Effects of combined aerobic, resistance and inspiratory training in patients with pulmonary hypertension: A systematic review.

BACKGROUND: Pulmonary hypertension (PH) is a serious progressive disorder of the modern world, characterized by endothelial dysfunction and impaired vasoreactivity. Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity. Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities. However, data regarding the effects of combined exercise training programs in patients with PH still remains limited. AIM: To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH. METHODS: Our search included all available randomized controlled trials (RCTs) regarding combined aerobic, resistance and inspiratory training programs in patients with PH in 4 databases (Pubmed, PEDro, Embase, CINAHL) from 2012 to 2022. Five RCTs were included in the final analysis. Functional capacity, assessed by peak VO2 or 6-min walking test (6MWT), as well as quality of life, assessed by the SF-36 questionnaire, were set as the primary outcomes in our study. RESULTS: Peak VO2 was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs. Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs (P < 0.05). Quality of life was measured in 4 out of 5 RCTs. Although patients improved their quality of life in each group, however, only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls. CONCLUSION: By this systematic review, we have demonstrated that combined aerobic, resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH. Such exercise training regimen may be part of the therapeutic strategy of the syndrome.

Intensive Care Unit Hyperglycemia After Cardiac Surgery: Risk Factors and Clinical Outcomes.

OBJECTIVES: Patients with hyperglycemia after cardiac surgery face increased morbidity and mortality due to postoperative complications. The main purpose of this study was to evaluate the incidence of postoperative hyperglycemia, the hyperglycemia risk factors, and its association with clinical outcomes in patients admitted to the cardiac surgery intensive care unit after cardiac surgery. DESIGN: Prospective, observational study. SETTING: Single-center hospital. PARTICIPANTS: Two hundred ten consecutive postoperative cardiac surgery patients admitted to the cardiac surgery intensive care unit. INTERVENTIONS: Patients' blood glucose levels were evaluated immediately after cardiac surgery and every 3 hours daily for 7 days or earlier upon discharge. Intravenous insulin was administered as per the institution's protocol. Perioperative predisposing risk factors for hyperglycemia and clinical outcomes were assessed. MEASUREMENTS AND MAIN RESULTS: Postoperative hyperglycemia, defined as glucose level ≥180 mg/dL, occurred in 30% of cardiac surgery patients. Diabetes mellitus (odds ratio [OR] 6.73; 95% CI [3.2-14.3]; p < 0.001), white blood cell count (OR 1.28; 95% CI [1.1-1.4]; p < 0.001), and EuroSCORE II (OR 1.20; 95% CI [1.1-1.4]; p = 0.004) emerged as independent prognostic factors for hyperglycemia. Moreover, patients with glucose ≥180 mg/dL had higher rates of acute kidney injury (34.9% v 18.9%, p = 0.013), longer duration of mechanical ventilation (959 v 720 min, p = 0.019), and sedation (711 v 574 min, p = 0.034), and higher levels of intensive care unit (ICU)-acquired weakness (14% v 5.5%, p = 0.027) and rate of multiorgan failure (6.3% v 0.7%, p = 0.02) compared with patients with glucose levels <180 mg/dL. CONCLUSIONS: In the intensive care unit, hyperglycemia occurs frequently in patients immediately after cardiac surgery. Diabetes, high EuroSCORE II, and preoperative leukocytosis are independent risk factors for postoperative hyperglycemia. Hyperglycemia is associated with worse clinical outcomes, including a higher rate of acute kidney injury and ICU-acquired weakness, greater duration of mechanical ventilation, and a higher rate of multiorgan failure.

Incidence and peri-operative risk factors for development of acute kidney injury in patients after cardiac surgery: A prospective observational study.

BACKGROUND: Patients admitted to intensive care unit (ICU) after cardiac surgery develop acute kidney injury (AKI) immediately post-operation. We hypothesized that AKI occurs mainly due to perioperative risk factors and may affect outcome. AIM: To assess peri-operative risk factors for AKI post cardiac surgery and its relationship with clinical outcome. METHODS: This was an observational single center, tertiary care setting study, which enrolled 206 consecutive patients, admitted to ICU after cardiac surgery. Patients were followed-up until ICU discharge or death, in order to determine the incidence of AKI, perioperative risk factors for AKI and its association with outcome. Univariate and multivariate logistic regression analysis was performed to assess predictor variables for AKI development. RESULTS: After ICU admission, 55 patients (26.7%) developed AKI within 48 h. From the logistic regression analysis performed, high EuroScore II (OR: 1.18; 95%CI: 1.06-1.31, P = 0.003), white blood cells (WBC) pre-operatively (OR: 1.0; 95%CI: 1.0-1.0, P = 0.002) and history of chronic kidney disease (OR: 2.82; 95%CI: 1.195-6.65, P = 0.018) emerged as independent predictors of AKI among univariate predictors. AKI that developed AKI had longer duration of mechanical ventilation [1113 (777-2195) vs 714 (511-1020) min, P = 0.0001] and ICU length of stay [70 (28-129) vs 26 (21-51) h, P = 0.0001], higher rate of ICU-acquired weakness (16.4% vs 5.3%, P = 0.015), reintubation (10.9% vs 1.3%, P = 0.005), dialysis (7% vs 0%, P = 0.005), delirium (36.4% vs 23.8%, P = 0.001) and mortality (3.6% vs 0.7%, P = 0.046). CONCLUSION: Patients present frequently with AKI after cardiac surgery. EuroScore II, WBC count and chronic kidney disease are independent predictors of AKI development. The occurrence of AKI is associated with poor outcome.

Modelling SARS-CoV-2 Binding Antibody Waning 8 Months after BNT162b2 Vaccination.

Several lines of evidence suggest that binding SARS-CoV-2 antibodies such as anti-SARS-CoV-2 RBD IgG (anti-RBD) and neutralising antibodies (NA) are correlates of protection against SARS-CoV-2, and the correlation of anti-RBD and NA is very high. The effectiveness (VE) of BNT162b2 in preventing SARS-CoV-2 infection wanes over time, and this reduction is mainly associated with waning immunity, suggesting that the kinetics of antibodies reduction might be of interest to predict VE. In a study of 97 health care workers (HCWs) vaccinated with the BNT162b2 vaccine, we assessed the kinetics of anti-RBD 30-250 days after vaccination using 388 individually matched plasma samples. Anti-RBD levels declined by 85%, 92%, and 95% at the 4th, 6th, and 8th month from the peak, respectively. The kinetics were estimated using the trajectories of anti-RBD by various models. The restricted cubic splines model had a better fit to the observed data. The trajectories of anti-RBD declines were statistically significantly lower for risk factors of severe COVID-19 and the absence of vaccination side effects. Moreover, previous SARS-CoV-2 infection was associated with divergent trajectories consistent with a slower anti-RBD decline over time. These results suggest that anti-RBD may serve as a harbinger for vaccine effectiveness (VE), and it should be explored as a predictor of breakthrough infections and VE.

Modalities of Exercise Training in Patients with Extracorporeal Membrane Oxygenation Support.

The aim of this qualitative systematic review is to summarize and analyze the different modalities of exercise training and its potential effects in patients on extracorporeal membrane oxygenation (ECMO) support. ECMO is an outbreaking, life-saving technology of the last decades which is being used as a gold standard treatment in patients with severe cardiac, respiratory or combined cardiorespiratory failure. Critically ill patients on ECMO very often present intensive care unit-acquired weakness (ICU-AW); thus, leading to decreased exercise capacity and increased mortality rates. Early mobilization and physical therapy have been proven to be safe and feasible in critically ill patients on ECMO, either as a bridge to lung/heart transplantation or as a bridge to recovery. Rehabilitation has beneficial effects from the early stages in the ICU, resulting in the prevention of ICU-AW, and a decrease in episodes of delirium, the duration of mechanical ventilation, ICU and hospital length of stay, and mortality rates. It also improves functional ability, exercise capacity, and quality of life. Rehabilitation requires a very careful, multi-disciplinary approach from a highly specialized team from different specialties. Initial risk assessment and screening, with appropriate physical therapy planning and exercise monitoring in patients receiving ECMO therapy are crucial factors for achieving treatment goals. However, more randomized controlled trials are required in order to establish more appropriate individualized exercise training protocols.

Exercise training in heart transplantation.

Heart transplantation remains the gold standard in the treatment of end-stage heart failure (HF). Heart transplantation patients present lower exercise capacity due to cardiovascular and musculoskeletal alterations leading thus to poor quality of life and reduction in the ability of daily self-service. Impaired vascular function and diastolic dysfunction cause lower cardiac output while decreased skeletal muscle oxidative fibers, enzymes and capillarity cause arteriovenous oxygen difference, leading thus to decreased peak oxygen uptake in heart transplant recipients. Exercise training improves exercise capacity, cardiac and vascular endothelial function in heart transplant recipients. Pre-rehabilitation regular aerobic or combined exercise is beneficial for patients with end-stage HF awaiting heart transplantation in order to maintain a higher fitness level and reduce complications afterwards like intensive care unit acquired weakness or cardiac cachexia. All hospitalized patients after heart transplantation should be referred to early mobilization of skeletal muscles through kinesiotherapy of the upper and lower limbs and respiratory physiotherapy in order to prevent infections of the respiratory system prior to hospital discharge. Moreover, all heart transplant recipients after hospital discharge who have not already participated in an early cardiac rehabilitation program should be referred to a rehabilitation center by their health care provider. Although high intensity interval training seems to have more benefits than moderate intensity continuous training, especially in stable transplant patients, individualized training based on the abilities and needs of each patient still remains the most appropriate approach. Cardiac rehabilitation appears to be safe in heart transplant patients. However, long-term follow-up data is incomplete and, therefore, further high quality and adequately-powered studies are needed to demonstrate the long-term benefits of exercise training in this population.

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19.

INTRODUCTION: Greece is a country with limited spread of SARS-CoV-2 and cumulative infection attack rate of 0.12% (95% CI 0.06-0.26). Health care workers (HCWs) are a well-recognized risk group for COVID-19. The study aimed to estimate the seroprevalence of antibodies to SARS-CoV-2 in a nosocomial setting and assess potential risk factors. METHODS: HCWs from two hospitals participated in the study. Hospital-1 was a tertiary university affiliated center, involved in the care of COVID-19 patients while hospital-2 was a tertiary specialized cardiac surgery center not involved in the care of these patients. A validated, CE, rapid, IgM/IgG antibody point-of-care test was used. Comparative performance with a reference globally available assay was assessed. RESULTS: 1,495 individuals consented to participate (response rate 77%). The anti-SARS-CoV-2 weighted prevalence was 1.26% (95% CI 0.43, 3.26) overall and 0.53% (95% CI 0.06, 2.78) and 2.70% (95% CI 0.57, 9.19) in hospital-1 and hospital-2, respectively although the study was underpowered to detect statistically significant differences. The overall, hospital-1, and hospital-2 seroprevalence was 10, 4 and 22 times higher than the estimated infection attack rate in general population, respectively. Suboptimal use of personal protective equipment was noted in both hospitals. CONCLUSIONS: These data have implications for the preparedness of a second wave of COVID-19 epidemic, given the low burden of SARS-CoV-2 infection rate, in concordance with national projections.

Sonographic muscle mass assessment in patients after cardiac surgery.

BACKGROUND: Patients undergoing cardiac surgery particularly those with comorbidities and frailty, experience frequently higher rates of post-operative morbidity, mortality and prolonged hospital length of stay. Muscle mass wasting seems to play important role in prolonged mechanical ventilation (MV) and consequently in intensive care unit (ICU) and hospital stay. AIM: To investigate the clinical value of skeletal muscle mass assessed by ultrasound early after cardiac surgery in terms of duration of MV and ICU length of stay. METHODS: In this observational study, we enrolled consecutively all patients, following their admission in the Cardiac Surgery ICU within 24 h of cardiac surgery. Bedside ultrasound scans, for the assessment of quadriceps muscle thickness, were performed at baseline and every 48 h for seven days or until ICU discharge. Muscle strength was also evaluated in parallel, using the Medical Research Council (MRC) scale. RESULTS: Of the total 221 patients enrolled, ultrasound scans and muscle strength assessment were finally performed in 165 patients (patients excluded if ICU stay < 24 h). The muscle thickness of rectus femoris (RF), was slightly decreased by 2.2% [(95% confidence interval (CI): - 0.21 to 0.15), n = 9; P = 0.729] and the combined muscle thickness of the vastus intermedius (VI) and RF decreased by 3.5% [(95%CI: - 0.4 to 0.22), n = 9; P = 0.530]. Patients whose combined VI and RF muscle thickness was below the recorded median values (2.5 cm) on day 1 (n = 80), stayed longer in the ICU (47 ± 74 h vs 28 ± 45 h, P = 0.02) and remained mechanically ventilated more (17 ± 9 h vs 14 ± 9 h, P = 0.05). Moreover, patients with MRC score ≤ 48 on day 3 (n = 7), required prolonged MV support compared to patients with MRC score ≥ 49 (n = 33), (44 ± 14 h vs 19 ± 9 h, P = 0.006) and had a longer duration of extracorporeal circulation was (159 ± 91 min vs 112 ± 71 min, P = 0.025). CONCLUSION: Skeletal quadriceps muscle thickness assessed by ultrasound shows a trend to a decrease in patients after cardiac surgery post-ICU admission and is associated with prolonged duration of MV and ICU length of stay.

