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BACKGROUND: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. METHODS: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. RESULTS: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. CONCLUSION: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.
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Modelos Animais de Doenças , Embolia Pulmonar , Resistência Vascular , Animais , Embolia Pulmonar/fisiopatologia , Suínos , Resistência Vascular/fisiologia , Distribuição Aleatória , Gasometria , Função Ventricular Direita/fisiologia , Disfunção Ventricular Direita/fisiopatologia , Feminino , MasculinoRESUMO
Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n = 19), primary biliary cholangitis (PBC, n = 15), and primary sclerosing cholangitis (PSC, n = 6). Healthy individuals (n = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n = 18) were included as controls. Blood samples were collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH and MASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early on in their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.
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Glicemia , Hepatite Autoimune , Resistência à Insulina , Insulina , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Glicemia/metabolismo , Estudos Transversais , Adulto , Insulina/sangue , Hepatite Autoimune/sangue , Hepatite Autoimune/metabolismo , Hepatite Autoimune/complicações , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/sangue , Polipeptídeo Inibidor Gástrico/sangue , Polipeptídeo Inibidor Gástrico/metabolismo , Idoso , Teste de Tolerância a Glucose , Colangite Esclerosante/sangue , Colangite Esclerosante/metabolismo , Colangite Esclerosante/complicações , Glucagon/sangue , Glucagon/metabolismo , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/metabolismo , Cirrose Hepática Biliar/complicações , Peptídeo C/sangueRESUMO
INTRODUCTION: Abdominal ultrasound (US) and CT are important tools for the initial evaluation of patients with liver disease. Our study aimed to determine the accuracy of these methods for diagnosing cirrhosis. METHODS: In all, 377 participants from 4 prospective cohort studies evaluating patients with various liver diseases were included. All patients were included between 2017 and 2022 and had undergone a liver biopsy as well as US and/or CT. Using the histological assessment as the gold standard, we calculated diagnostic accuracy for US and CT. Liver biopsies were evaluated by expert histopathologists and diagnostic scans by experienced radiologists. RESULTS: The mean age was 54 ± 14 years and 47% were female. Most patients had NAFLD (58.3%) or alcohol-associated liver disease (25.5%). The liver biopsy showed cirrhosis in 147 patients (39.0%). Eighty-three patients with cirrhosis had Child-Pugh A (56.4% of patients with cirrhosis) and 64 had Child-Pugh B/C (43.6%). Overall, the sensitivity for diagnosing cirrhosis by US was 0.71 (95% CI 0.62-0.79) and for CT 0.74 (95% CI 0.64-0.83). The specificity was high for US (0.94, 95% CI 0.90-0.97) and for CT (0.93, 95% CI 0.83-0.98). When evaluating patients with Child-Pugh A cirrhosis, sensitivity was only 0.62 (95% CI 0.49-0.74) for US and 0.60 (95% CI 0.43-0.75) for CT. For patients with Child-Pugh B/C, sensitivity was 0.83 (95% CI 0.70-0.92) for US and 0.87 (95% CI 0.74-0.95) for CT. When limiting our analysis to NAFLD (20% with cirrhosis), the sensitivity for US was 0.45 (95% CI 0.28-0.64) and specificity was 0.97 (95% CI 0.93-0.99). CONCLUSION: US and CT show moderate sensitivity and may potentially overlook compensated cirrhosis underlining the need for additional diagnostic testing.
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Hepatopatias Alcoólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Estudos Prospectivos , Cirrose Hepática/diagnóstico por imagem , Ultrassonografia , Tomografia Computadorizada por Raios XRESUMO
Background and Aim: Little are known about differences in eosinophilic esophagitis (EoE) patients in the general population compared with patients treated at academic hospitals. This might affect the generalizability of study results. The aims of the study were to compare clinical features, and complications of EoE between patients from a population-based cohort (DanEoE) and patients from an academic hospital cohort in Copenhagen (EoE-Cph). Methods: The DanEoE cohort is a population- and register-based cohort including all 236 adult EoE patients diagnosed in the North Denmark Region in 2007-2017 previously described in detail. The new EoE-Cph cohort consists of 245 consecutively referred adult patients to a dedicated EoE center in an Academic Hospital in the Danish capital in 2013-2020. Data were collected from medical registries and medical files. Results: Patients in the academic cohort were at symptom debut 12 (SD 16) years younger (P = 0.001). At the time of diagnosis they were 5.4 (SD 15) years younger (P < 0.001). Where Gastro-esophageal reflux disease (GORD) was present in one-third of the population-based cohort, this was only observed in 14% of the EoE-Cph group (P < 0.05). Food bolus obstruction before diagnosis was 24% less common in the EoE-Cph patients (P < 0.001). Conclusion: Results indicated that EoE patients referred to a Danish EoE center is a selected subgroup with disease debut at a younger age, less comorbid GORD, and rarely food bolus obstruction before diagnosis. This suggests that study results from academic hospitals might not have generalizability to the average EoE patient in a population.
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Fatty liver disease has mainly been characterized under fasting conditions. However, as the liver is essential for postprandial homeostasis, identifying postprandial disturbances may be important. Here, we investigated postprandial changes in markers of metabolic dysfunction between healthy individuals, obese individuals with non-alcoholic fatty liver disease (NAFLD) and patients with cirrhosis. We included individuals with biopsy-proven NAFLD (n = 9, mean age 50 years, mean BMI 35 kg/m2 , no/mild fibrosis), cirrhosis with hepatic steatosis (n = 10, age 62 years, BMI 32 kg/m2 , CHILD A/B) and healthy controls (n = 10, age 23, BMI 25 kg/m2 ), randomized 1:1 to fasting or standardized mixed meal test (postprandial). None of the patients randomized to mixed meal test had type 2 diabetes (T2D). Peripheral blood was collected for 120 min. After 60 min, a transjugular liver biopsy and liver vein blood was taken. Plasma levels of glucose, insulin, C-peptide, glucagon, and fibroblast growth factor 21 (FGF21) were measured. Postprandial peak glucose and C-peptide were significantly increased in NAFLD, and cirrhosis compared with healthy. Patients with NAFLD and cirrhosis had hyperglucagonemia as a potential sign of glucagon resistance. FGF21 was increased in NAFLD and cirrhosis independent of sampling from the liver vein versus peripheral blood. Glucagon levels were higher in the liver vein compared with peripheral blood. Patients with NAFLD and cirrhosis without T2D showed impaired glucose tolerance, hyperinsulinemia, and hyperglucagonemia after a meal compared to healthy individual. Postprandial characterization of patients with NAFLD may be important to capture their metabolic health.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Adulto , Hepatopatia Gordurosa não Alcoólica/metabolismo , Glucagon , Diabetes Mellitus Tipo 2/metabolismo , Peptídeo C , Fígado/metabolismo , Glucose/metabolismo , Cirrose Hepática/metabolismoRESUMO
The risk of pulmonary complications is high after major abdominal surgery but may be reduced by prophylactic postoperative noninvasive ventilation using continuous positive airway pressure (CPAP). This study compared the effects of intermittent mask CPAP (ICPAP) and continuous helmet CPAP (HCPAP) on oxygenation and the risk of pulmonary complications following major abdominal surgery. Patients undergoing open abdominal aortic aneurysm repair or pancreaticoduodenectomy were randomized (1:1) to either postoperative ICPAP or HCPAP. Oxygenation was evaluated as the partial pressure of oxygen in arterial blood fraction of inspired oxygen ratio (PaO2/FIO2) at 6 h, 12 h, and 18 h postoperatively. Pulmonary complications were defined as X-ray verified pneumonia/atelectasis, clinical signs of pneumonia, or supplementary oxygen beyond postoperative day 3. Patient-reported comfort during CPAP treatment was also evaluated. In total, 96 patients (ICPAP, n = 48; HCPAP, n = 48) were included, and the type of surgical procedure were evenly distributed between the groups. Oxygenation did not differ between the groups by 6 h, 12 h, or 18 h postoperatively (p = 0.1, 0.08, and 0.67, respectively). Nor was there any difference in X-ray verified pneumonia/atelectasis (p = 0.40) or supplementary oxygen beyond postoperative day 3 (p = 0.53). Clinical signs of pneumonia tended to be more frequent in the ICPAP group (p = 0.06), yet the difference was not statistically significant. Comfort scores were similar in both groups (p = 0.43), although a sensation of claustrophobia during treatment was only experienced in the HCPAP group (11% vs. 0%, p = 0.03). Compared with ICPAP, using HCPAP was associated with similar oxygenation (i.e., PaO2/FIO2 ratio) and a similar risk of pulmonary complications. However, HCPAP treatment was associated with a higher sensation of claustrophobia.
