Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 70
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Mol Ther ; 31(2): 435-453, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36184851

RESUMO

Treating osteoporosis and associated bone fractures remains challenging for drug development in part due to potential off-target side effects and the requirement for long-term treatment. Here, we identify recombinant adeno-associated virus (rAAV)-mediated gene therapy as a complementary approach to existing osteoporosis therapies, offering long-lasting targeting of multiple targets and/or previously undruggable intracellular non-enzymatic targets. Treatment with a bone-targeted rAAV carrying artificial microRNAs (miRNAs) silenced the expression of WNT antagonists, schnurri-3 (SHN3), and sclerostin (SOST), and enhanced WNT/ß-catenin signaling, osteoblast function, and bone formation. A single systemic administration of rAAVs effectively reversed bone loss in both postmenopausal and senile osteoporosis. Moreover, the healing of bone fracture and critical-sized bone defects was also markedly improved by systemic injection or transplantation of AAV-bound allograft bone to the osteotomy sites. Collectively, our data demonstrate the clinical potential of bone-specific gene silencers to treat skeletal disorders of low bone mass and impaired fracture repair.


Assuntos
Fraturas Ósseas , Osteoporose , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Osteoporose/genética , Osteoporose/terapia , Fraturas Ósseas/genética , Fraturas Ósseas/terapia , Osso e Ossos , Terapia Genética
2.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731827

RESUMO

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 µm as primary pores, 40-70 µm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.


Assuntos
Regeneração Óssea , Tíbia , Alicerces Teciduais , Animais , Cães , Alicerces Teciduais/química , Tíbia/diagnóstico por imagem , Projetos Piloto , Osteogênese , Porosidade , Microtomografia por Raio-X , Durapatita , Transplante Ósseo/métodos , Substitutos Ósseos
3.
Surg Endosc ; 36(8): 6067-6075, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35141775

RESUMO

BACKGROUND: Conversion rates during minimally invasive surgery are generally examined in the limited scope of a particular procedure. However, for a hospital or payor, the cumulative impact of conversions during commonly performed procedures could have a much larger negative effect than what is appreciated by individual surgeons. The aim of this study is to assess open conversion rates during minimally invasive surgery (MIS) across common procedures using laparoscopic/thoracoscopic (LAP/VATS) and robotic-assisted (RAS) approaches. STUDY DESIGN: Retrospective cohort study using the Premier Database on patients who underwent common operations (hysterectomy, lobectomy, right colectomy, benign sigmoidectomy, low anterior resection, inguinal and ventral hernia repair, and partial nephrectomy) between January 2013 and September 2015. ICD-9 and CPT codes were used to define procedures, modality, and conversion. Propensity scores were calculated using patient, hospital, and surgeon characteristics. Propensity-score matched analysis was used to compare conversions between LAP/VATS and RAS for each procedure. RESULTS: A total of 278,520 patients had MIS approaches of the ten operations. Conversion occurred in 5% of patients and was associated with a 1.77 day incremental increase in length of stay and $3441 incremental increase in cost. RAS was associated with a 58.5% lower rate of conversion to open surgery compared to LAP/VATS. CONCLUSION: At a health system or payer level, conversion to open is detrimental not just for the patient and surgeon but also puts a significant strain on hospital resources. Use of RAS was associated with less than half of the conversion rate observed for LAP/VATS.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Colectomia/métodos , Feminino , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Torácica Vídeoassistida/métodos
4.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500635

RESUMO

A new category of commercial bulk fill composite resins (CRs) enables the placement of 4-mm-thick layers as an alternative to the traditional time-consuming incremental technique. The purpose of the present study was to compare the efficiency of the polymerization, adaptation and porosity of two high-viscosity 'sculptable' bulk fill CRs (Filtek™ Bulk Fill (3M™ ESPE, St. Paul, MN, USA) and Tetric EvoCeram® Bulk Fill (Ivoclar Vivadent AG, Schwan, Liechtenstein)) and two low-viscosity 'flowable' bulk fill CRs (SureFil® SDR™ flow (Dentsply Sirona, Charlotte, NC, USA) and Tetric EvoFlow® Bulk Fill (Ivoclar Vivadent AG, Schaan, Liechtenstein)). Cylindrical samples of the bulk fill CRs (4 mm height × 10 mm diameter) were analyzed by Fourier-transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Additionally, occlusal cavities were prepared in twelve extracted human molars and restored with the bulk fill CRs (n = 3 for each CR). The adaptation and porosity of the bulk fill CRs were evaluated by X-ray microcomputed tomography (µCT) with a 3D morphometric analysis, and the adaptation was also analyzed by scanning electron microscopy (SEM) on longitudinal vestibulo-oral sections of the restored teeth. The AFM analysis demonstrated that the surface roughness of the SureFil® SDR™ flow was higher than that of the Tetric EvoFlow® Bulk Fill and that the surface roughness of Filtek™ Bulk Fill was higher than that of Tetric EvoCeram® Bulk Fill. µCT and SEM confirmed that the flowable bulk fill CRs had excellent adaptation to the cavity walls. The 3D morphometric analysis showed the highest and lowest degrees of porosity in Filtek™ Bulk Fill and Tetric EvoFlow® Bulk Fill, respectively. In general, the flowable bulk fill CRs exhibited better adaptation, a higher efficiency of polymerization and lower porosity than the sculptable materials.

5.
J Craniofac Surg ; 30(1): 149-153, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30480634

RESUMO

Hydroxyapatite (HA) is the main mineral component of bone and teeth. HA is often used as a bone substitute and especially in its granular form it is osteoconductive and osseointegrating as shown by many investigations in animals and humans. HA granules are used for filling bone defects, but they have poor handling qualities and retention at the surgical site, leading to graft voids between the granules and bone tissue and resulting in mechanical instability. Furthermore HA implantation is not constantly followed by favorable results, especially when it is carried out for augmentation of the alveolar ridge. This article offers a protocol for bone reconstruction and predictable implant treatment outcomes. We provide a step-by-step description of both the recipient site and composite graft preparations using coralline HA granules (CHAG) and homologous fibrin glue (HFG). In the present study, 20 randomly selected patients (12 women and 8 men) underwent bone regeneration using CHAG-HFG before a dental implant procedure. Radiographic imaging, physical examination, and histological analysis were performed during a 2-year period. Biopsies were obtained at second-stage surgery before implant insertion using a 2.8-mm trephine bur. A morphological study of 20 bioptic human specimens was performed. Our results demonstrate that this surgical protocol for the preparation of the recipient site associated with a mixture of coralline HA granules with homologous fibrin glue provides reliable bone regeneration, thus reducing failures and minimizing risks of postoperative morbidity.


Assuntos
Aumento do Rebordo Alveolar/métodos , Substitutos Ósseos/uso terapêutico , Fosfatos de Cálcio/uso terapêutico , Cerâmica/uso terapêutico , Durapatita/uso terapêutico , Hidroxiapatitas/uso terapêutico , Alicerces Teciduais , Adulto , Regeneração Óssea , Implantes Dentários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osseointegração , Estudos Retrospectivos
6.
Ann Surg ; 267(3): 484-488, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28151801

