Search

Hereditary spastic paraplegias are rare genetic disorders characterized by corticospinal tract impairment. Spastic paraplegia 83 (SPG83) is associated with biallelic mutations in the HPDL gene, leading to varied severities from neonatal to juvenile onset. The function of HPDL is unclear, though it is speculated to play a role in alternative coenzyme Q10 biosynthesis. Here, we report the generation of hiPS lines from primary skin fibroblasts derived from three SPG83 patients with different HPDL mutations, using episomal reprogramming. The patients' clinical characteristics are carefully listed. The hiPS lines were meticulously characterized, demonstrating typical pluripotent characteristics through immunofluorescence assays for stemness markers (OCT4, TRA1-60, NANOG, and SSEA4) and RT-PCR for endogenous gene expression. Genetic integrity and identity were confirmed via Sanger sequencing and short tandem repeat analysis. These hiPS cells displayed typical pluripotent characteristics and were able to differentiate into neocortical neurons via a dual SMAD inhibition protocol. In addition, HPDL mutant neurons assessed via long-term culturing were able to achieve effective maturation, similarly to their wild-type counterparts. The HPDL hiPS lines we generated will provide a valuable model for studying SPG83, offering insights into its molecular mechanisms and potential for developing targeted therapies.

Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments on outcomes in ABI patients and experimental animals and defining the trend of nucleosome levels in biological samples post injury. We performed a search in Pubmed/Medline and Embase databases for randomized controlled trials and cohort studies involving humans or experimental settings with various causes of ABI. We formulated the search using the PICO method, considering ABI patients or animal models as population (P), comparing pharmacological and non-pharmacological therapy targeting the nucleosome as Intervention (I) to standard of care or no treatment as Control (C). The outcome (O) was mortality or functional outcome in experimental animals and patients affected by ABI undergoing anti-NET treatments. We identified 28 studies from 1246 articles, of which 7 were experimental studies and 21 were human clinical studies. Among these studies, only four assessed the effect of anti-NET therapy on circulating markers. Three of them were preclinical and reported better outcome in the interventional arm compared to the control arm. All the studies observed a significant reduction in circulating NET-derived products. NETosis could be a target for new treatments. Monitoring NET markers in blood and cerebrospinal fluid might predict mortality and long-term outcomes. However, longitudinal studies and randomized controlled trials are warranted to fully evaluate their potential, as current evidence is limited.

Hereditary spastic paraplegias (HSPs) a group of rare, clinically, and genetically heterogeneous disorders characterized by progressive degeneration of the corticospinal tract. Among these HSPs, SPG31 is due to autosomal dominant mutations in the receptor expression-enhancing protein 1 (REEP1) gene. Over 80 genes have been associated with HSPs, and the list is constantly growing as research progresses. This study is aimed to create a patient-derived human induced pluripotent stem cell (hiPSC) line with a specific nonsense mutation to better characterize the etiopathogenesis of the disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hereditary spastic paraplegias (HSPs) comprise a family of degenerative diseases mostly hitting descending axons of corticospinal neurons. Depending on the gene and mutation involved, the disease could present as a pure form with limb spasticity, or a complex form associated with cerebellar and/or cortical signs such as ataxia, dysarthria, epilepsy, and intellectual disability. The progressive nature of HSPs invariably leads patients to require walking canes or wheelchairs over time. Despite several attempts to ameliorate the life quality of patients that have been tested, current therapeutical approaches are just symptomatic, as no cure is available. Progress in research in the last two decades has identified a vast number of genes involved in HSP etiology, using cellular and animal models generated on purpose. Although unanimously considered invaluable tools for basic research, those systems are rarely predictive for the establishment of a therapeutic approach. The advent of induced pluripotent stem (iPS) cells allowed instead the direct study of morphological and molecular properties of the patient's affected neurons generated upon in vitro differentiation. In this review, we revisited all the present literature recently published regarding the use of iPS cells to differentiate HSP patient-specific neurons. Most studies have defined patient-derived neurons as a reliable model to faithfully mimic HSP in vitro, discovering original findings through immunological and -omics approaches, and providing a platform to screen novel or repurposed drugs. Thereby, one of the biggest hopes of current HSP research regards the use of patient-derived iPS cells to expand basic knowledge on the disease, while simultaneously establishing new therapeutic treatments for both generalized and personalized approaches in daily medical practice.

