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1.
Chest ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34384789

RESUMO

BACKGROUND: The landscape of guided bronchoscopy for the sampling of pulmonary parenchymal lesions is evolving rapidly. Shape-sensing robotic-assisted bronchoscopy (ssRAB) recently was introduced as means to allow successful sampling of traditionally challenging lesions. RESEARCH QUESTION: What are the feasibility, diagnostic yield, determinants of diagnostic sampling, and safety of ssRAB in patients with pulmonary lesions? STUDY DESIGN AND METHODS: Data from 131 consecutive ssRAB procedures performed at a US-based cancer center between October 2019 and July 2020 were captured prospectively and analyzed retrospectively. Definitions of diagnostic procedures were based on prior standards. Associations of procedure- and lesion-related factors with diagnostic yield were examined by univariate and multivariate general linear mixed models. RESULTS: A total of 159 pulmonary lesions were targeted during 131 ssRAB procedures. The median lesion size was 1.8 cm, 59.1% of lesions were in the upper lobe, and 66.7% of lesions were beyond a sixth-generation airway. The navigational success rate was 98.7%. The overall diagnostic yield was 81.7%. Lesion size of ≥ 1.8 cm and central location were associated significantly with a diagnostic procedure in the univariate analysis. In the multivariate model, lesions of ≥ 1.8 cm were more likely to be diagnostic compared with lesions < 1.8 cm, after adjusting for lung centrality (OR, 12.22; 95% CI, 1.66-90.10). The sensitivity and negative predictive value of ssRAB for primary thoracic malignancies were 79.8% and 72.4%, respectively. The overall complication rate was 3.0%, and the pneumothorax rate was 1.5%. INTERPRETATION: This study was the first to provide comprehensive evidence regarding the usefulness and diagnostic yield of ssRAB in the sampling of pulmonary parenchymal lesions. ssRAB may represent a significant advancement in the ability to access and sample successfully traditionally challenging pulmonary lesions via the bronchoscopic approach, while maintaining a superb safety profile. Lesion size seems to remain the major predictor of a diagnostic procedure.

2.
Cancers (Basel) ; 13(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34359558

RESUMO

During the last two decades, next-generation sequencing (NGS) has played a key role in enhancing non-small cell lung cancer treatment paradigms through the application of "targeted therapy" in advanced and metastatic disease. The use of specific tyrosine kinase inhibitors in patients with oncogenic driver alterations, such as EGFR, ALK, ROS1, BRAF V600E, MET, and NTRK mutations, among others, has changed treatment approaches and improved outcomes in patients with late-stage disease. Although NGS technology has mostly been used in the setting of systemic therapy to identify targets, response to therapy, and mechanisms of resistance, it has multiple potential applications for patients with earlier-stage disease, as well. In this review, we discuss the emerging role of NGS technologies to better understand tumor biology in patients with non-small cell lung cancer who are undergoing surgery with curative intent. In this patient cohort, we examine tumor heterogeneity, the underlying tumor genomics associated with lung adenocarcinoma subtypes, the prediction of recurrence after complete surgical resection, the use of plasma circulating tumor DNA for detection of early cancers and monitoring for minimal residual disease, the differentiation of separate primaries from intrapulmonary metastases, and the use of NGS to guide induction and adjuvant therapies.

4.
Br J Anaesth ; 127(1): 75-84, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34147159

RESUMO

BACKGROUND: Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and intra-tumoural opioid receptor gene alterations, but no study has investigated whether the tumour genome interacts with opioid exposure to affect survival. We sought to determine whether intraoperative opioid exposure is associated with recurrence-specific survival and overall survival in early-stage lung adenocarcinoma, and whether selected tumour genomics are associated with this relationship. Associations between ketamine and dexmedetomidine and outcomes were also studied. METHODS: Surgical patients (N=740) with pathological stage I-III lung adenocarcinoma and next-generation sequencing data were retrospectively reviewed from a prospectively maintained database. RESULTS: On multivariable analysis, ketamine administration was protective for recurrence-specific survival (hazard ratio = 0.44, 95% confidence interval 0.24-0.80; P=0.007), compared with no adjunct. Higher intraoperative oral morphine milligram equivalents were significantly associated with worse overall survival (hazard ratio=1.09/10 morphine milligram equivalents, 95% confidence interval 1.02-1.17; P=0.010). Significant interaction effects were found between morphine milligram equivalents and fraction genome altered and morphine milligram equivalents and CDKN2A, such that higher fraction genome altered or CDKN2A alterations were associated with worse overall survival at higher morphine milligram equivalents (P=0.044 and P=0.052, respectively). In contrast, alterations in the Wnt (P=0.029) and Hippo (P=0.040) oncogenic pathways were associated with improved recurrence-specific survival at higher morphine milligram equivalents, compared with unaltered pathways. CONCLUSIONS: Intraoperative opioid exposure is associated with worse overall survival, whereas ketamine exposure is associated with improved recurrence-specific survival in patients with early-stage lung adenocarcinoma. This is the first study to investigate tumour-specific genomic interactions with intraoperative opioid administration to modify survival associations.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Analgésicos Opioides/efeitos adversos , Genômica/tendências , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/genética , Adenocarcinoma de Pulmão/mortalidade , Idoso , Analgésicos Opioides/administração & dosagem , Feminino , Humanos , Cuidados Intraoperatórios/efeitos adversos , Cuidados Intraoperatórios/tendências , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida/tendências
5.
Clin Cancer Res ; 27(9): 2604-2612, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33593884

RESUMO

PURPOSE: KRAS G12C is the most common KRAS mutation in primary lung adenocarcinoma. Phase I clinical trials have demonstrated encouraging clinical activity of KRAS G12C inhibitors in the metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features in patients with surgically resected KRAS G12C-mutant lung adenocarcinoma. EXPERIMENTAL DESIGN: Patients who underwent resection of stage I-III lung adenocarcinoma and next-generation sequencing (NGS) were evaluated. Exclusion criteria were receipt of induction therapy, incomplete resection, and low-quality NGS. Mutations were classified as KRAS wild-type (KRAS wt), G12C (KRAS G12C), or non-G12C (KRAS other). DFS was compared between groups using the log-rank test; factors associated with DFS were assessed using Cox regression. Mutual exclusivity and cooccurrence, tumor clonality, and mutational signatures were assessed. RESULTS: In total, 604 patients were included: 374 KRAS wt (62%), 95 KRAS G12C (16%), and 135 KRAS other (22%). Three-year DFS was not different between KRAS-mutant and KRAS wt tumors. However, 3-year DFS was worse in patients with KRAS G12C than KRAS other tumors (log-rank P = 0.029). KRAS G12C tumors had more lymphovascular invasion (51% vs. 37%; P = 0.032) and higher tumor mutation burden [median (interquartile range), 7.0 (5.3-10.8) vs. 6.1 (3.5-9.7); P = 0.021], compared with KRAS other tumors. KRAS G12C mutation was independently associated with worse DFS on multivariable analysis. Our DFS findings were externally validated in an independent The Cancer Genome Atlas cohort. CONCLUSIONS: KRAS G12C mutations are associated with worse DFS after complete resection of stage I-III lung adenocarcinoma. These tumors harbor more aggressive clinicopathologic and genomic features than other KRAS-mutant tumors. We identified a high-risk group for whom KRAS G12C inhibitors may be investigated to improve survival.

6.
Ann Thorac Surg ; 111(3): 1028-1035, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32739257

RESUMO

BACKGROUND: Outcomes after segmentectomy compare favorably with those after lobectomy in patients with stage I non-small cell lung cancer (NSCLC). Whether long-term outcomes vary by segmentectomy location is unclear. We investigated whether disease-free survival (DFS) and overall survival (OS) differ by segmentectomy location after intentional segmentectomy for clinical T1 N0 M0 NSCLC. METHODS: Patients who received intentional segmentectomy for cT1 N0 M0 NSCLC from 2000 to 2018 were reviewed. Patients with prior lung cancer, forced expiratory volume in 1 second of less than 50%, or R1/R2 resection were excluded. Segmentectomy groups were left (L) basilar, L segment 6, L lingula, L trisegment; right (R): basilar (R_Bas), segment 6 (R_S6), and R upper. The 5- and 10-year DFS and OS were estimated using Kaplan-Meier and compared between groups using the log-rank test. Factors associated with DFS and OS were determined using Cox proportional hazards models. RESULTS: In total, 416 patients met the inclusion criteria. Segmentectomy groups differed with regard to surgical approach, mediastinal lymphadenectomy, lymphovascular invasion, tumor histology, margin distance, and adjuvant therapy. Long-term outcomes were worst after R_S6 resection (5-year DFS, 57.6% [95% confidence interval {CI}, 45.7%-72.7%]; OS, 66.3% [95% CI, 54.7%-80.3%]) and best after R_Bas resection (5-year DFS, 77.1% [95% CI, 59.2%-100%]; OS, 79.5% [95% CI, 60.9%-100%]). On multivariable analysis, R_S6 resection was independently associated with DFS vs R_Bas (hazard ratio, 2.89; 95% CI, 1.18-7.08; P = .02) and OS vs R_Bas (hazard ratio, 4.35; 95% CI, 1.61-11.76; P = .004). CONCLUSIONS: Resection of R_S6 is independently associated with worse DFS and OS in patients receiving intentional segmentectomy for cT1 N0 M0 NSCLC and may warrant more extensive resection, complete lymph node dissection, and closer postoperative surveillance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Pontuação de Propensão , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento
7.
J Thorac Oncol ; 15(12): 1844-1856, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32791233

