In vivo biocompatibility and pacing function study of silver ion-based antimicrobial surface technology applied to cardiac pacemakers

INTRODUCTION Evidence suggests that the rate of cardiovascular implantable electronic device (CIED) infections is increasing more rapidly than the rates of CIED implantation and is associated with considerable mortality, morbidity and health economic impact. Antimicrobial surface treatments are being developed for CIEDs to reduce the risk of postimplantation infection within the subcutaneous implant pocket. METHODS AND ANALYSIS The feasibility of processing cardiac pacemakers with the Agluna antimicrobial silver ion surface technology and in vivo biocompatibility were evaluated. Antimicrobially processed (n=6) and control pacemakers (n=6) were implanted into subcutaneous pockets and connected to a part of the muscle using an ovine model for 12 weeks. Pacemaker function was monitored preimplantation and postimplantation. RESULTS Neither local infection nor systemic toxicity were detected in antimicrobial or control devices, and surrounding tissues showed no abnormal pathology or over-reactivity. Semiquantitative scores of membrane formation, cellular orientation and vascularity were applied over five regions of the pacemaker capsule and average scores compared. Results showed no significant difference between antimicrobially processed and control pacemakers. Silver analysis of whole blood at 7 days found that levels were a maximum of 10 parts per billion (ppb) for one sample, more typically ≤2 ppb, compared with <2 ppb for preimplantation levels, well below reported toxic levels. CONCLUSIONS There was no evidence of adverse or abnormal pathology in tissue surrounding antimicrobially processed pacemakers, or deleterious effect on basic pacing capabilities and parameters at 12 weeks. This proof of concept study provides evidence of basic biocompatibility and feasibility of applying this silver ion-based antimicrobial surface to a titanium pacemaker surface

Comparison of Polyethylene Glycol Powder and Polyethylene Glycol 40% Syrup in Treatment of Chronic Idiopathic Constipation in Pediatrics

Introduction: Constipation is one of the most common gastrointestinal complaints in children that can lead to many complications. The aim of this study was to compare the efficacy of polyethylene glycol powder and polyethylene glycol 40% syrup to treat constipation. Materials and Methods: This study was a nonrandomized semi-experimental clinical trial. The current study was conducted on 80 patients with constipation, referring to Imam Ali (PBUH) Clinic, Shahrekord randomly assigned to two groups of 40 each. Subjects were children under 15 years old with functional constipation selected by simple sampling since 2015. Group 1 was treated with polyethylene glycol powder and Group 2 was treated with polyethylene glycol 40% syrup for two months. During the treatment, the patients were examined five times with 2-week intervals and their symptoms consisting of defecation frequency, stool consistency, painful defecation, bloody defecation, and stool incontinence were registered in a checklist. Data were analyzed using SPSS24. Results: The comparison of patients' total status before and after intervention shows that two groups were assessed in the weak level in the polyethylene glycol powder group 28(0.70%) cases and syrup group 36(0.90%), while after intervention, polyethylene glycol powder group was assessed in the high level 35(87.5%) cases and syrup group 37(92%) cases and most of patients after intervention promoted from weak and intermediate level before intervention to High level. Conclusion: The findings indicated similar efficacy and treatment response of the PEG powder and syrup. However, the PEG syrup can be used instead of its powder because of pleasant taste and ease of use. Keywords Author Keywords:Constipation; functional constipation; polyethylene glycol KeyWords Plus:CHILDHOOD CONSTIPATION; FUNCTIONAL CONSTIPATION; CHILDREN; DISORDERS; LAXATIVES; SPECTRU

Surgical treatment of symptomatic pineal cysts without hydrocephalus-meta-analysis of the published literature

Background To examine published data and assess evidence relating to safety and efficacy of surgical management of symptomatic pineal cysts without hydrocephalus (nhSPC), we performed a systematic review of the literature and meta-analysis. Methods Following the PRISMA guidelines, we searched Pubmed and SCOPUS for all reports with the query 'Pineal Cyst' AND 'Surgery' as of March 2021, without constraints on study design, publication year or status (PROSPERO_CRD:42,021,242,517). Assessment of 1537 hits identified 26 reports that met inclusion and exclusion criteria. Results All 26 input studies were either case reports or single-centre retrospective cohorts. The majority of outcome data were derived from routine physician-recorded notes. A total of 294 patients with surgically managed nhSPC were identified. Demographics: Mean age was 29 (range: 4-63) with 77% females. Mean cyst size was 15 mm (5-35). Supracerebellar-infratentorial approach was adopted in 90% of cases, occipital-transtentorial in 9%, and was not reported in 1%. Most patients were managed by cyst resection (96%), and the remainder by fenestration. Mean post-operative follow-up was 35 months (0-228). Presentation: Headache was the commonest symptom (87%), followed by visual (54%), nausea/vomit (34%) and vertigo/dizziness (31%). Other symptoms included focal neurology (25%), sleep disturbance (17%), cognitive impairment (16%), loss of consciousness (11%), gait disturbance (11%), fatigue (10%), 'psychiatric' (2%) and seizures (1%). Mean number of symptoms reported at presentation was 3 (0-9). Outcomes: Improvement rate was 93% (to minimise reporting bias only consecutive cases from cohort studies were considered, N= 280) and was independent of presentation. Predictors of better outcomes were large cyst size (OR= 5.76; 95% CI: 1.74-19.02) and resection over fenestration (OR= 12.64; 3.07-52.01). Age predicted worse outcomes (OR= 0.95; 0.91-0.99). Overall complication rate was 17% and this was independent of any patient characteristics. Complications with long-term consequences occurred in 10 cases (3.6%): visual disturbance (3), chronic incisional pain (2), sensory disturbance (1), fatigue (1), cervicalgia (1), cerebellar stroke (1) and mortality due to myocardial infarction (1). Conclusions Although the results support the role of surgery in the management of nhSPCs, they have to be interpreted with a great deal of caution as the current evidence is limited, consisting only of case reports and retrospective surgical series. Inherent to such studies are inhomogeneity and incompleteness of data, selection bias and bias related to assessment of outcome carried out by the treating surgeon in the majority of cases. Prospective studies with patient-reported and objective outcome assessment are needed to provide higher level of evidence.Peer reviewe