Aneurysmal subarachnoid hemorrhage is a medical condition that can lead to intracranial hypertension, negatively impacting patients' outcomes. This review article explores the underlying pathophysiology that causes increased intracranial pressure (ICP) during hospitalization. Hydrocephalus, brain swelling, and intracranial hematoma could produce an ICP rise. Although cerebrospinal fluid withdrawal via an external ventricular drain is commonly used, ICP monitoring is not always consistently practiced. Indications for ICP monitoring include neurological deterioration, hydrocephalus, brain swelling, intracranial masses, and the need for cerebrospinal fluid drainage. This review emphasizes the importance of ICP monitoring and presents findings from the Synapse-ICU study, which supports a correlation between ICP monitoring and treatment with better patient outcomes. The review also discusses various therapeutic strategies for managing increased ICP and identifies potential areas for future research., (© 2023. The Author(s).)

Mechanical stimulation modulates neural development and neuronal activity. In a previous study, magnetic "nano-pulling" is proposed as a tool to generate active forces. By loading neural cells with magnetic nanoparticles (MNPs), a precise force vector is remotely generated through static magnetic fields. In the present study, human neural stem cells (NSCs) are subjected to a standard differentiation protocol, in the presence or absence of nano-pulling. Under mechanical stimulation, an increase in the length of the neural processes which showed an enrichment in microtubules, endoplasmic reticulum, and mitochondria is found. A stimulation lasting up to 82 days induces a strong remodeling at the level of synapse density and a re-organization of the neuronal network, halving the time required for the maturation of neural precursors into neurons. The MNP-loaded NSCs are then transplanted into mouse spinal cord organotypic slices, demonstrating that nano-pulling stimulates the elongation of the NSC processes and modulates their orientation even in an ex vivo model. Thus, it is shown that active mechanical stimuli can guide the outgrowth of NSCs transplanted into the spinal cord tissue. The findings suggest that mechanical forces play an important role in neuronal maturation which could be applied in regenerative medicine., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Background: Intracranial pressure (ICP) monitoring and its management in aneurysmal subarachnoid hemorrhage (aSAH) is variable worldwide. The present study aimed to explore the practice of ICP monitoring, its variability across countries, and the association with 6-month outcomes in aSAH., Methods: This was a preplanned subanalysis of SYNAPSE-ICU, a multicenter, international, prospective, observational cohort study focused on patients diagnosed with aSAH. We evaluated the variability in ICP monitoring across countries through a logistic regression model adjusted for case-mix and considered countries as a random effect. The association between ICP probe insertion and 6-month mortality and a poor neurological outcome, defined as an Glasgow Outcome Score Extended ≤ 4, was assessed by using a propensity score approach., Results: A total of 423 patients with aSAH from 92 centers across 32 countries were included in this analysis. ICP monitoring was used in 295 (69.7%) patients. Significant between-country variability in ICP insertion was observed, with an incidence ranging between 4.7% and 79.9% (median odd ratio 3.04). The median duration of ICP monitoring was 12 days (first quartile [Q1] through third quartile [Q3] range 8-18), with an overall daily median ICP value of 14 mm Hg (Q1-Q3 10-19) and a median maximum value of 21 mm Hg (Q1-Q3 16-30). Patients monitored with ICP received more aggressive therapy treatments compared with non-monitored patients (therapy intensity level, TIL, score 10.33 [standard deviation 3.61] vs. 6.3 [standard deviation 4.19], p < 0.001). In more severe patients, ICP monitoring was significantly associated with better 6-month outcome (poor neurological outcome: odds ratio 0.14, 95% confidence interval 0.02-0.53, p = 0.0113; mortality: hazard ratio 0.25, 95% confidence interval 0.13-0.49, p < 0.0001). However, no significant effect was observed in patients with both reactive pupils., Conclusions: Our cohort demonstrated high variability in ICP insertion practice among countries. A more aggressive treatment approach was applied in ICP-monitored patients. In patients with severe aSAH, ICP monitoring might reduce unfavorable outcomes and mortality at 6 months., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Neuroprotective drug delivery to the posterior segment of the eye represents a major challenge to counteract vision loss. This work focuses on the development of a polymer-based nanocarrier, specifically designed for targeting the posterior eye. Polyacrylamide nanoparticles (ANPs) were synthesised and characterised, and their high binding efficiency was exploited to gain both ocular targeting and neuroprotective capabilities, through conjugation with peanut agglutinin (ANP:PNA) and neurotrophin nerve growth factor (ANP:PNA:NGF). The neuroprotective activity of ANP:PNA:NGF was assessed in an oxidative stress-induced retinal degeneration model using the teleost zebrafish. Upon nanoformulation, NGF improved the visual function of zebrafish larvae after the intravitreal injection of hydrogen peroxide, accompanied by a reduction in the number of apoptotic cells in the retina. Additionally, ANP:PNA:NGF counteracted the impairment of visual behaviour in zebrafish larvae exposed to cigarette smoke extract (CSE). Collectively, these data suggest that our polymeric drug delivery system represents a promising strategy for implementing targeted treatment against retinal degeneration.

