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BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that early surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to,

STUDY DESIGN: Clinical practice guideline development following the GRADE process. OBJECTIVES: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets. METHODS: A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences. RESULTS: The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the lower limit, but not actively augmented beyond an upper limit of 90-95 mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the target MAP was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG suggested that MAP be augmented for a duration of 3-7 days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence. CONCLUSION: We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI.

STUDY DESIGN: Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process. OBJECTIVE: The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI. METHODS: All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created. RESULTS: Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at high risk for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG. CONCLUSION: We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal sentinel surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortiums aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

The global decline of shark populations, largely driven by overfishing to supply the shark fin trade, poses a significant threat to marine ecosystems. Southeast Asia, and particularly Singapore, is a key hub for the transit and trade of shark fins that contribute to the exploitation of these apex predators. Through the use of DNA barcoding techniques, this study aimed to determine what species of shark are involved in the Singapore shark fin trade. Fins were collected from markets, dried goods shops and traditional Chinese medicine halls throughout Singapore. In total, DNA was extracted from 684 fins collected in January 2024 and PCR amplification targeted a fragment of the mitochondrial COI gene for species identification. Results revealed fins from 24 species across 16 genera, with 19 species listed on CITES Appendices II, and 16 listed as threatened on the IUCN Red List (critically endangered = 2, endangered = 4, vulnerable = 10). The top five most frequently identified species were Carcharhinus falciformis, Galeorhinus galeus, Rhizoprionodon oligolinx, Sphyrna lewini and Rhizoprionodon acutus. Of these, four are listed on CITES Appendix II and four are listed as threatened on the IUCN Red List.

Summary: Background: Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in patients receiving mechanical ventilation in India. Surveillance of VAP is essential to implement data-based preventive measures. Implementation of ventilator-associated events (VAE) criteria for surveillance has major constraints for low resource settings, which can lead to significant underreporting. Surveillance of VAP using common protocols in a large network of hospitals would give meaningful estimates of the burden of VAP in low resource settings. This study leverages a previously established healthcare-associated infections (HAI) surveillance network to develop and test a modified VAP definition adjusted for Indian settings. Methods: In this observational pilot study, thirteen hospitals from the existing HAI surveillance network were selected for developing and testing a modified VAP definition between February 2021 and April 2023. The criteria used for diagnosing VAP were adapted from the CDC’s Pediatric VAP definition and modified to cater to the needs of Indian hospitals. Designated nurses recorded each VAP event in a case report form (CRF) and also collected denominator data. The data was entered into an indigenously developed database for validation and analysis. At the time of data analysis, a questionnaire was sent to sites to get feedback on the performance of the modified VAP definitions. Findings: Out of 133,445 patient days and 40,533 ventilator days, 261 VAP events were recorded, with an overall VAP rate of 6.4 per 1000 ventilator days and a device utilization ratio (DUR) of 0.3. A total of 344 organisms were reported from the VAP events. Of these, Acinetobacter spp (29.6%, 102) was the most frequent, followed by Klebsiella spp (26.7%, 92). Isolates of Acinetobacter spp (98%) and Enterobacterales (85.5%) showed very high resistance against Carbapenem. Colistin resistance was observed in 6% of Enterobacterales and 3.2% of Acinetobacter spp. Interpretation: Data from this pilot study needs to validated in the larger Indian HAI surveillance network so that it can help in wider implementation of this protocol in order to assess its applicability p VAP across India. Funding: This work was supported by a grant received from the Indian Council of Medical Research (code I-1203).

Few studies have investigated the acceptability of wearable technology in patients with long-term respiratory disease. We conducted a 24-item cross-sectional survey (September 2022–February 2023), developed using four common themes universal to previously described models of technology acceptance and social behavioural therapy, to explore the acceptability of wearable technology spanning the breadth of chronic respiratory disease. A total of 74 valid survey responses were analysed with 50 % aged 51–70years; 72 % female; 63 % white British ethnicity; 79 % having an income less than £50,000, and 93 % having at least obstructive airways disease. A third of participants current used wearables with 85 % using smart watches. Most of these participants used wearables to monitor their symptoms (69 %) and as a general health measurement device (85 %). Likert scale questions (ranked 1–7) showed that participants valued accuracy and approval of wearables by regulatory bodies (median (IQR) rank score 7 (Huberty et al., 2015; Preusse et al., 2016) 6–76–7 and felt that wearables would increase their confidence in managing their long-term health condition (median (IQR) rank score 6 (Huberty et al., 2015; Preusse et al., 2016) 6–76–7. Favourable product characteristics for wearables were accuracy (73 %), easy to learn (63 %) and easy to use (50 %). They were less concerned about aesthetics (23 %) and battery life (27 %). This survey will guide future developers to produce a wearable for a population with chronic respiratory disease which will improve acceptability, usability and longevity.