RESUMO

OBJECTIVE: The aim of this study was to determine the accuracy of clinical staging, to assess survival with surgical resection alone, and to determine factors associated with understaging in patients with esophageal adenocarcinoma thought to have limited local-regional disease. BACKGROUND: Primary surgical resection is the preferred treatment in patients with esophageal adenocarcinoma clinically staged to have limited nodal disease. This approach requires reliable clinical staging. METHODS: A retrospective chart review was performed of all patients who had primary esophagectomy for clinical stage T1-3 N0-1 adenocarcinoma (seventh edition AJCC) from January 2002 to May 2013. Clinical and pathologic stages were compared and overall survival was analyzed. RESULTS: There were 88 patients who met inclusion criteria. Final pathology confirmed appropriate clinical staging (≤T3N1) in 76% of patients (67/88). There were 21 patients who were understaged (>T3N1), and in all cases, understaging was based on the presence of advanced nodal (N2 or N3) disease. Factors independently associated with understaging were the presence of dysphagia, tumor length >3 cm, and poor differentiation. At a median follow-up of 35 months, 63% of all patients (55/88) remain alive. The 5-year survival in correctly staged patients was 67%, compared with 33% for those who were understaged (P < 0.0001). CONCLUSIONS: Modern clinical staging will accurately identify the majority of patients with esophageal adenocarcinoma and limited local-regional disease (≤pT3N1). Survival with surgery alone in correctly staged patients was excellent and unlikely to be improved with neoadjuvant therapy. A combination of dysphagia, poor differentiation, and tumor length >3 cm was associated with understaging in 92% of patients. Patients with these factors are likely to have more advanced disease than clinically suspected and may benefit from neoadjuvant therapy before resection.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/diagnóstico por imagem , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
7.
J Esthet Restor Dent ; 30(3): 187-192, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29349909

RESUMO

The presence of endogenous acids from bacteria acting on a suitable substrate combined with sources of exogenous biocorrosives such as exogenous acids and proteolytic enzymes in areas of stress concentration are hypothesized to lead to the development and progression of cervical and root caries (RC). Quantifying the effects of each of the mechanisms (stress and biocorrosion) is a daunting task to investigate since so many factors are involved at various times in the etiology of noncarious cervical lesions (NCCLs), cervical caries (CC), and RC. Frictional action of the tongue has a cleansing effect and lingual serous saliva, which has a high flow rate buffering capacity from bicarbonates seem to account for the paucity of lingual NCCLs, cervical, and RC in these areas of teeth. Future studies are indicated to determine the effects of stress and biocorrosion and their factors in the etiology of CC and RC. CLINICAL SIGNIFICANCE: This manuscript presents hypothetical and literary information that the combined effects of stress concentration and biocorrosion contribute to the formation as well as progression of cervical and root caries.


Assuntos
Cárie Dentária , Cárie Radicular , Humanos , Saliva
8.
Ann Surg Oncol ; 24(13): 3921-3925, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28975518

RESUMO

BACKGROUND: Intramucosal esophageal adenocarcinoma can be reliably treated endoscopically. Controversy exists about the use of endotherapy versus esophagectomy for submucosal tumors. Increasingly endotherapy is considered for submucosal tumors in part because of the presumed high mortality with esophagectomy and the perceived poor prognosis in patients with nodal disease. This study was designed to assess survival following primary en bloc esophagectomy (EBE) in patients with submucosal esophageal adenocarcinoma (EAC). METHODS: This is a retrospective review of all patients who underwent EBE for submucosal EAC between 1998 and 2015. No patient had neoadjuvant therapy. RESULTS: There were 32 patients (28M/4F; median age 64 years). The median tumor size was 1.5 cm (0.4-8.0), and the median number of resected nodes was 48 (23-85). There was one perioperative death. Lymph node metastases were present in 7 patients (22%). There was one involved node in four patients and 2, 3, and 31 nodes in one patient each. The one N3 patient received adjuvant therapy. The median follow-up was 87 months. Overall survival at 5 and 10 years was 84 and 70% respectively. Disease-specific survival at 10 years was 90%. Eight patients died, but only three deaths (9%) were related to EAC. Disease-specific survival at 10 years in node-positive patients was 71%. CONCLUSIONS: Survival after primary en bloc esophagectomy for submucosal adenocarcinoma was excellent even in node-positive patients. Mortality with esophagectomy was low and far less than the 22% risk of node metastases in patients with submucosal tumor invasion. Esophagectomy should remain the preferred treatment for T1b esophageal adenocarcinoma.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Linfonodos/patologia , Mucosa/patologia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mucosa/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
10.
Surg Endosc ; 30(4): 1310-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26173543

