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1.
Am J Physiol Renal Physiol ; 327(4): F655-F666, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39205660

RESUMO

Renal transporters (cotransporters, channels, and claudins) mediate homeostasis of fluids and electrolytes and are targets of hormonal and therapeutic regulators. Assessing renal transporter abundance with antibody probes by immunoblotting is an essential tool for mechanistic studies. Although journals require authors to demonstrate antibody specificity, there are no consensus guidelines for kidney sample preparation leading to lab-to-lab variability in immunoblot results. In this study, we determined the impact of sample preparation, specifically freeze-thawed (Frozen) versus freshly processed (Fresh) kidneys (female and male rats and mice) on immunoblot signal detection of 15 renal transporters and the impact of protease inhibitors during homogenization. In female Sprague-Dawley rat kidneys homogenized with aprotinin, Na2EDTA, PMSF, and phosphatase inhibitors, immunodetection signals were ∼50% lower in Frozen versus Fresh samples for most transporters. Inclusion of additional inhibitors (Roche cOmplete Protease Inhibitor, "+") only partially increased transporter immunoblot signals to near Fresh levels. In male Sprague-Dawley rats, immunoblot signal density was lower in Frozen+ versus Fresh+ despite additional inhibitors. In C57BL/6 male mice, immunoblot signals from proximal tubule transporters were lower in Frozen versus Fresh by ∼25-50% and greater in Frozen+. In contrast, immunodetection signal was equivalent in female Frozen+ versus female Fresh+ for claudin 2, villin, AQP1, NKCC2, NCC, ENaCß, ENaCÉ£, claudin 7, AQP2, NKAα1, and NKAß1. Thus, kidney sample preparation variables, including freeze-thaw and protease inhibition, have substantial transporter-specific effects on quantification of renal transporter abundance by immunoblot. These findings underscore the critical importance of assessing and reporting the impact of sample preparation protocols on transporter recovery to ensure robust rigor and reproducibility. NEW & NOTEWORTHY Freeze-thawing kidneys before homogenization is widely accepted in renal research. This study demonstrates that if kidneys are freeze-thawed just once before homogenization, immunoblot signals are reduced in a transporter-specific manner in rats and mice dependent on sex and that immunoblot signals can be partially recovered by adding additional protease inhibitors. These findings underscore the critical importance of assessing the impact of sample preparation, including freeze-thaw versus fresh, to ensure robust rigor and reproducibility.


Assuntos
Rim , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Animais , Feminino , Masculino , Rim/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Congelamento , Ratos , Camundongos , Inibidores de Proteases/farmacologia
2.
Ann Surg ; 279(5): 850-856, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37641957

RESUMO

OBJECTIVE: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT). BACKGROUND: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers. METHODS: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT. RESULTS: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers. CONCLUSIONS: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers.


Assuntos
Neoplasias , Qualidade de Vida , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Avaliação de Resultados da Assistência ao Paciente
3.
Haematologica ; 109(6): 1677-1688, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38832423

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy is a new and effective treatment for patients with hematologic malignancies. Clinical responses to CAR T cells in leukemia, lymphoma, and multiple myeloma have provided strong evidence of the antitumor activity of these cells. In patients with refractory or relapsed B-cell acute lymphoblastic leukemia (ALL), the infusion of autologous anti-CD19 CAR T cells is rapidly gaining standard-of-care status and might eventually be incorporated into frontline treatment. In T-ALL, however, leukemic cells generally lack surface molecules recognized by established CAR, such as CD19 and CD22. Such deficiency is particularly important, as outcome is dismal for patients with T-ALL that is refractory to standard chemotherapy and/or hematopoietic stem cell transplant. Recently, CAR T-cell technologies directed against T-cell malignancies have been developed and are beginning to be tested clinically. The main technical obstacles stem from the fact that malignant and normal T cells share most surface antigens. Therefore, CAR T cells directed against T-ALL targets might be susceptible to self-elimination during manufacturing and/or have suboptimal activity after infusion. Moreover, removing leukemic cells that might be present in the cell source used for CAR T-cell manufacturing might be problematic. Finally, reconstitution of T cells and natural killer cells after CAR T-cell infusion might be impaired. In this article, we discuss potential targets for CAR T-cell therapy of T-ALL with an emphasis on CD7, and review CAR configurations as well as early clinical results.


Assuntos
Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/imunologia , Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/transplante , Animais , Resultado do Tratamento , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia
4.
Lung ; 202(3): 281-289, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38713421

RESUMO

INTRODUCTION: Immunoglobulins play a vital role in host immune response and in the pathogenesis of conditions like asthma. Therapeutic agents such as monoclonal antibodies target specific elements of the asthmatic inflammatory cascade. Decisions to utilize these medications are often based on systemic inflammatory profiling without direct insight into the airway inflammatory profile. We sought to investigate the relationship between immunoglobulin and cytokine profiles in the airway and systemic immune compartments of adult asthmatics. METHODS: Blood sampling and bronchoscopy with bronchoalveolar lavage (BAL) were performed in 76 well-defined adult asthmatics. Antibody and cytokine profiles were measured in both BAL and serum using ELISA and quantibody arrays. RESULTS: There was no relationship between BAL and serum levels of IgE. This is of significance in an asthma population. For some analytes, correlation analysis was significant (P < 0.05) indicating representativeness of our cohort and experimental setup in those cases. Nevertheless, the predictive power (r2) of the BAL-to-serum comparisons was mostly low except for TNF-α (r2 = 0.73) when assuming a simple (linear) relationship. CONCLUSION: This study highlights the importance of sample site when investigating the roles of immunoglobulins and cytokines in disease pathogenesis and suggests that both localized and systemic immune responses are at play. The prescription of asthma monoclonal therapy is generally based on systemic evaluation of cytokine and immunoglobulin levels. Our research suggests that this approach may not fully reflect the pathophysiology of the disease and may provide insight into why some patients respond to these targeted therapies while others do not.


Assuntos
Asma , Líquido da Lavagem Broncoalveolar , Broncoscopia , Citocinas , Imunoglobulina E , Humanos , Asma/imunologia , Asma/tratamento farmacológico , Asma/sangue , Adulto , Masculino , Feminino , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Pessoa de Meia-Idade , Citocinas/sangue , Imunoglobulina E/sangue , Adulto Jovem , Imunoglobulinas/sangue , Idoso
5.
Opt Express ; 31(12): 19818-19827, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381389

RESUMO

Stimulated Brillouin scattering is an emerging technique for probing the mechanical properties of biological samples. However, the nonlinear process requires high optical intensities to generate sufficient signal-to-noise ratio (SNR). Here, we show that the SNR of stimulated Brillouin scattering can exceed that of spontaneous Brillouin scattering with the same average power levels suitable for biological samples. We verify the theoretical prediction by developing a novel scheme using low duty cycle, nanosecond pulses for the pump and probe. A shot noise-limited SNR over 1000 was measured with a total average power of 10 mW for 2 ms or 50 mW for 200 µs integration on water samples. High-resolution maps of Brillouin frequency shift, linewidth, and gain amplitude from cells in vitro are obtained with a spectral acquisition time of 20 ms. Our results demonstrate the superior SNR of pulsed stimulated Brillouin over spontaneous Brillouin microscopy.

6.
J Asthma ; 60(2): 393-402, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35748303

RESUMO

Objective: Information on the preferences of people with asthma for support in managing a flare-up can inform service design which may facilitate appropriate help-seeking. To date, little is known about support preferences for managing a flare-up. The aim of this study was to develop and pilot a discrete choice experiment (DCE) to elicit the preferences of people with asthma with regards to support in managing a flare-up.Methods: Steps in developing the DCE included identification and selection of attributes and levels of the support services, construction of choice tasks, experimental design, construction of DCE instrument, and pretest (n=16) and pilot (n=38) studies of the DCE instrument. A multinomial logit model was used to examine the strength and direction of the six attributes in the pilot study.Results: Our results indicate that from a patient perspective, having a healthcare professional that listens to their concerns was the most valued attribute of support in asthma flare-up management. The other features of support valued by participants were timely access to consultation, a healthcare professional with knowledge of their patient history, a specialist doctor and face-to-face communication. Having a written action plan was the least valued attribute.Conclusions: Our findings suggest patient preference for a model of support in managing their symptoms which includes timely, face-to-face access to a healthcare professional that knows them and listens to their concerns. The findings of the pilot study need to be verified with a larger sample and using models to account for preference heterogeneity.