NIV (Non-invasive ventilation) and HFNC (High Flow nasal cannula) are being used in patients with acute respiratory failure. HACOR score has been exclusively calculated for patients on NIV, on other hand ROX index is being used for patients on HFNC. This is first study where ROX index has been used in patients on NIV to predict failure.

Background and Objectives: Bloodstream infection (BSI) is defined by the presence of viable microorganisms in the bloodstream. BSI is one of the major causes of sepsis and subsequent adverse clinical outcomes all across the globe. The present study was undertaken to identify clinico-epidemio-microbiological variables associated with 30-day mortality in patients having BSI with WHO priority pathogens. Materials and Methods: The study was conducted at a public sector tertiary care institute in central India from April 2019 to March 2021. Blood samples collected from patients with clinical suspicion of sepsis, were processed by automated bacterial culture system and interpreted as per CLSI guidelines. Calculated sample size was 150. Data was analyzed by R software. Results: Respiratory tract infection was the most common source (43.3%) of BSI, followed by the gastrointestinal (20%) and urinary tract (18.7%). Among the patients, 33% required invasive mechanical ventilation, and 31% required inotropes. Diabetes mellitus (DM) was the most common co-morbidity (34%). The incidence of multi-drug resistant organisms (MDRO) was 59.3%. Escherichia coli was the most commonly (24%) isolated organism, followed by Klebsiella pneumoniae (17.3%) and Acinetobacter baumannii (16%). Conclusion: Higher age, higher qSOFA score / SIRS score / mean SOFA score at presentation had higher mortality. Use of mechanical ventilation and inotropes during treatment and isolation of critical category organisms of WPP and multi drug resistant organisms were independent 30-day mortality predictors.

Background: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. Materials and Methods: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. Results: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. Conclusion: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846]

Introduction: Blau syndrome is a progressive disease with an unknown etiology and pathogenesis. It can cause severe damage, especially in the eye with severe involvement. Case Presentation: A six-year-old female was referred to us complaining about blurry vision and floaters in both eyes for 1 year. She had been diagnosed with Blau syndrome and Blau syndrome-associated anterior uveitis. Her best-corrected visual acuity in the right and left eyes was 20/70 and 20/80, respectively. Slit-lamp exam revealed faint bilateral band keratopathy along with 1+ anterior chamber cells and posterior synechia 360° in both eyes. During dilated fundoscopy, 2+ haze in the media was observed, along with swollen and hyperemic disc OU. Based on changes in optical coherence tomography, fluorescein angiography, and indocyanine green angiography, she was diagnosed with panuveitis and retinal vasculitis. Given her complicated history, we decided to proceed with an intravitreal fluocinolone acetonide 0.19 mg implant implantation in both eyes. During the 1-month follow-up visit, vitreous haze, retinal vasculitis, and active choroiditis were resolved. At 6-month follow-up visit, no changes were observed compared to the 1-month follow-up visit. Conclusion: In cases of Blau syndrome that display resistance to systemic immunomodulatory therapies, the inclusion of local treatments, such as the intravitreal fluocinolone acetonide 0.19 mg implant, should be considered as an adjunctive therapeutic option.

Feline hepatic lipidosis (FHL), characterised by an accumulation of triglycerides in the cytoplasm of hepatocytes, is a common and potentially fatal liver disorder in cats. Hepatic lipidosis in cats can develop due to any condition that will impair nutrient uptake and is often presented with non-specific clinical signs. The present study describes the diagnosis of FHL based on clinicobiochemical, ultrasonographic, and cytological changes and evaluates the diagnostic utility of blood beta-hydroxybutyric acid (βHBA) estimation in FHL. Anorexia, weight loss, lethargy, vomiting, dehydration, and jaundice were the common clinical findings in cats with hepatic lipidosis. Serum biochemical evaluation revealed elevations in alkaline phosphatase (ALP), triglycerides, glucose, and total bilirubin. Ultrasonography revealed an enlarged hyperechoic liver. Fine-needle aspiration cytology of the liver revealed mild to severe vacuolation in the cytoplasm of hepatocytes. Blood beta-hydroxybutyric acid levels were found higher in cats with hepatic lipidosis than in healthy cats and cats with other hepatic disorders. Therefore, βHBA estimation, being a quick and non-invasive method, could be considered as a diagnostic marker in the early diagnosis of FHL.