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Pneumonia , Atelectasia Pulmonar , Humanos , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Oxigênio , Atelectasia Pulmonar/complicações , Atelectasia Pulmonar/prevenção & controle , Pneumonia/prevenção & controleRESUMO
Pulmonary embolism response teams (PERT) aim to improve treatment of acute pulmonary embolism (PE). PERT focus on intermediate- and high-risk PE patients, but recent multicenter studies show that low-risk PE patients compose one in five of all PERT cases. Conversely, not all intermediate- and high-risk PE patients elicit a PERT activation. The factors leading to PERT activations remain unknown. This study aims to describe the patient characteristics associated with PERT activation for low-risk PE patients and characteristics precluding PERT activation for intermediate/high-risk PE patients. We analysed data from all patients with confirmed PE diagnosed in the Massachusetts General Hospital Emergency Department from August 2013 to February 2017 and cross-referred these data with patients who received a PERT activation and patients who did not. Patients were stratified into low-risk or intermediate/high-risk PE. Univariate analyses were performed within each risk group comparing patients with a PERT activation and patients without. Fifteen percent (56/374) of low-risk PE patients triggered a PERT activation. Patient characteristics associated with PERT activation were: (1) vascular disease, (2) pulmonary diseases, (3) thrombophilia, (4) current use of anticoagulants, (5) central PE and (6) concurrent DVT. Thirty-five percent (110/283) of intermediate/high-risk PE patients did not elicit a PERT activation. Patient characteristics precluding a PERT activation were: (1) vascular disease, (2) malignancies and (3) asymptomatic presentation. Low-risk PE patients with PERT activations had more extensive clot burden, complex comorbidities, or had failed anticoagulation treatment. Intermediate/high-risk PE patients without PERT activations tended to have malignancies or vascular disease.
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Equipe de Assistência ao Paciente , Embolia Pulmonar , Anticoagulantes , Humanos , Massachusetts/epidemiologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Fatores de RiscoRESUMO
[This corrects the article DOI: 10.1016/j.jhepr.2021.100287.].
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Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.
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Cateterismo Cardíaco , Coração , Animais , Catéteres , Ventrículos do Coração , SuínosRESUMO
BACKGROUND & AIMS: Prognostic models of cirrhosis underestimate disease severity for patients with cirrhosis and ascites. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein linked to hepatic neoangiogenesis and fibrogenesis. We investigated ascites MFAP4 as a predictor of transplant-free survival in patients with cirrhosis and ascites. METHODS: A dual-centre observational study of patients with cirrhosis and ascites recruited consecutively in relation to a paracentesis was carried out. Patients were followed up for 1 year, until death or liver transplantation (LTx). Ascites MFAP4 was tested with the model for end-stage liver disease (MELD-Na), CLIF Consortium Acute Decompensation (CLIF-C AD), and Child-Pugh score in Cox regression models. RESULTS: Ninety-three patients requiring paracentesis were included. Median ascites MFAP4 was 29.7 U/L [22.3-41.3], and MELD-Na was 19 [16-23]. A low MELD-Na score (<20) was observed in 49 patients (53%). During follow-up, 20 patients died (22%), and 6 received LTx (6%). High ascites MFAP4 (>29.7 U/L) was associated with 1-year transplant-free survival (p = 0.002). In Cox regression, ascites MFAP4 and MELD-Na independently predicted 1-year transplant-free survival (hazard ratio [HR] = 0.97, p = 0.03, and HR = 1.08, p = 0.01, respectively). Ascites MFAP4 and CLIF-C AD also predicted survival independently (HR = 0.96, p = 0.02, and HR = 1.05, p = 0.03, respectively), whereas only ascites MFAP4 did, controlling for the Child-Pugh score (HR = 0.97, p = 0.03, and HR = 1.18, p = 0.16, respectively). For patients with MELD-Na <20, ascites MFAP4 but not ascites protein predicted 1-year transplant-free survival (HR 0.91, p = 0.02, and HR = 0.94, p = 0.17, respectively). CONCLUSIONS: Ascites MFAP4 predicts 1-year transplant-free survival in patients with cirrhosis and ascites. In patients with low MELD-Na scores, ascites MFAP4, but not total ascites protein, significantly predicted 1-year transplant-free survival. LAY SUMMARY: Patients with cirrhosis who have fluid in the abdomen, ascites, are at an increased risk of death and in need for liver transplantation. Our study identified patients with ascites and a poor prognosis by measuring microfibrillar associated protein 4 (MFAP4), a protein present in the abdominal fluid. Patients with low levels of the MFAP4 protein are at particularly increased risk of death or liver transplantation, suggesting that clinical care should be intensified in this group of patients.
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OBJECTIVES: To investigate if oxygen could unload the right ventricle and improve right ventricle function in a porcine model mimicking intermediate-high risk acute pulmonary embolism. DESIGN: Controlled, blinded, animal study. SETTING: Tertiary university hospital, animal research laboratory. SUBJECTS: Female, Danish pigs (n = 16, approximately 60 kg). INTERVENTIONS: Acute autologous pulmonary embolism was induced until doubling of baseline mean pulmonary arterial pressure. Group 1 animals (n = 8) received increasing Fio2 (40%, 60%, and 100%) for time intervals of 15 minutes returning to atmospheric air between each level of Fio2. In group 2 (n = 8), the effects of Fio2 40% maintained over 75 minutes were studied. In both groups, pulmonary vasodilatation from inhaled nitric oxide (40 parts per million) was used as a positive control. MEASUREMENTS AND MAIN RESULTS: Effects were evaluated by biventricular pressure-volume loop recordings, right heart catheterization, and arterial and mixed venous blood gasses. Pulmonary embolism increased mean pulmonary arterial pressure from 15 ± 4 to 33 ± 6 mm Hg (p = 0.0002) and caused right ventricle dysfunction (p < 0.05) with troponin release (p < 0.0001). In group 1, increasing Fio2 lowered mean pulmonary arterial pressure (p < 0.0001) and pulmonary vascular resistance (p = 0.0056) and decreased right ventricle volumes (p = 0.0018) and right ventricle mechanical work (p = 0.034). Oxygenation was improved and pulmonary shunt was lowered (p < 0.0001). Maximal hemodynamic effects were seen at Fio2 40% with no additional benefit from higher fractions of oxygen. In group 2, the effects of Fio2 40% were persistent over 75 minutes. Supplemental oxygen showed the same pulmonary vasodilator efficacy as inhaled nitric oxide (40 parts per million). No adverse effects were observed. CONCLUSIONS: In a porcine model mimicking intermediate-high risk pulmonary embolism, oxygen therapy reduced right ventricle afterload and lowered right ventricle mechanical work. The effects were immediately present and persistent and were similar to inhaled nitric oxide. The intervention is easy and safe. The study motivates extended clinical evaluation of supplemental oxygen in acute pulmonary embolism.