RESUMO

OBJECTIVE: The use of robotic-assisted surgery (RS) has rapidly increased, but public perceptions about RS are largely unknown. The aim of this study was to gain insight into public perceptions about RS, hospitals that have robots, and surgeons that use them. METHODS: A Web-based survey was distributed worldwide. Surveys were collected from July to September 2014, and those with 50% or greater completion were used for analysis. RESULTS: There were 789 surveys, and 747 (95%) were used for analysis. The mean age of respondents was 38.5 years. Most (94%) were from the USA. Over half (53%) had a background in health care, and 13% were physicians. The majority of respondents (86%) had previously heard of RS, but almost 25% indicated that RS was like open, laser, or scarless surgery. Over 20% of respondents indicated that the robot had some degree of autonomy during surgery. Most respondents (72%) indicated that RS was safer, faster, and less painful or offered better results, but when asked if they would choose to have RS, 55% would prefer to have conventional minimally invasive surgery. Hospitals with a robot were thought to be better hospitals by 53% of the respondents. Fewer physicians perceived advantages to RS (30% physicians vs 78% non-physicians p < 0.001), and fewer physicians would prefer RS if they needed surgery (30 vs 49% p = 0.001). One-half of respondents would prefer remote RS by a renowned expert they had never met over having RS by a local non-expert surgeon. CONCLUSIONS: Most respondents perceived benefits to RS, but still preferred conventional minimally invasive surgery if necessary. Misperceptions about the robot indicate a need for patient education prior to RS. Interest by 50% of respondents in remote surgery might allow expert surgeons to do complex procedures without necessitating regionalization of care. Issues identified in this survey merit further exploration.


Assuntos
Opinião Pública , Procedimentos Cirúrgicos Robóticos , Adulto , Feminino , Humanos , Masculino , Cirurgiões , Inquéritos e Questionários
11.
Ann Surg ; 262(1): 74-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25029436

RESUMO

OBJECTIVE: The aim of the study was to evaluate laser-assisted fluorescent-dye angiography (LAA) to assess perfusion in the gastric graft and to correlate perfusion with subsequent anastomotic leak. BACKGROUND: Anastomotic leaks are a major source of morbidity after esophagectomy with gastric pull-up (GPU). In large part, they occur as a consequence of poor perfusion in the gastric graft. METHODS: Real-time intraoperative perfusion was assessed using LAA before bringing the graft up through the mediastinum. When there was a transition from rapid and bright to slow and less robust perfusion, this site was marked with a suture. The location of the anastomosis relative to the suture was noted and the outcome of the anastomosis ascertained by retrospective record review. RESULTS: Intraoperative LAA was used to assess graft perfusion in 150 consecutive patients undergoing esophagectomy with planned GPU reconstruction. An esophagogastric anastomosis was performed in 144 patients. A leak was found in 24 patients (16.7%) and were significantly less likely when the anastomosis was placed in an area of good perfusion compared with when the anastomosis was placed in an area of less robust perfusion by LAA (2% vs 45%, P < 0.0001). By multivariate analysis perfusion at the site of the anastomosis was the only significant factor associated with a leak. CONCLUSIONS: Intraoperative real-time assessment of perfusion with LAA correlated with the likelihood of an anastomotic leak and confirmed the critical relationship between good perfusion and anastomotic healing. The use of LAA may contribute to reduced anastomotic morbidity.


Assuntos
Fístula Anastomótica/etiologia , Doenças do Esôfago/cirurgia , Esofagectomia/efeitos adversos , Angiofluoresceinografia , Estômago/irrigação sanguínea , Idoso , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/prevenção & controle , Esofagectomia/métodos , Feminino , Humanos , Período Intraoperatório , Lasers , Masculino , Pessoa de Meia-Idade , Estômago/transplante
12.
World J Urol ; 33(1): 93-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24671610

RESUMO

PURPOSE/OBJECTIVE(S): Recent in vitro and in vivo evidence has suggested that statin medications may have anticancer activity. We sought to determine whether statin use was associated with improved clinical outcome in men treated with brachytherapy for prostate cancer. MATERIALS/METHODS: A database of men with prostate cancer treated with permanent Iodine-125 brachytherapy between January 1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e., American Brachytherapy Society selection criteria) were used for selecting patients for brachytherapy. Biochemical failure was defined using the Phoenix definition. RESULTS: From a total of 247 men with prostate adenocarcinoma treated with brachytherapy, 174 patients (70 %) were identified as using statin medications, either during initial visit or during follow-up. Median PSA follow-up was 51 months after date of implant (range 9.4-140.35). Overall biochemical failure rate was 7.3 % (18 patients). On univariate analysis, statin use was associated with significantly improved freedom from biochemical failure [hazard ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate Cox analysis performed with the variables statin use, pretreatment PSA, clinical T stage, Gleason score, and D90 or V100, statin use remained significantly associated with improved freedom from biochemical failure (HR 0.288; 95 % CI 0.086-0.886; p = 0.0299). CONCLUSIONS: Statin use was associated with a significant improvement in freedom from biochemical failure in this cohort of men treated with brachytherapy for prostate cancer. Further investigation into the favorable effect of statin use on brachytherapy and radiation therapy in general is warranted, including prospective trials.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Próstata/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Surg Endosc ; 29(6): 1363-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25249148

RESUMO

BACKGROUND: Three variants of Achalasia have been described using high-resolution esophageal manometry (HRM). While manometrically distinct, their clinical significance has yet to be established. Our objective was to compare the outcome after myotomy in patients with these Achalasia subtypes. METHODS: A retrospective chart review was performed to identify patients with Achalasia who had HRM and who underwent Heller myotomy or Per oral endoscopic myotomy (POEM). Symptoms and esophageal clearance by timed barium study were compared before and after treatment. RESULTS: We identified 49 patients, 21 males and 28 females, with a median age of 52 years. The primary symptom in all patients was dysphagia, with a median duration of 4 years (range 4 months-50 years). By HRM, ten patients (20 %) were classified as Type I, 30 (61 %) as Type II, and 9 (18 %) as Type III. At a median follow-up of 16 months after myotomy (range 1-63 months), the median Eckardt score was zero and was similar across subtypes. Relief of dysphagia was also similar across subtypes (80 % of Type I, 93 % of Type II and 89 % of Type III). On pre-treatment timed barium study, no patient had complete emptying at 1 or 5 min. After myotomy, complete emptying occurred within 1 min in 50 % (20/40) and within 5 min in 60 % (24/40) and was similar across groups. CONCLUSION: Myotomy for Achalasia results in excellent symptomatic outcome and improvement in esophageal clearance. There was no difference among the described HRM Achalasia variants. This calls into question the clinical utility of Achalasia sub-classification and affirms the benefit of myotomy for this disease.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Acalasia Esofágica/cirurgia , Adulto , Idoso , Acalasia Esofágica/classificação , Acalasia Esofágica/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Manometria/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
J Mater Sci Mater Med ; 25(8): 1991-2001, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24796626

RESUMO

The development of a biomaterial substitute that can promote bone regeneration in massive defects has remained as a significant clinical challenge even using bone marrow cells or growth factors. Without an active, thriving cell population present throughout and stable anchored to the construct, exceptional bone regeneration does not occur. An engineered micro-channel structures scaffold within each trabecular has been designed to overcome some current limitations involving the cultivation and habitation of cells in large, volumetric scaffolds to repair massive skeletal defect. We created a scaffold with a superior fluid retention capacity that also may absorb bone marrow cells and provide growth factor-containing body fluids such as blood clots and/or serum under physiological conditions. The scaffold is composed of 3 basic structures (1) porous trabecular network (300-400 µm) similar to that of human trabecular bones, (2) micro-size channels (25-70 µm) within each trabecular septum which mimic intra-osseous channels such as Haversian canals and Volkmann's canals with body fluid access, diffusion, nutritional supply and gas exchange, and (3) nano-size pores (100-400 nm) on the surface of each septum that allow immobilized cells to anchor. Combinatorial effects of these internal structures result in a host-adapting construct that enhances cell retention and habitation throughout the 3 cm-height and 4 cm-length bridge-shaped scaffold.


