit. The remaining 10 passes were uneventful. Our findings support the view that patients with diverse diagnoses can safely be provided leave from an inpatient setting with adequate planning and support, yielding a low incidence of adverse events.


Assuntos
COVID-19 , Psiquiatria , Adulto , Vacinas contra COVID-19 , Humanos , Pacientes Internados , Estudos Retrospectivos
10.
Res Nurs Health ; 45(4): 477-487, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35411623

RESUMO

In the context of a global pandemic, the need for reliable analysis of qualitative data in healthcare has never been more pressing. Open-ended questions are a feasible way for both researchers and organizational stakeholders to gain deeper insight into complex situations when timely research is needed. However, the interpretation of brief, textual responses can prove problematic. Both manual and automated/semiautomated methods of coding qualitative data have been associated with errors and costly temporal delays. Data obtained from the qualitative analysis of open-ended questions have been questioned for lacking robust insights. The present article introduces an innovative, manual, team-based method of analyzing responses to open-ended survey questions. This method was developed and implemented at the outset of the COVID-19 pandemic to understand the needs of nurses and their perceptions of organizational strategies that were implemented to address pandemic-related challenges. This framework utilizes a dedicated project management structure, general purpose software for data collection and analysis, frame-of-reference training designed for an interdisciplinary team of coders, and data analysis procedures that align with qualitative content analysis procedures. In concert, these techniques empower researchd team members with varying backgrounds and disparate levels of experience to provide unique human insights to data analysis procedures, refine the coding process, and support the abstraction of meaningful themes that were used to prioritize organizational strategies and further support nurses as the pandemic progressed.


Assuntos
COVID-19 , Pandemias , Humanos , Pesquisa Qualitativa , Pesquisadores , Inquéritos e Questionários
11.
J Biol Chem ; 295(49): 16529-16544, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-32934006

RESUMO

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR-one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)-have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.


Assuntos
Membrana Celular/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Ativação do Canal Iônico , Microscopia de Fluorescência , Aminofenóis/farmacologia , Animais , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Regulador de Condutância Transmembrana em Fibrose Cística/química , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Deleção de Genes , Humanos , Processamento de Imagem Assistida por Computador , Ativação do Canal Iônico/efeitos dos fármacos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mutação de Sentido Incorreto , Estrutura Terciária de Proteína , Quinolonas/farmacologia , Ratos , Temperatura , Proteína Vermelha Fluorescente
12.
Support Care Cancer ; 29(10): 5729-5739, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33728487

RESUMO

PURPOSE: Evidence documents the role of modifiable lifestyle behaviors in optimizing physical and mental health outcomes for survivors of cancer. Fruit and vegetable consumption is one such behavior, and understanding survivor sensory perceptions of produce can inform interventions aimed at improving dietary patterns. The objective of this study was to assess the sensory perceptions of survivors of cancer and their caregivers when asked to evaluate garden-harvested and grocery-purchased produce. METHODS: Participants enrolled in a garden-based biobehavioral intervention and their caregivers (n=32) were invited to participate in a sensory evaluation of four produce types: tangerine cherry tomatoes, green cabbage, green beans, and green bell peppers. Samples were coded and distributed in a random fashion, and participants completed validated sensory surveys (preference, liking/acceptability, and discrimination) for each type of produce. RESULTS: Upon initial blinded evaluation, a significant preference for grocery-purchased produce was noted for green cabbage, green beans, and green bell peppers but not tomatoes (all p<0.05). After self-labeling, however, participants reported a preference for perceived garden-harvested produce (all p≤0.001) even when incorrectly labeled. Liking/acceptability scores were significantly higher among self-labeled garden-harvested versus self-labeled grocery-purchased for all types of produce (all p≤0.001). These data reveal survivors of cancer and their caregivers perceive garden-harvested produce as superior to grocery-purchased, though were unable to accurately identify the two sources based upon sensory factors such as taste, smell, and texture alone when blinded for three of the four types of produce. CONCLUSION: Findings indicate future interventions should address perceptions of produce to facilitate improvements in consumption in these vulnerable individuals.


Assuntos
Cuidadores , Neoplasias , Frutas , Humanos , Percepção , Sobreviventes , Verduras
13.
J Obstet Gynaecol Res ; 47(3): 1082-1089, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33559303

RESUMO

OBJECTIVES: The primary objective was to evaluate the impact of a multimodal perioperative pain regimen on length of hospital stay for patients undergoing laparotomy with a gynecologic oncologist. METHODS: We compared 52 patients who underwent laparotomy with a gynecologic oncologist at a single institution between 2017 and 2018, after implementation of a multimodal perioperative pain regimen, to a historic cohort of 94 patients (2016-2017). The multimodal pain regimen included pre- and post-operative administration of oral acetaminophen, gabapentin, and celecoxib, in addition to standard narcotics and optional epidural analgesia. Demographic, surgical, and post-operative data were collected. RESULTS: On multivariable analysis, bowel resection, stage, surgery length, age, and cohort group were retained as significant independent predictors of length of stay. Patients undergoing laparotomy prior to the pain protocol had a length of stay 1.26 times longer than patients during the post-implementation period (p < 0.01). For complex surgical patients, this translated into a reduction in length of hospital stay of 1.73 days. There was a significant reduction in pain scale score on post-operative day zero from 5 to 3 (p = 0.02) and a non-significant overall reduction of post-operative morphine equivalents, with similar adverse outcomes. CONCLUSION: Implementation of a multimodal perioperative pain regimen in patients undergoing gynecologic oncology laparotomy was associated with a significant reduction of length of hospital stay and improved patient-perceived pain, even in the absence of a complete Enhanced Recovery After Surgery (ERAS) protocol.


