Group sequential designs for pragmatic clinical trials with early outcomes: methods and guidance for planning and implementation.

BACKGROUND: Group sequential designs are one of the most widely used methodologies for adaptive design in randomized clinical trials. In settings where early outcomes are available, they offer large gains in efficiency compared to a fixed design. However, such designs are underused and used predominantly in therapeutic areas where there is expertise and experience in implementation. One barrier to their greater use is the requirement to undertake simulation studies at the planning stage that require considerable knowledge, coding experience and additional costs. Based on some modest assumptions about the likely patterns of recruitment and the covariance structure of the outcomes, some simple analytic expressions are presented that negate the need to undertake simulations. METHODS: A model for longitudinal outcomes with an assumed approximate multivariate normal distribution and three contrasting simple recruitment models are described, based on fixed, increasing and decreasing rates. For assumed uniform and exponential correlation models, analytic expressions for the variance of the treatment effect and the effects of the early outcomes on reducing this variance at the primary outcome time-point are presented. Expressions for the minimum and maximum values show how the correlations and timing of the early outcomes affect design efficiency. RESULTS: Simulations showed how patterns of information accrual varied between correlation and recruitment models, and consequentially to some general guidance for planning a trial. Using a previously reported group sequential trial as an exemplar, it is shown how the analytic expressions given here could have been used as a quick and flexible planning tool, avoiding the need for extensive simulation studies based on individual participant data. CONCLUSIONS: The analytic expressions described can be routinely used at the planning stage of a putative trial, based on some modest assumptions about the likely number of outcomes and when they might occur and the expected recruitment patterns. Numerical simulations showed that these models behaved sensibly and allowed a range of design options to be explored in a way that would have been difficult and time-consuming if the previously described method of simulating individual trial participant data had been used.

Early outcomes of experience warm surgery in children undergoing complete repair of tetralogy of Fallot in developing countries.

OBJECTIVES: While significant evidence supports the benefits of normothermic cardiopulmonary bypass (NCPB) over hypothermic techniques, many institutions in developing countries, including ours, continue to employ hypothermic methods. This study aimed to assess the early postoperative outcomes of normothermic cardiopulmonary bypass (NCPB) for complete surgical repair via the Tetralogy of Fallot (TOF) within our national context. METHODS: We conducted this study in the Pediatric Cardiac Intensive Care Unit (PCICU) at the University Children's Hospital. One hundred patients who underwent complete TOF repair were enrolled and categorized into two groups: the normothermic group (n = 50, temperature 35-37 °C) and the moderate hypothermic group (n = 50, temperature 28-32 °C). We evaluated mortality, morbidity, and postoperative complications in the PCICU as outcome measures. RESULTS: The demographic characteristics were similar between the two groups. However, the cardiopulmonary bypass (CPB) time and aortic cross-clamp (ACC) time were notably longer in the hypothermic group. The study recorded seven deaths, yielding an overall mortality rate of 7%. No significant differences were observed between the two groups concerning mortality, morbidity, or postoperative complications in the PCICU. CONCLUSIONS: Our findings suggest that normothermic procedures, while not demonstrably effective, are safe for pediatric cardiac surgery. Further research is warranted to substantiate and endorse the adoption of this technique.

Prognostic risk factors for early outcomes of patients with myelomeningocele: a prospective study.

INTRODUCTION: Myelomeningocele (MMC) is a prevalent form of neural tube defect. Despite advancements in treatment, MMC still poses significant health risks, including complications leading to chronic disability and mortality. Identifying prognostic risk factors for early outcomes is crucial for tailored intervention strategies. METHODS: This prospective study involved newborns and infants diagnosed with MMC who underwent surgery between 2020 and 2023 at Urmia University of Medical Sciences. Demographic data and surgical outcomes were collected, and participants were followed up for six months. Statistical analyses were conducted using descriptive statistics, Chi-Square, and independent t-test. RESULTS: The study included 29 MMC cases, with an incidence rate of 1.4 per 10,000 live births. Lesions were predominantly located in the lumbar spine. Although mortality rates appeared to increase with ascending lesion sites, this trend was not statistically significant. Short-term outcomes revealed high morbidity and mortality rates, with neurological deficits being the most prevalent complication. Multivariable analysis identified head circumference as a significant predictor of adverse outcomes (IRR = 1.37, 95% CI = 1.02 to 1.86, p = 0.04). Furthermore, an increase in birth weight was associated with a reduction in the incidence of requiring a ventriculoperitoneal shunt (IRR = 0.99, 95% CI = 0.998 to 0.999, p = 0.02). CONCLUSION: This prospective study highlights prognostic risk factors for early outcomes in MMC patients, emphasizing the need for personalized intervention strategies. By addressing modifiable risk factors and implementing targeted interventions, healthcare providers can strive to improve outcomes and enhance the quality of life for MMC patients.

Improved patient reported outcomes with the direct anterior approach versus the posterior approach for total hip arthroplasty in the early post-operative period.

BACKGROUND: Patients undergoing total hip arthroplasty (THA) with the direct anterior approach (DAA) may experience faster recovery but may also have better baseline health than those who undergo THA with the posterior approach (PA). This study aimed to compare patient-reported outcome measures (PROMs) between the DAA and PA while controlling for baseline factors. METHODS: This is a secondary data analysis from a prospective cohort study of patients utilizing a smartphone-based care management platform following THA. The primary outcomes were HOOS JR and EQ-5D-5L through 1 year and change from baseline. Longitudinal regression models were created to control for baseline characteristics and investigate the impact of surgical approach on PROMs. RESULTS: Of 1364 THAs evaluated, 731 (53.6%) were female, and 840 (61.6%) used the PA. Patients in the PA group were of similar age but had higher body mass index and comorbidity scores. Pre-operative HOOS JR and EQ-5D-5L were comparable, but higher post-operatively in the DAA group through 6 months (p = 0.03 and p = 0.005). At 1 year post-operatively, HOOS JR and EQ-5D-5L did not vary between groups (p = 0.48 and p = 0.56), nor did changes from baseline (p = 0.47 and p = 0.11). After controlling baseline characteristics, DAA was significantly associated with higher average HOOS JR through 6 months (p = 0.03) and EQ-5D-5L through 3 months (p = 0.005), but not at 12 months (p = 0.89 and p = 0.56). CONCLUSION: THA patients undergoing DAA demonstrate earlier improvements in HOOS JR and EQ-5D-5L. However, these differences may not be clinically significant and are not evident at 1-year post-operative. Patient selection and surgeon training may continue to affect outcomes by surgical approach.

The influence of mental health on early outcomes following total hip arthroplasty.

BACKGROUND: Poor mental health is difficult to recognize and as a result, its association with recovery from total joint arthroplasty is difficult to assess. The purpose of this study was to investigate the relationship between overall mental health scores and outcomes in the early postoperative period following unilateral total hip arthroplasty (THA). METHODS: This is a retrospective review of prospectively collected data involving 142 patients who underwent primary unilateral THA. Independent variables included patient demographics and preoperative Patient-Reported Outcomes Measurement Information System (PROMIS), Global Physical Health (GPH) and Global Mental Health (GMH) and Hip Disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS JR) scores as well as diagnoses of depression or anxiety. Dependent variables included length of stay (LOS), disposition at discharge, narcotic consumption until discharge, 6-week postoperative GPH, GMH and HOOS JR scores and magnitude of change compared to preoperative scores. Preoperative GMH and postoperative outcomes were compared using Pearson correlation coefficient, independent t-tests, Pearson's Chi-Square test, and univariate logistic regression. RESULTS: Patients with preoperative GMH scores below the 25% quartile were less likely to be discharged home and resulted in lower GPH, GMH and HOOS JR scores at 6-week follow-up compared to patients with preoperative GMH scores in the top 25% quartile. However, patients with low preoperative GMH scores demonstrated a greater magnitude of improvement in both the GPH and GMH scores compared to patients in the top 25% quartile. There was no difference in opioid consumption or LOS between either groups. When comparing patients with and without depression/anxiety, no difference was seen in any of the outcomes measured. CONCLUSION: Unilateral THA offers significant improvements in both physical and mental function to patients with hip osteoarthritis and poor mental health, though overall scores remain lower than in those with better mental health.

