Superior Neurological Outcomes Research Articles

Surgery With or Without Radiotherapy Versus Radiotherapy Alone for Malignant Spinal Cord Compression : An Updated Meta-analysis.

A systematic review and meta-analysis. To conduct a meta-analysis of studies that compared surgery with or without radiotherapy to radiotherapy alone for patients with malignant spinal cord compression, and a subgroup analysis of patients stratified by hematologic and solid malignancies. Two previous meta-analyses showed that surgery with or without radiotherapy was better than radiotherapy alone in patients with malignant spinal cord compression. Nevertheless, there was no stratification by tumor type, leading to uncertainty regarding the best approach for patients with hematologic malignancies. We searched PubMed, Scopus, and Web of Science, for studies comparing surgery with or without radiotherapy to radiotherapy alone in patients with malignant spinal cord compression. The primary outcomes were improvement in ambulatory status and survival at 12 months. For neurological outcomes, we included studies involving both locally advanced primary malignancies of the spine and metastatic tumors. We restricted our analysis to studies on metastases for survival outcomes. We included 2536 patients from 18 studies. Surgery was performed in 890 (35%) patients. The pooled analysis of all studies revealed that improvement in ambulatory status [odds ratio (OR): 2.65; 95% CI: 1.60-4.39] and survival at 12 months (OR: 1.66; 95% CI: 1.10-2.52) were significantly higher in patients who underwent surgery with or without radiotherapy. Improvement in ambulatory status (OR: 1.92; 95% CI: 1.19-3.09) and survival at 12 months (OR: 4.24; 95% CI: 2.35-7.66) were significantly higher in patients with hematologic malignancies in the surgical arm. The primary outcomes were not significantly different between patients with solid malignancies. Surgical intervention demonstrates superior neurological outcomes and increased survival compared with radiotherapy alone. Subgroup analysis revealed that patients with hematologic malignancies in the surgery group experienced superior primary outcomes; however, the high risk of bias of the included studies precludes definitive changes in standard care based on this data. These findings underscore the need for further research regarding the efficacy of surgical versus radiotherapeutic approaches for specific tumor types. Level II.

Propofol-Based Anesthesia Maintenance and/or Volatile Anesthetics during Intracranial Aneurysm Repair: A Comparative Analysis of Neurological Outcomes

Background: Volatile and intravenous anesthetics have substantial effects on physiological functions, notably influencing neurological function and susceptibility to injury. Despite the importance of the anesthetic approach, data on its relative risks or benefits during surgical clipping or endovascular treatments for unruptured intracranial aneurysms (UIAs) remains scant. We investigated whether using volatile anesthetics alone or in combination with propofol infusion yields superior neurological outcomes following UIA obliteration. Methods: We retrospectively reviewed 1001 patients who underwent open or endovascular treatment for UIA, of whom 596 had short- and long-term neurological outcome data (modified Rankin Scale) recorded. Multivariable ordinal regression analysis was performed to examine the association between the anesthetic approach and outcomes. Results: Of 1001 patients, 765 received volatile anesthetics alone, while 236 received propofol infusion and volatile anesthetics (combined anesthetic group). Short-term neurological outcome data were available for 619 patients and long-term data for 596. No significant correlation was found between the anesthetic approach and neurologic outcomes, irrespective of the type of procedure (open craniotomy or endovascular treatment). The combined anesthetic group had a higher rate of ICU admission (p < 0.001) and longer ICU and hospital length of stay (LOS, p < 0.001). Similarly, a subgroup analysis revealed longer ICU and hospital LOS (p < 0.0001 and p < 0.001, respectively) in patients who underwent endovascular UIA obliteration under a combined anesthetic approach (n = 678). Conclusions: The addition of propofol to volatile anesthetics during UIA obliteration does not provide short- or long-term benefits to neurologic outcomes. Compared to volatile anesthetics alone, the combination of propofol and volatile anesthetics may be associated with an increased rate of ICU admission, as well as longer ICU and hospital LOS.

Treatment of Idiopathic Normal Pressure Hydrocephalus with a Novel Programmable Valve: Prospective Evaluation of Costs, Efficacy, and Safety.