Assuntos
Laparotomia , Dor Pós-Operatória , Analgésicos Opioides , Feminino , Procedimentos Cirúrgicos em Ginecologia , Hospitais , Humanos , Tempo de Internação , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos
14.
Int J Mol Sci ; 22(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34298872

RESUMO

Connexins can assemble into either gap junctions (between two cells) or hemichannels (from one cell to the extracellular space) and mediate cell-to-cell signalling. A subset of connexins (Cx26, Cx30, Cx32) are directly sensitive to CO2 and fluctuations in the level within a physiological range affect their open probability, and thus, change cell conductance. These connexins are primarily found on astrocytes or oligodendrocytes, where increased CO2 leads to ATP release, which acts on P2X and P2Y receptors of neighbouring neurons and changes excitability. CO2-sensitive hemichannels are also found on developing cortical neurons, where they play a role in producing spontaneous neuronal activity. It is plausible that the transient opening of hemichannels allows cation influx, leading to depolarisation. Recently, we have shown that dopaminergic neurons in the substantia nigra and GABAergic neurons in the VTA also express Cx26 hemichannels. An increase in the level of CO2 results in hemichannel opening, increasing whole-cell conductance, and decreasing neuronal excitability. We found that the expression of Cx26 in the dopaminergic neurons in the substantia nigra at P7-10 is transferred to glial cells by P17-21, displaying a shift from being inhibitory (to neuronal activity) in young mice, to potentially excitatory (via ATP release). Thus, Cx26 hemichannels could have three modes of signalling (release of ATP, excitatory flickering open and shut and inhibitory shunting) depending on where they are expressed (neurons or glia) and the stage of development.


Assuntos
Dióxido de Carbono/metabolismo , Conexinas/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Animais , Astrócitos/metabolismo , Comunicação Celular/fisiologia , Humanos
15.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298918

RESUMO

The gold standard for classification of neurodegenerative diseases is postmortem histopathology; however, the diagnostic odyssey of this case challenges such a clinicopathologic model. We evaluated a 60-year-old woman with a 7-year history of a progressive dystonia-ataxia syndrome with supranuclear gaze palsy, suspected to represent Niemann-Pick disease Type C. Postmortem evaluation unexpectedly demonstrated neurodegeneration with 4-repeat tau deposition in a distribution diagnostic of progressive supranuclear palsy (PSP). Whole-exome sequencing revealed a new heterozygous variant in TGM6, associated with spinocerebellar ataxia type 35 (SCA35). This novel TGM6 variant reduced transglutaminase activity in vitro, suggesting it was pathogenic. This case could be interpreted as expanding: (1) the PSP phenotype to include a spinocerebellar variant; (2) SCA35 as a tau proteinopathy; or (3) TGM6 as a novel genetic variant underlying a SCA35 phenotype with PSP pathology. None of these interpretations seem adequate. We instead hypothesize that impairment in the crosslinking of tau by the TGM6-encoded transglutaminase enzyme may compromise tau functionally and structurally, leading to its aggregation in a pattern currently classified as PSP. The lessons from this case study encourage a reassessment of our clinicopathology-based nosology.


Assuntos
Proteínas tau/genética , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Fenótipo , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/patologia , Paralisia Supranuclear Progressiva/genética , Paralisia Supranuclear Progressiva/patologia , Transglutaminases/genética
16.
Clin Obstet Gynecol ; 63(1): 3-11, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31815773

RESUMO

Although rates of cervical cancer in the United States have been declining due to vaccination and screening efforts, it remains the fourth most common cancer in women worldwide and is still far from being eradicated, even in developed nations. This review discusses recent developments in cervical cancer treatment and reviews the literature supporting recent practice changes encompassing staging, surgical management, radiation, chemotherapy, targeted agents including immunotherapy, and imaging.