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

Sarcopenia Adversely Affects Outcomes following Cardiac Surgery:A Systematic Review and Meta-Analysis

Background: Sarcopenia is a degenerative condition characterised by the loss of skeletal muscle mass and strength. Its impact on cardiac surgery outcomes remains poorly investigated. This meta-analysis aims to provide a comprehensive synthesis of the available evidence to determine the effect of sarcopenia on cardiac surgery outcomes. Methods: A systematic review and meta-analysis followed PRISMA guidelines from inception to April 2023 in EMBASE, MEDLINE, Cochrane database, and Google Scholar. Twelve studies involving 2717 patients undergoing cardiac surgery were included. Primary outcomes were early and late mortality; secondary outcomes included surgical time, infection rates, and functional outcomes. Statistical analyses were performed using appropriate methods. Results: Sarcopenic patients (906 patients) had a significantly higher risk of early mortality (OR: 2.40, 95% CI: 1.44 to 3.99, p = 0.0007) and late mortality (OR: 2.65, 95% CI: 1.57 to 4.48, p = 0.0003) compared to non-sarcopenic patients (1811 patients). There were no significant differences in overall surgical time or infection rates. However, sarcopenic patients had longer ICU stays, higher rates of renal dialysis, care home discharge, and longer intubation times. Conclusion: Sarcopenia significantly increases the risk of early and late mortality following cardiac surgery, and sarcopenic patients also experience poorer functional outcomes

Dietary Modifications in Critically-Ill Patients: A Comparison of Persian Medicine and Conventional Medicine Perspectives

In Persian Medicine (PM) literature, a crisis is the culmination of the body’s response to illness, which necessitates fundamental dietary modification to improve prognosis. In this narrative review, authentic PM textbooks as well as articles on diets for critically-ill patients (CIPs) obtained from PubMed and Google Scholar databases, were reviewed, and after gathering data, they were classified, coded, analyzed, and compared. In the acute phase, both PM and conventional medicine agree on relative food restriction, but PM lays a special focus on the use of meat in cases of weakness. There are both similarities and differences between PM and conventional medicine regarding nutritional recommendations in critical illness. For example, recommendations for food restriction and protein intake are similar in both schools, but recommendations for carbohydrate intake are different. The variables addressed and emphasized in PM require further evaluation in clinical trials

Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis

Background: Besides the central role of the adaptive immune system, a disturbance of innate immune system is also suggested to be involved in the pathogenesis of multiple sclerosis (MS). CD14, a receptor upregulated in activated microglia, is known to be an essential mediator of inflammation in innate immune responses. Therefore, in this study we aimed to assess possible roles of CD14-159 and -260 gene polymorphisms in MS susceptibility and the effects of those polymorphisms to its protein producing capacity in Iranian population. Methods: In this case control study, CD14-159 and -260 polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 200 MS patients and 200 healthy controls matched in age and gender. Serum levels of soluble CD14 (sCD14) was determined by enzyme-linked immunosorbent assay (ELISA). Results: There were significant differences in genotype distribution of CD14-159 and -260 polymorphisms between patients and controls (P = 0.01, for-both). Mean serum level of sCD14 was significantly higher in MS patients than in control subjects (3340.30 ± 612.50 ng/ml vs 2353.73 ± 539.07 ng/ml; P < 0.01). Conclusion: In summary, we conclude that CD14-159 and -260 polymorphisms are associated with the risk of MS in Iranian population and affects CD14 promoter activity, thereby regulating CD14 expression. Furthermore, our study provides preliminary evidence for the activation of innate immunity in the pathogenesis of MS. In addition, the findings of the present study suggest serum level of sCD14 as candidate biomarker of MS severity

Undergraduate neurosurgical conferences–what role do they play?

Introduction: Undergraduate student conferences provide networking opportunities for students interested in exploring a speciality. The ability to meet with like-minded students, engage with senior clinicians and experience the practical side of a speciality are valuable in shaping the career trajectory of undergraduates. We report our experience of developing a national undergraduate neurosurgery conference – a combined project between the medical students of King’s College London School of Medicine and the neurosurgery department at King’s College Hospital NHS Foundation Trust. Design: Evaluation of conference design and student feedback. Methods: The conference was organised by medical students with support from a neurosurgical unit. Senior clinicians and trainees helped design practical workshops and a focused programme. Questionnaires were distributed before and after the conference to assess the quality of content and impact of the conference on students. Results: Prior to the conference, 80.7% of respondents stated they were interested in a career in neurosurgery. After the conference the figure rose to 88.9%. The percentage of students who felt they understood what a career in neurosurgery involves increased from 38.6% to 92.1% of respondents. 39.0% of participants had no neurosurgery exposure prior to the conference. 91.9% of participants agreed or strongly agreed they would be more confident engaging with a neurosurgical department following the conference. All participants agreed (29.0%) or strongly agreed (71.0%) that they would recommend this conference to a colleague. Conclusions: Student conferences are a valuable method of increasing exposure to a career in neurosurgery. They serve a great purpose in demystifying the specialty and guiding those with an interest through the steps required to enter and progress.</p