Objective Programmable valves provide an equal or superior neurological outcome when compared with fixed pressure ones, with fewer complications, in treating idiopathic normal pressure hydrocephalus (iNPH) patients. Long-term costs of these treatments have not been properly compared in literature. We sought to compare costs, efficacy, and safety of 1-year treatment of iNPH patients with programmable valve Sphera Pro and a fixed pressure valve. Materials and Methods A prospective cohort of iNPH patients treated with programmable valve was compared with a historical cohort of iNPH patients treated with fixed pressure valve. Our primary outcome was mean direct cost of treating iNPH up to 1 year. Efficacy in treating iNPH and safety were assessed as secondary outcomes. Statistical Analysis Proportions were compared using chi-square or Fisher's exact tests. Normally distributed variables were compared using the Student's t -test or the Mann-Whitney's U test. Differences in the evolution of the variables over time were assessed using generalized estimating equations. All tests were two-sided, with an α of 0.05. Results A total of 19 patients were analyzed in each group (mean age 75 years, the majority male). Comorbidities and clinical presentation were similar between groups. Both fixed pressure and programmable valve patients had neurological improvement over time ( p < 0.001), but no difference was seen between groups ( p = 0.104). The fixed pressure valve group had more complications than the programmable valve group (52.6% vs. 10.5%, respectively, p = 0.013). Annual treatment cost per patient was US$ 3,820 ± 2,231 in the fixed pressure valve group and US$ 3,108 ± 553 in the programmable valve group. Mean difference was US$712 (95% confidence interval, 393-1,805) in favor of the programmable valve group. Conclusion The Sphera Pro valve with gravitational unit had 1 year treatment cost not higher than that of fixed pressure valve, and resulted in similar efficacy and fewer complications.

410 Treatment of Idiopathic Normal Pressure Hydrocephalus With a Novel Programmable Valve With Gravitational Unit: Prospective Evaluation of Efficacy, Safety and Costs

INTRODUCTION: Programmable valves provide an equal or superior neurological outcome when compared to fixed pressure ones, with fewer complications, in treating idiopathic normal pressure hydrocephalus (iNPH) patients. Long-term costs of these treatments have not been properly compared in literature. METHODS: A prospective cohort of iNPH patients treated with programmable valve between January 2018 and May 2020 was compared to a historical cohort of iNPH patients treated with fixed pressure valve from January 2016 through December 2017. Our primary outcome was the mean cost of treating iNPH up to one year. Cost variables assessed included number of surgeries, length of ICU and hospital stay, and number of imaging tests. Efficacy in treating iNPH, measured by mean NPH Japanese Scale, and safety, measured by complications rates, were assessed as secondary outcomes. RESULTS: A total of 19 patients were analyzed in each group (mean age 75 years, the majority male). Comorbidities and clinical presentation were similar between groups. Both fixed pressure and programmable valve patients had neurological improvement over time (p &lt; 0.001), but no difference was seen between groups (p = 0.104). The fixed pressure valve group had more complications than programmable valve group (52.6% vs 10.5%, respectively, p = 0.013). Annual treatment cost per patient was US$ 3,820 ± 2,231 in the fixed pressure valve group and US$ 3,108 ± 553 in the programmable valve group. Mean difference was US$712 (95% CI, 393 – 1,805) in favor of the programmable valve group. CONCLUSIONS: The novel programmable valve with gravitational unit had one-year treatment cost not higher than that of fixed-pressure valve, and resulted in similar efficacy and fewer complications.

Long-term neurological cognitive, behavioral, functional, and quality of life outcomes after fetal myelomeningocele closure: a systematic review.

Myelomeningocele is a lifelong condition that features several comorbidities, such as hydrocephalus, scoliosis, club foot, and lower limb sensory and motor disabilities. Its management has progressed over time, ranging from supportive care to early postnatal closure to prenatal closure of the defect. Recent research discovered that fetal myelomeningocele closure (fMMC) provided superior neurological outcomes to those of postnatal closure. When performed at 12 months of age, fMMC can avert or delay the need for a ventriculoperitoneal shunt and reversed the hindbrain herniation. Moreover, fMMC reportedly enhanced motor function and mental development at 30 months of age. However, its long-term outcomes remain dubious. This systematic review aimed to determine the long-term neurological cognitive, behavioral, functional, and quality of life (QoL) outcomes after fMMC. The PubMed, Directory of Open Access Journals, EBSCO, and Cochrane databases were extensively searched for articles published in 2007-2022. Meta-analyses, clinical trials, and randomized controlled trials with at least 5 years of follow-up were given priority. A total of 11 studies were included. Most studies revealed enhanced long-term cognitive, behavioral, functional, and QoL outcomes after fMMC. Our results suggest that fMMC substantially enhanced patients' long-term neurological cognitive, behavioral, functional, and QoL outcomes.

Single-Center Experience With the Thoraflex™ Hybrid Prosthesis: Indications, Implantation Technique and Results.

ObjectiveThe aim of this study was to evaluate the early and mid-term results after the frozen elephant trunk (FET) procedure for the treatment of complex arch and proximal descending aortic disease in a single-center institution.MethodsFrom April 2015 to July 2021, 72 patients (25 women, 60.4 ± 10.3 years) underwent Thoraflex™ Hybrid implantation at our institution. The indications were thoracic aortic aneurysm (TAA) (n = 16, 22.2%), post-dissection aneurysm (n = 21, 29.2%), and acute aortic dissection (AAD) (n = 35, 48.6%). Antegrade cerebral perfusion under moderate hypothermia (28°C) was employed in all cases. Eighteen patients (25%) have already been operated due to heart or aortic disease.ResultsOverall in-hospital mortality was 12.5% (9 patients). Rates of permanent neurological dysfunction and spinal cord injury were 9.7 and 5.5%, respectively. The in-hospital mortality rate among patients operated on AAD, TAA, and post-dissection aneurysm were 8.6, 6.2, and 23.8%, respectively. At a mean follow-up of 26 ± 20 months, mortality was 9.7%. Furthermore, 23 patients (31.9%) required a subsequent procedure in distal aorta: endovascular stentgraft extension in 19 patients (26.4%) and open aortic surgery in 4 patients (5.5%). The mid-term survival of patients with type A aortic dissection was 97%.ConclusionsOur experience with the Thoraflex Hybrid prosthesis demonstrates its surgical applicability for different types of aortic pathologies with promising outcomes during early and midterm follow-up. Our technique and perioperative management lead to comparable or even superior neurological outcomes and mortality in urgent cases considering other high-volume centers.

Differential Effectiveness of Hypothermic Targeted Temperature Management According to the Severity of Post-Cardiac Arrest Syndrome.

International guidelines recommend targeted temperature management (TTM) to improve the neurological outcomes in adult patients with post-cardiac arrest syndrome (PCAS). However, it still remains unclear if the lower temperature setting (hypothermic TTM) or higher temperature setting (normothermic TTM) is superior for TTM. According to the most recent large randomized controlled trial (RCT), hypothermic TTM was not found to be associated with superior neurological outcomes than normothermic TTM in PCAS patients. Even though this represents high-quality evidence obtained from a well-designed large RCT, we believe that we still need to continue investigating the potential benefits of hypothermic TTM. In fact, several studies have indicated that the beneficial effect of hypothermic TTM differs according to the severity of PCAS, suggesting that there may be a subgroup of PCAS patients that is especially likely to benefit from hypothermic TTM. Herein, we summarize the results of major RCTs conducted to evaluate the beneficial effects of hypothermic TTM, review the recent literature suggesting the possibility that the therapeutic effect of hypothermic TTM differs according to the severity of PCAS, and discuss the potential of individualized TTM.

Reality of Accomplishing Surgery within 24 Hours for Complete Cervical Spinal Cord Injury: Clinical Practices and Safety.