Assuntos
Osso e Ossos/lesões , Alicerces Teciduais , Células 3T3 , Animais , Camundongos
15.
JTCVS Open ; 18: 234-252, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38690441

RESUMO

Objective: Randomized control trials are considered the highest level of evidence, yet the scalability and practicality of implementing randomized control trials in the thoracic surgical oncology space are not well described. The aim of this study is to understand what types of randomized control trials have been conducted in thoracic surgical oncology and ascertain their success rate in completing them as originally planned. Methods: The ClinicalTrials.gov database was queried in April 2023 to identify registered randomized control trials performed in patients with lung cancer who underwent surgery (by any technique) as part of their treatment. Results: There were 68 eligible randomized control trials; 33 (48.5%) were intended to examine different perioperative patient management strategies (eg, analgesia, ventilation, drainage) or to examine different intraoperative technical aspects (eg, stapling, number of ports, port placement, ligation). The number of randomized control trials was relatively stable over time until a large increase in randomized control trials starting in 2016. Forty-four of the randomized control trials (64.7%) were open-label studies, 43 (63.2%) were conducted in a single facility, 66 (97.1%) had 2 arms, and the mean number of patients enrolled per randomized control trial was 236 (SD, 187). Of 21 completed randomized control trials (31%), the average time to complete accrual was 1605 days (4.4 years) and average time to complete primary/secondary outcomes and adverse events collection was 2125 days (5.82 years). Conclusions: Given the immense investment of resources that randomized control trials require, these findings suggest the need to scrutinize future randomized control trial proposals to assess the likelihood of successful completion. Future study is needed to understand the various contributing factors to randomized control trial success or failure.

16.
Am J Physiol Cell Physiol ; 304(5): C431-9, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23255578

RESUMO

The interface between bone tissue and metal implants undergoes various types of mechanical loading, such as strain, compression, fluid pressure, and shear stress, from daily activities. Such mechanical perturbations create suboptimal environments at the host bone-implant junction, causing an accumulation of wear particles and debilitating osseous integration, potentially leading to implant failure. While many studies have focused on the effect of particles on macrophages or osteoprogenitor cells, differential and combined effects of mechanical perturbations and particles on such cell types have not been extensively studied. In this study, macrophages and osteoprogenitor cells were subjected to physiological and superphysiological mechanical stimuli in the presence and absence of Ti particles with the aim of simulating various microenvironments of the host bone-implant junction. Macrophages and osteoprogenitor cells were capable of engulfing Ti particles through actin remodeling and also exhibited changes in mRNA levels of proinflammatory cytokines under certain conditions. In osteoprogenitor cells, superphysiological strain increased proinflammatory gene expression; in macrophages, such mechanical perturbations did not affect gene expression. We confirmed that this phenomenon in osteoprogenitor cells occurred via activation of the ERK1/2 signaling pathway as a result of damage to the cytoplasmic membrane. Furthermore, AZD6244, a clinically relevant inhibitor of the ERK1/2 pathway, mitigated particle-induced inflammatory gene expression in osteoprogenitor cells and macrophages. This study provides evidence of more inflammatory responses under mechanical strains in osteoprogenitor cells than macrophages. Phagocytosis of particles and mechanical perturbation costimulate the ERK1/2 pathway, leading to expression of proinflammatory genes.


Assuntos
Inflamação/induzido quimicamente , Inflamação/genética , Macrófagos/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Próteses e Implantes , Titânio/toxicidade , Actinas/metabolismo , Animais , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Membrana Celular/metabolismo , Microambiente Celular/efeitos dos fármacos , Microambiente Celular/genética , Citocinas/genética , Citocinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Fagocitose/efeitos dos fármacos , Fagocitose/genética
17.
Surg Endosc ; 27(11): 4113-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23836124

RESUMO

BACKGROUND: Gastroesophageal reflux disease can be associated with extraesophageal symptoms (hoarseness, cough, asthma, and globus). However, these symptoms may have a multifactorial etiology. Proximal pH monitoring has been proposed as a means of identifying patients where reflux is the cause of the extraesophageal symptoms. The aim of this study was to determine whether proximal esophageal or pharyngeal pH monitoring better identified patients with extraesophageal symptoms that improved after antireflux surgery. METHODS: A retrospective chart review was performed to identify all patients who had esophageal and pharyngeal pH monitoring before an antireflux operation. A composite score was used to define an abnormal result with each test. A successful outcome was defined as improvement or resolution of extraesophageal symptoms. RESULTS: There were 20 patients identified. Antireflux surgery led to a successful outcome in 14 patients (70 %). Restech better identified patients with extraesophageal symptoms who had a successful outcome with antireflux surgery (12 of 14 [86 %] based on abnormal Restech versus 5 of 10 [50 %] based on abnormal proximal probe, p = 0.06). Comparing only the 15 patients who had both proximal esophageal and pharyngeal pH monitoring, Restech again better identified those who had a successful outcome with antireflux surgery (9 of 10 [90 %] based on abnormal Restech versus 5 of 10 [50 %] based on abnormal proximal probe, p = 0.05). The positive and negative predictive values for symptomatic improvement after a fundoplication were better for an abnormal Restech score than for an abnormal proximal esophageal score (80 vs. 71 % and 60 vs. 38 %, respectively). In two patients with a successful outcome, Restech was the only positive test. CONCLUSIONS: In patients with extraesophageal reflux symptoms, proximal esophageal pH monitoring failed to identify half of the patients who had a successful outcome after antireflux surgery. In contrast, an abnormal Restech pH test was present in 90 % of patients with a successful outcome. Further, a negative Restech study more reliably indicated the absence of reflux-induced extraesophageal symptoms. Our results indicate that Restech pharyngeal pH monitoring should be utilized in the evaluation of patients with extraesophageal symptoms that may be associated with reflux disease.


Assuntos
Monitoramento do pH Esofágico , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tosse/etiologia , Feminino , Fundoplicatura/métodos , Refluxo Gastroesofágico/complicações , Rouquidão/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Surg Endosc ; 27(12): 4532-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23949479

RESUMO

BACKGROUND: Laparoscopic paraesophageal hernia (PEH) repair is associated with an objective recurrence rate exceeding 50% at 5 years. Minimizing tension is a critical factor in preventing hernia recurrence. This study aimed to evaluate the outcomes of crural relaxing incisions in patients undergoing PEH repair. METHODS: Records were reviewed to identify patients who received a relaxing incision during laparoscopic PEH repair. The patients were followed by chest X-ray and videoesophagram at 3 months and then annually. RESULTS: From November 2010 to March 2013, 58 patients underwent PEH repair, and 15 patients received a relaxing incision to accomplish crural closure. The median age of the patients was 72 years (range 58-84 years). The relaxing incision was right-sided in 13 patients, left-sided in one patient, and bilateral in one patient. All the procedures were completed laparoscopically and included a fundoplication. Collis gastroplasty for a short esophagus was performed for 40% of the patients. No major complications occurred. During a median follow-up period of 4 months, one patient had an asymptomatic mildly elevated left hemidiaphragm, and one patient had a trivial recurrent hernia, as shown on esophagogastroduodenoscopy (EGD). CONCLUSION: Crural tension likely contributes to the high recurrence rate noted with laparoscopic PEH repair. Relaxing incisions are safe and allow crural approximation. Advanced laparoscopic surgeons should be aware of this option when faced with a large hiatus in a patient with PEH.