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Oxigenoterapia/normas , Embolia Pulmonar/fisiopatologia , Função Ventricular Direita/efeitos dos fármacos , Animais , Dinamarca , Oxigenoterapia/métodos , Oxigenoterapia/estatística & dados numéricos , Embolia Pulmonar/tratamento farmacológico , SuínosRESUMO
OBJECTIVE: The use of inferior vena cava (IVC) filters is controversial. However, the procedure is widely performed for secondary prophylaxis in patients with severe pulmonary embolism (PE), including those treated by a PE response team (PERT). In this study, we analyzed patient factors associated with the clinical decision to place an IVC filter in PERT patients. METHODS: Data were collected on all Massachusetts General Hospital patients who had a PERT activation from October 1, 2012, to January 29, 2019. Data describing demographics, medical history, PE characteristics and treatment were collected at the time of PERT activation and prospectively for one year after PERT activation. Univariate and multivariable regression analyses were performed to determine factors associated with IVC filter placement. RESULTS: We identified 834 patients, of whom 91 (10.9%) had an IVC filter placed in the first 7 days after PERT activation. The majority of patients receiving an IVC filter were male (55/91 [60.4%]; P =.096) with a mean age of 65 ± 15.0 years. Patients who received an IVC filter were less likely to have had a PERT referral from the Emergency Department (ED) (41/544 [7.5%]; P < .001) and more likely to have been referred from the intensive care unit (24/107 [22.43%]; P ≤ .001) compared with a floor referral. Patients who presented with syncope (15/86 [17.4%]; P = .040), a history of recent trauma (12/41 [29.3%]; P < .001), intracranial hemorrhage (11/39 [28.2%]; P = .002), a recent surgery or invasive procedure (30/188 [16.0%]; P = .012), a recent surgery (29/160 [18.1%]; P = .001) and a recent hospitalization (38/250 [15.2%]; P = .009) were more likely to have an IVC filter placed. Patients receiving an IVC filter were also more likely to have evidence of right heart dysfunction on a computed tomography pulmonary angiogram (61/359 [17.0%]; P < .001) and an echocardiogram (26/144 [18.1%]; P = .003). Compared with patients without an IVC filter, the 30-day venous thromboembolism recurrence rate was higher (4.7% vs 11.0%) in patients with IVC filters (10/45 [22.2%]; P = .023). CONCLUSIONS: Factors associated with venous thromboembolism severity (eg, PERT referral from intensive care unit and right ventricular dysfunction) and an increased bleeding risk (eg, recent surgery or trauma) were associated with IVC filter placement among PERT patients.
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Tomada de Decisão Clínica , Equipe de Assistência ao Paciente , Embolia Pulmonar/prevenção & controle , Prevenção Secundária , Filtros de Veia Cava , Idoso , Cuidados Críticos , Feminino , Hemorragia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Disfunção Ventricular Direita/complicações , Ferimentos e Lesões/complicaçõesRESUMO
OBJECTIVES: To compare the hemodynamic effects of increased versus decreased preload in a porcine model of acute intermediate-risk pulmonary embolism. DESIGN: Randomized, controlled animal study. SETTING: Tertiary medical center, animal research laboratory. SUBJECTS: Female, Danish slaughter pigs (n = 22, ~ 60 kg). INTERVENTIONS: Acute pulmonary embolism was induced by large emboli made from clotting of autologous blood. Sixteen animals were randomized to either fluid loading (n = 8, isotonic saline, 1 L/hr for 2 hr) or diuretic treatment (n = 8, furosemide, 40 mg every 30 min, total 160 mg) and compared with a vehicle group (n = 6, no treatment). MEASUREMENTS AND MAIN RESULTS: Hemodynamics were evaluated at baseline, after pulmonary embolism and after each dose by biventricular pressure-volume loops, invasive pressures, diuretic output, respiratory variables, and blood analysis. Pulmonary embolism increased mean pulmonary arterial pressure (p < 0.0001), pulmonary vascular resistance (p = 0.008), right ventricular arterial elastance (p = 0.003), and right ventricular end-systolic volume (p = 0.020) while right ventricular stroke volume and right ventricular ejection fraction were decreased (p = 0.047 and p = 0.0003, respectively) compared with baseline. Fluid loading increased right ventricular end-diastolic volume (+31 ± 13 mL; p = 0.004), right ventricular stroke volume (+23 ± 10 mL; p = 0.009), cardiac output (+2,021 ± 956 mL; p = 0.002), and right ventricular ejection fraction (+7.6% ± 1.5%; p = 0.032), whereas pulmonary vascular resistance decreased (-202 ± 65 dynes; p = 0.020) compared with vehicle. Diuretic treatment decreased right ventricular end-diastolic volume (-84 ± 11 mL; p < 0.001), right ventricular stroke volume (-40 ± 6 mL; p = 0.001), cardiac output (-3,327 ± 451 mL; p = 0.005), and mean pulmonary arterial pressure (-7 ± 1 mm Hg; p < 0.001) and increased right ventricular end-systolic elastance (+0.72 ± 0.2 mm Hg/mL; p < 0.001) and systemic vascular resistance (+1,812 ± 767 dynes; p < 0.001) with no effects on mean arterial pressure. CONCLUSIONS: In a porcine model of acute intermediate-risk pulmonary embolism, fluid loading increased right ventricular preload and right ventricular stroke volume, whereas diuretics decreased right ventricular preload and right ventricular stroke volume without affecting mean arterial pressure.
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Hemodinâmica , Embolia Pulmonar/fisiopatologia , Função Ventricular Direita , Animais , Pressão Sanguínea/fisiologia , Feminino , Hemodinâmica/fisiologia , Suínos , Resistência Vascular/fisiologia , Função Ventricular Direita/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: Refractory ascites markedly worsens prognosis in cirrhosis. Large volume paracentesis (LVP) is standard treatment, but complications are common. In a randomized controlled case-series, we assessed a permanent tunneled peritoneal catheter versus LVP in patients with cirrhosis and ascites. MATERIALS AND METHODS: Random allocation was computer-generated, and concealment used opaque envelopes. Patients were included from January 2017 to December 2018. Inclusion criteria were cirrhosis and recurrent ascites and expected survival of more than 3 months. RESULTS: Thirteen patients were enrolled (PleurX =6 versus LVP = 7). Seven were female, ranging in age from 51 to 80 years. No procedure-related complications occurred. Two patients died due to variceal bleeding (PleurX-group) and sepsis (LVP-group). One patient was withdrawn due to hyponatremia (PleurX-group). Two patients were withdrawn due to bacterial peritonitis and infection of unknown origin (control-group). In the PleurX-group, all patients colonized the catheter, two developed bacterial peritonitis. The most common bacterial colonization was Staph. Epidermidis (n = 4). CONCLUSIONS: In selected patients, the PleurX catheter mobilizes ascites and may be an alternative to LVP. The risk of infection should be considered in each case. The impact of colonization and risk of infections needs further investigation. The present trial does not allow for statistical conclusions.
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Ascite , Varizes Esofágicas e Gástricas , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Ascite/terapia , Feminino , Hemorragia Gastrointestinal , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , ParacenteseRESUMO
BACKGROUND: Inhaled nitric oxide (iNO) effectively reduces right ventricular afterload when administered in the immediate phase of acute pulmonary embolism (PE) in preclinical animal models. In a porcine model of intermediate-risk PE, we aimed to investigate whether iNO has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute PE. METHODS: Anesthetized pigs (n = 18) were randomized into three subgroups. An acute PE iNO-group (n = 6) received iNO at 40 ppm at one, three, six, nine and 12 hours after onset of PE. Vehicle animals (n = 6) received PE, but no active treatment. A third group of sham animals (n = 6) received neither PE nor treatment. Animals were evaluated using intravascular pressures, respiratory parameters, biochemistry and intracardiac pressure-volume measurements. RESULTS: The administration of PE increased mean pulmonary artery pressure (mPAP) (vehicle vs sham; 33.3 vs 17.7 mmHg, p < 0.0001), pulmonary vascular resistance (vehicle vs sham; 847.5 vs 82.0 dynes, p < 0.0001) and right ventricular arterial elastance (vehicle vs sham; 1.2 vs 0.2 mmHg/ml, p < 0.0001). Significant mPAP reduction by iNO was preserved at 12 hours after the onset of acute PE (vehicle vs iNO; 0.5 vs -3.5 mmHg, p < 0.0001). However, this response was attenuated over time (p = 0.0313). iNO did not affect the systemic circulation. CONCLUSIONS: iNO is a safe and effective pulmonary vasodilator both in the immediate and prolonged phase of acute PE in an in-vivo porcine model of intermediate-risk PE.