How Effective Is Phage Therapy for Prosthetic Joint Infections? A Preliminary Systematic Review and Proportional Meta-Analysis of Early Outcomes.

Background and Objectives: Despite the promise of phage therapy (PT), its efficacy in prosthetic joint infection (PJI) management is unknown. Much of the current literature is largely limited to case reports and series. Materials and Methods: In order to help inform power calculations for future clinical trials and comparative analyses, we performed a systematic review and proportional meta-analysis of early PT outcomes to provide a preliminary assessment of early phage therapy treatment outcomes for cases of PJI. Results: In a search of available literature across MEDLINE (Ovid, Wolters Kluwer, Alphen aan den Rijn, The Netherlands), Embase (Elsevier, Amsterdam, The Netherlands), the Web of Science Core Collection (Clarivate, London, UK), and Cochrane Central (Wiley, Hoboken, NJ, USA) up to 23 September 2023, we identified 37 patients with PJIs receiving adjunctive PT. Patients most frequently reported Staphylococcal species infection (95%) and intraarticular phage delivery (73%). Phage cocktail (65%) and antibiotic co-administration (97%) were common. A random-effects proportional meta-analysis suggested infection remission in 78% of patients (95% CI: 39%, 95%) (I2 = 55%, p = 0.08) and 83% with a minimum 12-month follow-up (95% CI: 53%, 95%) (I2 = 26%, p = 0.26). Conclusions: Our study provides a preliminary estimate of PT's efficacy in PJIs and informs future comparative studies.

Early Outcomes on Triple-Branch Arch Device With Retrograde Left Common Carotid Branch: A Case Series.

INTRODUCTION: Endovascular aortic arch repair using multibranch devices has been applied in patients considered at high risk for open repair. The aim of this case series was to report the early outcomes in patients managed with a new design 3 branch arch custom-made device, including a retrograde left common carotid artery (LCCA) branch. METHODS: The Preferred Reporting Of CaSe Series in Surgery (PROCESS) guidelines were followed. All consecutive patients undergoing endovascular repair of an aortic arch lesion with a custom-made triple-branch device, including a retrograde LCCA branch (Cook Medical, Bloomington, IN, USA), between October 27, 2022, and February 28, 2023, were included. The presence of an arch aneurysm (degenerative or post-dissection) with diameter ≥55 mm and high risk for a conventional open repair set the indication for treatment. The primary outcomes were technical success and mortality at 30 days. Early morbidity and reinterventions were considered as secondary outcomes. RESULTS: Eight elective patients (87.5% men, mean age 72.3±27.0 years) were included. Five of them (62.5%) had undergone a previous ascending aorta repair of an acute type A aortic dissection. All patients were asymptomatic, except one, with left recurrent laryngeal nerve compression. The mean maximum aortic diameter was 70.4±21.0 mm. Percutaneous femoral and axillary access was used in all cases except three in which a cut down for right carotid access was performed. Technical success was 100%. Femoral access to the LCCA and implantation of the bridging stent was performed without technical challenges. No death nor cerebrovascular event was recorded during the 30 day follow-up. Five patients (62.5%) presented major complications, 3 related to access needing reintervention and the remaining related to congestive heart failure (CHF), which were managed successfully with medical treatment. Follow-up (range 1-4 month) was uneventful, except for one patient who presented a secondary type Ia endoleak. CONCLUSIONS: According to our early experience, the presence of a retrograde branch facilitated the revascularization of the LCCA through femoral access, decreasing the risk of cerebrovascular morbidity. Further analyses with longer follow-up are needed to evaluate the safety and efficacy of the device. CLINICAL IMPACT: Data arising mainly from the retrograde branch for the revascularization of the LSA are encouraging from a variety of devices. The premiminary experience with a triple-branched arch device, with a retrograde branche for the LSA but also for the LCCA, was associated with no 30 day mortality and 100% technical success.The device's design allowed swift catheterization and completion of the LCCA revascularization using femoral access exclusively.

Comparing high and low energy outcomes on day one for SmartSight myopic-astigmatism treatments with the SCHWIND ATOS: a retrospective case series.

BACKGROUND: Impact of low energy asymmetric spacings vs. high energy symmetric spacings on the immediate/early (postoperative day 1 (POD1)) outcomes of SmartSight lenticule extraction for myopic astigmatism with a new femtosecond laser system. METHODS: The first 112 eyes of 56 patients consecutively treated using low energy asymmetric spacings (Group A; Study group) were compared at POD1 to the last 112 eyes of 56 patients consecutively treated using high energy symmetric spacings (Group S; Controls). Mean age of the patients was 28 ± 5 years with a mean spherical equivalent of -4.41 ± 1.76 diopters (D) and a mean magnitude of refractive astigmatism of 0.89 ± 0.82 D. RESULTS: Laser Energy was -25 ± 1nJ lower for asymmetric treatments (p < .0001); Spot and Track distances were + 0.7 ± 0.1 µm larger and -0.8 ± 0.1 µm tighter for asymmetric treatments, respectively (p < .0001 for both). At POD1, astigmatism was -0.08 ± 0.02D lower for asymmetric treatments (p < .0003); uncorrected and corrected visual acuities (UDVA and CDVA, respectively) were -0.03 ± 0.01logMAR better for asymmetric treatments (p < .0007); differences between postop UDVA and preop CDVA along with change in CDVA were + 0.3 ± 0.1lines better for asymmetric treatments (p < .0003). CONCLUSIONS: Lenticule extraction treatment using SmartSight is safe and efficacious already at POD1. Findings suggest that low energy asymmetric spacings may further improve the immediate and short-term outcomes of SmartSight lenticule extraction in the treatment of myopic astigmatism compared to conventional settings (high energy symmetric spacings).

Re-ruptures and early outcomes after surgical repair of acute Achilles tendon ruptures: prospective, comparative multicenter study.

PURPOSE: The primary objective of this study was to compare the re-rupture rate, clinical results, and functional outcomes six months after the surgical repair of an acute Achilles tendon rupture between three different techniques (open repair, percutaneous repair with the Tenolig®, and minimally invasive repair). METHODS: A prospective, comparative, multicenter, non-randomized study was performed and included 111 patients who had an acute ruptured Achilles tendon: 74 underwent an open repair, 22 underwent a percutaneous repair using the Tenolig® and 15 had a minimally invasive repair. At six months follow-up we analyzed the number of re-ruptures, phlebitis, infections, complex regional pain syndrome, clinical outcomes (muscle atrophy, ankle dorsal flexion), functional scores (ATRS, VISA-A, EFAS, SF-12), and return to running. RESULTS: There were more re-ruptures (p=0.0001) after repair with the Tenolig® (27%) than with open repairs (1.3%) and minimally invasive repairs (0%). The rate of other complications was not different. No clinical differences were found between the three groups. Only some functional scores EFAS Total (p=0.006), and VISA-A (p=0.015) were worse in the Tenolig® group. All the other results were similar between the three groups. CONCLUSION: Despite heterogeneous studies in literature, the results of this comparative and prospective study between three surgical techniques of Achilles tendon repair confirmed that Tenolig® repair increased the rate of early re-rupture compared to open or minimally invasive techniques.

Group sequential designs in pragmatic trials: feasibility and assessment of utility using data from a number of recent surgical RCTs.

BACKGROUND: Assessing the long term effects of many surgical interventions tested in pragmatic RCTs may require extended periods of participant follow-up to assess effectiveness and use patient-reported outcomes that require large sample sizes. Consequently the RCTs are often perceived as being expensive and time-consuming, particularly if the results show the test intervention is not effective. Adaptive, and particularly group sequential, designs have great potential to improve the efficiency and cost of testing new and existing surgical interventions. As a means to assess the potential utility of group sequential designs, we re-analyse data from a number of recent high-profile RCTs and assess whether using such a design would have caused the trial to stop early. METHODS: Many pragmatic RCTs monitor participants at a number of occasions (e.g. at 6, 12 and 24 months after surgery) during follow-up as a means to assess recovery and also to keep participants engaged with the trial process. Conventionally one of the outcomes is selected as the primary (final) outcome, for clinical reasons, with others designated as either early or late outcomes. In such settings, novel group sequential designs that use data from not only the final outcome but also from early outcomes at interim analyses can be used to inform stopping decisions. We describe data from seven recent surgical RCTs (WAT, DRAFFT, WOLLF, FASHION, CSAW, FIXDT, TOPKAT), and outline possible group sequential designs that could plausibly have been proposed at the design stage. We then simulate how these group sequential designs could have proceeded, by using the observed data and dates to replicate how information could have accumulated and decisions been made for each RCT. RESULTS: The results of the simulated group sequential designs showed that for two of the RCTs it was highly likely that they would have stopped for futility at interim analyses, potentially saving considerable time (15 and 23 months) and costs and avoiding patients being exposed to interventions that were either ineffective or no better than standard care. We discuss the characteristics of RCTs that are important in order to use the methodology we describe, particularly the value of early outcomes and the window of opportunity when early stopping decisions can be made and how it is related to the length of recruitment period and follow-up. CONCLUSIONS: The results for five of the RCTs tested showed that group sequential designs using early outcome data would have been feasible and likely to provide designs that were at least as efficient, and possibly more efficient, than the original fixed sample size designs. In general, the amount of information provided by the early outcomes was surprisingly large, due to the strength of correlations with the primary outcome. This suggests that the methods described here are likely to provide benefits more generally across the range of surgical trials and more widely in other application areas where trial designs, outcomes and follow-up patterns are structured and behave similarly.

Endovascular repair of an intrathoracic subclavian artery aneurysm with a single-branched thoracic endograft in a hostile anatomy.

OBJECTIVE: Subclavian artery aneurysms (SAA) are rare and usually involve the proximal segment of the artery. In this setting traditional surgical treatment or hybrid procedures are associated with significative morbidity rate so that new endovascular solutions are preferred. METHODS: Authors report a case of a patient with an intrathoracic left SAA involving the aortic arch's outer curve. Patient's comorbidities contraindicated open surgical treatment while anatomical issues were not favourable to hybrid or standard endovascular solutions. Thus a single-branched custom-made thoracic stent-graft (Castor, MicroPort Medical, Shanghai, China) was implanted. RESULTS: Technical success was achieved with no intra-operative complications and technical steps of the procedure are accurately described.A pre-discharge CT scan showed the correct position of the endograft, complete aneurysm exclusion and branch patency. CONCLUSION: Single-branched thoracic stentgrafts could be a good option in unfavourable anatomies with supra-aortic vessels disease involving the aortic arch, with good results in terms of morbidity and early outcomes.

Early outcomes after the on pump bidirectional Glenn procedure: A single center experience.

OBJECTIVE: Bidirectional Glenn procedure is a staged palliative procedure for patients with the univentricular hearts or complex congenital heart disease. We in our study, attempted to evaluate the preoperative characteristics, operative data and the early postoperative outcomes in the patients who underwent Bidirectional Glenn procedure at our center. METHODS: In our single center retrospective experience, 115 patients underwent Bidirectional Glenn procedure from January 2015 to December 2019. RESULTS: The mean age of the patients was 6.55 ± 6.5 years (range from 9 months to 48 years) and a median of 5 years. The most common anatomic diagnosis was double outlet right ventricle (n = 49, 42.6%). The primary diagnosis and the additional cardiac anamolies were not associated with the adverse outcomes. The increased cardiopulmonary bypass and operative time affect the postoperative outcomes. The median oxygen saturation in the patients postoperatively was 82%. The median postoperative stay was 8 days. The early postoperative complications were seen in 29 patients (25.2%). There were 12 early deaths (10.4%) in our study. The late age of presentation and poor preoperative nutrition, increased the risk of the postoperative morbidity and mortality. CONCLUSION: Bidirectional Glenn procedure is an effective procedure to improve efficacy of the gas exchange and reduce volume overload on the single ventricle at early as well as late stages. However, the late age of presentation increases the risk of the postoperative outcomes.