RESUMO

INTRODUCTION: The purpose of the study is to genomically characterize the biology and related therapeutic opportunities of prognostically important predominant histologic subtypes in lung adenocarcinoma (LUAD). METHODS: We identified 604 patients with stage I to III LUAD who underwent complete resection and targeted next-generation sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform. Tumors were classified according to predominant histologic subtype and grouped by architectural grade (lepidic [LEP], acinar or papillary [ACI/PAP], and micropapillary or solid [MIP/SOL]). Associations among clinicopathologic factors, genomic features, mutational signatures, and recurrence were evaluated within subtypes and, when appropriate, quantified using competing-risks regression, with adjustment for pathologic stage and extent of resection. RESULTS: MIP/SOL tumors had higher tumor mutational burden (p < 0.001), fraction of genome altered (p = 0.001), copy number amplifications (p = 0.021), rate of whole-genome doubling (p = 0.008), and number of oncogenic pathways altered ( p < 0.001) as compared with LEP and ACI/PAP tumors. Across all tumors, mutational signatures attributed to APOBEC activity were associated with the highest risk of postresection recurrence: SBS2 (p = 0.021) and SBS13 (p = 0.005). Three oncogenic pathways (p53, Wnt, Myc) were altered with statistical significance in MIP/SOL tumors. Compared with LEP and ACI/PAP tumors, MIP/SOL tumors had a higher frequency of targetable BRAF-V600E mutations (p = 0.046). Among ACI/PAP tumors, alterations in the cell cycle (p < 0.001) and PI3K (p = 0.002) pathways were associated with recurrence; among MIP/SOL tumors, only PI3K alterations were associated with recurrence (p = 0.049). CONCLUSIONS: These results provide the first in-depth assessment of tumor genomic profiling of predominant LUAD histologic subtypes, their associations with recurrence, and their correlation with targetable driver alterations in patients with surgically resected LUAD.


Assuntos
Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Idoso , Feminino , Genômica , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Prognóstico
9.
Orthop J Sports Med ; 6(12): 2325967118794928, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30560139

RESUMO

Background: Despite the increased attention to sports-related concussion, the literature lacks information about the environmental factors that contribute to concussion incidence. Previous investigators have noted a decreased rate of concussion in football games played at higher altitude. Purpose/Hypothesis: The purpose of this study was to investigate whether the protective effects of altitude on concussion rate, as described by previous investigators, were due to acute effects of altitude exposure or chronic adaptations to training at altitude. Our hypothesis was that these protective effects are not attributable to relative cerebral edema that occurs in conditions of altitude-associated hypobaric hypoxia, known as the "slosh effect," but rather result from long-term adaptations to training at altitude. Study Design: Descriptive epidemiology study. Methods: Athletes from the 2012, 2013, 2014, and 2015 National Football League (NFL) seasons were included in this analysis of publicly available data. Concussion rates were subdivided into 4 groups: (1) low-altitude teams playing below 644 feet (low-low), (2) low-altitude teams playing above 644 feet (low-high), (3) high-altitude teams playing below 644 feet (high-low), and (4) high-altitude teams playing above 644 feet (high-high). Results: Away teams had a significantly higher rate of concussion (0.32 concussions per exposure) compared with their home team counterparts (0.27 concussions per exposure; P = .03). Teams training and playing at high altitude had a 28% decreased concussion rate, which was significantly lower compared with concussion incidence rates for overall, low-low, and high-low groups (P < .05). In comparison, teams that trained at altitude but played below 644 feet had the highest rate of concussion, at 0.36 concussions per exposure (P < .05). Conclusion: These data indicate that living and training at altitude may have a protective effect on concussion rate, as evidenced by the significant reduction in the high-high group and the lack of an effect in the low-high group. However, teams from low altitude playing at high altitude did not have a statistically significant reduction in concussion rate. These results show that the slosh theory does not completely explain the effects of altitude on concussion incidence rate in the NFL. Further analyses are needed to investigate the true cause of altitude-induced protection in the NFL.

10.
Cureus ; 9(4): e1139, 2017 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-28484678

RESUMO

BACKGROUND: Postoperative surgical site infection (SSI) is a common complication after spine surgery. Reduction of SSI has many benefits including, but not limited to, the reduced length of stay, readmission rates, and morbidity and mortality. OBJECTIVE: To determine whether an enhanced antibiotic prophylaxis reduced the rate of surgical site infections in spine surgery. METHODS: This is a retrospective observation study which analyzed the incidence of postoperative SSI following a consecutive series of 1,486 cervical, thoracic and lumbar spine operations performed at a single institution by the senior author between the dates of October 2001 to March 2014. Patients with surgeries between October 2001 and November 2005 received a standard institutional antibiotic prophylaxis. Patients between December 2005 and March 2014 underwent an enhanced antibiotic protocol. RESULTS: A total of nine cases met the criteria for SSI. All nine cases were recorded during the initial time period when the standard institutional prophylaxis was used. Further, these cases were only observed under posterior operative approaches. No further cases of SSI were observed after the institution of the enhanced antibiotic prophylaxis (p < 0.0001). This was statistically significant in the cervical and lumbar regions (p < 0.0042 and p < 0.0119, respectively). CONCLUSIONS: Although difficult to predict the incidence of SSI, this study found that the use of an enhanced antibiotic prophylaxis protocol significantly reduced one surgeon's overall rates of surgical site infections after spine surgery.

11.
Int J Colorectal Dis ; 32(5): 753-756, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28091842

RESUMO

BACKGROUND: Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL. PURPOSE: We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL. RESULTS/OUTCOMES: Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas. DISCUSSION: This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.


Assuntos
Carcinoma de Células Escamosas/patologia , Colite Ulcerativa/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Neoplasias Retais/patologia , Reto/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Orthop J Sports Med ; 4(1): 2325967115622621, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26848481

RESUMO

BACKGROUND: In the United States alone, millions of athletes participate in sports with potential for head injury each year. Although poorly understood, possible long-term neurological consequences of repetitive sports-related concussions have received increased recognition and attention in recent years. A better understanding of the risk factors for concussion remains a public health priority. Despite the attention focused on mild traumatic brain injury (mTBI) in football, gaps remain in the understanding of the optimal methodology to determine concussion incidence and position-specific risk factors. PURPOSE: To calculate the rates of concussion in professional football players using established and novel metrics on a group and position-specific basis. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Athletes from the 2012-2013 and 2013-2014 National Football League (NFL) seasons were included in this analysis of publicly available data. Concussion incidence rates were analyzed using established (athlete exposure [AE], game position [GP]) and novel (position play [PP]) metrics cumulatively, by game unit and position type (offensive skill players and linemen, defensive skill players and linemen), and by position. RESULTS: In 480 games, there were 292 concussions, resulting in 0.61 concussions per game (95% CI, 0.54-0.68), 6.61 concussions per 1000 AEs (95% CI, 5.85-7.37), 1.38 concussions per 100 GPs (95% CI, 1.22-1.54), and 0.17 concussions per 1000 PPs (95% CI, 0.15-0.19). Depending on the method of calculation, the relative order of at-risk positions changed. In addition, using the PP metric, offensive skill players had a significantly greater rate of concussion than offensive linemen, defensive skill players, and defensive linemen (P < .05). CONCLUSION: For this study period, concussion incidence by position and unit varied depending on which metric was used. Compared with AE and GP, the PP metric found that the relative risk of concussion for offensive skill players was significantly greater than other position types. The strengths and limitations of various concussion incidence metrics need further evaluation. CLINICAL RELEVANCE: A better understanding of the relative risks of the different positions/units is needed to help athletes, team personnel, and medical staff make optimal player safety decisions and enhance rules and equipment.