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OBJECTIVE: Artificial proprioceptive feedback from a myoelectric prosthesis is an important aspect in enhancing embodiment and user satisfaction, possibly lowering the demand for visual attention while controlling a prosthesis in everyday tasks. Contemporary myoelectric prostheses are advanced mechatronic systems with multiple degrees of freedom, and therefore, to communicate the prosthesis state, the feedback interface needs to transmit several variables simultaneously. In the present study, two different configurations for conveying proprioceptive information of wrist rotation and hand aperture through multichannel electrotactile stimulation were developed and evaluated during online myoelectric control. APPROACH: Myoelectric recordings were acquired from the dominant forearm and electrotactile stimulation was delivered on the non-dominant forearm using a compact interface. The first feedback configuration, which was based on spatial coding, transmitted the information using a moving tactile stimulus, whereas the second, amplitude-based configuration conveyed the position via sensation intensity. Thirteen able-bodied subjects used pattern classification-based myoelectric control with both feedback configurations to accomplish a target-reaching task. MAIN RESULTS: High task performance (completion rate > 90%) was observed for both configurations, with no significant difference in completion rate, time to reach the target, distance error and path efficiency, respectively. SIGNIFICANCE: Overall, the results demonstrated that both feedback configurations allowed subjects to perceive and interpret two feedback variables delivered simultaneously, despite using a compact stimulation interface. This is an encouraging result for the prospect of communicating the full state of a multifunctional hand prosthesis.
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Membros Artificiais , Força da Mão , Eletromiografia , Retroalimentação , Retroalimentação Sensorial , Mãos , Humanos , Desenho de PróteseRESUMO
BACKGROUND: The haemodynamic response following acute, intermediate-risk pulmonary embolism is not well described. We aimed to describe the cardiovascular changes in the initial, critical phase 0-12 hours after acute pulmonary embolism in an in-vivo porcine model. METHODS: Pigs were randomly allocated to pulmonary embolism (n = 6) or sham (n = 6). Pulmonary embolism was administered as autologous blood clots (20 × 1 cm) until doubling of mean pulmonary arterial pressure or mean pulmonary arterial pressure was greater than 34 mmHg. Sham animals received saline. Cardiopulmonary changes were evaluated for 12 hours after intervention by biventricular pressure-volume loop recordings, invasive pressure measurements, arterial and central venous blood gas analyses. RESULTS: Mean pulmonary arterial pressure increased (P < 0.0001) and stayed elevated for 12 hours in the pulmonary embolism group compared to sham. Pulmonary vascular resistance and right ventricular arterial elastance (right ventricular afterload) were increased in the first 11 and 6 hours, respectively, after pulmonary embolism (P < 0.01 for both) compared to sham. Right ventricular ejection fraction was reduced (P < 0.01) for 8 hours, whereas a near-significant reduction in right ventricular stroke volume was observed (P = 0.06) for 4 hours in the pulmonary embolism group compared to sham. Right ventricular ventriculo-arterial coupling was reduced (P < 0.05) for 6 hours following acute pulmonary embolism despite increased right ventricular mechanical work in the pulmonary embolism group (P < 0.01) suggesting right ventricular failure. CONCLUSIONS: In a porcine model of intermediate-risk pulmonary embolism, the increased right ventricular afterload caused initial right ventricular ventriculo-arterial uncoupling and dysfunction. After approximately 6 hours, the right ventricular afterload returned to pre-pulmonary embolism values and right ventricular function improved despite a sustained high pulmonary arterial pressure. These results suggest an initial critical and vulnerable phase of acute pulmonary embolism before haemodynamic adaptation.