Assuntos
Hérnia Hiatal/cirurgia , Herniorrafia/métodos , Laparoscopia/métodos , Idoso , Idoso de 80 Anos ou mais , Diafragma/fisiopatologia , Diafragma/cirurgia , Feminino , Seguimentos , Fundoplicatura , Gastroplastia , Hérnia Hiatal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prevenção Secundária , Resultado do Tratamento
19.
J Robot Surg ; 17(2): 669-676, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36306102

RESUMO

Surgical training relies on subjective feedback on resident technical performance by attending surgeons. A novel data recorder connected to a robotic-assisted surgical platform captures synchronized kinematic and video data during an operation to calculate quantitative, objective performance indicators (OPIs). The aim of this study was to determine if OPIs during initial task of a resident's robotic-assisted lobectomy (RL) correlated with bleeding during the procedure. Forty-six residents from the 2019 Thoracic Surgery Directors Association Resident Boot Camp completed RL on an ex vivo perfused porcine model while continuous video and kinematic data were recorded. For this pilot study, RL was segmented into 12 tasks and OPIs were calculated for the initial major task. Cases were reviewed for major bleeding events and OPIs of bleeding cases were compared to those who did not. Data from 42 residents were complete and included in the analysis. 10/42 residents (23.8%) encountered bleeding: 10/40 residents who started with superior pulmonary vein exposure and 0/2 residents who started with pulmonary artery exposure. Twenty OPIs for both hands were assessed during the initial task. Six OPIs related to instrument usage or smoothness of motion were significant for bleeding. Differences were statistically significant for both hands (p < 0.05). OPIs showing bimanual asymmetry indicated lower proficiency. This study demonstrates that kinematic and video analytics can establish a correlation between objective performance metrics and bleeding events in an ex vivo perfused lobectomy. Further study could assist in the development of focused exercises and simulation on objective domains to help improve overall performance and reducing complications during RL.


Assuntos
Internato e Residência , Procedimentos Cirúrgicos Robóticos , Cirurgiões , Procedimentos Cirúrgicos Torácicos , Lesões do Sistema Vascular , Suínos , Humanos , Animais , Procedimentos Cirúrgicos Robóticos/métodos , Projetos Piloto , Competência Clínica
20.
Surgery ; 174(6): 1349-1355, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37718171

RESUMO

BACKGROUND: The Global Evaluative Assessment of Robotic Skills is a popular but ultimately subjective assessment tool in robotic-assisted surgery. An alternative approach is to record system or console events or calculate instrument kinematics to derive objective performance indicators. The aim of this study was to compare these 2 approaches and correlate the Global Evaluative Assessment of Robotic Skills with different types of objective performance indicators during robotic-assisted lobectomy. METHODS: Video, system event, and kinematic data were recorded from the robotic surgical system during left upper lobectomy on a standardized perfused and pulsatile ex vivo porcine heart-lung model. Videos were segmented into steps, and the superior vein dissection was graded independently by 2 blinded expert surgeons with Global Evaluative Assessment of Robotic Skills. Objective performance indicators representing categories for energy use, event data, movement, smoothness, time, and wrist articulation were calculated for the same task and compared to Global Evaluative Assessment of Robotic Skills scores. RESULTS: Video and data from 51 cases were analyzed (44 fellows, 7 attendings). Global Evaluative Assessment of Robotic Skills scores were significantly higher for attendings (P < .05), but there was a significant difference in raters' scores of 31.4% (defined as >20% difference in total score). The interclass correlation was 0.44 for 1 rater and 0.61 for 2 raters. Objective performance indicators correlated with Global Evaluative Assessment of Robotic Skills to varying degrees. The most highly correlated Global Evaluative Assessment of Robotic Skills domain was efficiency. Instrument movement and smoothness were highly correlated among objective performance indicator categories. Of individual objective performance indicators, right-hand median jerk, an objective performance indicator of change of acceleration, had the highest correlation coefficient (0.55). CONCLUSION: There was a relatively poor overall correlation between the Global Evaluative Assessment of Robotic Skills and objective performance indicators. However, both appear strongly correlated for certain metrics such as efficiency and smoothness. Objective performance indicators may be a potentially more quantitative and granular approach to assessing skill, given that they can be calculated mathematically and automatically without subjective interpretation.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgia Torácica , Animais , Suínos , Benchmarking , Dissecação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA