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Background: Large-volume therapeutic thoracocentesis may be associated with pulmonary congestion or a more serious complication; re-expansion pulmonary edema (RPE). We investigated whether monitoring pleural pressure with manometry during thoracocentesis would prevent these pulmonary symptoms/RPE and allow larger volume drainage. Methods: We did a randomized controlled trial involving 110 patients with large malignant pleural effusions. Patients were randomly allocated to obtain thoracocentesis with or without pleural manometry. We measured the incidence of pulmonary congestion symptoms, total fluid aspirated, and pleural pressures in both groups. This trial is listed on ClinicalTrials.gov as NCT04420663. Results: The mean amount of total thoracocentesis fluid withdrawn from the control group was 945.4±78.9 (mL) and 1690.9±681.0 (mL) from the intervention group (P<0.001). Clinical symptoms of pulmonary congestion appeared in (n=20) (36.3%) of patients in the intervention group while no symptoms appeared in controls (P<0.001). The difference between opening and closing pressures between the non-symptomatic cluster and the symptomatic cluster was (32.8±15.6 versus 42.2±13) respectively (P=0.02). Total fluid withdrawn from the non-symptomatic cluster was 1828.5±505 mL in comparison to 1,450±875 mL in the symptomatic cluster (P=0.04). Conclusion: Pleural manometry can be used to increase the volume of fluid removed on each occasion in patients with malignant pleural effusion. In our study, pleural manometry was associated with a larger number of pulmonary congestion symptoms/RPE. We believe that manometry may be a useful tool to not exceed a 17 cm H2O gradient in pleural pressure which should be avoided to prevent pulmonary congestion symptoms or RPE. Pulmonary congestion symptoms/RPE are not related to the amount of volume withdrawn but to the gradient of pleural pressure drop. Our conclusion does support the adoption of pleural manometry whenever large-volume thoracocentesis is intended.
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INTRODUCTION: As fellowship training after general surgery residency has become increasingly common, the impact on resident education must be considered. Patient safety and procedure outcomes are often used as justification by attendings who favor fellows over residents in certain minimally invasive surgery (MIS) operations. The aim of the present study was to compare the impact of trainee level on the outcomes of selected MIS operations to determine if giving preference to fellows on grounds of outcomes is warranted. METHODS: Patients who underwent elective laparoscopic hiatal hernia repair (LHHR), laparoscopic sleeve gastrectomy (LSG), laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic splenectomy (LS), laparoscopic cholecystectomy (LC), or laparoscopic ventral hernia repair (LVHR) with assistance of a general surgery chief resident or fellow were identified from the American College of Surgeon's National Surgical Quality Improvement Program database (2007-2012). Patients were matched 1:1 based on propensity score for the odds of undergoing operations assisted by a fellow. RESULTS: 5145 patients underwent LHHR, 1396 LSG, 9656 LRYGB, 863 LS, 13,434 LC, and 3069 LVHR. Fellows assisted in 41.7% of LHHR, 49.2% of LSG, 56.4% of LRYGB, 25.7% of LS, 17.1% of LC, and 27.0% of LVHR cases. After matching, overall and severe complication rates were comparable between cases performed with assistance of a fellow or chief resident. Median operative time was longer for LSG, LRYGB, and LC when a fellow assisted. CONCLUSIONS: Surgical outcomes were similar between fellow and chief resident assistance in MIS operations, arguing that increased resident participation in basic and complex laparoscopic operations is appropriate without compromising patient safety.