The Impact of the Pulmonary Artery Index and Aortopulmonary Collateral Artery Coil Embolization on Intractable Pleural Effusions After a Fontan Surgery.

An intractable pleural effusion is a common comorbidity of a Fontan operation, occasionally leading to undesirable outcomes. The preventive effect of aortopulmonary collateral (APC) coil embolization against a pleural effusion before a Fontan operation is still controversial.This is a retrospective single-center study; among 227 Fontan cases, 57 cases with complete MRI data were analyzed at first. Factors associated with the duration of pleural drainage (median: 6 (2-41) days) and that of postoperative hospital stay (median: 25 (14-91) days) were analyzed using a multiple regression analysis. The pulmonary artery index (PAI; Nakata index) was associated with both the pleural drainage duration (P < 0.05, r2 = 0.17) and postoperative hospital stay (P < 0.05, r2 = 0.10).Thereafter, all the 227 patients were classified into the following three groups: Group A (12 patients in whom the embolization was performed within 30 days before the Fontan surgery), Group B (131 patients in whom the embolization was performed more than 30 days before the Fontan surgery), and Group C (84 patients in whom the embolization was not performed). Patients in Group A were found to be associated with the shortest length of both periods (P < 0.05).Lower PAI values were related to a prolonged pleural drainage duration and postoperative hospital stay. APC coil embolizations may reduce the risk if they are performed shortly (less than 30 days) before the operation.

Is Perioperative Antibiotic Necessary in Straightforward Implant Placement Procedures?

The purpose of this nonrandom retrospective cohort study was to evaluate the impact of perioperative antibiotic on early outcomes, including postoperative pain, swelling, bleeding, and cyanosis, in patients undergoing dental implant placement before prosthetic loading. Seventy-five patients (45 men, 30 women) who had completed dental implant placement were included in the study. Patients who used perioperative antibiotics comprised the experimental group, and those who did not comprised the control group. The experimental group received 2 g amoxicillin + clavulanic acid 1 hour before surgery and 1 g amoxicillin + clavulanic acid twice a day for 5 days after surgery. The control group received no perioperative antibiotic therapy. Data on pain, swelling, bleeding, cyanosis, flap dehiscence, suppuration, and implant failure were analyzed on postoperative days 2, 7, and 14 and at week 12. No statistically significant difference was detected between the 2 groups with regard to pain and swelling on postoperative days 2, 7, and 14 and week 12 (P > .05), while the severity of pain and swelling were greater on day 2 than on days 7 and 14 and week 12 in both groups (P = .001 and P < .05, respectively). Similarly, no significant difference was found between the 2 groups with regard to postoperative bleeding and cyanosis. Although flap dehiscence was more severe on day 7 in the experimental group, no significant difference was found between the 2 groups with regard to the percentage of flap dehiscence assessed at other time points. Within the limitations of the study, it has been demonstrated that antibiotic use has no effect on implant failure rates in dental implant surgery with a limited number of implants. We conclude that perioperative antibiotic use may not be required in straightforward implant placement procedures. Further randomized controlled clinical studies with more patients and implants are needed to substantiate our findings.

Spinal Anesthesia Associated With Increased Length of Stay Compared to General Anesthesia for Ankle Open Reduction Internal Fixation: A Propensity-Matched Analysis.