Substantial clinical data support an association between superior neurological outcomes and early (within 24 h) surgical decompression for those with traumatic cervical spinal cord injury (SCI). Despite this, much discussion persists around feasibility and safety of this time threshold, particularly for those with a complete cervical SCI. This study aims to assess clinical practices and the safety profile of early surgery across a large sample of North American trauma centers. Data were derived from the Trauma Quality Improvement Program database from 2010-2016. Adult patients with a complete cervical SCI (American Spinal Injury Association [ASIA] A) who underwent surgery were included. Patients were stratified into those receiving surgery at or before 24 h and those receiving delayed intervention. Risk-adjusted variability in surgical timing across trauma centers was investigated using mixed-effects regression. In-hospital adverse events including death, major complications, and immobility-related complications were compared between groups after propensity score matching. There were 2862 patients from 353 North American trauma centers included; 1760 (61.5%) underwent surgery within 24 h. Case-mix and hospital-level characteristics explained only 6% of the variability in surgical timing both between centers and within centers. No significant differences in adverse events were identified between groups. These findings suggest a relatively large proportion of patients are not receiving surgery within the recommended time frame, despite apparent safety. Moreover, patient and hospital-level characteristics explain little of the variability in time-to-surgery. Further knowledge translation is needed to increase the proportion of patients in whom surgery is performed before the 24-h threshold so patients might reach their greatest potential for neurological recovery.

Gangliosides: Treatment Avenues in Neurodegenerative Disease.

Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown to attenuate ischemic neuronal injuries in diabetes patients by suppression of ERK1/2 phosphorylation and reduction of stress to the endoplasmic reticulum. There is level-I evidence from 5 RCTs of a significantly faster recovery with GM1 vs. placebo in patients with acute and chronic spinal cord injury (SCI), disturbance of consciousness after subarachnoid hemorrhage, or craniocerebral injuries due to closed head trauma. In Parkinson's disease (PD), two RCTs provided evidence of GM1 to be superior to placebo in improving motor symptoms and long-term to result in a slower than expected symptom progression, suggesting disease-modifying potential. In Alzheimer's disease (AD), the role of gangliosides has been controversial, with some studies suggesting a “seeding” role for GM1 in amyloid β polymerization into toxic forms, and others more recently suggesting a rather protective role in vivo. In Huntington's disease (HD), no clinical trials have been conducted yet. However, low GM1 levels observed in HD cells were shown to increase cell susceptibility to apoptosis. Accordingly, treatment with GM1 increased survival of HD cells in vitro and consistently ameliorated pathological phenotypes in several murine HD models, with effects seen at molecular, cellular, and behavioral level. Given that in none of the clinical trials using GM1 any clinically relevant safety issues have occurred to date, current data supports expanding GM1 clinical research, particularly to conditions with high, unmet medical need.

Preserved brain morphology after controlled automated reperfusion of the whole body following normothermic circulatory arrest time of up to 20 minutes.

Clinical outcomes following cardiac arrest (CA) and resuscitation remain a cause for concern. The use of Controlled Automated Reperfusion of the whoLe body (CARL) confers superior neurological outcome even after extended periods of CA. We aimed at investigating clinical outcome and brain morphology preservation when employing CARL following CA periods of 20 min. Twenty-eight pigs were allocated to four extracorporeal circulation treatment strategies; seven others served as magnetic resonance imaging (MRI) controls. In prompt cardiopulmonary resuscitation (CPR; n = 6), induced circulatory arrest was followed immediately by open cardiac massage of 15 min, thereafter by CARL for 60 min. In delayed CPR (n = 6), induced CA was maintained for 15 min, after that open cardiac massage of 10 min duration was performed prior to extracorporeal CPR (ECPR) of 60 min. Induced CA times of 15 min in the ECPR 15' group (n = 6) and CA of 20 min in the CARL 20' group (n = 10) were followed by ECPR of 60 min and CARL of 60 min, respectively, without prior CPR. Daily neurological deficit scoring (NDS) up to the seventh day, markers of cellular injury [alanine transaminase (ALT), aspartate transaminase (AST) and neuron-specific enolase (NSE)] and brain MRI were performed. 100% survival and normal NDSs were achieved in all animals in the prompt CPR and ECPR 15' groups. In CARL 20', nine animals survived. In contrast, only one animal in the delayed CPR group survived; three animals died within 24 h with a further two dying on Days 4 and 5, respectively. All markers of cellular injury were elevated in the delayed CPR group, ALT [38 (20.3) to 206 U/l (158.2); P = 0.0095], AST [26 (18.8) to 97 U/l (1965.8); P = 0.0095] and NSE [0.45 (0.25) to 7.95 µg/l (24.03); P = 0.0095]. In the ECPR 15' group, only NSE [0.45 (0.15) to 1.20 µg/l (2.40); P = 0.0065] remained elevated. In the CARL 20' group, differences in ALT [36 (10) to 53 U/l (20); P = 0.0005] and NSE [0.50 (0.40) to 1.5 µg/l (0.40); P < 0.0001] values were evident. T2-weighted MR images of the cerebellum [454 (28) to 495 mm2/s (55); U = 11; P = 0.0311], caudate nucleus [400 (59) to 467 mm2/s (42); U = 9; P = 0.0156], lentiform nucleus [377 (89) to 416 mm2/s (55); U = 11; P = 0.0311] and hippocampus [421 (109) to 511 mm2/s (58); U = 9; P = 0.0164] in the CARL 20' group showed higher signal intensities compared with controls. In delayed CPR, corresponding regions of interest on early apparent diffusion coefficient images showed a restricted diffusion. In our experimental animal model of CA, CARL results in satisfactory survival at CA periods of 20 min despite detected enzyme and morphological changes. These changes did not translate to clinical neurological deficits.

Neurological Recovery after Traumatic Cervical Spinal Cord Injury is Superior if Surgical Decompression and Instrumented Fusion are Performed within 8 h versus 8–24 h after Injury: A Single Centre Experience

Introduction Traumatic spinal cord injury (tSCI) is a catastrophic event with enormous personal, social and economic impact. Despite recent progress in understanding the pathophysiology of acute tSCI and the positive effects of acute spinal cord decompression on neurological recovery reported in standardized preclinical studies, neurological benefits of early surgical decompression (SD) remain elusive in the clinical setting. Material and Methods A prospective study was performed to evaluate the impact of SD and instrumented fusion within 8 hour versus 8–24 hour after injury on neurological recovery after cervical tSCI in patients operated on in the UMC Ljubljana, Slovenia. Only patients with the ASIA Impairment Scale (AIS) grades of A through C and with MRI-confirmed spinal cord compression were enrolled. The primary outcome was the change in AIS grade at the six-month follow-up. Results Of the 48 enrolled patients, 22 patients who underwent surgery within 8h (Group-8h) and 20 patients who underwent surgery between 8 and 24h (Group-8–24h) after injury concluded the study. At admission, there was no statistically significant difference in AIS grade between the study groups. At the six-month follow-up, an improvement of at least two AIS grades was found in 45.5% of patients in Group-8h and in 10% of patients in Group-8–24h ( p = 0.017). In a multivariate analysis, adjusted for the preoperative AIS grade and the degree of spinal canal compromise, the odds of an at least two-grade AIS improvement were at least 106% higher for patients in Group-8h than for patients in Group-8–24h (OR = 11.08, p = 0.004). No statistically significant difference was found in the rate of pneumonia, the number of ventilator-dependent days or the mortality between the groups. Conclusion Our results suggest that the patients with tSCI who undergo SD within 8h after injury have superior neurological outcomes than patients who undergo SD 8 to 24h after injury, without any increase in the rate of adverse effects.

Abstract WP11: Comparative Safety and Efficacy of the Trevo, Penumbra and Solitaire Devices in Treatment of Acute Ischemic Stroke

Background and Purpose: We performed a systematic review and meta-analysis comparing rates of recanalization, good neurological outcome, and mortality between patients treated with three modern devices used for endovascular treatment of acute ischemic stroke. Materials and Methods: We performed a comprehensive literature search on studies reporting outcomes of endovascular treatment of acute ischemic stroke. We selected studies including≥30 patients treated with either the Trevo stent-retriever, Penumbra aspiration system or the Solitaire stent-retriever. Outcomes studied included mrs≤2, 90-day mortality, symptomatic and intracranial hemorrhage (sICH), recanalization. Outcomes were pooled across studies using a random-effects meta-analysis. Results: 27 articles with 2666 patients were included (1514 Solitaire, 260 Trevo and 892 Penumbra). Rates of good neurological outcome (mRS≤2) were higher in the Solitaire group (54.0%, 95%CI=49.0-58.0%) than the Penumbra group (39.0%, 95%CI=31.0%-47.0%) (P&lt;0.01). There was a trend towards higher rates of good neurological outcome in the Solitaire compared to the Trevo group (P=0.08). Rates of 90-day mortality were significantly lower in the Solitaire group (16.0%, 95%CI=11.0%-22.0%) than in the Penumbra group (27.0%, 95%CI=24.0%-30.0%) (P&lt;0.01) and the Trevo group (23.0%, 95%CI=13.0-33.0)(P=0.01). Recanalization rates were similar between groups at 80.0% (95%CI=75.0%-84.0% for the Solitaire group, 82.0% (95%CI=75.0%-88.0%) for the Penumbra group (P=0.54) and 76.0% (95%CI=68.0-83.0) for the Trevo group (P=0.13 vs Penumbra and P=0.27 vs. Solitaire). Conclusions: Meta-analysis of incidence rates in noncomparative series reporting on over 2500 patients suggests that the Solitaire device maybe associated with superior neurological outcomes and lower rates of 90-day mortality. Comparative studies are needed to confirm these observations.

Analysis of Delays to Surgery for Cervical Spinal Cord Injuries

Study design A retrospective study of surgically treated patients with cervical spinal cord injury (SCI) from the National Trauma Data Bank Research Data Set. Objective To determine how time to surgery differs between SCI subtypes, where delays before surgery occur, and what factors are associated with delays. Summary of background data Studies have shown that patients with cervical SCI undergoing surgery within 24 hours after injury have superior neurological outcomes to patients undergoing later surgery, with most evidence coming from the incomplete SCI subpopulation. Methods Surgically treated patients with cervical SCI from 2011 and 2012 were identified in National Trauma Data Bank Research Data Set and divided into subpopulations of complete, central, and other incomplete SCIs. Relationships between surgical timing and patient and injury characteristics were analyzed using multivariate regression. Results A total of 2636 patients with cervical SCI were identified: 803 with complete SCI, 950 with incomplete SCI, and 883 with central SCI. The average time to surgery was 51.1 hours for patients with complete SCI, 55.3 hours for patients with incomplete SCI, and 83.1 hours for patients with central SCI. Only 44% of patients with SCI underwent surgery within the first 24 hours after injury, including only 49% of patients with incomplete SCI.The vast majority of time between injury and surgery was after admission, rather than in the emergency department or in the field. Upper cervical SCIs and greater Charlson Comorbidity Index were associated with later surgery in all 3 SCI subpopulations. Conclusion The majority of patients with SCI do not undergo surgery within the first 24 hours after injury, and the majority of delays occur after inpatient admission. Factors associated with these delays highlight areas of focus for expediting care in these patient populations. Level of evidence 4.

Neurological Recovery after Traumatic Cervical Spinal Cord Injury Is Superior if Surgical Decompression and Instrumented Fusion Are Performed within 8 Hours versus 8 to 24 Hours after Injury: A Single Center Experience.

A prospective study was performed to evaluate the impact of surgical decompression (SD) and instrumented fusion within 8 h versus 8-24 h after injury on neurological recovery after cervical traumatic spinal cord injury (tSCI) in patients operated on in the UMC Ljubljana, Slovenia. Only patients with the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades of A through C and with MRI-confirmed spinal cord compression were enrolled. The primary outcome was the change in AIS grade at the 6-month follow-up. Of the 48 enrolled patients, 22 patients who underwent surgery within 8 h (group 8 h) and 20 patients who underwent surgery between 8 and 24 h (Group 8-24 h) after injury concluded the study. At admission, there was no statistically significant difference in AIS grade between the study groups. At the 6-month follow-up, an improvement of at least two AIS grades was found in 45.5% of patients in group 8 h and in 10% of patients in group 8-24 h (p=0.017). The median improvement in the ASIA motor score was 38.5 (10.0-61.0) motor points in group 8 h and 15.0 (8.8-34.0) motor points in group 8-24 h (p=0.0468). In a multivariate analysis, adjusted for the preoperative AIS grade and the degree of spinal canal compromise, the odds of an at least two-grade AIS improvement were at least 106% higher for patients in group 8 h than for patients in group 8-24 h (odds ratio=11.08, p=0.004). No statistically significant difference was found in the rate of perioperative complications, pneumonia, and the number of ventilator-dependent days or the mortality between the groups. Our results suggest that the patients with tSCI who undergo SD within 8 h after injury have superior neurological outcomes than patients who undergo SD 8-24 h after injury, without any increase in the rate of adverse effects.

Thyroid hormone in the frontier of cell protection, survival and functional recovery.

Thyroid hormone (TH) exerts important actions on cellular energy metabolism, accelerating O2 consumption with consequent reactive oxygen species (ROS) generation and redox signalling affording cell protection, a response that is contributed by redox-independent mechanisms. These processes underlie genomic and non-genomic pathways, which are integrated and exhibit hierarchical organisation. ROS production led to the activation of the redox-sensitive transcription factors nuclear factor-κB, signal transducer and activator of transcription 3, activating protein 1 and nuclear factor erythroid 2-related factor 2, promoting cell protection and survival by TH. These features involve enhancement in the homeostatic potential including antioxidant, antiapoptotic, antiinflammatory and cell proliferation responses, besides higher detoxification capabilities and energy supply through AMP-activated protein kinase upregulation. The above aspects constitute the molecular basis for TH-induced preconditioning of the liver that exerts protection against ischemia-reperfusion injury, a strategy also observed in extrahepatic organs of experimental animals and with other types of injury, which awaits application in the clinical setting. Noteworthy, re-adjusting TH to normal levels results in several beneficial effects; for example, it lengthens the cold storage time of organs for transplantation from brain-dead donors; allows a superior neurological outcome in infants of <28 weeks of gestation; reduces the cognitive side-effects of lithium and improves electroconvulsive therapy in patients with bipolar disorders.

Experience with the conventional and frozen elephant trunk techniques: a single-centre study

The treatment of patients with extensive thoracic aortic disease involving the arch and descending/thoracoabdominal aorta is often performed using an elephant trunk procedure. We retrospectively analysed our results comparing two different techniques: the conventional elephant trunk (cET) and the frozen elephant trunk (FET) operation. Between January 2003 and December 2011, 171 consecutive patients underwent total aortic arch replacement with either a cET (n = 125) or FET (n = 46) technique. The mean age was 64 ± 13 years and was significantly higher in the FET group (P < 0.01). Acute Type A aortic dissection was the indication for surgery in 53.6% of cET and 17.4% of FET patients, and degenerative or atherosclerotic aneurysm accounted for 33.6% of cET and 58.7% of FET patients. The remaining patients were operated on for chronic Type A or acute or chronic Type B dissections with arch involvement. In-hospital mortality was 21.6 vs 8.7% for cET and FET patients, respectively (P = 0.1). Logistic regression analysis revealed Type A aortic dissection (odds ratio (OR) 3.1, P = 0.01) as the only independent predictor of hospital mortality. Stroke occurred in 16 vs 13% of cET vs FET patients (P = 0.4). Type A aortic dissection was an independent predictor of stroke by multivariable analysis (OR 2.6, P = 0.03), and axillary arterial cannulation was protective against stroke (OR 0.4, P = 0.04). The occurrence of new-onset paraplegia was significantly higher in the FET group (21.7 vs 4.0%, P < 0.001), and aortic repair with the FET technique was an independent predictor for paraplegia (OR 6.6, P = 0.001). Among patients receiving FET, a body core temperature during circulatory arrest of ≥ 28 °C in combination with a prolonged circulatory arrest time of >40 min was an independent predictor for permanent spinal cord injury (OR 5.0, 95% CI 1.1-20, P = 0.038). The estimated 1-, 3- and 5-year survival were 70 ± 4, 70 ± 4 and 68 ± 4% (cET) and 4 ± 7 and 60 ± 9, 40 ± 1% (FET), with mean survival time 5.2 ± 0.3 vs 3.8 ± 0.5 years (cET vs FET, log-rank P = 0.9). The FET procedure for extensive thoracic aortic disease is associated with an acceptable mortality rate, but with a higher incidence of perioperative spinal cord injury than cET. Arch replacement with a cET technique should be strongly considered in patients with expected prolonged circulatory arrest times, particularly if operated on under mild or moderate hypothermia. Axillary cannulation is associated with superior neurological outcomes and Type A acute aortic dissection is a risk factor for mortality and poor neurological outcomes in this patient population.

Off-pump surgery using no touch techniques provides superior neurological outcomes for patients with a high calcific load

Off-pump surgery using no touch techniques provides superior neurological outcomes for patients with a high calcific load

Central aortic canulation in acute type A dissection and the use of selective antegrade perfusion provides superior neurological outcome

Central aortic canulation in acute type A dissection and the use of selective antegrade perfusion provides superior neurological outcome

Periodic acceleration (pGz) CPR in a swine model of asphyxia induced cardiac arrest: Short-term hemodynamic comparisons

Asphyxia is one of the most common causes of pediatric cardiac arrest, and becoming a more frequently recognized cause in adults. Periodic acceleration (pGz) is a novel method of cardiopulmonary resuscitation (CPR). pGz is achieved by rapid motion of the supine body headward-footward that generates adequate perfusion and ventilation during cardiac arrest. In a swine ventricular fibrillation cardiac arrest model, pGz produced a higher return of spontaneous circulation (ROSC), superior neurological outcome, less echocardiography evidence of post resuscitation myocardial stunning, and decreased indices of tissue injury. In contrast to standard chest compression CPR, pGz does not produce rib fractures. We investigated the feasibility of pGz in severe asphyxia cardiac arrest and assessed whether beneficial effects seen in the VF model of cardiac arrest could be realized. Sixteen swine weight 4+/-1 kg were anesthetized, tracheally intubated, and instrumented to measure, hemodynamics and echocardiography. Asphyxia was induced by occlusion of the tracheal tube. After loss of aortic pulsations (median time 10 min) animals were observed for three additional minutes following which all were in cardiac arrest. The animals were then randomized to receive 10 min of pGz or standard chest compression ventilation performed with a commercial device (Thumper). A single dose of epinephrine (adrenaline) and sodium bicarbonate were given and defibrillation attempted if appropriate for a maximum of 10 min. Both groups received fractional inspired O2 concentration of 100% during CPR and after resuscitation. Four animals in each group (50%) had an initial ROSC, however only two of the four initial survivors remained alive 3h after ROSC. There were no significant differences in blood pressure, coronary perfusion pressure during CPR and after early ROSC between groups. pGz treated animals had significantly lower pulmonary artery pressure; 20+/-4 mmHg compared to Thumper 46+/-5 mmHg, 30 min after ROSC (p<0.01). Surviving animals in both groups had severe myocardial dysfunction at 30 min after ROSC. At necropsy, 25% of the Thumper treated animals had rib fractures, while none occurred in the pGz group. In a lethal model of asphyxia cardiac arrest, pGz is equivalent to standard CPR, with respect to acute outcomes and resuscitation survival rates but is associated with significantly lower pulmonary artery pressures and does not produce traumatic rib fractures.

Hypoxaemic reperfusion ameliorates the histopathological changes in the pig brain after a severe global cerebral ischaemic insult.

We have recently shown that hypoxaemic reperfusion, after an ischaemic brain insult, improves neurological outcome and decreases lipid peroxidation. In the present study, we investigated the effect of hypoxaemic reperfusion on brain histopathological changes. Sixteen pigs subjected to a 10-min global cerebral ischaemia were either hypoxaemically (PaO2 = 35 mmHg, hypoxaemic reperfusion (HR) group, n = 8) or hyperoxaemically (PaO2 > 300 mmHg, control (C) group, n = 8) reperfused. The brains were removed 24 h after reperfusion and six neuropathological abnormalities were evaluated blindly and scored semi-quantitatively (0: normal to 3: severe injury) on eight representative regions of the brain. The overall cumulative score of the abnormalities and their regional prevalence, as well as the neurological outcome, were compared between the two groups. The neuronal degeneration, assessed in terms of cumulative score (P = 0.002) and regional prevalence (P = 0.025 to P = 0.041), was lower in the HR group than in the C group. Spongy degeneration attained statistically significant difference only in cerebellum (P = 0.002) and inflammation only in hippocampus (P = 0.046) but the difference in the cumulative score of these abnormalities was not statistically significant. The difference of the three neurological assessments over time was statistically significant between the two groups, i.e. after resuscitation (P = 0.001), at 8 h (P = 0.006) and at 24 h (P = 0.001) after reperfusion. Hypoxaemic reperfusion during resuscitation from a severe global ischaemic cerebral insult is associated with statistically significantly fewer histopathological changes of the brain than in controls. This is associated with a superior neurological outcome.