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Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Gastrectomia/métodos , Derivação Gástrica/métodos , Humanos , Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Several studies demonstrated language that discordant care between may lead to mixed outcomes and increased use of hospital-resources. In the setting of bariatric surgery, which relies heavily on intensive pre-operative and post-operative counseling, we hypothesized that patients with LEP would have less favorable outcomes compared to English-proficient (EP) patients. METHODS: All patients 18 years and older, who underwent laparoscopic sleeve gastrectomy (SG) or laparoscopic gastric bypass (LGBP) from January 2013 to December 2017 were included. Language proficiency was determined by chart review for the use of an interpreter at least once during the study period. Outcomes of interest at 30-days and 1 year included: emergency department (ED) visits, readmission, length of stay (LOS), chief-complaint on readmission, and post-operative complications. Additionally, comorbidity remission and weight loss at one year was recorded. RESULTS: A total of 671 patients were categorized as LEP (40%) and spoke 6 unique languages. Within the 1 year post-operative period, EP patients presented to the ED more than LEP patients (23% vs. 14% p < 0.001). After multivariable regression for potential confounders this difference persisted; adjusted OR = 0.65 (95% CI 0.43-0.95; p = 0.029). However, despite more frequent ED visits by EP patients, there was no significant difference in readmission within one year; adjusted OR = 0.94 (95% CI 0.56-1.55; p = 0.50). Both groups demonstrated similar successful weight loss at 1 year: EP-31.85% (LGBP) and - 28.02% (SG) vs. LEP-30.17% (LGBP) and - 28.36% (SG). EP and LEP patients also had similar remission of obesity-related comorbidities. CONCLUSION: There were no differences in outcomes following bariatric surgery when comparing patients with limited English proficiency to those who are proficient in English. Bariatric surgical care can be delivered in a safe and effective manner with equivalent outcomes between patients who are and are not English-language proficient.
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Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Gastrectomia , Humanos , Idioma , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Redução de PesoRESUMO
Background: In 2014, Ozaki et al. introduced the neo-cuspidation (Ozaki procedure), a new valve from the pericardium, to reduce or even prevent the risk of chronic autoimmune inflammation and subsequent rejection or valve degeneration. Thus, the authors aimed to assess the safety and efficacy of the Ozaki technique in treating aortic valve diseases. Materials and methods: A comprehensive search was performed via PubMed, the Cochrane Library, Scopus, and the Web of Science up to 20 February 2022. Random-effects meta-analysis models were employed to estimate the pooled mean and SD or event to the total of the Ozaki procedure. Relevant records were retrieved and analyzed by OpenMeta analyst software. Results: A total of 2863 patients from 21 studies were finally included in our analysis. Ac. Ozaki technique showed statistical significance in terms of mean cardiopulmonary bypass time of 148 mins (95% CI 144-152.2, P<0.001), mean aortic cross-clamp time of 112.46 mins (95% CI 105.116, 119.823, P<0.001), reoperation with a low risk of 0.011 (95% CI 0.005, 0.016, P=0.047), conversion to aortic valve replacement with a low risk of 0.004 (95% CI -0.001, 0.008, P=0.392), finally ICU stay (days) and hospital length of stay (days) with a mean of 2.061 days (95% CI 1.535, 2.587, P<0.001) and 8.159 days (95% CI 7.183-9.855, P<0.001), respectively. Conclusion: The Ozaki procedure provides a safe surgical technique with low mean cardiopulmonary bypass time and aortic cross-clamp time; moreover, a mean of 2-day-postoperative hospital stay was observed with the Ozaki procedure with a low risk of conversion to aortic valve replacement, reoperation, ICU and hospital stay, and death.
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BACKGROUND: The "I COUGH" protocol is associated with improved postoperative pulmonary outcomes, and ambulation is an essential component. I COUGH is an acronym for Incentive spirometry, Coughing, Oral care, Understanding (patient and staff education), Getting-out-of-bed, and Head-of-bed elevation. This trial sought to enhance one component, specifically ambulation after operations. METHODS: Randomized trial of inpatients in a safety-net, academic medical center. The intervention group received standard I COUGH education along with text message reminders to ambulate postoperatively, whereas the control group received standard education alone. Postoperative walking frequency was compared to each participant's ambulation on the day prior to enrollment. RESULTS: The intervention group had an average improvement of 1.8 ± 1.8 walks per day per patient, while the average change for the control group was 0.2 ± 1.0 walks per day per patient. This represents a 9-fold increase in ambulation for the intervention group (p = 0.03). CONCLUSIONS: Implementation of text message reminders increased ambulation and improved adherence to the I COUGH protocol following operations. This system should be further investigated as an adjunct to postoperative care.
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Envio de Mensagens de Texto , Tosse , Hospitais , Humanos , Projetos Piloto , CaminhadaRESUMO
BACKGROUND: The Caprini risk assessment model is a well-validated tool that identifies patients who would benefit from extended venous thromboembolism (VTE) prophylaxis beyond hospital discharge. VTE, particularly portal mesenteric vein thrombosis (PMVT), is a potentially devastating complication of laparoscopic sleeve gastrectomy (LSG); therefore, we sought to examine whether the model can be safely applied to LSG patients. We hypothesized that its use can minimize the incidence of postoperative VTE, including PMVT, without increasing the likelihood of bleeding complications. MATERIALS AND METHODS: We conducted a retrospective chart review of those patients who underwent LSG at our institution from 2010 and 2018, at which time the Caprini risk assessment model was already our institutional standard. We determined the patients' Caprini scores at the time of discharge and whether patients at high risk of VTE were discharged from hospital on extended courses of VTE prophylaxis. We also recorded if bleeding complications or VTE events occurred in the first 180 days after LSG. RESULTS: Six hundred thirty-eight patients underwent LSG, including 521 (81.7%) women, with an average preoperative body mass index (BMI) of 44.4 kg/m2 (SD 6.8). One hundred fifty-eight (24.8%) patients had Caprini scores that warranted extended courses of VTE prophylaxis beyond hospital discharge. Three patients (0.47%) developed a postoperative VTE, but no patient developed PMVT. No bleeding complications were observed among patients who received extended VTE prophylaxis. CONCLUSION: The Caprini risk assessment model can effectively identify patients after LSG who might benefit from extended courses of VTE prophylaxis. Extended VTE prophylaxis does not seem to confer increased bleeding risk in this patient population.
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Gastrectomia , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Feminino , Gastrectomia/efeitos adversos , Humanos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
OBJECTIVES: Catamenial pneumothorax CP is a rare form of spontaneous pneumothorax in females forming part of thoracic endometriosis syndrome. Studies have suggested possible benefit from postoperative hormonal administration. As this treatment is inconsistent, we aimed at performing the first meta-analysis to study the efficacy of adding hormonal treatment after surgery to reduce the chances of recurrent catamenial pneumothorax. METHODS: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched from inception up to December 15, 2021. Studies reporting five or more patients with end point outcome were included. The main outcome assessed was postoperative recurrence of CP after hormonal manipulation. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. meta- regression for the effect of patient age and follow up period were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42022325377. RESULTS: Our electronic search retrieved 644 citations, 48 of which were selected for full-text review. Eleven studies with a combined population of 111 patients fulfilled the inclusion criteria. All patients reached an endpoint of follow up for postoperative recurrence of catamenial pneumothorax after receiving hormonal treatment. Overall study validity was acceptable, with a median score of 6 on the Newcastle Ottawa scale NOS appraising the quality of observational studies. CP is almost always a right-side disease (107/111 = 96.3 %). The risk of postoperative recurrence with hormonal treatment was 17.3 % (8.9 - 25.8 %) with moderate non-significant heterogeneity (I2 = 40.85 %; P = 0.076). The cumulative risk of recurrence for all patients not receiving postoperative hormonal therapy included in our study was 54.2 % (19/35 patients). Meta regression showed age to be a significant predictor of postoperative recurrence (p = 0.03). As the age increases one year, the risk of recurrence decreases by 6 % (0.2 - 3 %). Publication bias was detected by visualizing the funnel plot of standard error, Egger's test with p < 0.01 and Begg & Mazumdar test with p < 0.01. CONCLUSION: The study included the largest number of CP patients with outcome findings of postoperative recurrence with hormonal treatment despite the small number of studies, non-randomised fashion and publication bias. Our findings recommend the use of hormonal manipulation after thoracic surgical intervention for catamenial pneumothorax unless evident contraindications. Younger patients are at a higher risk of recurrence after surgery.