General and spinal anesthesia are both utilized for patients undergoing open reduction internal fixation of the ankle, but there are little data comparing early complication rates. The purpose of this study was to compare duration of surgery, length of stay, and rates of postoperative adverse events within 30 days in patients undergoing open reduction internal fixation of ankle fracture using spinal versus general anesthesia. Adult patients who underwent open reduction internal fixation of a closed ankle fracture from 2012 to 2016 were retrospectively identified from American College of Surgeons National Surgical Quality Improvement Program. Duration of surgery, length of stay, 30-day adverse events, and unplanned readmissions were compared between patients who received general anesthesia and spinal anesthesia. Propensity adjustment with respect to known risk factors for complications and adjunctive regional block was used to match patients. Of the 10,795 patients included after applying the inclusion and exclusion criteria, 9862 (91.36%) received general anesthesia and 933 (8.64%) received spinal anesthesia. Using propensity-scored matching, 841 patients in the spinal cohort were matched to 3364 patients in the general cohort. Spinal anesthesia was associated with increased length of stay (+0.5 days, 95% confidence interval 0.23-0.77, p < .001). There were no differences in the rates of major/minor complications, mortality, transfusions, unplanned readmissions, or duration of surgery. General anesthesia is predominantly used for fixation of ankle fractures. While spinal anesthesia is associated with lower complication rates in hip and knee surgery, we found that it is associated with increased length of stay in patients undergoing open reduction internal fixation of the ankle within 30 days of surgery.

Impact of Lactate Clearance on Early Outcomes in Pediatric ECMO Patients.

Background and Objectives: Pediatric extracorporeal membrane oxygenation (ECMO) support is often the ultimate therapy for neonatal and pediatric patients with congenital heart defects after cardiac surgery. The impact of lactate clearance in pediatric patients during ECMO therapy on outcomes has been analyzed. Materials andMethods: We retrospectively analyzed data from 41 pediatric vaECMO patients between January 2006 and December 2016. Blood lactate and lactate clearance have been recorded prior to ECMO implantation and 3, 6, 9 and 12 h after ECMO start. Receiver operating characteristic (ROC) analysis was used to identify cut-off levels for lactate clearance. Results: Lactate levels prior to ECMO therapy (9.8 mmol/L vs. 13.5 mmol/L; p = 0.07) and peak lactate levels during ECMO support (10.4 mmol/L vs. 14.7 mmol/L; p = 0.07) were similar between survivors and nonsurvivors. Areas under the curve (AUC) of lactate clearance at 3, 9 h and 12 h after ECMO start were significantly predictive for mortality (p = 0.017, p = 0.049 and p = 0.006, respectively). Cut-off values of lactate clearance were 3.8%, 51% and 56%. Duration of ECMO support and respiratory ventilation was significantly longer in survivors than in nonsurvivors (p = 0.01 and p < 0.001, respectively). Conclusions: Dynamic recording of lactate clearance after ECMO start is a valuable tool to assess outcomes and effectiveness of ECMO application. Poor lactate clearance during ECMO therapy in pediatric patients is a significant marker for higher mortality.

An updated systematic review and meta-analysis of early outcomes after left atrial appendage occlusion.

BACKGROUND: Left atrial appendage occlusion (LAAO) is a promising intervention for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Early outcomes following LAAO have been published in many studies with variable results. OBJECTIVE: This updated meta-analysis aims to provide a summary of the early outcomes of LAAO. METHODS: Medline/Pubmed, Ovid Journals, Clinical trials, Abstract meetings, Cochrane databases were searched from January 1st, 1999 to November 30th, 2016. RESULTS: This meta-analysis included 49 studies involving 12 415 patients. The median age was 73.5 years (IQR 72-75 years) and 43% were males. Hypertension and diabetes were present in 36% and 15% of the population, respectively. There was a prior history of stroke and congestive heart failure in 14% and 18% of the population, respectively. The median CHADS2 score was 2.9 (IQR 2.6-3.3) and the median HASBLED score was 3.3 (IQR 3-4). LAAO implantation was successful in 96.3% of patients (95.40-97.08, I2 = 76.1%). The pooled proportion of all-cause mortality was 0.28% (0.19-0.38, I2 = 0%). The pooled proportion of all-cause stroke was 0.31% (0.22-0.42, I2 = 9.4%), major bleeding requiring transfusion was 1.71% (1.13-2.41, I2 = 73.2%), and pericardial effusion was 3.25% (2.46-4.14, I2 = 79%). Sub analysis of randomized clinical trials comparing LAAO devices to warfarin showed lower mortality (P = 0.03) with similar bleeding risk (P = 0.20) with LAAO. CONCLUSIONS: This meta-analysis concludes that LAAO occlusion is a safe and effective stroke prevention strategy in patients with NVAF.

Impact of hypertension on early outcomes and long-term survival of patients undergoing aortic repair with Stanford A dissection.

INTRODUCTION: Stanford A acute aortic dissection (AAD) is a life-threatening emergency, typically occurring in hypertensive patients, requiring immediate surgical repair. The aim of this study was to evaluate early outcomes and long-term survival of hypertensive patients in comparison to normotensive patients suffering from Stanford A AAD. METHODS: In our center, 240 patients with Stanford A AAD underwent aortic surgical repair from January 2006 to April 2015. After statistical and logistic regression analysis, Kaplan-Meier survival estimation was performed, with up to 9-year follow-up. RESULTS: The proportion of hypertensive patients suffering from Stanford A AAD was 75.4% (n=181). There were only few statistically significant differences in terms of basic demographics, comorbidities, preoperative baseline and clinical characteristics of hypertensive patients in comparison to normotensive patients. Hypertensive patients were significantly older (p=0.008), more frequently received hemi-arch repair (p=0.028) and selective brain perfusion (p=0.001). Our study showed similar statistical results in terms of 30-day mortality (p=0.196), long-term overall cumulative survival of patients (Log-Rank p=0.506) and survival of patients free from cerebrovascular events (Log-Rank p=0.186). Furthermore, subgroup analysis for long-term survival in terms of men (Log-Rank p=0.853), women (Log-Rank p=0.227), patients under and above 65 years of age (Log-Rank p=0.188 and Log-Rank p=0.602, respectively) and patients undergoing one of the three types of aortic repair surgery showed similar results for normotensive and hypertensive patient groups. Subgroup analysis for long-term survival of patients free from cerebrovascular events for women, patients under 65 years of age and patients undergoing aortic arch repair showed significant differences between the two groups in favor of hypertensive patients. CONCLUSIONS: Hypertensive patients suffering from Stanford A AAD were older, more frequently received hemi-arch replacement and were not associated with increased risk of 30-day mortality and poorer long-term survival compared to normotensive patients.

Prolonged pre-operative hospital stay as a predictive factor for early outcomes and mortality after geriatric hip fracture surgery: a single institution open prospective cohort study.

INTRODUCTION: The aim of this open prospective cohort study was to determine if a prolonged pre-operative hospital stay is a true predictor of higher morbidity or mortality in geriatric patients with hip fractures. MATERIALS AND METHODS: We analysed early outcome parameters, such as functional independence measure (FIM), at discharge and four months post-operatively, peri-operative nonsurgical complications, intra-hospital and one year mortality compared with prolonged pre-operative hospital stay in 308 patients from a continuous cohort of 344. RESULTS: Average pre-operative stay was 8.39 ± 5.80 days. Delaying surgery for > 72 hours was independently predictive for general complications and lower motor FIM gain at four months. All findings worsen progressively after the fifth day of delay. Pre-operative period was not found to be an independent predictor of mortality. CONCLUSION: In all observed outcome parameters except mortality, pre-operative delay > 72 hours was shown to be a true predictive factor.

Sex-based differences in outcomes with bivalirudin or unfractionated heparin for transcatheter aortic valve replacement: Results from the BRAVO-3 randomized trial.

BACKGROUND: Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. RESULTS: The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. CONCLUSIONS: There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.