In dental clinics, the infections may be acquired through contaminated devices, air, and water. Aerosolized water may contain bacteria, grown into the biofilm of dental unit waterlines (DUWLs). We evaluated a disinfection method based on water osmosis and chlorination with chlorine dioxide (O-CD), applied to DUWL of five dental clinics. Municipal water was chlorinated with O-CD device before feeding all DUWLs. Samplings were performed on water/air samples in order to research total microbial counts at 22-37 °C, Pseudomonas aeruginosa , Legionella spp., and chlorine values. Water was collected from the taps, spittoons, and air/water syringes. Air was sampled before, during, and after 15 min of aerosolizing procedure. Legionella and P. aeruginosa resulted as absent in all water samples, which presented total microbial counts almost always at 0 CFU/mL. Mean values of total chlorine ranged from 0.18-0.23 mg/L. Air samples resulted as free from Legionella spp. and Pseudomonas aeruginosa. Total microbial counts decreased from the pre-aerosolizing (mean 2.1 × 10 2 CFU/m 3 ) to the post-aerosolizing samples (mean 1.5 × 10 CFU/m 3 ), while chlorine values increased from 0 to 0.06 mg/L. O-CD resulted as effective against the biofilm formation in DUWLs. The presence of residual activity of chlorine dioxide also allowed the bacteria reduction from air, at least at one meter from the aerosolizing source.

Congenital alterations in the levels of the transcription factor Forkhead box g1 (FOXG1) coding gene trigger "FOXG1 syndrome," a spectrum that recapitulates birth defects found in the "congenital Zika syndrome," such as microcephaly and other neurodevelopmental conditions. Here, we report that Zika virus (ZIKV) infection alters FOXG1 nuclear localization and causes its downregulation, thus impairing expression of genes involved in cell replication and apoptosis in several cell models, including human neural progenitor cells. Growth factors, such as EGF and FGF2, and Thr271 residue located in FOXG1 AKT domain, take part in the nuclear displacement and apoptosis protection, respectively. Finally, by progressive deletion of FOXG1 sequence, we identify the C-terminus and the residues 428-481 as critical domains. Collectively, our data suggest a causal mechanism by which ZIKV affects FOXG1, its target genes, cell cycle progression, and survival of human neural progenitors, thus contributing to microcephaly., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To highlight recent findings on the evaluation and impact of frailty in the management of patients with traumatic brain injury (TBI)., Recent Findings: Frailty is not a direct natural consequence of aging. Rather, it commonly results from the intersection of age-related decline with chronic diseases and conditions. It is associated with adverse outcomes such as institutionalization, falls, and worsening health status. Growing evidence suggests that frailty should be a key consideration both in care planning and in adverse outcome prevention. The prevalence of elderly patients with TBI is increasing, and low-energy trauma (i.e., ground or low-level falls, which are typical in frail patients) is the major cause. Establishing the real incidence of frailty in TBI requires further studies. Failure to detect frailty potentially exposes patients to interventions that may not benefit them, and may even harm them. Moreover, considering patients as 'nonfrail' purely on the basis of their age is unacceptable. The future challenge is to shift to a new clinical paradigm characterized by more appropriate, goal-directed care of frail patients., Summary: The current review highlights the crucial importance of frailty evaluation in TBI, also given the changing epidemiology of this condition. To ensure adequate assessment, prevention and management, both in and outside hospital, there is an urgent need for a valid screening tool and a specific frailty-based and comorbidity-based clinical approach., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Postoperative complications impact on early and long-term patients' outcome. Appropriate perioperative fluid management is pivotal in this context; however, the most effective perioperative fluid management is still unclear. The enhanced recovery after surgery pathways recommend a perioperative zero-balance, whereas recent findings suggest a more liberal approach could be beneficial. We conducted this trial to address the impact of restrictive vs. liberal fluid approaches on overall postoperative complications and mortality., Methods: Systematic review and meta-analysis, including randomised controlled trials (RCTs). We performed a systematic literature search using MEDLINE (via Ovid), EMBASE (via Ovid) and the Cochrane Controlled Clinical trials register databases, published from 1 January 2000 to 31 December 2019. We included RCTs enrolling adult patients undergoing elective abdominal surgery and comparing the use of restrictive/liberal approaches enrolling at least 15 patients in each subgroup. Studies involving cardiac, non-elective surgery, paediatric or obstetric surgeries were excluded., Results: After full-text examination, the metanalysis finally included 18 studies and 5567 patients randomised to restrictive (2786 patients; 50.0%) or liberal approaches (2780 patients; 50.0%). We found no difference in the occurrence of severe postoperative complications between restrictive and liberal subgroups [risk difference (95% CI) = 0.009 (- 0.02; 0.04); p value = 0.62; I 2 (95% CI) = 38.6% (0-66.9%)]. This result was confirmed also in the subgroup of five studies having a low overall risk of bias. The liberal approach was associated with lower overall renal major events, as compared to the restrictive [risk difference (95% CI) = 0.06 (0.02-0.09); p value  = 0.001]. We found no difference in either early (p value  = 0.33) or late (p value  = 0.22) postoperative mortality between restrictive and liberal subgroups CONCLUSIONS: In major abdominal elective surgery perioperative, the choice between liberal or restrictive approach did not affect overall major postoperative complications or mortality. In a subgroup analysis, a liberal as compared to a restrictive perioperative fluid policy was associated with lower overall complication renal major events, as compared to the restrictive., Trial Registration: CRD42020218059; Registration: February 2020, https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=218059 .