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Endometriose , Pneumotórax , Feminino , Humanos , Pneumotórax/cirurgia , Recidiva , Endometriose/complicações , Endometriose/tratamento farmacológico , Endometriose/cirurgia , Período Pós-OperatórioRESUMO
A best evidence topic was written according to a structured protocol. The question addressed was: In patients with mesothelioma who develop a local recurrence after macroscopic complete resection (MCR) surgery, does performing a second radical surgery lead to improvement in survival? A total of 2076 papers were identified using the reported search, of which 3 represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. The 2 largest studies included 16 patients each who underwent a second surgery for radical resection of recurrence after MCR for mesothelioma. One study (with 16 chest wall resections) had no in-hospital mortality, whereas the other study showed 2/16 (12.5%) patients dying in the hospital, both of whom had a contralateral pleurectomy. One study correlated the median survival after the second surgery with the time to recurrence and epithelioid pathology. The other study showed better post-recurrence survival after a second surgery, with patients having a significantly longer median post-recurrence survival (16 months) compared with those who received other types of second-line therapy (9 months) and those who received no therapy at all (2 months) (P < 0.0005), although selection bias is a possibility. The last study included 8 patients who underwent a second surgery for radical intent after MCR for mesothelioma. The median time to recurrence was 29 months and the survival after second surgery was 14.5 months with no correlation to disease-free interval (expected due to the small number of patients). In patients presenting with recurrence of mesothelioma after an MCR procedure, radical surgery to resect the recurrent tumour could have a role in improvement of survival in selected patients. Positive prognostic factors include epithelioid pathology and a longer disease-free interval after the first procedure.
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Mesotelioma , Humanos , Neoplasias Pulmonares/cirurgia , Mesotelioma/cirurgia , Mesotelioma Maligno , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pleurais/cirurgia , Pneumonectomia/efeitos adversos , Resultado do TratamentoRESUMO
Background: COVID 19 is the most recent cause of adult respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We conducted a systematic review and meta-analysis on ECMO for COVID-associated ARDS to study its outcome. Main body: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched from inception to May 28, 2020. Studies reporting five or more patients with COVID-19 infection treated venovenous with ECMO were included. The main outcome assessed was mortality and ICU/hospital discharge. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. The validity of all the included observational studies was appraised with the Newcastle Ottawa scale. Meta-regression and publication bias were tested. This trial was registered with PROSPERO under registration number CRD42020183861.From 1647 initial citations, 34 full-text articles were analyzed and 12 studies were selected, including 194 patients with confirmed COVID-19 infection requiring ICU admission and venovenous ECMO treatment. Median Newcastle-Ottawa scale was 6 indicating acceptable study validity. One hundred thirty-six patients reached an endpoint of weaning from ECMO with ICU/hospital discharge or death while the rest were still on ECMO or in the ICU. The median Berlin score for ARDS prior to starting ECMO was III. Patients received mechanical ventilation before ECMO implementation for a median of 4 days and ECMO was maintained for a median of 13 days. In hospital and short-term mortality were highly variable among the included studies ranging between 0 and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.49 (95% confidence interval 0.259 to 0.721; I2 = 94%). Subgroup analysis according to country of origin showed persistent heterogeneity only in the 7 Chinese studies with pooled estimate mortality risk ratio of 0.66 (I2 = 87%) (95% CI = 0.39-0.93), while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.41 (95% CI 0.28-0.53) with homogeneity (p=0.67) similar to France with a pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p=0.86). Meta-regression showed only younger age as a predictor of mortality (p=0.02). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p=0.566, and Begg and Mazumdar test with p=0.373. Conclusion: The study included the largest number of patients with outcome findings of ECMO in this current pandemic. Our findings showed that the use of venovenous ECMO at high-volume ECMO centers may be beneficial for selected COVID 19 patients with severe ARDS. However, none of the included studies involve prospective randomized analyses; and therefore, all the included studies were of low or moderate quality according to the Newcastle-Ottawa scale. In the current era and environment of the pandemic, it will likely be very challenging to conduct a prospective randomized trial of ECMO versus no-ECMO for COVID-19. Therefore, the information contained in this systematic review of the literature is valuable and provides important guidance. Trial registration: The study protocol link is at www.crd.yorl.ac.uk/PROSPERO under registration number CRD42020183861.
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INTRODUCTION: DNA methylation constitutes one important epigenetic mechanism that regulates gene expression in human cells. With regard to obesity, bariatric surgery-induced weight loss has been associated with promoter methylation changes in several genes. Hyperleptinemia is a characteristic feature of obesity. The underlying regulating mechanisms have not yet been completely elucidated. METHODS: We investigated the methylation of the promoters of the leptin gene (LEP) and the leptin receptor gene (LEPR) as well as leptin expression in pre- and postbariatric surgery patients using a comparative cross-sectional design. RESULTS: Our results revealed significantly higher LEP promoter methylation patterns in prebariatric surgery patients compared to postoperatively. DNA methylation of the LEPR promoter was significantly higher in the postoperative group. Moreover, we found significantly higher leptin serum levels in patients before the bariatric surgery than afterwards. DISCUSSION: These findings strengthen the suggestion that there is an association between LEP expression and LEP methylation in obesity. We suggest that the epigenetic profile of LEP might be influenced by leptin serum levels in the form of a regulating feedback mechanism.
