Glutamate-evoked redox state alterations are involved in tissue transglutaminase upregulation in primary astrocyte cultures

AbstractThe aim of this study was to evaluate the involvement of oxidative stress in glutamate-evoked transglutaminase (TGase) upregulation in astrocyte cultures (14 DIV). A 24 h exposure to glutamate caused a dose-dependent depletion of glutathione intracellular content and increased the ROS production in cell cultures. These effects were receptor-mediated, as demonstrated by inhibition with GYKI 52466. The pre-incubation with glutathione ethyl ester or cysteamine recovered oxidative status and was effective in significantly reducing glutamate-increased tissue TGase. These data suggest that tissue TGase upregulation may be part of a biochemical response to oxidative stress induced by a prolonged exposure of astrocyte cultures to glutamate

Why laparoscopists may opt for three-dimensional view: a summary of the full HTA report on 3D versus 2D laparoscopy by S.I.C.E. (Società Italiana di Chirurgia Endoscopica e Nuove Tecnologie)

Background: Three-dimensional view in laparoscopic general, gynaecologic and urologic surgery is an efficient, safe and sustainable innovation. The present paper is an extract taken from a full health technology assessment report on three-dimensional vision technology compared with standard two-dimensional laparoscopic systems. Methods: A health technology assessment approach was implemented in order to investigate all the economic, social, ethical and organisational implications related to the adoption of the innovative three-dimensional view. With the support of a multi-disciplinary team, composed of eight experts working in Italian hospitals and Universities, qualitative and quantitative data were collected, by means of literature evidence, validated questionnaire and self-reported interviews, applying a final MCDA quantitative approach, and considering the dimensions resulting from the EUnetHTA Core Model. Results: From systematic search of literature, we retrieved the following studies: 9 on general surgery, 35 on gynaecology and urology, both concerning clinical setting. Considering simulated setting we included: 8 studies regarding pitfalls and drawbacks, 44 on teaching, 12 on surgeons’ confidence and comfort and 34 on surgeons’ performances. Three-dimensional laparoscopy was shown to have advantages for both the patients and the surgeons, and is confirmed to be a safe, efficacious and sustainable vision technology. Conclusions: The objective of the present paper, under the patronage of Italian Society of Endoscopic Surgery, was achieved in that there has now been produced a scientific report, based on a HTA approach, that may be placed in the hands of surgeons and used to support the decision-making process of the health providers

Intracellular fate and impact on gene expression of doxorubicin/cyclodextrin-graphene nanomaterials at sub-toxic concentration

The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field

Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype

OBJECTIVE To assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role. METHODS Antibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay. RESULTS Of 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex. CONCLUSIONS Our findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment. CLASSIFICATION OF EVIDENCE This study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%)

Pediatric trauma and emergency surgery: an international cross-sectional survey among WSES members

Background: In contrast to adults, the situation for pediatric trauma care from an international point of view and the global management of severely injured children remain rather unclear. The current study investigates structural management of pediatric trauma in centers of different trauma levels as well as experiences with pediatric trauma management around the world. Methods: A web-survey had been distributed to the global mailing list of the World Society of Emergency Surgery from 10/2021-03/2022, investigating characteristics of respondents and affiliated hospitals, case-load of pediatric trauma patients, capacities and infrastructure for critical care in children, trauma team composition, clinical work-up and individual experiences with pediatric trauma management in response to patients´ age. The collaboration group was subdivided regarding sizes of affiliated hospitals to allow comparisons concerning hospital volumes. Comparable results were conducted to statistical analysis. Results: A total of 133 participants from 34 countries, i.e. 5 continents responded to the survey. They were most commonly affiliated with larger hospitals (> 500 beds in 72.9%) and with level I or II trauma centers (82.0%), respectively. 74.4% of hospitals offer unrestricted pediatric medical care, but only 63.2% and 42.9% of the participants had sufficient experiences with trauma care in children ≤ 10 and ≤ 5 years of age (p = 0.0014). This situation is aggravated in participants from smaller hospitals (p < 0.01). With regard to hospital size (≤ 500 versus > 500 in-hospital beds), larger hospitals were more likely affiliated with advanced trauma centers, more elaborated pediatric intensive care infrastructure (p < 0.0001), treated children at all ages more frequently (p = 0.0938) and have higher case-loads of severely injured children < 12 years of age (p = 0.0009). Therefore, the majority of larger hospitals reserve either pediatric surgery departments or board-certified pediatric surgeons (p < 0.0001) and in-hospital trauma management is conducted more multi-disciplinarily. However, the majority of respondents does not feel prepared for treatment of severe pediatric trauma and call for special educational and practical training courses (overall: 80.2% and 64.3%, respectively). Conclusions: Multi-professional management of pediatric trauma and individual experiences with severely injured children depend on volumes, level of trauma centers and infrastructure of the hospital. However, respondents from hospitals at all levels of trauma care complain about an alarming lack of knowledge on pediatric trauma management

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries