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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.

Miliary tuberculosis (TB) is an uncommon yet severe condition that can pose substantial risks to pregnant women and their unborn child. This case study describes a 22-year-old pregnant female at 23 weeks of gestation presented with breathlessness, fever accompanied by chills, dry cough, and loss of appetite. With no significant comorbidities, her initial symptoms were inconclusive, leading to her initial diagnosis as a case of pyrexia of unknown origin. Despite receiving iron supplements for anemia and broad-spectrum antibiotics, her health continued to decline, prompting her transfer to a specialized medical center where advanced molecular testing ultimately confirmed a diagnosis of miliary TB. Upon admission, she was promptly started on anti-TB therapy and managed in the intensive care unit, where her clinical course included the development of acute respiratory distress syndrome (ARDS) requiring ventilatory support. Through meticulous monitoring and multidisciplinary intervention, the patient stabilized and ultimately delivered a healthy baby girl through normal vaginal delivery. Miliary TB, though rare, is challenging to diagnose during pregnancy due to overlapping symptoms with other conditions. This case underscores the critical importance of recognizing the atypical presentations of miliary TB in pregnant women, particularly in the context of previous exposure. It highlights the need for high clinical suspicion, timely diagnosis, and comprehensive management strategies to ensure favorable outcomes for both mother and child in the face of such challenging clinical scenarios.

Introduction: Phlyctenular keratoconjunctivitis is an inflammatory condition arising from a type IV hypersensitivity reaction, presenting with inflamed nodules on the conjunctiva and cornea. Scleritis is a severe ocular inflammation linked to systemic diseases, potentially vision threatening, and involving immune responses similar to phlyctenular keratoconjunctivitis. This case report discusses a patient with a history of herpes simplex virus (HSV)-2 infection who primarily developed phlyctenular conjunctivitis and later progressed to nodular scleritis. Case Presentation: A 66-year-old female presented with pain, redness, and a foreign body sensation in her left eye for 2 days. Initial treatment for epidemic keratoconjunctivitis with tobramycin-dexamethasone improved her symptoms. However, 3 weeks later, she developed a conjunctival phlyctenule. Diagnostic tests, including blood work and conjunctival swabs, were conducted. While most tests were negative, HSV-2 IgG was positive. The patient failed topical corticosteroid monotherapy; however, she responded to oral valacyclovir. Follow-up examinations showed significant improvement, with resolution of the conjunctival phlyctenule and nodular scleritis, and her best-corrected visual acuity returned to 20/20. Conclusion: This case highlights the importance of considering HSV-2 in atypical presentations of phlyctenular conjunctivitis and scleritis. The patient’s response to antiviral therapy underscores the potential role of HSV-2 in such ocular inflammation. Thorough infectious workups and alternative treatment approaches are crucial in managing unconventional cases. Experimental treatments based on laboratory findings can be valuable for patients preferring conservative management, emphasizing the need for close follow-up and personalized care in ocular inflammatory diseases.

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]).

An organobase assisted approach is adopted to synthesize pyranopyrazole derivatives in one pot. Three-component condensation reaction of 3-methylpyrazolin-5-ones, aromatic aldehydes and malononitrile were catalyzed by 5 mol% of 4-dimethylaminopyridine (DMAP) in ethanol at room temperature. Key aspects of this approach are simple filtration without the need of time-consuming column purification; good yields; cost-effectiveness and use of easily available solid organo-base as a catalyst. A broad substrate scope and variety of functional group tolerance permit diversity generation in a one pot operation. In silico, molecular-docking studies of the compounds were performed with anti-inflammatory active drugs i.e. indomethacin and celecoxib and the compounds were also studied for their pharmacokinetic properties absorption, distribution, metabolism, and excretion (ADME). The results obtained for most of the synthesized compounds are promising and all of them comply well satisfying the Lipinski rule of 5 (RO5) with 0 violation.

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).

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.

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.

Aim: This research set out to determine whether or not there was a connection between the types of lip print patterns found on people’s lips and their blood types, as well as between the tongue print patterns found on people’s tongues and their blood types. Material and Methods: One hundred and three females and 51 males participated in our research after providing informed permission after hearing about the study’s objectives and potential therapeutic applications. Results: One hundred and three females and 51 males participated in our research after providing informed permission after hearing about the study’s objectives and potential therapeutic applications. Conclusion: While we did find gender differences in lip print and tongue pattern distribution and blood group, our research did not find statistically significant outcomes between these variables.

PURPOSE: Postoperative radiation therapy (RT) is an underused standard-of-care intervention for patients with prostate cancer and recurrence/adverse pathologic features after radical prostatectomy. Although stereotactic body RT (SBRT) is a well-studied and convenient option for definitive treatment, data on the postprostatectomy setting are extremely limited. The purpose of this study was to evaluate short-term physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities and patient-reported outcomes after postprostatectomy SBRT. METHODS AND MATERIALS: The SCIMITAR trial was a phase 2, dual-center, open-label, single-arm trial that enrolled patients with postoperative prostate-specific antigen >0.03 ng/mL or adverse pathologic features. Coprimary endpoints were 4-year biochemical recurrence-free survival, physician-scored acute and late GU and GI toxicities by the Common Terminology Criteria for Adverse Events (version 4.03) scale, and patient-reported quality-of-life (QOL) outcomes, as represented by the Expanded Prostate Cancer Index-26 and the International Prostate Symptom Score. Patients received SBRT 30 to 34 Gy/5 fractions to the prostate bed ± bed boost ± pelvic nodes with computed tomography (CTgRT) or magnetic resonance imaging guidance (MRgRT) in a nonrandomized fashion. Physician-scored toxicities and patient-reported QOL outcomes were collected at baseline and at 1, 3, and 6 months of follow-up. Univariable and multivariable analyses were performed to evaluate predictors of toxicities and QOL outcomes. RESULTS: One hundred participants were enrolled (CTgRT, n = 69; MRgRT, n = 31). The median follow-up was 29.5 months (CTgRT: 33.3 months, MRgRT: 22.6 months). The median (range) prostate bed dose was 32 (30-34) Gy. Acute and late grade 2 GU toxicities were both 9% while acute and late grade 2 GI toxicities were 5% and 0%, respectively. Three patients had grade 3 toxicity (n = 1 GU, n = 2 GI). No patient receiving MRgRT had grade 3 GU or grade ≥2 GI toxicity. Compared with CTgRT, MRgRT was associated with a 30.5% (95% confidence interval, 11.6%-49.5%) reduction in any-grade acute GI toxicity (P = .006). MRgRT was independently associated with improved any-grade GI toxicity and improved bowel QOL. CONCLUSIONS: Postprostatectomy SBRT was well tolerated at short-term follow-up. MRgRT may decrease GI toxicity. Longer toxicity and/or efficacy follow-up and randomized studies are needed.

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.

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.

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]

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.

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 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.

Despite the rising global incidence of central nervous system (CNS) disorders, CNS drug development remains challenging, with high costs, long pathways to clinical use and high failure rates. The CNS is highly protected by physiological barriers, in particular, the blood-brain barrier and the blood-cerebrospinal fluid barrier, which limit access of most drugs. Biomaterials can be designed to bypass or traverse these barriers, enabling the controlled delivery of drugs into the CNS. In this Review, we first examine the effects of normal and diseased CNS physiology on drug delivery to the brain and spinal cord. We then discuss CNS drug delivery designs and materials that are administered systemically, directly to the CNS, intranasally or peripherally through intramuscular injections. Finally, we highlight important challenges and opportunities for materials design for drug delivery to the CNS and the anticipated clinical impact of CNS drug delivery.

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.