Assuntos
Asma , Humanos , Projetos Piloto , Comportamento de Escolha , Modelos Logísticos , Pessoal de Saúde , Preferência do Paciente
7.
Cancer ; 128(7): 1483-1492, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34994403

RESUMO

BACKGROUND: Segmentectomy is increasingly used for parenchyma sparing anatomical resection for small stage I non-small cell lung cancer (NSCLC). This study characterizes the national outcomes for lymph node assessment and perioperative outcomes of segmentectomy for clinical stage I NSCLC by robotic-assisted surgery (RATS), video-assisted thoracoscopic surgery (VATS), and open thoracotomy approach. METHODS: A retrospective cohort study was conducted of patients who underwent segmentectomy for clinical stage I NSCLC captured in the national Society of Thoracic Surgeons General Thoracic Surgery Database between years 2012 and 2018. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Lymph node (LN) staging and 30-day outcomes were compared by approach. RESULTS: A total of 3680 patients (VATS 61.9%, RATS 20%, open 18%) underwent segmentectomy. The IPTW adjusted rate of pathologic LN upstaging (pN1/pN2) was 6.2% (RATS 6.3%, VATS 5.6%, open 8.6%; P = .05). On multivariate analysis, there was no differences in pN1/N2 upstaging between RATS (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.44-1.49) or VATS (OR, 0.96; 95% CI, 0.57-1.63) with open segmentectomy. The RATS and VATS approach was associated with fewer postoperative events (RATS 31.3%, VATS 28.8%, open 38.3%; P < .001) and shorter length of stay (RATS 4.3 days, VATS 4.4 days, open 5.2 days; P < .001) as compared with thoracotomy. RATS segmentectomy-specific complications included a higher rate of pneumothorax after chest tube removal and discharge with chest tube. Major complications were lower after RATS and VATS as compared with open segmentectomy (RATS 5.9%, VATS 4.5%, open 7.2%; P = .028). CONCLUSIONS: Segmentectomy by VATS and robotic approach resulted in similar high rates of lymph node upstaging as a global marker of the quality of lymph node dissection and were associated with lower overall morbidity and shorter length of stay as compared with open thoracotomy. These national outcomes may serve as benchmarks for future comparative studies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Benchmarking , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos
8.
Pediatr Allergy Immunol ; 33(12): e13892, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36564884

RESUMO

Early life dietary patterns and timely maturation of mucosa-associated microbial communities are important factors influencing immune development and for establishing robust immune tolerance networks. Microbial fermentation of dietary components in vivo generates a vast array of molecules, some of which are integral components of the molecular circuitry that regulates immune and metabolic functions. These in turn protect against aberrant inflammatory processes and promote effector immune responses that quickly eliminate pathogens. Multiple studies suggest that changes in dietary habits, altered microbiome composition, and microbial metabolism are associated with asthma risk and disease severity. While it remains unclear whether these microbiome alterations are a cause or consequence of dysregulated immune responses, there is significant potential for using diet in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health. In this article, we will summarize our knowledge to date on the role of dietary patterns and microbiome activities on immune responses within the airways. Given the malleability of the human microbiome, its integration into the immune system, and its responsiveness to diet, this makes it a highly attractive target for therapeutic and nutritional intervention in children with asthma.


Assuntos
Asma , Microbioma Gastrointestinal , Microbiota , Criança , Humanos , Asma/etiologia , Dieta , Sistema Imunitário
9.
Respiration ; 101(10): 931-938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36037803

RESUMO

BACKGROUND: The development of single-use flexible or disposable bronchoscopes (SUFBs) has accelerated in recent years, with the reduced risk of infectious transmission and reduced need for endoscopy staffing particularly advantageous in the COVID-19 pandemic era. OBJECTIVE: The objective of this study was to assess the performance of a novel single-use bronchoscope in an academic quaternary referral centre with on-site interventional pulmonology programme. METHODS: With ethical approval in a quaternary referral centre, we prospectively collected data on sequential bronchoscopy procedures using The Surgical Company Broncoflex© range of SUFBs. Data collected included demographic, procedural, scope performance, user satisfaction, and complication parameters in a tertiary bronchoscopy service. RESULTS: 139 procedures were performed by five pulmonology faculty from January to July 2021. The majority were carried out for infection (45%) and malignancy (32%). Most were performed in the endoscopy suite and 8% were COVID positive or suspected. Most procedures reported the highest score in satisfaction (85%) with technical limitations reported in 15% (predominately related to scope suction or inadequate image quality) reverting to a reusable scope in 2.8 %. CONCLUSION: In our subset of patients in a bronchoscopy unit, SUFBs are safe, and both routine and advanced bronchoscopy procedures can be performed with high satisfaction reported.