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BACKGROUND: COVID 19 is the most recent cause of Adult respiratory distress syndrome ARDS. Invasive mechanical ventilation IMV can support gas exchange in patients failing non-invasive ventilation, but its reported outcome is highly variable between countries. We conducted a systematic review and meta-analysis on IMV for COVID-associated ARDS to study its outcome among different countries. METHODS: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched up to August 8, 2020. Studies reporting five or more patients with end point outcome for severe COVID 19 infection treated with IMV were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. Subgroup analysis for different countries was performed. Meta-regression for the effect of study timing and patient age and were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42020190365. FINDINGS: Our electronic search retrieved 4770 citations, 103 of which were selected for full-text review. Twenty-one studies with a combined population of 37359 patients with COVID-19 fulfilled the inclusion criteria. From this population, 5800 patients were treated by invasive mechanical ventilation. Out of those, 3301 patients reached an endpoint of ICU discharge or death after invasive mechanical ventilation while the rest were still in the ICU. Mortality from IMV was highly variable among the included studies ranging between 21% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.70 (95% confidence interval 0.608 to 0.797; I2 = 98%). Subgroup analysis according to country of origin showed homogeneity in the 8 Chinese studies with high pooled mortality risk ratio of 0.97 (I2 = 24%, p = 0.23) (95% CI = 0.94-1.00), similar to Italy with a low pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p = 0.86) while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.60 (95% CI 0.43-0.76) with persistent heterogeneity (I2 = 98%, p<0.001). Meta-regression showed that outcome from IMV improved with time (p<0.001). Age had no statistically significant effect on mortality (p = 0.102). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p = 0.714 and Begg&Mazumdar test with p = 0.334. INTERPRETATION: The study included the largest number of patients with outcome findings of IMV in this current pandemic. Our findings showed that the use of IMV for selected COVID 19 patients with severe ARDS carries a high mortality, but outcome has improved over the last few months and in more recent studies. The results should encourage physicians to use this facility when indicated for severely ill COVID-19 patients.
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COVID-19 , Respiração Artificial , Síndrome do Desconforto Respiratório , SARS-CoV-2 , COVID-19/mortalidade , COVID-19/terapia , Humanos , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapiaRESUMO
BACKGROUND: The coronavirus disease 2019 pandemic has claimed many lives and strained the US health care system. At Boston Medical Center, a regional safety-net hospital, the Department of Surgery created a dedicated coronavirus disease 2019 Procedure Team to ease the burden on other providers coping with the surge of infected patients. As restrictions on social distancing are lifted, health systems are bracing for additional surges in coronavirus disease 2019 cases. Our objective is to quantify the volume and types of procedures performed, review outcomes, and highlight lessons for other institutions that may need to establish similar teams. METHODS: Procedures were tracked prospectively along with patient demographics, immediate complications, and time from donning to doffing of the personal protective equipment. Retrospective chart review was conducted to obtain patient outcomes and delayed adverse events. We hypothesized that a dedicated surgeon-led team would perform invasive bedside procedures expeditiously and with few complications. RESULTS: From March 30, 2020 to April 30, 2020, there were 1,196 coronavirus disease 2019 admissions. The Procedure Team performed 272 procedures on 125 patients, including placement of 135 arterial catheters, 107 central venous catheters, 25 hemodialysis catheters, and 4 thoracostomy tubes. Specific to central venous access, the average procedural time was 47 minutes, and the rate of immediate complications was 1.5%, including 1 arterial cannulation and 1 pneumothorax. CONCLUSION: Procedural complication rate was less than rates reported in the literature. The team saved approximately 192 hours of work that could be redirected to other patient care needs. In times of crisis, redeployment of surgeons (who arguably have the most procedural experience) into procedural teams is a practical approach to optimize outcomes and preserve resources.