Background: Appropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients' hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid)., Results: The metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%, p value = 0.23 and 54.8% vs. 39.8%; p value = 0.09, respectively]. Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = - 0.10 (- 0.14, - 0.07); Chi 2  = 30.97; p value < 0.0001], but not to a reduction of perioperative mortality [pooled risk difference (95%CI) = - 0.016 (- 0.0334; 0.0014); p value = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (p value = 0.52) nor cardiovascular (p value = 0.86) or pulmonary (p value = 0.14) or neurological (p value = 0.44) or infective (p value = 0.12) complications., Conclusions: Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality., Trial Registration: CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=168866.

Aim: We aimed to characterise a large population of coronavirus disease 2019 (COVID-19) patients with moderate-to-severe hypoxaemic acute respiratory failure (ARF) receiving continuous positive airway pressure (CPAP) outside the intensive care unit (ICU), and to ascertain whether the duration of CPAP application increased the risk of mortality for patients requiring intubation., Methods: In this retrospective, multicentre cohort study, we included adult COVID-19 patients, treated with CPAP outside ICU for hypoxaemic ARF from 1 March to 15 April, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay and 60-day in-hospital mortality., Results: The study included 537 patients with a median (interquartile range (IQR) age of 69 (60-76) years. 391 (73%) were male. According to the pre-defined CPAP therapeutic goal, 397 (74%) patients were included in the full treatment subgroup, and 140 (26%) in the do not intubate (DNI) subgroup. Median (IQR) CPAP duration was 4 (1-8) days, while hospital length of stay was 16 (9-27) days. 60-day in-hospital mortality was 34% (95% CI 0.304-0.384%) overall, and 21% (95% CI 0.169-0.249%) and 73% (95% CI 0.648-0.787%) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95% CI 0.345-0.488%) for 180 (45%) CPAP failures requiring intubation, and 2% (95% CI 0.008-0.035%) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality (hazard ratio 1.093, 95% CI 1.010-1.184)., Conclusions: We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures., Competing Interests: Conflict of interest: R. Vaschetto has nothing to disclose. Conflict of interest: F. Barone-Adesi has nothing to disclose. Conflict of interest: F. Racca reports personal fees from Philips Respironics outside the submitted work. Conflict of interest: C. Pissaia has nothing to disclose. Conflict of interest: C. Maestrone has nothing to disclose. Conflict of interest: D. Colombo reports personal fees for lectures from Nestlé Healthcare Nutrition outside the submitted work. Conflict of interest: C. Olivieri has a patent 102016000114357 with royalties paid to Intersurgical SpA. Conflict of interest: N. De Vita has nothing to disclose. Conflict of interest: E. Santangelo has nothing to disclose. Conflict of interest: L. Scotti has nothing to disclose. Conflict of interest: L. Castello has nothing to disclose. Conflict of interest: T. Cena has nothing to disclose. Conflict of interest: M. Taverna has nothing to disclose. Conflict of interest: L. Grillenzoni has nothing to disclose. Conflict of interest: M.A. Moschella has nothing to disclose. Conflict of interest: G. Airoldi has nothing to disclose. Conflict of interest: S. Borrè has nothing to disclose. Conflict of interest: F. Mojoli reports personal fees for lecturing from GE Healthcare, Medical and Seda Spa, outside the submitted work; and a consultancy agreement between University of Pavia and Hamilton Medical. Conflict of interest: F. Della Corte has nothing to disclose. Conflict of interest: M. Baggiani has nothing to disclose. Conflict of interest: S. Baino has nothing to disclose. Conflict of interest: P. Balbo has nothing to disclose. Conflict of interest: S. Bazzano has nothing to disclose. Conflict of interest: V. Bonato has nothing to disclose. Conflict of interest: S. Carbonati has nothing to disclose. Conflict of interest: F. Crimaldi has nothing to disclose. Conflict of interest: V. Daffara has nothing to disclose. Conflict of interest: L. De Col has nothing to disclose. Conflict of interest: M. Maestrone has nothing to disclose. Conflict of interest: M. Malerba has nothing to disclose. Conflict of interest: F. Moroni has nothing to disclose. Conflict of interest: R. Perucca has nothing to disclose. Conflict of interest: M. Pirisi has nothing to disclose. Conflict of interest: V. Rondi has nothing to disclose. Conflict of interest: D. Rosalba has nothing to disclose. Conflict of interest: L. Vanni has nothing to disclose. Conflict of interest: F. Vigone has nothing to disclose. Conflict of interest: P. Navalesi reports personal fees from Intersurgical SpA, Resmed, Philips, Novartis, MSD, Getinge and Orion Pharma, and research equipment (institutional) from Draeger, outside the submitted work; in addition, he has a patent 102020000008305 pending to Università di Padova (no profit) and a patent 102016000114357 with royalties paid to Intersurgical SpA. Conflict of interest: G. Cammarota has nothing to disclose., (Copyright ©ERS 2021.)

Building and functioning of the human brain requires the precise orchestration and execution of myriad molecular and cellular processes, across a multitude of cell types and over an extended period of time. Dysregulation of these processes affects structure and function of the brain and can lead to neurodevelopmental, neurological, or psychiatric disorders. Multiple environmental stimuli affect neural stem cells (NSCs) at several levels, thus impairing the normal human neurodevelopmental program. In this review article, we will delineate the main mechanisms of infection adopted by several neurotropic pathogens, and the selective NSC vulnerability. In particular, TORCH agents, i.e., Toxoplasma gondii , others (including Zika virus and Coxsackie virus), Rubella virus, Cytomegalovirus, and Herpes simplex virus, will be considered for their devastating effects on NSC self-renewal with the consequent neural progenitor depletion, the cellular substrate of microcephaly. Moreover, new evidence suggests that some of these agents may also affect the NSC progeny, producing long-term effects in the neuronal lineage. This is evident in the paradigmatic example of the neurodegeneration occurring in Alzheimer's disease.