Life-threatening antineutrophil cytoplasmic antibody-associated vasculitis after influenza A H1N1 infection requiring veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Antineutrophil cytoplasmic autoantibody-associated vasculitis is an immune-mediated necrotizing vasculitis, affecting small- and medium-sized vessels. CASE REPORT: A 22-year-old female patient with free medical history presented with life-threatening pulmonary hemorrhage due to antineutrophil cytoplasmic autoantibody-associated vasculitis, temporarily associated with influenza A H1N1 infection. Due to rapidly worsening respiratory failure, despite conventional management, veno-venous peripheral extracorporeal membrane oxygenation was initiated and continued for 26 days, with subsequent renal replacement therapy. DISCUSSION: We present a case of severe antineutrophil cytoplasmic autoantibody-associated pulmonary vasculitis, managed with veno-venous extracorporeal membrane oxygenation at the initial phase. Despite the significant challenges raised with the use of extracorporeal membrane oxygenation in pulmonary hemorrhage cases, extracorporeal membrane oxygenation may have a significant impact on outcome in this setting, by providing adequate time for a successful immunosuppressive treatment.

Missed Heparin-Induced Thrombocytopenia (HIT) Diagnosis in a Patient with Acute Stent Thrombosis.

BACKGROUND Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy, characterized by thrombocytopenia and high risk for venous and arterial thrombosis. CASE REPORT We report an unusual case of acute stent thrombosis secondary to delayed HIT. A 74-year-old man with non-ST-segment elevation myocardial infarction had a coronary angiography which revealed 2-vessel disease. A bolus of unfractionated heparin (UFH) was administered at admission and he received fondaparinux during his hospitalization. We performed elective percutaneous coronary intervention (PCI) with stents to LAD and LCx. Two hours after PCI, the patient developed acute pulmonary edema, and repeat angiography revealed an occlusive thrombus in the ostial LAD and the LCx. A turbidimetric assay for the rapid detection of plasma anti-PF4/heparin antibodies was negative. After repeated unsuccessful attempts of balloon angioplasty and continuous thrombosis, the patient was transferred for emergency surgical revascularisation and was treated with additional UFH followed by enoxaparin. Platelets decreased gradually to 38 k/µl 7 days after surgery, at which time enoxaparin was replaced with fondaparinux. The subsequent HIT test results were positive. CONCLUSIONS HIT should be considered in patients with multiple recent exposures to anticoagulants, independent of the platelet count, if there are signs and symptoms of thrombosis.

Biovigilance for the Quality and Safety of Medical Products of Human Origin.

Progress in science and technology in the health services has led to the development of methods of regenerating and replacing solid organs, tissues and cells, using human body components to create medical products of human origin intended for clinical use. In the activities in which products of human origin are used, however, from the point of donation and harvesting to the subsequent care of the recipient, medical products of human origin are exposed to the risk of specific complications related to the transmission of infectious diseases, and further side-effects. Biovigilance system application is a basic requirement for ensuring the quality and safety of tissues and cells intended for human use. The quality system focuses on error prevention, maintaining a consistent pattern of agreed assays for tissues and cells intended for clinical use. The implementation of quality and safety standards, the development of medical protocols and cooperation protocols between member states, the implementation of Single European Code (SEC), and the development of electronic traceability systems, all aim at vigilance and the surveillance of medical products of human origin from donation to transplantation.

Clinical presentation and treatment of cardiac myxoma in 153 patients.

Cardiac myxoma (CM) is the most common benign cardiac tumor. We retrospectively reviewed our single center experience in 153 patients with CM over a period 25 years.From November 1993 to May 2017, 153 patients were operated in our institution with diagnosis of a CM. In all patients preoperative, perioperative, and postoperative data were recorded including the long-term follow-up. All patients followed up in the outpatient's clinics and echocardiography at regular intervals.Mean age 59 ±â€Š12 years old. There were 104 women and 49 men. Preoperative clinical manifestations of the patients were hemodynamic consequences (47.7%), asymptomatic (46.4%), systemic embolism (4.5%), systemic manifestations-fever (0.7%), and hemoptysis (0.7%). The most common location of CM was in the left atrium in 82.4% patients. Mean tumors diameter was 4.5 ±â€Š1.9 cm. In addition, we were observed that the age of the patients have differences between sex groups women versus men, 60.3 and 54.8 years old respectively (P = .02). On the other hand the tumor size have not differences between the sex groups (P = .56). Combine operations were performed in 24 (15.7%) patients. New cerebrovascular accident was observed in 2 patients post-op. Mean in-hospital stay was 8.02 ±â€Š2.8 days. In-hospital mortality was 1 patient (0.7%) (from sepsis). During median follow-up 3.7 ±â€Š4.3 years CM recurrence was identified in 5 (3.3%) patients.Surgical resection of CMs contributes in an excellent prognosis and associated with low complications and recurrences rate. Regular long-term follow-up is recommended in all patients with CM.