ABSTRACT: Objectives: We prospectively implemented a diagnostic stewardship care-bundle checklist, ‘Sepsis-48 DSB’, with the aim of reducing intervening duration of key steps of automated blood culture diagnostics (aBCD). Methods: Sepsis-48 DSB was implemented for automated blood culture bottles (BCBs) received from adult intensive care units (AICUs) during the intervention period (P2; July 2020–June 2021) and intervening durations were compared with those during the retrospective, pre-intervention period (P1; March–June 2020). During both periods, provisional blood culture reports (pBCR) were issued wherein direct microbial identification (dID) was performed in BCBs with Gram-negatives by directly inoculating conventional biochemical tests and direct antimicrobial susceptibility testing (dAST) using EUCAST RAST method. The results were compared with the standard of care (SoC) method (i.e. full incubation followed by identification and AST by VITEKⓇ-2 Compact). Results: During P2, significant reductions in loading time (LT; median: 63.5 vs. 32 minutes, P < 0.001), time to dID+dAST performance (TTD; 186 vs. 115 minutes, P = 0.0018) and an increase in compliance to bundle targets (LT ≤45: 44% vs. 66%, P = 0.006 and TTD ≤120: 34% vs. 51.7%, P = 0.03) were observed. Using dID+dAST method, results were read 694 minutes earlier than SoC method. Of 176 pBCR, 165 (94%) were concordant with SoC in microbial identification of species. Categorical agreement for any drug-bug combination was 92.7% (1079/1164) and corresponding major, very major, and minor error rates were 8.8% (19/216), 4.9% (45/921), and 1.8% (21/1164), respectively. Conclusion: The ‘diagnostic stewardship care-bundle’ strategy was successfully implemented with considerable diagnostic accuracy leading to significant reductions in duration of targeted steps of aBCD.

Abstract Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is associated with multiple medical and psychological comorbidities. Therefore, future strategies to improve COPD management and outcomes are needed for the betterment of patient care. Wearable technology interventions offer considerable promise in improving outcomes, but prior reviews fall short of assessing their role in the COPD population. In this systematic review and meta-analysis we searched ovid-MEDLINE, ovid-EMBASE, CINAHL, CENTRAL, and IEEE databases from inception to April 2023 to identify studies investigating wearable technology interventions in an adult COPD population with prespecified outcomes of interest including physical activity promotion, increasing exercise capacity, exacerbation detection, and quality-of-life. We identified 7396 studies, of which 37 were included in our review. Meta-analysis showed wearable technology interventions significantly increased: the mean daily step count (mean difference (MD) 850 (494–1205) steps/day) and the six-minute walk distance (MD 5.81 m (1.02–10.61 m). However, the impact was short-lived. Furthermore, wearable technology coupled with another facet (such as health coaching or pulmonary rehabilitation) had a greater impact that wearable technology alone. Wearable technology had little impact on quality-of-life measures and had mixed results for exacerbation avoidance and prediction. It is clear that wearable technology interventions may have the potential to form a core part of future COPD management plans, but further work is required to translate this into meaningful clinical benefit.

Abstract Background Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post‐injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non‐neuronal markers or pan‐neuronal markers with constitutive expressions. Methods In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA‐sequencing and qRT‐PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme‐linked immune‐sorbent assay (ELISA) kits. Results Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. Conclusions ATF3 is an easily measurable, neuron‐specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. Highlights ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Neurosarcoidosis, a rare inflammatory condition, poses a diagnostic challenge due to its various clinical presentations and potential mimics. This comprehensive review delves into the complexities of neurosarcoidosis, emphasizing the importance of a thorough diagnostic workup and the consideration of alternative conditions, such as fungal mimics. The study explores the intricacies of the diagnostic process, particularly the role of histopathology, imaging, and laboratory tests. The current state of neurosarcoidosis management is examined, such as the use of corticosteroids as well as novel therapies including Rituximab and JAK-STAT inhibitors. The clinical spectrum is described in detail for both the peripheral and central nervous systems, offering insights into the many presentations, which include ocular manifestations and syndromes like Heerfordt's syndrome. The complexities of neurosarcoidosis necessitate further research in its diagnosis, pharmacotherapy, and management. The inclusion of information on ongoing research and clinical trials underscores the need for tailored therapeutic approaches.

Purpose: In this study, we report a patient who presented with both chronic myelocytic leukemia (CML) and Susac syndrome (SS). Observations: A 45-year-old male diagnosed with CML in the blast phase sought consultation due to a deterioration in vision in his right eye. He also had hearing loss and severe migraneous headaches. Best corrected visual acuity was light perception and 20/20 in the right and left eyes, respectively. The slit lamp examination and intraocular pressure were within normal ranges for both eyes. Upon dilated fundoscopy, organized vitreous hemorrhage was observed in the right eye, while the left eye exhibited extensive sclerotic vessels with retinal neovascularization in the periphery. Ultrasound of the right eye showed tractional retinal detachment. Optical coherence tomography of the left retina showed thinning of the retina in temporal macula. Fluorescein angiography revealed a substantial nonperfused region in the peripheral left retina, accompanied by arterioarterial and arteriovenous collaterals, along with microaneurysms. MRI showed scattered foci of hyperintensity within the supratentorial white matter, mostly subcortical on T2-weighted and fluid-attenuated inversion-recovery. The patient received a diagnosis of SS and was subsequently referred to the neurology service for further assessment and potential treatment. Conclusion and importance: SS may manifest as a presentation of CML. It is advisable to conduct investigations for SS in CML patients experiencing neurological, ophthalmological, or otological symptoms.

Complete traumatic cervical fracture-dislocation with spinal cord transection in children is a rare entity with no evidence-based guidelines on management. The authors reviewed the literature for pediatric spinal cord injury and present the case of a 3-year-old with traumatic cervical fracture-dislocation and spinal cord transection who presented as a cervical-6 complete spinal cord injury (ASIA A). His other organ systems injured included liver, spleen, bowel, and abdominal aortic injury. The patient underwent halo placement for preoperative reduction followed by open reduction and internal fixation with posterior segmental instrumented fusion. Intraoperatively, the patient had motor evoked potential signals present below the level of his injury. Early postoperative follow-up demonstrated that, although his leg function did not improve, he did demonstrate improvement in upper extremities. This is a rare case of complete cervical spinal cord transection in a pediatric patient. We elected to manage this challenging case with initial external reduction and orthosis with a halo vest followed by acute posterior cervical fusion. Despite a cervical-6 injury level on clinical exam, there was electrographic evidence of function below that level on intraoperative neuromonitoring. Postoperatively the patient has recovered some lost function.

Background: Evaluation of type, nature, and prevalence of common oral pathology lesions involving periodontium and implant in patients of tertiary level dental hospital in Hazaribagh City, Jharkhand. Materials and Methods: A total of 2467 people were requested to take part in the oral examination. The current study cohort was made up of the 62.4% of the initial subgroup who participated in the clinical oral examination and granted their agreement for the use of the data. Between January 2023 and June 2023, the clinical oral examination was completed. Results: No changes were observed in 89.6% of study participants. 88.2% males had no changes while 90.4% females had no changes. Normal variations were observed in 3.4% of study participants. 4.3% males had normal variations while 2.7% females had normal variations. Infectious oral pathology was observed in 3.3% of study participants. 2.4% males had infectious oral pathology while 3.2% females had infectious oral pathology Ulcerative lesions were observed in 4.1% of study participants. 3.6% males had ulcerative lesions while 2.4% females had ulcerative lesions. White lesions were observed in 6.7% of study participants. 8.2% males had white lesions while 5.6% females had white lesions. Conclusion: This study provided a detailed evaluation of type, nature, and prevalence of different oral pathology lesions focusing on periodontium and implant.

Objective:Though airway ultrasonography (USG) is used to assess difficult laryngoscopy (DL), there is still ambiguity about approach followed and parameters assessed. There is need of a simple, stepwise sonographic assessment with clearly defined parameters for DL prediction. The primary objective of this study was to find diagnostic accuracy of sonographic parameters measured by a stepwise Airway-USG in DL prediction (DLP).Methods:This prospective, observational cohort study was done in 217 elective surgical adult patients administered general anaesthesia with tracheal intubation using conventional laryngoscopy from 1st May 2019 to 31st July 2020, after ethical approval. A sagittal Airway-USG was done using 2-6 Hz transducer in three steps specifying probe placement and head position. Demographic, clinical and Airway-USG measurements were noted. Correlation of the clinical/sonographic parameters was made with Cormack-Lehane score on DL. After receiver operating characteristic curve plotting, the sensitivity, specificity, positive predictive value, negative predictive value (NPV) of DL was calculated for each parameter using open-epi software.Results:DL was observed in 19/217 patients. Airway-USG parameters of skin to epiglottis distance >2.45 cm, hyomental distance with head extension 3.93 cm and maximum skin to tongue distance >5.45 cm were statistically significant in predicting DL. DLP score with presence of >3 positive parameters showed 98% specificity, 98% NPV and 96% diagnostic accuracy to predict DL.Conclusion:DLP score derived from Airway-USG may be used as a screening and diagnostic tool for DL.

PurposeOur goal was to evaluate the comparative effectiveness of robot-assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) in a multicenter study.Materials and methodsWe evaluated men with localized prostate cancer at 11 high-volume academic medical centers in the United States from the PROST-QA (2003-2006) and the PROST-QA/RP2 cohorts (2010-2013) with a pre-specified goal of comparing RALP (549) and ORP (545). We measured longitudinal patient-reported health-related quality of life (HRQOL) at pre-treatment and at 2, 6, 12, and 24 months, and pathological and perioperative outcomes/complications.ResultsDemographics, cancer characteristics, and margin status were similar between surgical approaches. ORP subjects were more likely to undergo lymphadenectomy (89% vs 47%; p

ImportanceBlack men have a 2-fold increased risk of dying from prostate cancer compared with White men. However, race-specific differences in response to initial treatment remain unknown.ObjectiveTo compare overall and treatment-specific outcomes of Black and White men with localized prostate cancer receiving definitive radiotherapy (RT).Data sourcesA systematic search was performed of relevant published randomized clinical trials conducted by the NRG Oncology/Radiation Therapy Oncology Group between January 1, 1990, and December 31, 2010. This meta-analysis was performed from July 1, 2019, to July 1, 2021.Study selectionRandomized clinical trials of definitive RT for patients with localized prostate cancer comprising a substantial number of Black men (self-identified race) enrolled that reported on treatment-specific and overall outcomes.Data extraction and synthesisIndividual patient data were obtained from 7 NRG Oncology/Radiation Therapy Oncology Group randomized clinical trials evaluating definitive RT with or without short- or long-term androgen deprivation therapy. Unadjusted Fine-Gray competing risk models, with death as a competing risk, were developed to evaluate the cumulative incidences of end points. Cox proportional hazards models were used to evaluate differences in all-cause mortality and the composite outcome of distant metastasis (DM) or death. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.Main outcomes and measuresSubdistribution hazard ratios (sHRs) of biochemical recurrence (BCR), DM, and prostate cancer-specific mortality (PCSM).ResultsA total of 8814 patients (1630 [18.5%] Black and 7184 [81.5%] White) were included; mean (SD) age was 69.1 (6.8) years. Median follow-up was 10.6 (IQR, 8.0-17.8) years for surviving patients. At enrollment, Black men were more likely to have high-risk disease features. However, even without adjustment, Black men were less likely to experience BCR (sHR, 0.88; 95% CI, 0.58-0.91), DM (sHR, 0.72; 95% CI, 0.58-0.91), or PCSM (sHR, 0.72; 95% CI, 0.54-0.97). No significant differences in all-cause mortality were identified (HR, 0.99; 95% CI, 0.92-1.07). Upon adjustment, Black race remained significantly associated with improved BCR (adjusted sHR, 0.79; 95% CI, 0.72-0.88; P

Introduction Mission Thrombectomy, established in 2016 by the Society of Vascular and Interventional Neurology, aims to enhance global accessibility to mechanical thrombectomy surgery for strokes caused by large vessel occlusion in the brain. High school students interested in exposure to global health have limited access to get exposure in this rapidly expanding area of public health. The MT2020+ student internship was designed in collaboration with MT2020+ to provide such an experience to US High School students. Students designed and carried out projects to raise stroke awareness among other high school students and communities while studying the barriers to stroke treatment. We report on this novel internship program's methodology, results, and outcomes. Methods The MT2020+ internship program followed a comprehensive framework. Three phases were implemented: Phase A involved secondary research, stakeholder identification, and the formation of a detailed survey and interview questions. Stakeholders included neurologists, neuro‐interventionalists, neuro‐radiologists, and members of stroke societies. Countries in the region of interest were categorized into three groups based on stroke and COVID‐19 data. A survey template was created in Phase B, and stakeholders were contacted for data collection. Interviews were conducted to delve deeper into survey responses. Phase C focused on analyzing the collected data, articulating the key barriers, and generating a written report. Interns also developed interventions to address key barriers identified during the research. Results The first cohort (2020) comprised 8 interns who investigated barriers to stroke treatment across different regions. The interns received survey responses and conducted interviews with stakeholders. Their research covered the U.S. & North America, Latin America, Europe, Africa, Asia, and Australia. The outcomes varied, with different levels of engagement. One student developed an app in Peru to address transportation, educational, and rehabilitation barriers. The second cohort (2021) had 2 interns who focused on Latin America and Asia, working on rehabilitation apps. The third cohort (2022) included 4 interns studying Asia, Australia/New Zealand, North America/US, and Latin America. Their interventions ranged from creating stroke awareness clubs to organizing virtual conferences. Conclusion The MT2020+ student internship provided a novel opportunity for high school students to get exposure to global health implementation. The student research in this internship has contributed valuable insights into stroke treatment barriers and raised awareness among high school students worldwide.