Assuntos
Detecção Precoce de Câncer/métodos , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Feminino , Humanos , Imunoterapia/métodos , Programas de Rastreamento/estatística & dados numéricos , Estadiamento de Neoplasias/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia
17.
J Low Genit Tract Dis ; 24(4): 358-362, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32881787

RESUMO

OBJECTIVES: The aims of the study were to identify whether obese women are less appropriately screened for cervical cancer before diagnosis and to explore related cancer outcomes. METHODS: We retrospectively reviewed all cervical cancer patients at a single institution between 1986 and 2016 and collected demographic information including age, cancer stage, body mass index (BMI), screening information, and cancer outcomes. Morbid obesity was defined as BMI of 40 kg/m or greater, obesity as BMI of 30 to less than 40 kg/m, and nonobese as BMI of less than 30 kg/m. χ, Fisher exact, and Wilcoxon rank sum tests were used to compare variables between BMI categories. Cox regression models were used to evaluate recurrence-free survival and overall survival (OS). RESULTS: A total of 1,080 patients were reviewed, of whom 311 (29.4%) were obese and 107 (10.1%) morbidly obese. A significant association between BMI and cytology screening was evidenced with morbidly obese women having the highest incorrect rate (64.4%), followed by obese (51.5%) and nonobese women (46.0%, p < .01). There was no significant difference in presence of symptoms at presentation (p = .12) or stage (p = .06) between BMI categories. In multivariable analysis of cancer outcomes, higher BMI was associated with worse OS (p < .01) with a hazard ratio of 1.25 (95% CI = 0.92-1.69) for obese women and hazard ratio 2.27 (95% CI = 1.56-3.31) for morbidly obese women relative to normal weight but recurrence-free survival did not differ between BMI groups (p = .07). CONCLUSIONS: Our study strengthens evidence that obese and morbidly obese women have disproportionate inappropriate screening before cervical cancer diagnosis, and morbidly obese women have worse OS than their counterparts.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Obesidade , Neoplasias do Colo do Útero/diagnóstico , Negro ou Afro-Americano , Índice de Massa Corporal , Carcinoma/patologia , Feminino , Humanos , Iowa , Obesidade/psicologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
18.
J Minim Invasive Gynecol ; 26(6): 1088-1094, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30389582

RESUMO

STUDY OBJECTIVE: To compare the parenting and career patterns of female and male gynecology subspecialists. DESIGN: Cross-sectional survey study (Canadian Task Force classification II-3). SETTING: Survey administered electronically in February 2015 to physician members of the Society of Gynecologic Oncology, the American Society for Reproductive Medicine, and the American Urogynecologic Society. PARTICIPANTS: All physician members of the 3 national gynecology subspecialty organizations listed above. MEASUREMENTS AND MAIN RESULTS: There were 75 questions in 4 domains: demographics, mentoring issues, work-life balance, and caregiving responsibilities. Data were analyzed for survey sampling weights. Six hundred seventy-seven physicians completed the survey, 62% of whom were women (n = 420; 20.2% response rate). Sixty-four percent were aged 36 to 55 years. Eighty-two percent of respondents had at least 1 child, and men had more children than women (42% of men had 3 or more children compared with 20% of women, p <.0001). Thirty-seven percent of women reported that career plans affected the decision to become a parent somewhat or very much compared with 23% of men (p = .0006). Eighty-three percent of women believed career affected the timing of becoming a parent somewhat or very much compared with 48% of men (p <.0001). In addition, 76% of female physicians perceived that having children decreased their academic productivity compared with 54% of male physicians (p <.0001). Most men and women believed having children had no effect or increased their clinical performance (76% and 65%, respectively), but this was significantly lower in women (p = .01). CONCLUSION: Female gynecology subspecialists perceive that their career impacted decisions on parenting more frequently than their male counterparts. They were also more likely than men to report that having children had a negative impact on academic and, to a lesser extent, clinical performance. Increased support for combining childbirth and parenting with training and academic careers is needed.


Assuntos
Ginecologia/estatística & dados numéricos , Poder Familiar , Médicos/estatística & dados numéricos , Equilíbrio Trabalho-Vida/estatística & dados numéricos , Carga de Trabalho/estatística & dados numéricos , Atividades Cotidianas/psicologia , Adulto , Criança , Estudos Transversais , Eficiência , Feminino , Humanos , Masculino , Casamento/estatística & dados numéricos , Pessoa de Meia-Idade , Poder Familiar/psicologia , Médicos/psicologia , Fatores Sexuais , Inquéritos e Questionários , Estados Unidos/epidemiologia , Carga de Trabalho/psicologia
20.
Can J Infect Dis Med Microbiol ; 2018: 1905360, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29623137

RESUMO

BACKGROUND: Anesthesia machines are known reservoirs of bacterial species, potentially contributing to healthcare associated infections (HAIs). An inexpensive, disposable, nonpermeable, transparent anesthesia machine wrap (AMW) may reduce microbial contamination of the anesthesia machine. This study quantified the density and diversity of bacterial species found on anesthesia machines after terminal cleaning and between cases during actual anesthesia care to assess the impact of the AMW. We hypothesized reduced bioburden with the use of the AMW. METHODS: In a prospective, experimental research design, the AMW was used in 11 surgical cases (intervention group) and not used in 11 control surgical cases. Cases were consecutively assigned to general surgical operating rooms. Seven frequently touched and difficult to disinfect "hot spots" were cultured on each machine preceding and following each case. The density and diversity of cultured colony forming units (CFUs) between the covered and uncovered machines were compared using Wilcoxon signed-rank test and Student's t-tests. RESULTS: There was a statistically significant reduction in CFU density and diversity when the AMW was employed. CONCLUSION: The protective effect of the AMW during regular anesthetic care provides a reliable and low-cost method to minimize the transmission of pathogens across patients and potentially reduces HAIs.

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