An alternative technique to safely close the chest after placing a child on central venoarterial extracorporeal membrane oxygenation.

Central venoarterial (VA) placement of extracorporeal membrane oxygenation (ECMO) is performed surgically, and in the majority of cases, the patient remains with an open sternum. Herein, a case of a 3-year-old patient who underwent insertion of a central VA ECMO for heart failure due to acute myocarditis is described. An alternative technique for ECMO placement providing sternal closure and minimizing infection risk for the safe patient transport is described.

Association between lymphocyte expression of the apoptotic receptor Fas and pain in critically ill patients.

OBJECTIVE: Lymphocyte apoptosis in critical illness is associated with immunosuppression. We explored for the first time the associations between pain ratings and expression of the apoptotic receptor Fas on B and T cells in critically ill patients and the potential mediating effects of adrenocorticotropic hormone (ACTH), cortisol, and substance P (SP). DESIGN: This is an exploratory correlational study with repeated measurements (14 days followup) and cross-sectional comparisons. SETTING: This study was conducted in a state hospital in the metropolitan area of Athens, Greece. PARTICIPANTS: The participants were 36 consecutive critically ill patients and 36 matched controls. OUTCOME MEASURES: Pain measured by the self-reported numeric rating scale [NRS], the behavioral pain scale, and the pain assessment scale was the primary outcome measure. Flow cytometry (Fas), electrochemiluminescence (ACTH and cortisol) and enzyme-linked immunosorbent assay (SP) were used. Mixed linear models for repeated measurements and bivariable associations at discrete time points were employed. RESULTS: Significant pain at rest was noted. Pain ratings associated with Fas expression on cytotoxic T cells (P=0.041) and B cells (P=0.005), even after adjustment for a number of clinical treatment factors (P=0.006 and P=0.052, respectively). On the day that more patients were able to communicate, Fas on B cells (r=0.897, P=0.029) and cytotoxic T cells (r=0.832; P=0.037) associated with NRS ratings. Associations between pain ratings and ACTH serum levels were noted (P<0.05). When stress neuropeptide levels were added to the model, the statistical significance of the associations between pain ratings and Fas expression was attenuated (P=0.052-0.063), suggesting that stress neuropeptides may partially mediate the association. CONCLUSION: Preliminary evidence for the association between pain and lymphocyte apoptotic susceptibility is provided. The role of pain management in maintaining immunocompetence in critical illness is worth exploring.

Determinants of prolonged intensive care unit stay in patients after cardiac surgery: a prospective observational study.

BACKGROUND: Prolonged intensive care unit (ICU) stay of patients after cardiac surgery has a major impact on overall cost and resource utilization. The aim of this study was to identify perioperative factors which prolong stay in ICU. METHODS: All adult patients from a single, specialized cardiac center who were admitted to the ICU after cardiac surgery during a 2-month period were included. Demographic and clinical characteristics, comorbidities, preoperative use of drugs, intraoperative variables, and postoperative course were recorded. Hemodynamic and blood gas measurements were recorded at four time intervals during the first 24 postoperative hours. Routine hematologic and biochemical laboratory results were recorded preoperatively and in the first postoperative hours. RESULTS: During the study period 145 adult patients underwent cardiac surgery: 65 (45%) underwent coronary artery bypass graft surgery, 38 (26%) valve surgery, 26 (18%) combined surgery and 16 (11%) other types of cardiac operation. Seventy nine (54%) patients had an ICU stay of less than 24 hours. Random forests analysis identified four variables that had a major impact on the length of stay (LOS) in ICU; these variables were subsequently entered in a logistic regression model: preoperative hemoglobin [odds ratio (OR) =0.68], duration of aortic clamping (OR =1.01) and ratio of arterial oxygen partial pressure to inspired oxygen fraction (PaO2/FiO2) (OR =0.99) and blood glucose during the first four postoperative hours (OR =1.02). ROC curve analysis showed an AUC =0.79, P<0.001, 95% CI: 0.71-0.86. CONCLUSIONS: Low preoperative hemoglobin, prolonged aortic clamping time and low PaO2/FiO2 ratio and blood glucose measured within the first postoperative hours, were strongly related with prolonged LOS in ICU.