13.
J Clin Sleep Med ; 9(11): 1161-4, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24235897

RESUMO

STUDY OBJECTIVES: The current gold-standard method of diagnosing obstructive sleep apnea (OSA) is polysomnography, which can be inefficient. We therefore sought to determine a method to triage patients at risk of OSA, without using subjective data, which are prone to mis-reporting. We hypothesized that acoustic pharyngometry in combination with age, gender, and neck circumference would predict the presence of moderate-to-severe OSA. METHODS: Untreated subjects with suspected OSA were recruited from a local sleep clinic and underwent polysomnography. We also included a control group to verify differences. While seated in an upright position and breathing through the mouth, an acoustic pharyngometer was used to measure the minimal cross-sectional area (MCA) of the upper airway at end-exhalation. RESULTS: Sixty subjects were recruited (35 males, mean age 42 years, range 21-81 years; apnea-hypopnea index (AHI) 33 ± 30 events/h (mean ± standard deviation), Epworth Sleepiness Scale score 11 ± 6, body mass index 34 ± 8 kg/m(2)). In univariate logistic regression, MCA was a significant predictor of mild-no OSA (AHI < 15). A multivariate logistic regression model including MCA, age, gender, and neck circumference significantly predicted AHI < 15, explaining approximately one-third of the total variance (χ(2)(4) = 37, p < 0.01), with only MCA being a significant independent predictor (adjusted odds ratio 54, standard error 130; p < 0.01). CONCLUSIONS: These data suggest that independent of age, gender, and neck size, objective anatomical assessment can significantly differentiate those with mild versus moderate-to-severe OSA in a clinical setting, and may have utility as a component in stratifying risk of OSA.


Assuntos
Pesos e Medidas Corporais/métodos , Faringe/anatomia & histologia , Faringe/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico , Acústica , Adulto , Pesos e Medidas Corporais/estatística & dados numéricos , Feminino , Humanos , Masculino , Razão de Chances , Polissonografia/métodos , Polissonografia/estatística & dados numéricos , Reprodutibilidade dos Testes , Apneia Obstrutiva do Sono/fisiopatologia , Índices de Gravidade do Trauma
14.
Sleep ; 36(2): 281-5, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23372276

RESUMO

STUDY OBJECTIVES: The magnitude of the post-apnea/hypopnea ventilatory overshoot following arousal may perpetuate subsequent respiratory events in obstructive sleep apnea (OSA) patients, potentially contributing to the disorder's severity. As acetazolamide can reduce apnea severity in some patients, we examined the effect of acetazolamide on the ventilatory response to spontaneous arousals in CPAP-treated OSA patients. DESIGN: We assessed the ventilatory response to arousal in OSA patients on therapeutic CPAP before and after administration of acetazolamide for 7 days. SETTING: Sleep research laboratory. PARTICIPANTS: 12 (7M/5F) CPAP-treated OSA patients. INTERVENTIONS: Sustained-release acetazolamide 500 mg by mouth twice daily for one week. MEASUREMENTS AND RESULTS: A blinded investigator identified spontaneous arousals (3-15 s) during NREM sleep. Breath-by-breath measurements of minute ventilation, end-tidal CO(2), tidal volume, expiratory/inspiratory-time, and total breath duration were determined (4-s intervals) 32 s prior and 60 s following each arousal. Acetazolamide significantly increased resting ventilation (7.3 ± 0.2 L/min versus 8.2 ± 0.4 L/min; P < 0.05) and attenuated the percent increase in ventilation following arousal by ~2.5 fold (122.0% ± 4.4% versus 108.7% ± 3.5% pre-arousal level; P < 0.05). There was a positive correlation between the mean increase in ventilatory response to arousal and mean AHI (r(2) = 0.44, P = 0.01). However, absolute peak levels of ventilation following arousal remained unchanged between conditions (8.8 ± 0.4 L/min versus 8.9 ± 0.1 L/min). CONCLUSIONS: Acetazolamide substantially attenuates the increase in ventilation following spontaneous arousal from sleep in OSA patients. This study suggests an additional mechanism by which acetazolamide may contribute to the improvement in ventilatory instability and OSA severity. The data also provide support for reinforcing the importance of ventilatory control in OSA pathogenesis.


Assuntos
Acetazolamida/uso terapêutico , Nível de Alerta/efeitos dos fármacos , Inibidores da Anidrase Carbônica/uso terapêutico , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Apneia Obstrutiva do Sono/tratamento farmacológico , Acetazolamida/administração & dosagem , Administração Oral , Nível de Alerta/fisiologia , Inibidores da Anidrase Carbônica/administração & dosagem , Pressão Positiva Contínua nas Vias Aéreas , Estudos Cross-Over , Preparações de Ação Retardada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Método Simples-Cego , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia
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