Objectives COVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination.Design Prospective observational cross-sectional study.Setting Secondary care tertiary hospital in the UK.Participants This study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021).Outcome measures Associations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively.Results 322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44).Conclusions Patients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome.

Study designInternational, multicenter, prospective, longitudinal observational cohort.ObjectiveTo assess how new motor deficits affect patient reported quality of life scores after adult deformity surgery.Summary of background dataAdult spinal deformity surgery is associated with high morbidity, including risk of new postoperative motor deficit. It is unclear what effect new motor deficit has on Health-related Quality of Life scores (HRQOL) scores.MethodsAdult spinal deformity patients were enrolled prospectively at 15 sites worldwide. Other inclusion criteria included major Cobb more than 80°, C7-L2 curve apex, and any patient undergoing three column osteotomy. American Spinal Injury Association (ASIA) scores and standard HRQOL scores were recorded pre-op, 6 weeks, 6 months, and 2 years.ResultsTwo hundred seventy two complex adult spinal deformity (ASD) patients enrolled. HRQOL scores were worse for patients with lower extremity motor score (LEMS). Mean HRQOL changes at 6 weeks and 2 years compared with pre-op for patients with motor worsening were: ODI (+12.4 at 6 weeks and -4.7 at 2 years), SF-36v2 physical (-4.5 at 6 weeks and +2.3 at 2 years), SRS-22r (0.0 at 6 weeks and +0.4 at 2 years). Mean HRQOL changes for motor-neutral patients were: ODI (+0.6 at 6 weeks and -12.1 at 2 years), SF-36v2 physical (-1.6 at 6 weeks and +5.9 at 2 years), and SRS-22r (+0.4 at 6 weeks and +0.7 at 2 years). For patients with LEMS improvement, mean HRQOL changes were: ODI (-0.6 at 6 weeks and -16.3 at 2 years), SF-36v2 physical (+1.0 at 6 weeks and +7.0 at 2 years), and SRS-22r (+0.5 at 6 weeks and +0.9 at 2 years).ConclusionIn the subgroup of deformity patients who developed a new motor deficit, total HRQOLs and HRQOL changes were negatively impacted. Patients with more than 2 points of LEMS worsening had the worst changes, but still showed overall HRQOL improvement at 6 months and 2 years compared with pre-op baseline.Level of Evidence: 3.

Study designRetrospective hospital-registry study.ObjectiveTo characterize the microbial epidemiology of surgical site infection (SSI) in spinal fusion surgery and the burden of resistance to standard surgical antibiotic prophylaxis.Summary of background dataSSI persists as a leading complication of spinal fusion surgery despite the growth of enhanced recovery programs and improvements in other measures of surgical quality. Improved understandings of SSI microbiology and common mechanisms of failure for current prevention strategies are required to inform the development of novel approaches to prevention relevant to modern surgical practice.MethodsSpinal fusion cases performed at a single referral center between January 2011 and June 2019 were reviewed and SSI cases meeting National Healthcare Safety Network criteria were identified. Using microbiologic and procedural data from each case, we analyzed the anatomic distribution of pathogens, their differential time to presentation, and correlation with methicillin-resistant Staphylococcus aureus screening results. Susceptibility of isolates cultured from each infection were compared with the spectrum of surgical antibiotic prophylaxis administered during the index procedure on a per-case basis. Susceptibility to alternate prophylactic agents was also modeled.ResultsAmong 6727 cases, 351 infections occurred within 90 days. An anatomic gradient in the microbiology of SSI was observed across the length of the back, transitioning from cutaneous (gram-positive) flora in the cervical spine to enteric (gram-negative/anaerobic) flora in the lumbosacral region (correlation coefficient 0.94, P