Background: In patients in the prone position, the reliability of pulse pressure variation and stroke volume variation (PPV and SVV) and the use of functional hemodynamic tests to predict fluid responsiveness have not previously been established. Perioperatively, in this setting, optimizing fluid management can be challenging, and fluid overload is associated with both intraoperative and postoperative complications. We designed this study to assess the sensitivity and specificity of baseline PPV and SVV, the tidal volume (VT) challenge (VTC) and the end-expiratory occlusion test (EEOT) in predicting fluid responsiveness during elective spinal surgery., Methods: The study protocol was started during a period of intraoperative hemodynamic stability after prone positioning and before the administration of any vasopressor: (1) at baseline, the controlled ventilation was set at 6 mL/kg of predicted body weight (PBW) (T0); (2) patients underwent the first EEOT (EEOT6) by interrupting the mechanical ventilation for 30 seconds; (3) the ventilation was set again at 6 mL/kg PBW for 1 minute (T1); (4) the VTC was applied by increasing the VT up to 8 mL/kg PBW for 1 minute; (5) the ventilation was kept at 8 mL/kg PBW for 1 minute (T2); (6) a second EEOT (EEOT8) was performed; (7) the VT was reduced back to 6 mL/kg PBW for 1 minute (T3); (8) a fluid challenge of 250 mL of Ringer's solution was infused over 10 minutes. After each step, a complete set of hemodynamic measurements was recorded., Results: Neither PPV and SVV values recorded at T3 nor the EEOT6 or the EEOT8 predicted fluid responsiveness. The change in PPV after VTC application predicted fluid responsiveness with an area under the curve of 0.96 (95% confidence interval, 0.87-1.00), showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 12.2%. The change in SVV after VTC application predicted fluid responsiveness with an area under the curve 0.96 (95% confidence interval, 0.89-1.00) showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 8.0%. A linear correlation between stroke volume index changes after fluid challenge administration and the changes in PPV and SVV after VTC application was observed (r = 0.71; P < .0001 and r = 0.68; P < .0001, respectively)., Conclusions: In prone elective neurosurgical patients, the baseline values of PPV and SVV and the EEOT fail to predict fluid responsiveness, while the VTC is a very reliable functional hemodynamic test and could be helpful in guiding intraoperative fluid therapy.

Background: Bedside functional hemodynamic assessment has gained in popularity in the last years to overcome the limitations of static or dynamic indexes in predicting fluid responsiveness. The aim of this systematic review and metanalysis of studies is to investigate the reliability of the functional hemodynamic tests (FHTs) used to assess fluid responsiveness in adult patients in the intensive care unit (ICU) and operating room (OR)., Methods: MEDLINE, EMBASE, and Cochrane databases were screened for relevant articles using a FHT, with the exception of the passive leg raising. The QUADAS-2 scale was used to assess the risk of bias of the included studies. In-between study heterogeneity was assessed through the I 2 indicator. Bias assessment graphs were plotted, and Egger's regression analysis was used to evaluate the publication bias. The metanalysis determined the pooled area under the receiving operating characteristic (ROC) curve, sensitivity, specificity, and threshold for two FHTs: the end-expiratory occlusion test (EEOT) and the mini-fluid challenge (FC)., Results: After text selection, 21 studies met the inclusion criteria, 7 performed in the OR, and 14 in the ICU between 2005 and 2018. The search included 805 patients and 870 FCs with a median (IQR) of 39 (25-50) patients and 41 (30-52) FCs per study. The median fluid responsiveness was 54% (45-59). Ten studies (47.6%) adopted a gray zone analysis of the ROC curve, and a median (IQR) of 20% (15-51) of the enrolled patients was included in the gray zone. The pooled area under the ROC curve for the end-expiratory occlusion test (EEOT) was 0.96 (95%CI 0.92-1.00). The pooled sensitivity and specificity were 0.86 (95%CI 0.74-0.94) and 0.91 (95%CI 0.85-0.95), respectively, with a best threshold of 5% (4.0-8.0%). The pooled area under the ROC curve for the mini-FC was 0.91 (95%CI 0.85-0.97). The pooled sensitivity and specificity were 0.82 (95%CI 0.76-0.88) and 0.83 (95%CI 0.77-0.89), respectively, with a best threshold of 5% (3.0-7.0%)., Conclusions: The EEOT and the mini-FC reliably predict fluid responsiveness in the ICU and OR. Other FHTs have been tested insofar in heterogeneous clinical settings and, despite promising results, warrant further investigations.

Enhancing CPR knowledge in schools is the key to improving bystander CPR rate and survival after an out-of-hospital cardiac arrest, but the best method to do so in a whole area is unknown. We wanted to assess if a province-based project, which involves the Secondary Schools of a whole Province, is effective in teaching schoolchildren CPR, and how well the skills are retained. We trained 100 teachers from the 21 Secondary Schools of the Province of Pavia with a BLS/AED course and we supplied each school with 10 low-budget manikins and four educational videos. These videos, about 2 min each, consist of a motivational part, an instructive part, a demonstrative part and a practice-while-watching part. We explained to the teachers how to use manikins and videos in a 2-h course. We carried out both a theoretical and a practical test in 21 classes, randomly selected between the classes trained by the teachers, 3 months and 6 months after the training. In the first 5 months of the project, 5146 schoolchildren aged 14-19, in the 21 Secondary Schools of our Province, were trained by their teachers. We tested 304 students 3 months after the course and 318 students 6 months after the course, with good results both in theoretical and practical skills. Our study demonstrates that the ScuolaSalvaVita project is able to effectively teach CPR through teachers using a video-based training in the Secondary Schools of a whole Province obtaining good long-term memory of CPR skills.

