Preoperative supervised exercise and outcomes following elective abdominal aortic aneurysm repair

ObjectiveThe aim of this research was to evaluate the role of preoperative supervised exercise training on perioperative outcomes and cardiopulmonary exercise testing (CPET) parameters in patients undergoing elective abdominal aortic aneurysm (AAA) repair, and to analyse the value of different preoperative risk assessment tools in predicting postoperative complications following this intervention.MethodsParticipants in this project were patients with large AAA (≥ 5.5 cm), awaiting elective open or endovascular repair.Study 1: was a prospective randomised controlled trial. Participants were randomised in two parallel groups: a 6-week preoperative exercise training programme or standard treatment.The primary outcome measure was the composite endpoint of postoperative cardiac, pulmonary and renal complications. Secondary outcome measures were: lengths of hospital and critical care stay, APACHE II scores recorded within 6 hours postoperatively, SIRS criteria, thirty-day mortality, reoperation and postoperative bleeding. Patients were followed up for 3 months postoperatively.Study 2: was a sub-group study within Study 1.A sub-group of patients from Study 1 consented to undergo two rather than one preoperative CPETs: the first at baseline, and a second following completion of 6 weeks of exercise or on the day immediately prior to surgery. The primary outcome measure was the effect of exercise on CPET parameters.Study 3 utilised univariate and multivariate analysis to assess the value of different preoperative risk assessment tools in predicting postoperative complications in patients undergoing elective AAA repair.Results:Study 1: 136 patients were recruited, 12 withdrew before operative interventions and were not included in the analysis. A total of 124 patients (62 in each group) were included (111 men, mean (s.d.) age 73 (7) years), of which 46 patients underwent EVAR (23 in each group).14 patients (22.6 per cent) sustained postoperative complications in the exercise group, compared to 26 (41.9 per cent) in the non-exercise group (P=0.021). Four patients (3.2 per cent; 2 in each group) died within 30 days postoperatively.Length of hospital stay was significantly shorter in the exercise group (median (IQR) 7 (5-9) days) than the control group (median (IQR) 8 (6.0 - 12.3) days) (P=0.025).There were no significant differences in the length of critical care stay (P=0.845), APACHE II scores (P=0.256), incidence of re-operations (P=1.000) or postoperative bleeding (P=0.343) between the two study groups.Study 2: 48 patients were recruited: 33 patients in the exercise group, and 15 in the control group. All participants completed their two CPET assessments. A 6-week exercise schedule improved aerobic fitness parameters compared to the control group. Median (IQR) VO2 peak improved from 18.4 (15.0-20.9) to 20.0 (16.9-21.3) ml O2/kg/min; P=0.004, and median AT improved from 12.0 (10.4-14.5) to 13.9 (10.6-15.1) ml O2/kg/min; P=0.012. There were no statistically significant changes in CPET parameters in the control group.Study 3: In 124 patients undergoing elective AAA repair, lower AT (OR 0.59, 9% C.I. 0.38 to 0.89, p=0.014) and higher V-POSSUM scores (OR 1.42, 95% C.I. 1.16 to 1.75, p=0.001) were the only independent predictors of postoperative complications.A low AT was an independent predictor of cardiac complications (OR 0.59, 95% C.I. 0.36 to 0.96, p=0.034) and a high VE/VCO2 predicted pulmonary complications (OR 1.24, 95% C.I. 1.03 to 1.51, p=0.027).ConclusionPreoperative supervised exercise training appears to reduce postoperative complications and length of hospital stay in patients undergoing elective AAA repair. The mechanism appears to be an improvement in aerobic fitness preoperatively.CPET is a valuable preoperative assessment tool for elective AAA patients as it predicts organ-specific complications and may be useful in directing perioperative care

Attitudes towards the surgical safety checklist and factors associated with its use : a global survey of frontline medical professionals:a global survey of frontline medical professionals

Background: The Surgical Safety Checklist (SSC) has been shown to reduce perioperative errors and complications and its implementation is recommended by the World Health Organisation (WHO). However, it is unknown how widely this intervention is used. We investigated attitudes and factors associated with use of WHO SSC in frontline medical professionals across the globe using a survey distributed through social networks. Methods: A survey of usage and opinions regarding the SSC was posted on the Facebook and Twitter pages of a not-for-profit surgical news website for one month (March 2013). Respondents were grouped into four groups based on their country's Gross National Income: high, upper middle, lower middle and low income. Univariate and multivariate analyses were performed to investigate how different factors were associated with the use of the SSC. Results: 6269 medical professionals from 69 countries responded to the survey: most respondents were from lower middle (47.4%) countries, followed by: high (35.0%), upper middle (14.6%), and low (3.0%) income countries. In total, 57.5% reported that they used the WHO SSC perioperatively. Fewer respondents used the WHO SSC in upper middle, lower middle and low income countries (LMICs) compared to high income countries (43.5% vs. 83.5%, p < 0.001). Female (61.3% vs. 56.4% males, p = 0.001), consultant surgeons (59.6% vs. 53.2% interns, p < 0.001) and working in university hospitals (61.4% vs. 53.7% non-university hospitals, p < 0.001) were more likely to use the SSC. Believing the SSC was useful, did not work or caused delays was independently associated with the respondents reported use of the SSC (OR 1.22 95% CI 1.07–1.39; OR 0.47 95% CI 0.36–0.60; OR 0.64 95% CI 0.53–0.77, respectively). Conclusion: This study suggests the use of the WHO SSC is variable across countries, especially in LMICs where it has the most potential to improve patient safety. Critical appraisal of the documented benefits of the WHO SSC may improve its adoption by those not currently using it

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan–Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency.

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan-Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals

Outcomes after open repair of ruptured abdominal aortic aneurysms in octogenarians: a 20-year, single-center experience

BackgroundThe purpose of this study was to evaluate morbidity, mortality, and survival in octogenarians undergoing open repair of ruptured abdominal aortic aneurysms (RAAAs) in comparison to younger patients.MethodsThis investigation was a retrospective analysis of a prospectively maintained database from a tertiary referral center. We included all consecutive RAAA patients who underwent open repair from 1990 to 2011. Univariate and multivariate analyses were used to identify predictors of inferior short- and long-term outcomes.ResultsOverall, 463 patients were identified, of whom 138 (30%) were octogenarians (group 2), with a mean age of 84 ± 0.47 years. There were 96 (69%) men and 42 women (31%). There were more women in group 2 (31%) compared with the 0.05). Median preoperative hemoglobin (P < 0.001) and creatinine (P = 0.031) levels were significantly different between the groups. There was no significant difference between the two groups in terms of postoperative complications and length of hospital stay. Median long-term survival for octogenarians (group 2) was 5.4 years compared with 12.4 years for the younger patient group (group 1) (P < 0.001). Multivariate analysis identified age as an independent predictor of 30-day mortality (odds ratio [OR] = 1.154, 95% confidence interval [CI] 1.037-1.285) and inferior long-term survival (OR = 1.074, 95% CI 1.011-1.141). History of cigarette smoking also predicted worse long-term outcomes (OR = 3.044, 95% CI 1.318-7.032) as did multiorgan failure in the postoperative course (OR = 1.363, 95% CI 1.080-14.130).ConclusionsAdvanced age is associated with high surgical mortality; however, for octogenarians surviving surgical repair, long-term outcome is acceptable. Therefore, with responsible decision-making, surgical intervention is justifiable in the elderly. Smoking and multiorgan failure were both predictive of worse survival

Role of pre-operative multiple gated acquisition scanning in predicting long-term outcome in patients undergoing elective abdominal aortic aneurysm repair

ObjectiveTo determine whether resting pre-operative left ventricular ejection fraction (LVEF) estimated by multiple gated acquisition scanning (MUGA) predicts long-term survival in patients undergoing elective abdominal aortic aneurysm (AAA) repair. Methods A retrospective study of MUGA scans which were performed to estimate pre-operative resting LVEF in 127 patients [106 (83%) males, mean age 74&plusmn;7.6years] who underwent elective AAA repair over a period of 4years from March 2007. We compared outcomes and long-term survival between patients who had a pre-operative LVEF&le;40% (Group 1, n=60) and LVEF&gt;40% (Group 2, n=67). Results Overall 19 (15%) patients died during the follow-up period (13 patients in group 1 and 6 patients in group 2). 30-day mortality was 8%. There was no significant difference between group 1 and 2 in terms of patients' mean age or median length of hospital stay (8days for both groups, p=0.61). However, group 2 had more females than group 1(18 vs. 3, p=0.001). Median survival for patients in group 2 was significantly higher than patients in group 1 (1,258days vs. 1,000days, p=0.03). In a Cox regression model which included age, sex, smoking status and LVEF as covariates, only smoking status and LVEF predicted survival [Hazard ratio (HR)=1.06, p=0.04 and HR=0.93, p=0.00, respectively]. Conclusion This study shows that there is a role for pre-operative MUGA scan assessment of resting LVEF in predicting long-term survival post elective AAA repair and that the lower the pre-operative LVEF the poorer the long-term outcome

Graphitized mango seed as an effective 3D anode in batch and continuous mode microbial fuel cells for sustainable wastewater treatment and power generation

Herein, we explored the utilization of graphitized mango seeds as 3D-packed anodes in microbial fuel cells (MFCs) powered by sewage wastewater. Mango seeds were graphitized at different temperatures (800 °C, 900 °C, 1000 °C, and 1100 °C) and their effectiveness as anodes was evaluated. Surface morphology analysis indicated that the proposed anode was characterized by layered branches and micro-sized deep holes, facilitating enhanced biofilm formation and microorganism attachment. Maximum power densities achieved in the MFCs utilizing the mango seed-packed anodes graphitized at 1100 °C and 1000 °C were 2170.8 ± 90 and 1350.6 ± 125 mW m-2, respectively. Furthermore, the weight of the graphitized seed anode demonstrated a positive correlation with the generated power density and cell potential. Specifically, MFCs fabricated with 9 g and 6 g anodes achieved maximum power densities of 2170.8 ± 90 and 1800.5 ± 40 mW m-2, respectively. A continuous mode air cathode MFC employing the proposed graphitized mango anode prepared at 1100 °C and operated at a flow rate of 2 L h-1 generated a stable current density of approximately 12 A m-2 after 15 hours of operation, maintaining its stability for 75 hours. Furthermore, a chemical oxygen demand (COD) removal efficiency of 85% was achieved in an assembled continuous mode MFC. Considering that the proposed MFC was driven by sewage wastewater without the addition of external microorganisms, atmospheric oxygen was used as the electron acceptor through an air cathode mode, agricultural biomass waste was employed for the preparation of the anode, and a higher power density was achieved (2170.8 mW m-2) compared to reported values; it is evident that the proposed graphitized mango seed anode exhibits high efficiency for application in MFCs.</p