Prolonged extracorporeal membrane oxygenation in pediatrics: How long did we wait?

BACKGROUND: In this study, we aimed to evaluate the duration of extracorporeal membrane oxygenation (ECMO) and its effect on outcomes. Also, we sought to identify hospital mortality predictors and determine when ECMO support began to be ineffective. METHODS: This was a single-center, retrospective cohort study conducted between January 2014 and January 2022. The prolonged ECMO (pECMO) cut-off point was accepted as 14 days. RESULTS: Thirty-one (29.2%) of 106 patients followed up with ECMO had pECMO. The mean follow-up period of the patients who underwent pECMO was 22 (range, 15-72) days, and the mean age was 75 ± 72 months. According to the results of our heterogeneous study population, life expectancy decreased dramatically towards the 21st day. Hospital mortality predictors were determined in the logistic regression analysis in all ECMO groups in our study as high Pediatric Logistic Organ Dysfunction (PELOD) two score, continuous renal replacement therapy (CRRT) use, and sepsis. The pECMO mortality was 61.2% and the overall mortality was 53.0%, with the highest mortality rate in the bridge-to-transplant group (90.9%) because of lack of organ donation in our country. CONCLUSIONS: In our study, the PELOD two score, presence of sepsis, and use of CRRT were found to be in the predictors of in-hospital ECMO mortality model. Considering the complications, in the COX regression model analysis, the factors affecting the probability of dying in patients followed under ECMO were found to be bleeding, thrombosis, and thrombocytopenia.

Hybrid extracorporeal membrane oxynegation in pediatric intensive care patients: A single center experience: More is better?

BACKGROUND: The initial extracorporeal membrane oxygenation (ECMO) configuration is inefficient for patient oxygenation and flow, but by adding a Y-connector, a third or fourth cannula can be used to support the system, which is called hybrid ECMO. METHODS: This was a single-center retrospective study consisting of patients receiving hybrid and standard ECMO in our PICU between January 2014 and January 2022. RESULTS: The median age of the 12 patients who received hybrid ECMO and were followed up with hybrid ECMO was 140 (range, 82-213) months. The total median ECMO duration of the patients who received hybrid ECMO was 23 (8-72) days, and the median follow-up time on hybrid ECMO was 18 (range, 3-46) days. The mean duration of follow-up in the PICU was 34 (range, 14-184) days. PICU length of stay was found to be statistically significant and was found to be longer in the hybrid ECMO group (p = 0.01). Eight (67%) patients died during follow-up with ECMO. Twenty-eight-day mortality was found to be statistically significant and was found to be higher in the standard ECMO group (p = 0.03). The hybrid ECMO mortality rate was 66% (decannulation from ECMO). The hybrid ECMO hospital mortality rate was 75%. The standard ECMO mortality rate was 52% (decannulation from ECMO). The standard ECMO hospital mortality rate was 65%. CONCLUSIONS: Even though hybrid ECMO use is rare, with increasing experience and new methods, more successful experience will be gained. Switching to hybrid ECMO from standard ECMO at the right time with the right technique can increase treatment success and survival.

Early Neurologic Complications and Long-term Neurologic Outcomes of Extracorporeal Membrane Oxygenation Performed in Children.

BACKGROUND: We aimed at evaluating acute neurologic complications (ANC) and clinical outcome at a 2-year follow-up in children after extracorporeal membrane oxygenation (ECMO). METHODS: We conducted a single-center, retrospective review of our patient cohort aged between 1 month and 18 years at the time of ECMO support (between June 2014 to January 2017). Outcome analysis included ANC and their clinical consequences.The Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance Category (PCPC) were used for neurologic assessment performed at discharge from the hospital and at 2nd year follow-up. RESULTS: There were 35 children who required ECMO. The median ECMO time was 9 days (range 2-32 days). Decannulation from ECMO was achieved in 68.6% of patients, and overall, 42.8% survived (15 patients), The incidence of ANC in the surviving patients was 40% (6 children). ANC were intracranial hemorrhage, seizures, cerebral infarction, which occurred in one, two and three of the 15 surviving patients respectively (6.6, 13.3 and 20%). A higher rate of organ failure was related to death (p=0.043), whereas duration on ECMO was a risk factor for the development of ANC (p<0.05). At hospital discharge, the 14 patients evaluated had normal development or -mild disability in 73.2%, and at the 2-year follow-up, 93.4% had these scores. CONCLUSION: Children who receive ECMO have a risk to develop ANC, which was related to the length of ECMO treatment, while survival was related to less organ failure, Long-term neurological outcome was good in our patient cohort.

Temporary biventricular support as a bridge to recovery: A justifiable strategy for small children with fulminant myocarditis.

Short-term mechanical circulatory support can be life-saving in the pediatric population with acute cardiogenic shock (ACS). However, recovery from MCS is a rare entity. MCS options are limited for low-body-weight children in Turkey. Over the last decade, extracorporeal membrane oxygenation (ECMO) has been the primary bridging modality for children with end-stage heart failure in our country. However, VA-ECMO may cause increased wall stress and oxygen demand, which may alter myocardial recovery. Here, we describe using a Levitronix CentriMag Systems for biventricular support as a bridge to recovery in a 16-month-old boy (weight, 11 kg; BSA, 0.5 m2) with type A influenza related-fulminant myocarditis (FM). Levitronix CentriMag System provides a safe and efficient short-term, biventricular, paracorporeal support for infants, and small children with ACS.

Temporary Diverting End-Colostomy in Critically Ill Children with Severe Perianal Wound Infection.

ABSTRACT: Broad and deep perianal wounds are challenging in both adult and pediatric ICUs. These wounds, if contaminated with gastrointestinal flora, can cause invasive sepsis and death, and recovery can be prolonged. Controlling the source of infection without diverting stool from the perianal region is complicated. The option of protective colostomy is not well-known among pediatric critical care specialists, but it can help patients survive extremely complicated critical care management. These authors present three critically ill children who required temporary protective colostomy for perianal wounds because of various clinical conditions. Two patients were treated for meningococcemia, and the other had a total artificial heart implantation for dilated cardiomyopathy. There was extensive and profound tissue loss in the perianal region in the patients with meningococcemia, and the patient with cardiomyopathy had a large pressure injury. Timely, transient, protective colostomy was beneficial in these cases and facilitated the recovery of the perianal wounds. Temporary diverting colostomy should be considered as early as possible to prevent fecal transmission and accelerate perianal wound healing in children unresponsive to local debridement and critical care.

Pediatric extracorporeal cardiopulmonary resuscitation: single-center study

Background/aim: Extracorporeal cardiopulmonary resuscitation (ECPR) is defined as the venoarterial extracorporeal membrane oxygenation (VA-ECMO) support in a patient who experienced a sudden pulseless condition attributable to cessation of cardiac mechanical activity and circulation. We aimed to evaluate the clinical outcomes of our ECPR experience in a pediatric patient population. Materials and methods: Between September 2014 and November 2017, 15 children were supported with ECPR following in-hospital cardiac arrest (IHCA) in our hospitals. VA-ECMO setting was established for all patients. Pediatric cerebral performance category (PCPC) scales and long-term neurological prognosis of the survivors were assessed. Results: The median age of the study population was 60 (4­156) months. The median weight was 18 (4.8­145) kg, height was 115 (63­172) cm, and body surface area was 0.73 (0.27­2.49) m2. The cause of cardiac arrest was a cardiac and circulatory failure in 12 patients (80%) and noncardiac causes in 20%. Dysrhythmia was present in 46%, septic shock in 13%, bleeding in 6%, low cardiac output syndrome in 13%, and airway disease in 6% of the study population. Median low-flow time was 95 (range 20­320) min. Central VA- ECMO cannulation was placed in only 2 (13.3%) cases. However, the return of spontaneous circulation (ROSC) was obtained in 10 (66.6%) patients, and 5 (50%) of them survived. Overall, 5 patients were discharged from the hospital. Finally, survival following ECPR was 33.3%, and all survivors were neurologically intact at hospital-discharge. Conclusion: ECPR can be a life-saving therapeutic strategy using a promising technology in the pediatric IHCA population. Early initiation and a well-coordinated, skilled, and dedicated ECMO team are the mainstay for better survival rates.

Differential expression of genes participating in cardiomyocyte electrophysiological remodeling via membrane ionic mechanisms and Ca2+-handling in human heart failure.

Excitation-contraction coupling in normal cardiac function is performed with well balanced and coordinated functioning but with complex dynamic interactions between functionally connected membrane ionic currents. However, their genomic investigations provide essential information on the regulation of diseases by their transcripts. Therefore, we examined the gene expression levels of the most important voltage-gated ionic channels such as Na+-channels (SCN5A), Ca2+-channels (CACNA1C and CACNA1H), and K+-channels, including transient outward (KCND2, KCNA2, KCNA5, KCNA8), inward rectifier (KCNJ2, KCNJ12, KCNJ4), and delayed rectifier (KCNB1) in left ventricular tissues from either ischemic or dilated cardiomyopathy (ICM or DCM). We also examined the mRNA levels of ATP-dependent K+-channels (KCNJ11, ABCC9) and ERG-family channels (KCNH2). We further determined the mRNA levels of ryanodine receptors (RyR2; ARVC2), phospholamban (PLB or PLN), SR Ca2+-pump (SERCA2; ATP2A1), an accessory protein FKBP12 (PPIASE), protein kinase A (PPNAD4), and Ca2+/calmodulin-dependent protein kinase II (CAMK2G). The mRNA levels of SCN5A, CACNA1C, and CACNA1H in both groups decreased markedly in the heart samples with similar significance, while KvLQT1 genes were high with depressed Kv4.2. The KCNJ11 and KCNJ12 in both groups were depressed, while the KCNJ4 level was significantly high. More importantly, the KCNA5 gene was downregulated only in the ICM, while the KCNJ2 was upregulated only in the DCM. Besides, mRNA levels of ARVC2 and PLB were significantly high compared to the controls, whereas others (ATP2A1, PPIASE, PPNAD4, and CAMK2G) were decreased. Importantly, the increases of KCNB1 and KCNJ11 were more prominent in the ICM than DCM, while the decreases in ATP2A1 and FKBP1A were more prominent in DCM compared to ICM. Overall, this study was the first to demonstrate that the different levels of changes in gene profiles via different types of cardiomyopathy are prominent particularly in some K+-channels, which provide further information about our knowledge of how remodeling processes can be differentiated in HF originated from different pathological conditions.

Evaluation of the effect of energy drink consumption on retina and choroid: an optical coherence tomography and optical coherence tomography angiography study.

PURPOSE: Evaluation of retinal and choroidal changes after energy drink consumption by optical coherence tomography and optical coherence tomography angiography. METHODS AND MATERIAL: Forty-two healthy volunteers with neither systemic nor ocular diseases were enrolled in the study. The energy drink (250 mL Red Bull energy drink) was provided to all volunteers. The vascular density of superficial (SCP) and deep capillary plexus (DCP), vascular density in FAZ region, its circumference (PERIM) and vascular density around 300 micron (FD-300), and blood flow in outer retinal and choriocapillaris were measured by OCT-A (AngioVue RTVue XR Avanti, Optovue, Fremont, CA) before and 30 min after consumption of energy drink, in an interval of 1, 2, 3, 6, and 24 h. Central macular thickness (CMT) was measured by OCT (Heidelberg Engineering, Inc., Heidelberg, Germany), whereas choroid thickness (CT) and retinal nerve fibre layer (RNFL) measurements of the optic nerve were measured by enhanced depth imaging OCT. For control comparison, the same measurements were made after drinking 250 mL of water in the same healthy group. The obtained data were statistically analysed. RESULTS: Among 42 volunteers enrolled in the study, 25 (59,5%) were males and 17 (40,5%) were females, with an average age of 20,58 ± 0,71. The vascular density measurements of parafoveal and perifoveal deep capillary plexus obtained after energy drink consumption were statistically significant. This increase in vascular density of the deep capillary plexus after energy drink consumption seemed to start after half an hour and continued until measurement at 24th hour. On the other hand, the changes in measurements of vascular density from other regions, the blood flows, FAZ, CMT, CT and RNFL values were not statistically significant. In water consumption measurements; despite a statistically significant increase in choroidal thickness at 30 min and 1 h (p = 0.027, p = 0.045, respectively), no significant difference was found in other parameters between consecutive measurements. CONCLUSION: The consumption of energy drinks acutely leads to changes in retinal vascular density parameters.

Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting.

BACKGROUND: We previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial). METHODS: A total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years. RESULTS: There were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-pump CABG, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72) or in the rates of the components of the outcome, including repeat coronary revascularization, which was performed in 2.8% of the patients in the off-pump group and in 2.3% of the patients in the on-pump group (hazard ratio, 1.21; 95% CI, 0.85 to 1.73; P=0.29). The secondary outcome for the overall period of the trial - the mean cost in U.S. dollars per patient - also did not differ significantly between the off-pump group and the on-pump group ($15,107 and $14,992, respectively; between-group difference, $115; 95% CI, -$697 to $927). There were no significant between-group differences in quality-of-life measures. CONCLUSIONS: In our trial, the rate of the composite outcome of death, stroke, myocardial infarction, renal failure, or repeat revascularization at 5 years of follow-up was similar among patients who underwent off-pump CABG and those who underwent on-pump CABG. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294 .).

Right Ventricular Strain to Assess Early Right Heart Failure in the Left Ventricular Assist Device Candidate.

PURPOSE OF REVIEW: Right heart failure (RHF) following left ventricular assist device implantation (LVAD) remains the primary cause of postoperative mortality and morbidity, and prediction of RHF is the main interest of the transplantation community. In this review, we outline the role and impact of right ventricular strain in the evaluation of the right ventricle function before LVAD implantation. RECENT FINDINGS: Accumulating data suggest that measurement of right ventricular longitudinal strain (RVLS) has a critical role in predicting RHF preoperatively and may improve morbidity and mortality following LVAD implantation. However, the significant intraobserver, interobserver variability, the lack of multicenter, prospective studies, and the need for a learning curve remain the most critical limitations in the clinical practice at present. This review highlighted the importance of right ventricular strain in the diagnosis of RHF preoperatively and revealed that RVLS might have a crucial clinical measurement for the selection and management of LVAD patients in the future with the more extensive multicenter studies.

Increased free Zn2+ correlates induction of sarco(endo)plasmic reticulum stress via altered expression levels of Zn2+ -transporters in heart failure.

Zn2+ -homoeostasis including free Zn2+ ([Zn2+ ]i ) is regulated through Zn2+ -transporters and their comprehensive understanding may be important due to their contributions to cardiac dysfunction. Herein, we aimed to examine a possible role of Zn2+ -transporters in the development of heart failure (HF) via induction of ER stress. We first showed localizations of ZIP8, ZIP14 and ZnT8 to both sarcolemma and S(E)R in ventricular cardiomyocytes (H9c2 cells) using confocal together with calculated Pearson's coefficients. The expressions of ZIP14 and ZnT8 were significantly increased with decreased ZIP8 level in HF. Moreover, [Zn2+ ]i was significantly high in doxorubicin-treated H9c2 cells compared to their controls. We found elevated levels of ER stress markers, GRP78 and CHOP/Gadd153, confirming the existence of ER stress. Furthermore, we measured markedly increased total PKC and PKCα expression and PKCα-phosphorylation in HF. A PKC inhibition induced significant decrease in expressions of these ER stress markers compared to controls. Interestingly, direct increase in [Zn2+ ]i using zinc-ionophore induced significant increase in these markers. On the other hand, when we induced ER stress directly with tunicamycin, we could not observe any effect on expression levels of these Zn2+ transporters. Additionally, increased [Zn2+ ]i could induce marked activation of PKCα. Moreover, we observed marked decrease in [Zn2+ ]i under PKC inhibition in H9c2 cells. Overall, our present data suggest possible role of Zn2+ transporters on an intersection pathway with increased [Zn2+ ]i and PKCα activation and induction of HF, most probably via development of ER stress. Therefore, our present data provide novel information how a well-controlled [Zn2+ ]i via Zn2+ transporters and PKCα can be important therapeutic approach in prevention/treatment of HF.

Extended left hepatectomy for intrahepatic cholangiocarcinoma: hepatic vein reconstruction with in-situ hypothermic perfusion and extracorporeal membrane oxygenation.

BACKGROUND: Liver resection for intrahepatic cholangiocarcinoma (ICC) with invasion of the inferior vena cava (IVC) and hepatic veins (HV) is a challenging procedure. CASE PRESENTATION: We report a case of a 63-year-old woman with a 6-cm, centrally located liver mass. Her biochemistry results were normal except for a Ca19-9 level of 1199 U/ml. The liver biopsy was consistent with ICC and 60% macrosteatosis. Abdominal CT scans revealed a large central mass invading the left HV, middle HV and right HV, infringing on their junction with the vena cava. An operation was planned using a 3-dimensional (3D) computer simulation model using dedicated software. We also describe a novel veno-portal-venous extracorporeal membrane oxygenation (VPV-ECMO) support with in-situ hypothermic perfusion (IHP) during this procedure. We aimed to perform an extended left hepatectomy and reconstruct 3 right HV orifices with an interposition jump graft to the IVC with total vascular exclusion (TVE) and IHP A supplemental video describing the preoperative planning, the operative procedure with the postoperative follow-up in detail is presented. After the patient was discharged, she developed a hepatic venous outflow obstruction 3 months postoperatively, which was effectively managed with hepatic venous stenting by interventional radiology. She is currently symptom free and without tumour recurrence at the 1-year follow-up. CONCLUSIONS: This report demonstrates that extended left hepatectomy for IHC with IHP and VPV-ECMO is safe and feasible under the supervision of a highly experienced team.

A Retrospective Analysis of Surgical Femoral Artery Closure Techniques: Conventional versus Purse Suture Technique.

BACKGROUND: Different techniques have been reported for the exploration and repair of femoral artery (FA) in patients who undergo minimally invasive cardiac surgery (MICS) and endovascular aortic surgery. We used a modified approach alternative to the conventional technique (group CT) since May 2013, which specifies a shorter groin incision and diamond-shaped hemostatic purse sutures for arteriotomy closure without the requirement of cross-clamping (group PT [purse suture technique]) and evaluated early outcomes and the complication profiles of the 2 techniques for femoral access. METHODS: In our clinic, between May 2011 and December 2015, 503 FA cannulations were performed on 345 patients who underwent MICS (n = 109, mean age 64.1 ± 17.6 years, female/male ratio 71/38), endovascular abdominal aneurysm repair (n = 158, mean age 71.3 ± 10.2 years, female/male ratio 63/95), thoracal endovascular aneurysm repair (n = 50, mean age 65.0 ± 15.3 years, female/male ratio 15/35), and transaortic valve implantation (n = 28, mean age 80.8 ± 5.9 years, female/male ratio 13/15). A total of 295 FAs were exposed via mini incision and were repaired with the PT. We compared the duration of femoral closure (FC), wound infection, and vascular complications including bleeding hematoma, thromboembolic and ischemic events, pseudoaneurysm, seroma, surgical reintervention rates, delayed hospital stay for groin complications, and existence of postoperative local luminal narrowing (LLN) at the intervention site over 25% for both groups. RESULTS: FC time (CT 14.9 ± 3.16 min, PT 6.5 ± 1.12 min, P < 0.0001), bleeding hematoma frequency (CT 6.2%, PT 1.7%, P = 0.01), and prolonged hospital stay for groin complications (CT 14.9%, PT 3.4%, P < 0.0001) were significantly lower in the PT group. Rate of technical success (CT 80.3%, PT 87.4%, P = 0.03) and event-free patient (CT 66.1%, PT 77.5%, P = 0.03) were significantly better in the PT group. There were no differences between groups in terms of ischemic events, wound infection rates, development of pseudoaneurysm and seroma, surgical reintervention rates, and LLN of FA over 25% at 6-month duplex evaluation. CONCLUSIONS: The comparison of the 2 approaches revealed the advantages of the PT in terms of bleeding hematoma and shortening in FC time and the length of hospital stay. We suggest performing a smaller skin incision for FA access and utilizing purse sutures, which allows completing the procedure without cross-clamping, thus providing a favorable approach and excellent comfort for the surgeon.

Effects of Preoperative Tricuspid Valve Diameters on Early Postoperative Surgical Outcomes in Patients Undergoing Tricuspid Valve Surgery.

BACKGROUND: Many of the previous studies on tricuspid valve surgery were on the materials that were used and the advantages and disadvantages of them. In this study, effects of preoperative tricuspid valve diameter on early postoperative outcomes were investigated. Methods: A total of 43 patients who underwent tricuspid valve repair surgery with the ring between the years 2012-2014 were included in this study. Tricuspid valve diameters and other cardiac functions of patients undergoing tricuspid intervention were evaluated with transthoracic echocardiography.Patients included in this study were divided into 2 groups: those with minimal, minimal-to-1st degree and 1st-degree tricuspid valve regurgitation found on thoracic echocardiography in the early postoperative period were considered as having a successful tricuspid repair (Group 1). Those with 1st-2nd degree and higher degrees of tricuspid regurgitation were considered as having an unsuccessful tricuspid repair (Group 2).The relationship between tricuspid valve dimensions and early tricuspid valve regurgitation was assessed with the help of preoperative, intraoperative, and postoperative data. RESULTS: Thirty patients (Group 1) were found to have a successful tricuspid valve repair in the postoperative period. The mean annulus diameter of the tricuspid valve at end-diastole in patients from Group 1 was similar to Group 2 (4.24 ± 0.44 cm versus 3.99 ± 0.40; P = .080). Also, tricuspid valve end-systolic diameter in Group 1 was similar to patients in Group 2 (3.59 ± 0.38 cm versus 3.42 ± 0.33 cm; P = .151). Conclusion: A direct relationship was not found between tricuspid valve diameter and post-operative development of moderate to severe regurgitation in tricuspid valve surgery in this study.

A retrospective cohort analysis of percutaneous versus side-graft perfusion techniques for veno-arterial extracorporeal membrane oxygenation in patients with refractory cardiogenic shock.

OBJECTIVES: This study was designed to compare vascular complications and the outcomes of ultrasound (US)-guided percutaneous cannulation with distal perfusion catheter (PC-DP) and arterial side-graft perfusion (SGP) techniques in patients who require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for refractory cardiogenic shock (RCS). METHODS: We conducted a retrospective, observational cohort study of consequtive patients with RCS treated with VA-ECMO at a single transplant center from March 2010 until August 2015. Overall, 148 patients underwent VA-ECMO for RCS (99 men, aged 56.6 ± 12.0 years; BSA, 1.85 ± 0.19). Patients were categorized based on VA-ECMO perfusion technique into PC-DP via femoral artery and SGP via axillary/femoral artery groups. RESULTS: The median duration of VA-ECMO support was 5 days (range, 8 hours-80 days). Hospital mortality (PC-DP group, 54.7%; SGP group, 64.4%; p=0.23) and overall ECMO survival (PC-DP group, 36.9%; SGP group, 32.2%; p=0.47) was similar between the groups. There were no significant between-group differences in the rate of acute limb ischemia (PC-DP group, 4/75, 5.3%; SGP group, 2/73, 2.7%; p=0.68). However, the rate of surgical/cannulation site bleeding (PC-DP, 9/75 (12%) vs SGP, 18/73 (24.7%), p=0.05) and hyperperfusion syndrome (PC-DP, 2/75 (2.7%) vs SGP, 22/73 (30.1%),p=0.001) were higher in the SGP group than in the PC-DP group. CONCLUSIONS: We observed no significant difference in major vascular complications or survival between patients who underwent the PC-DP technique and those who underwent arterial SGP.

Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year.

BACKGROUND: Previously, we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death, myocardial infarction, stroke, or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report results on quality of life and cognitive function and on clinical outcomes at 1 year. METHODS: We enrolled 4752 patients with coronary artery disease who were scheduled to undergo CABG and randomly assigned them to undergo the procedure off-pump or on-pump. Patients were enrolled at 79 centers in 19 countries. We assessed quality of life and cognitive function at discharge, at 30 days, and at 1 year and clinical outcomes at 1 year. RESULTS: At 1 year, there was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (12.1% and 13.3%, respectively; hazard ratio with off-pump CABG, 0.91; 95% confidence interval [CI], 0.77 to 1.07; P=0.24). The rate of the primary outcome was also similar in the two groups in the period between 31 days and 1 year (hazard ratio, 0.79; 95% CI, 0.55 to 1.13; P=0.19). The rate of repeat coronary revascularization at 1 year was 1.4% in the off-pump group and 0.8% in the on-pump group (hazard ratio, 1.66; 95% CI, 0.95 to 2.89; P=0.07). There were no significant differences between the two groups at 1 year in measures of quality of life or neurocognitive function. CONCLUSIONS: At 1 year after CABG, there was no significant difference between off-pump and on-pump CABG with respect to the primary composite outcome, the rate of repeat coronary revascularization, quality of life, or neurocognitive function. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294.).

Activation of histone deacetylase-6 induces contractile dysfunction through derailment of α-tubulin proteostasis in experimental and human atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is characterized by structural remodeling, contractile dysfunction, and AF progression. Histone deacetylases (HDACs) influence acetylation of both histones and cytosolic proteins, thereby mediating epigenetic regulation and influencing cell proteostasis. Because the exact function of HDACs in AF is unknown, we investigated their role in experimental and clinical AF models. METHODS AND RESULTS: Tachypacing of HL-1 atrial cardiomyocytes and Drosophila pupae hearts significantly impaired contractile function (amplitude of Ca(2+) transients and heart wall contractions). This dysfunction was prevented by inhibition of HDAC6 (tubacin) and sirtuins (nicotinamide). Tachypacing induced specific activation of HDAC6, resulting in α-tubulin deacetylation, depolymerization, and degradation by calpain. Tachypacing-induced contractile dysfunction was completely rescued by dominant-negative HDAC6 mutants with loss of deacetylase activity in the second catalytic domain, which bears α-tubulin deacetylase activity. Furthermore, in vivo treatment with the HDAC6 inhibitor tubastatin A protected atrial tachypaced dogs from electric remodeling (action potential duration shortening, L-type Ca(2+) current reduction, AF promotion) and cellular Ca(2+)-handling/contractile dysfunction (loss of Ca(2+) transient amplitude, sarcomere contractility). Finally, atrial tissue from patients with AF also showed a significant increase in HDAC6 activity and reduction in the expression of both acetylated and total α-tubulin. CONCLUSIONS: AF induces remodeling and loss of contractile function, at least in part through HDAC6 activation and subsequent derailment of α-tubulin proteostasis and disruption of the cardiomyocyte microtubule structure. In vivo inhibition of HDAC6 protects against AF-related atrial remodeling, disclosing the potential of HDAC6 as a therapeutic target in clinical AF.

Off-pump or on-pump coronary-artery bypass grafting at 30 days.

BACKGROUND: The relative benefits and risks of performing coronary-artery bypass grafting (CABG) with a beating-heart technique (off-pump CABG), as compared with cardiopulmonary bypass (on-pump CABG), are not clearly established. METHODS: At 79 centers in 19 countries, we randomly assigned 4752 patients in whom CABG was planned to undergo the procedure off-pump or on-pump. The first coprimary outcome was a composite of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days after randomization. RESULTS: There was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (9.8% vs. 10.3%; hazard ratio for the off-pump group, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P=0.59) or in any of its individual components. The use of off-pump CABG, as compared with on-pump CABG, significantly reduced the rates of blood-product transfusion (50.7% vs. 63.3%; relative risk, 0.80; 95% CI, 0.75 to 0.85; P<0.001), reoperation for perioperative bleeding (1.4% vs. 2.4%; relative risk, 0.61; 95% CI, 0.40 to 0.93; P=0.02), acute kidney injury (28.0% vs. 32.1%; relative risk, 0.87; 95% CI, 0.80 to 0.96; P=0.01), and respiratory complications (5.9% vs. 7.5%; relative risk, 0.79; 95% CI, 0.63 to 0.98; P=0.03) but increased the rate of early repeat revascularizations (0.7% vs. 0.2%; hazard ratio, 4.01; 95% CI, 1.34 to 12.0; P=0.01). CONCLUSIONS: There was no significant difference between off-pump and on-pump CABG with respect to the 30-day rate of death, myocardial infarction, stroke, or renal failure requiring dialysis. The use of off-pump CABG resulted in reduced rates of transfusion, reoperation for perioperative bleeding, respiratory complications, and acute kidney injury but also resulted in an increased risk of early revascularization. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294.).

Statin pretreatment and risk of in-hospital atrial fibrillation among patients undergoing cardiac surgery: a collaborative meta-analysis of 11 randomized controlled trials.

AIMS: Statin pretreatment in patients undergoing cardiac surgery is understood to prevent postoperative atrial fibrillation (AF). However, this is based on observational and limited randomized trial evidence, resulting in uncertainty about any genuine anti-arrhythmic benefits of these agents in this setting. We therefore aimed to quantify precisely the association between statin pretreatment and postoperative AF among patients undergoing cardiac surgery. METHODS AND RESULTS: A detailed search of MEDLINE and PubMed databases (1st January 1996 to 31st July 2012) was conducted, followed by a review of the reference lists of published studies and correspondence with trial investigators to obtain individual-participant data for meta-analysis. Evidence was combined across prospective, randomized clinical trials that compared the risk of postoperative AF among individuals randomized to statin pretreatment or placebo/control medication before elective cardiac surgery. Postoperative AF was defined as episodes of AF lasting ≥5 min. Overall, 1105 participants from 11 trials were included; of them, 552 received statin therapy preoperatively. Postoperative AF occurred in 19% of these participants when compared with 36% of those not treated with statins (odds ratio 0.41, 95% confidence interval 0.31-0.54, P < 0.00001, using a random-effects model). Atrial fibrillation prevention by statin pretreatment was consistent across different subgroups. CONCLUSION: Short-term statin pretreatment may reduce the risk of postoperative AF among patients undergoing cardiac surgery.

Treatment of lipoid proteinosis with ablative Er:YAG laser resurfacing.

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis characterized by deposition of amorphous hyaline material in different parts of the body, especially the skin and mucous membranes. Disfiguring lesions predominantly affect facial appearance. There is no curative therapy and treatment options are limited to symptomatic approaches. Facial disfigurement in this disease may have an huge negative effect on the patients' psychology and quality of life. With this regard, the patients may benefit very much from symptomatic treatments. Four patients with LP were treated with Er:YAG laser to ablate disfiguring lesions on the face. Patients were followed up for 14 months to 2 years. We obtained favorable clinical and aesthetic results in all cases with Er:YAG laser treatment and did not observe any recurrences during the follow-up. Depending on our observations Er-YAG laser can be accepted as an effective tool for dermal accumulations and scars of LP with precise ablation capability and favorable esthetic results.