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Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Pandemias , Equipamento de Proteção Individual/provisão & distribuição , Pneumonia Viral/epidemiologia , Provedores de Redes de Segurança/organização & administração , Cirurgiões/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/transmissão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Pneumonia Viral/transmissão , Estudos Retrospectivos , SARS-CoV-2 , Estados Unidos/epidemiologia , Adulto JovemAssuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Humanos , Diabetes Mellitus Tipo 2/cirurgia , Estudos de Coortes , Cirurgia Bariátrica/efeitos adversos , Glicemia , Reino Unido/epidemiologia , Obesidade Mórbida/cirurgia , Obesidade Mórbida/etiologia , Estudos RetrospectivosAssuntos
Cirurgia Bariátrica , Minorias Étnicas e Raciais , Etnicidade , Humanos , Grupos Minoritários , Estados UnidosRESUMO
Endochondral ossification is the process where cartilage forms prior to ossification and in which new bone forms during both fracture healing and ectopic bone formation. Transitioning to ossification is a highly coordinated process between hypertrophic chondrocytes, vascular endothelial cells, osteoblasts and osteoclasts. A critical biological process that is central to the interactions of these various cell types is angiogenesis. Although it is well established that angiogenesis is crucial for fracture repair, less is known pertaining to the role of angiogenesis in ectopic bone formation. Furthermore, fracture repair models are complicated by extensive trauma, subsequent inflammatory responses and concurrent repair processes in multiple tissues. In order to more definitively characterize the relationship between angiogenesis and postnatal endochondral ossification, a model of ectopic bone formation was used. Human demineralized bone matrix (DBM) was implanted in immune-deficient mice (rag null (B6.129S7-Rag1tm1/MOM/J)) to induce ectopic bone. Inhibition of angiogenesis with either a small molecule (TNP-470) or a targeted biological (Vascular Endothelial Growth Factor Receptor type 2 [VEGFR2] blocking antibody) prevented ectopic bone formation by 83% and 77%, respectively. Most striking was that the progression of chondrogenesis was halted during very early phases of chondrocyte differentiation between condensation and prehypertrophy (TNP-470) or the proliferative phase (VEGFR2 blockade) prior to hypertrophy, while osteoclast recruitment and resorption were almost completely inhibited. Our results demonstrate angiogenesis plays a developmental role in endochondral bone formation at a much earlier phase of chondrogenesis than suggested by prior findings.
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Desenvolvimento Ósseo/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Animais , Cartilagem/citologia , Cartilagem/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Cicloexanos/farmacologia , Humanos , Imuno-Histoquímica , Masculino , Camundongos , O-(Cloroacetilcarbamoil)fumagilol , RNA Ribossômico , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Sesquiterpenos/farmacologiaAssuntos
Obstrução Intestinal , Laparoscopia , Obesidade Mórbida , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Suturas/efeitos adversosRESUMO
Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and the lung. The formation of caveolae is dependent on the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency in mice leads to loss of caveolae formation and to development of a lipodystrophic phenotype. In this study, we sought to investigate the functional role of Cavin1 in the lung. Cavin1 deficient mice possessed dramatically altered distal lung morphology and exhibited significant physiological alterations, notably, increased lung elastance. The changes in distal lung architecture were associated with hypercellularity and the accumulation of lung macrophages. The increases in lung macrophages occurred without changes to circulating numbers of mononuclear cells and without evidence for increased proliferation. However, the increases in lung macrophages were associated with higher levels of macrophage chemotactic factors CXCL2 and CCL2 in BAL fluid from Cavin1-/- mice suggesting a possible mechanism by which these cells accumulate. In addition, lung macrophages from Cavin1-/- mice were larger and displayed measurable differences in gene expression when compared to macrophages from wild-type mice. Interestingly, macrophages were also increased in adipose tissue but not in liver, kidney or skeletal muscle from Cavin1-/- mice, and similar tissue specificity for macrophage accumulation was observed in lungs and adipose tissue from Caveolin1-/- mice. In conclusion, this study demonstrates an important role for Cavin1 in lung homeostasis and suggests that caveolae structural proteins are necessary for regulating macrophage number and phenotype in the lung.