Assuntos
Broncoscopia , COVID-19 , Broncoscópios , Humanos , Pandemias , Encaminhamento e Consulta
10.
J Surg Oncol ; 124(4): 521-528, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34061359

RESUMO

BACKGROUND: Racial disparities currently exist for the utilization rate of esophagectomy for Black patients with operable esophageal carcinoma. METHODS: A total of 37 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Database were analyzed between 2004 and 2016. A multivariable-adjusted logistic regression model was used to evaluate differences in the odds ratio of esophagectomy not being recommended based on race. Kaplan-Meier curves and log-rank tests were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting (IPTW) was used to balance baseline differences in patient demographics. RESULTS: After IPTW adjustment, we identified 30 552 White patients and 3529 Black patients with clinical stage I-III esophageal carcinoma. Black patients had three times greater odds of not being recommended for esophagectomy (odds ratio: 3.03, 95% confidence interval: 2.67-3.43, p < 0.0001) compared to White patients. Black patients demonstrated significantly worse 3- and 5-year overall survival rates compared to White patients (log-rank p < 0.0001). CONCLUSION: Black patients with clinical stage I-III esophageal cancer were significantly less likely to be recommended for esophagectomy even after adjusting for baseline demographic covariates compared to White patients.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias Esofágicas/cirurgia , Esofagectomia/estatística & dados numéricos , Pessoal de Saúde/psicologia , Disparidades em Assistência à Saúde , Padrões de Prática Médica/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/patologia , Esofagectomia/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
11.
J Surg Oncol ; 123(4): 881-890, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33333590

RESUMO

BACKGROUND: Locally advanced esophageal carcinoma is treated with neoadjuvant chemoradiation and esophagectomy. Patients may still experience recurrence and death despite undergoing potentially curative trimodality therapy. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after the completion of trimodality therapy. METHODS: A total of 215 patients with esophageal adenocarcinoma underwent trimodality therapy from September 2010 to April 2018. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts. RESULTS: On multivariate analysis, clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, body mass index, age, and number of lymph nodes removed were predictive variables for overall survival. Clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, age, and positive lymph nodes were significant predictors of RFS in a multivariate model. The nomogram for OS had good predictive ability (Harrell's Concordance index [C-index]: 0.71 [95% confidence interval {CI}: 0.66-0.76]). The nomogram for RFS also performed well (C-index: 0.70 [95% CI: 0.65-0.74]). CONCLUSION: Our nomograms can accurately predict OS and RFS after trimodality therapy and may provide guidance regarding adjuvant therapy and surveillance.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia/mortalidade , Nomogramas , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
12.
Chron Respir Dis ; 18: 14799731211063886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34854787

RESUMO

Motor neuron disease (MND) is a neurodegenerative disorder which leads to progressive muscle weakness including respiratory muscle decline. The introduction of non-invasive ventilation (NIV) has been shown to improve quality of life, survival and slow the rate of pulmonary function decline. A retrospective chart analysis of patients who attended the MND clinic from 2014 to 2019 at a tertiary-referral, academic, teaching hospital was carried out to evaluate if NIV and greater compliance with NIV was associated with improved survival. 111 patients were included. The mean age at diagnosis was 63.8 years and 61.3% were males. 66.7% of our cohort used NIV and of this 66.7%, 44.1% were compliant. There was a significantly longer survival in those who used NIV (p = 0.002) and in those who used NIV optimally (p = 0.02) when both groups were compared to those who did not use NIV. In the bulbar MND group those who were compliant with NIV survived longer than who those who did not use NIV (p = 0.001). We found a significantly longer survival with the use of NIV, the use of NIV optimally and with use of NIV in those with bulbar onset MND compared to those who did not use NIV.