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BACKGROUND: The haemodynamic response following acute, intermediate-risk pulmonary embolism is not well described. We aimed to describe the cardiovascular changes in the initial, critical phase 0-12 hours after acute pulmonary embolism in an in-vivo porcine model. METHODS: Pigs were randomly allocated to pulmonary embolism (n = 6) or sham (n = 6). Pulmonary embolism was administered as autologous blood clots (20 × 1 cm) until doubling of mean pulmonary arterial pressure or mean pulmonary arterial pressure was greater than 34 mmHg. Sham animals received saline. Cardiopulmonary changes were evaluated for 12 hours after intervention by biventricular pressure-volume loop recordings, invasive pressure measurements, arterial and central venous blood gas analyses. RESULTS: Mean pulmonary arterial pressure increased (P < 0.0001) and stayed elevated for 12 hours in the pulmonary embolism group compared to sham. Pulmonary vascular resistance and right ventricular arterial elastance (right ventricular afterload) were increased in the first 11 and 6 hours, respectively, after pulmonary embolism (P < 0.01 for both) compared to sham. Right ventricular ejection fraction was reduced (P < 0.01) for 8 hours, whereas a near-significant reduction in right ventricular stroke volume was observed (P = 0.06) for 4 hours in the pulmonary embolism group compared to sham. Right ventricular ventriculo-arterial coupling was reduced (P < 0.05) for 6 hours following acute pulmonary embolism despite increased right ventricular mechanical work in the pulmonary embolism group (P < 0.01) suggesting right ventricular failure. CONCLUSIONS: In a porcine model of intermediate-risk pulmonary embolism, the increased right ventricular afterload caused initial right ventricular ventriculo-arterial uncoupling and dysfunction. After approximately 6 hours, the right ventricular afterload returned to pre-pulmonary embolism values and right ventricular function improved despite a sustained high pulmonary arterial pressure. These results suggest an initial critical and vulnerable phase of acute pulmonary embolism before haemodynamic adaptation.
RESUMO
BACKGROUND: Inhaled nitric oxide (iNO) effectively reduces right ventricular afterload when administered in the immediate phase of acute pulmonary embolism (PE) in preclinical animal models. In a porcine model of intermediate-risk PE, we aimed to investigate whether iNO has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute PE. METHODS: Anesthetized pigs (n = 18) were randomized into three subgroups. An acute PE iNO-group (n = 6) received iNO at 40 ppm at one, three, six, nine and 12 hours after onset of PE. Vehicle animals (n = 6) received PE, but no active treatment. A third group of sham animals (n = 6) received neither PE nor treatment. Animals were evaluated using intravascular pressures, respiratory parameters, biochemistry and intracardiac pressure-volume measurements. RESULTS: The administration of PE increased mean pulmonary artery pressure (mPAP) (vehicle vs sham; 33.3 vs 17.7 mmHg, p < 0.0001), pulmonary vascular resistance (vehicle vs sham; 847.5 vs 82.0 dynes, p < 0.0001) and right ventricular arterial elastance (vehicle vs sham; 1.2 vs 0.2 mmHg/ml, p < 0.0001). Significant mPAP reduction by iNO was preserved at 12 hours after the onset of acute PE (vehicle vs iNO; 0.5 vs -3.5 mmHg, p < 0.0001). However, this response was attenuated over time (p = 0.0313). iNO did not affect the systemic circulation. CONCLUSIONS: iNO is a safe and effective pulmonary vasodilator both in the immediate and prolonged phase of acute PE in an in-vivo porcine model of intermediate-risk PE.