OBJECTIVE Severe bleeding during neurosurgical operations can result in acute stress affecting the bimanual psychomotor performance of the operator, leading to surgical error and an adverse patient outcome. Objective methods to assess the influence of acute stress on neurosurgical bimanual psychomotor performance have not been developed. Virtual reality simulators, such as NeuroTouch, allow the testing of acute stress on psychomotor performance in risk-free environments. Thus, the purpose of this study was to explore the impact of a simulated stressful virtual reality tumor resection scenario by utilizing NeuroTouch to answer 2 questions: 1) What is the impact of acute stress on bimanual psychomotor performance during the resection of simulated tumors? 2) Does acute stress influence bimanual psychomotor performance immediately following the stressful episode? METHODS Study participants included 6 neurosurgeons, 6 senior and 6 junior neurosurgical residents, and 6 medical students. Participants resected a total of 6 simulated tumors, 1 of which (Tumor 4) involved uncontrollable "intraoperative" bleeding resulting in simulated cardiac arrest and thus providing the acute stress scenario. Tier 1 metrics included extent of blood loss, percentage of tumor resected, and "normal" brain tissue volume removed. Tier 2 metrics included simulated suction device (sucker) and ultrasonic aspirator total tip path length, as well as the sum and maximum forces applied in using these instruments. Advanced Tier 2 metrics included efficiency index, coordination index, ultrasonic aspirator path length index, and ultrasonic aspirator bimanual forces ratio. All metrics were assessed before, during, and after the stressful scenario. RESULTS The stress scenario caused expected significant increases in blood loss in all participant groups. Extent of tumor resected and brain volume removed decreased in the junior resident and medical student groups. Sucker total tip path length increased in the neurosurgeon group, whereas sucker forces increased in the senior resident group. Psychomotor performance on advanced Tier 2 metrics was altered during the stress scenario in all participant groups. Performance on all advanced Tier 2 metrics returned to pre-stress levels in the post-stress scenario tumor resections. CONCLUSIONS Results demonstrated that acute stress initiated by simulated severe intraoperative bleeding significantly decreases bimanual psychomotor performance during the acute stressful episode. The simulated intraoperative bleeding event had no significant influence on the advanced Tier 2 metrics monitored during the immediate post-stress operative performance.

Objective: Current selection methods for neurosurgical residents fail to include objective measurements of bimanual psychomotor performance. Advancements in computer-based simulation provide opportunities to assess cognitive and psychomotor skills in surgically naive populations during complex simulated neurosurgical tasks in risk-free environments. This pilot study was designed to answer 3 questions: (1) What are the differences in bimanual psychomotor performance among neurosurgical residency applicants using NeuroTouch? (2) Are there exceptionally skilled medical students in the applicant cohort? and (3) Is there an influence of previous surgical exposure on surgical performance?, Design: Participants were instructed to remove 3 simulated brain tumors with identical visual appearance, stiffness, and random bleeding points. Validated tier 1, tier 2, and advanced tier 2 metrics were used to assess bimanual psychomotor performance. Demographic data included weeks of neurosurgical elective and prior operative exposure., Setting: This pilot study was carried out at the McGill Neurosurgical Simulation Research and Training Center immediately following neurosurgical residency interviews at McGill University, Montreal, Canada., Participants: All 17 medical students interviewed were asked to participate, of which 16 agreed., Results: Performances were clustered in definable top, middle, and bottom groups with significant differences for all metrics. Increased time spent playing music, increased applicant self-evaluated technical skills, high self-ratings of confidence, and increased skin closures statistically influenced performance on univariate analysis. A trend for both self-rated increased operating room confidence and increased weeks of neurosurgical exposure to increased blood loss was seen in multivariate analysis., Conclusions: Simulation technology identifies neurosurgical residency applicants with differing levels of technical ability. These results provide information for studies being developed for longitudinal studies on the acquisition, development, and maintenance of psychomotor skills. Technical abilities customized training programs that maximize individual resident bimanual psychomotor training dependant on continuously updated and validated metrics from virtual reality simulation studies should be explored., (Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)