Assuntos
Doença dos Neurônios Motores , Ventilação não Invasiva , Insuficiência Respiratória , Estudos de Coortes , Humanos , Masculino , Doença dos Neurônios Motores/terapia , Qualidade de Vida , Insuficiência Respiratória/terapia , Estudos Retrospectivos
13.
Bioinformatics ; 35(13): 2243-2250, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445488

RESUMO

MOTIVATION: In clinical trials, individuals are matched using demographic criteria, paired and then randomly assigned to treatment and control groups to determine a drug's efficacy. A chief cause for the irreproducibility of results across pilot to Phase-III trials is population stratification bias caused by the uneven distribution of ancestries in the treatment and control groups. RESULTS: Pair Matcher (PaM) addresses stratification bias by optimizing pairing assignments a priori and/or a posteriori to the trial using both genetic and demographic criteria. Using simulated and real datasets, we show that PaM identifies ideal and near-ideal pairs that are more genetically homogeneous than those identified based on competing methods, including the commonly used principal component analysis (PCA). Homogenizing the treatment (or case) and control groups can be expected to improve the accuracy and reproducibility of the trial or genetic study. PaM's ancestral inferences also allow characterizing responders and developing a precision medicine approach to treatment. AVAILABILITY AND IMPLEMENTATION: PaM is freely available via Rhttps://github.com/eelhaik/PAM and a web-interface at http://elhaik-matcher.sheffield.ac.uk/ElhaikLab/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Software , Estudos de Casos e Controles , Análise de Componente Principal , Reprodutibilidade dos Testes
14.
Allergy ; 75(5): 1146-1154, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31605638

RESUMO

BACKGROUND: It is suggested that airway fungi, in particular Aspergillus may impinge on clinical phenotype in asthma. Indeed, the term severe asthma with fungal sensitization (SAFS) has been coined. We aimed to ascertain whether the presence of fungi, in particular Aspergillus fumigatus, in the airway correlated with asthma severity and control. Furthermore, we aimed to determine whether traditional markers of Aspergillus sensitization related to the presence of Aspergillus within the airway. METHODS: Sixty-nine patients characterized by asthma severity (GINA) and level of control (ACQ-7) underwent bronchoscopy and bronchoalveolar lavage (BAL). Serum was assessed for A fumigatus-specific IgE and total IgE. Galactomannan and relevant cytokine levels were assessed in serum, plasma and BAL. BAL was analyzed for the presence of A fumigatus. RESULTS: In BAL, fungi were visible by microscopy in 70% and present by qPCR in 86% of patients, while A fumigatus was detectable by qPCR in 46%. Plasma and BAL IL-4, IL-6, IL-10, IL-13 and TNF-α correlated with BAL fungal presence, while plasma IL-17 correlated with BAL fungal presence. Aspergillus positive BAL correlated with increased plasma and BAL IL-6 and BAL IL-13. There was no relationship between fungal airway presence and steroid dose, asthma severity or control. The presence of Aspergillus within the airway did not relate to serum IgE positivity for Aspergillus. CONCLUSIONS: Fungi were present in a large proportion of our asthmatic patients' airways, but their presence was not predicted by traditional markers of sensitization, nor did it appear to be related to measures of disease severity or control.


Assuntos
Aspergilose Broncopulmonar Alérgica , Asma , Aspergillus fumigatus , Asma/diagnóstico , Líquido da Lavagem Broncoalveolar , Humanos , Imunoglobulina E , Índice de Gravidade de Doença
15.
Surg Endosc ; 34(4): 1696-1703, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31286257

RESUMO

BACKGROUND: Minimally invasive esophagectomy is associated with significant morbidity, which can substantially influence the hospital length of stay for patients. Anastomotic leak is the most devastating complication. Minimizing major postoperative complications can facilitate adherence to a clinical pathway protocol and can decrease hospital length of stay. METHODS: This is a retrospective study of 130 patients who underwent an elective laparoscopic and thoracoscopic Ivor Lewis esophagectomy for esophageal carcinoma between August 2014 and June 2018. A total of 112 patients (86%) underwent neoadjuvant chemoradiation. All of the 130 patients underwent a laparoscopic gastric devascularization procedure a median of 15 days prior to the esophagectomy. The target discharge date was postoperative day number 8. RESULTS: Thirty patients (23.08%) had postoperative complications. Atrial fibrillation (20 patients) [15.38%] was the most frequent complication. Four patients (3.1%) developed an anastomotic leak. There was one postoperative death (0.77%) in the cohort of patients. The median length of stay was 8 days. The mean length of stay for patients without complications was 8 days ± 1.2 days and 12.4 days ± 7.1 days for patients with one or more complications (p = 0.002). CONCLUSION: The development of postoperative complications after minimally invasive Ivor Lewis esophagectomy significantly increases hospital length of stay. Performing the operation with a specialized tandem surgical team and including preoperative ischemic preconditioning of the stomach minimizes overall and anastomotic complications and facilitates on time hospital discharge as defined by a perioperative clinical pathway protocol.


Assuntos
Carcinoma/cirurgia , Procedimentos Clínicos , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Laparoscopia/métodos , Toracoscopia/métodos , Idoso , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Estudos de Coortes , Esofagectomia/efeitos adversos , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Estômago/cirurgia , Toracoscopia/efeitos adversos , Resultado do Tratamento
16.
Surg Endosc ; 33(12): 3880-3888, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31376007

RESUMO

BACKGROUND: Controversy exists as to what constitutes a learning curve to achieve competency, and how the initial learning period of robotic thoracic surgery should be approached. METHODS: We conducted a systematic review of the literature published prior to December 2018 using PubMed/MEDLINE for studies of surgeons adopting the robotic approach for anatomic lung resection or thymectomy. Changes in operating room time and outcomes based on number of cases performed, type of procedure, and existing proficiency with video-assisted thoracoscopic surgery (VATS) were examined. RESULTS: Twelve observational studies were analyzed, including nine studies on robotic lung resection and three studies on thymectomy. All studies showed a reduction in operative time with an increasing number of cases performed. A steep learning curve was described for thymectomy, with a decrease in operating room time in the first 15 cases and a plateau after 15-20 cases. For anatomic lung resection, the number of cases to achieve a plateau in operative time ranged between 15-20 cases and 40-60 cases. All but two studies had at least some VATS experience. Six studies reported on experience of over one hundred cases and showed continued gradual improvements in operating room time. CONCLUSION: The learning curve for robotic thoracic surgery appears to be rapid with most studies indicating the steepest improvement in operating time occurring in the initial 15-20 cases for thymectomy and 20-40 cases for anatomic lung resection. Existing data can guide a standardized robotic curriculum for rapid adaptation, and aid credentialing and quality monitoring for robotic thoracic surgery programs.


Assuntos
Curva de Aprendizado , Pneumonectomia/métodos , Procedimentos Cirúrgicos Robóticos/educação , Timectomia/métodos , Humanos , Duração da Cirurgia
18.
Eur Respir J ; 51(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29301919

RESUMO

In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence.Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis.The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% versus 63%; 95% CI 2.8%-17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%).Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy.


Assuntos
Asma/tratamento farmacológico , Asma/terapia , Biorretroalimentação Psicológica , Adesão à Medicação , Nebulizadores e Vaporizadores , Administração por Inalação , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório , Estudos Prospectivos
19.
Opt Lett ; 43(21): 5467-5470, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30383034

RESUMO

The standard single-mode fiber has been demonstrated as an optomechanical sensor recently to measure the acoustic impedances of surrounding liquids by means of the generation and detection of forward-stimulated Brillouin scattering (FSBS). FSBS allows the mechanical properties of an external material to be probed directly through the interaction of guided light and transverse sound waves that occurs entirely inside the fiber structure. In this technique, having a low-loss interface between the fiber bulk and the external medium is essential for precise measurement; however, it leads to the necessary but impractical removal of the thick polymer fiber coating in most reported methods. Here, we use a commercially available 80-µm-diameter optical fiber coated with a 8-µm-thick polyimide coating layer to measure the acoustic impedances of the surrounding liquids, showing accurate measurement results while retaining the mechanical strength of the fiber.

20.
Opt Lett ; 43(7): 1487-1490, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29601011

RESUMO

Elastic vibrations in subwavelength structures have gained importance recently in fundamental light-matter studies and various optoacoustic applications. Existing techniques have revealed the presence of distinct acoustic resonances inside silica microwires yet remain unable to individually localize them. Here, we locally activate distinct classes of acoustic resonances inside a tapered fiber using a phase-correlation distributed Brillouin method. Experimental results verify the presence of surface and hybrid acoustic waves at distinct fiber locations and demonstrate, to the best of our knowledge, the first distributed surface acoustic wave measurement. This technique is important for understanding properties of optoacoustic interactions and enabling designs of novel optomechanical devices.

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