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Jonathan Corren,1 Sarbjit S Saini,2 Remi Gagnon,3 Mark H Moss,4 Gordon Sussman,5 Joshua Jacobs,6 Elizabeth Laws,7 Elinore S Chung,8 Tatiana Constant,8 Yiping Sun,8 Jennifer Maloney,8 Jennifer D Hamilton,8 Marcella Ruddy,8 Claire Q Wang,8 Meagan P O’Brien8 1Departments of Medicine and Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; 2Department of Internal Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA; 3Clinique Spécialisée en Allergie de la Capitale, Québec, QC, Canada; 4Departments of Medicine and Pediatrics, Division of Allergy, Pulmonary and Critical Care, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 5Department of Medicine, University of Toronto, Toronto, ON, Canada; 6Allergy and Asthma Clinical Research, Inc, Walnut Creek, CA, USA; 7Sanofi, Bridgewater, NJ, USA; 8Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USACorrespondence: Meagan P O’BrienRegeneron Pharmaceuticals, Inc, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USATel +1 914 826-5271Email meagan.obrien@regeneron.comJonathan CorrenDepartments of Medicine and Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, 90095, USATel +1 310 312-5050, ext 250Email jcorren@ucla.eduBackground: Subcutaneous immunotherapy (SCIT) has been proven as an effective therapy against some allergens for seasonal allergic rhinitis (SAR) patients unresponsive to intranasal corticosteroids and/or antihistamines but carries risk of systemic allergic reactions. Dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation in multiple diseases.Objective: To evaluate the efficacy and safety of SCIT+dupilumab vs SCIT alone.Methods: This phase 2a, multicenter, double-blind, placebo-controlled parallel-group study conducted in 103 adults with grass pollen-induced SAR (NCT03558997) randomized patients 1:1:1:1 to SCIT, dupilumab (300 mg every 2 weeks), SCIT+dupilumab, or placebo. SCIT was administered using an 8-week cluster protocol followed by 8 weeks of maintenance injections. Primary endpoint was change from pre-treatment baseline in area under the curve (AUC) in total nasal symptom score (TNSS) 0– 1 h following nasal allergen challenge (NAC) with timothy grass extract at Week 17.Results: Although 16 weeks of treatment with SCIT+dupilumab did not significantly improve TNSS AUC (0– 1 h) following NAC at Week 17 vs SCIT (least squares mean − 56.76% vs − 52.03%), a higher proportion of SCIT+dupilumab-treated patients (61.5%) achieved SCIT maintenance dose vs SCIT (46.2%). A lower proportion of SCIT+dupilumab-treated patients (7.7%) required epinephrine rescue treatment vs SCIT (19.2%). There were significantly fewer withdrawals in the SCIT+dupilumab group than in the SCIT group (n = 2 [7.7%] vs n = 8 [30.8%]; P = 0.0216); the majority of SCIT group withdrawals were due to SCIT-related intolerability, compared with no discontinuations from the SCIT+dupilumab group.Conclusion: In SAR patients, 16 weeks of SCIT+dupilumab may improve SCIT tolerability but did not incrementally reduce post-allergen challenge nasal symptoms compared with SCIT alone.Clinical Study Number: NCT03558997.Keywords: dupilumab, seasonal allergic rhinitis, subcutaneous immunotherapy, nasal allergen responses

In this paper, we present the design and fabrication of a plasmonic metasurface based on titanium dioxide (TiO 2 ) nanowire arrays integrated with plasmonic layers. The structure is engineered to produce Fano resonances within the visible spectrum, resulting from the coupling of localized surface plasmon resonances, lattice modes, and nanowire's optical modes. Experimentally, we show that by tuning the geometrical features of the metasurface, such as the length, diameter, and period of the nanowires, a high-quality factor single peak can be achieved in the reflection spectra, resulting in vivid structural colors in bright field. To our knowledge, this is the first demonstration of such vivid colors with nanowire arrays in bright field reflections. When characterized by refractive index fluids around the refractive index of water, the plasmonic metasurface also showed great potential for biochemical colorimetric sensing. The best design demonstrated a bulk sensitivity of 183 nm/RIU with high Q resonance features and linear changes in color values using image processing., (Creative Commons Attribution license.)

Chronic urticaria can be divided into 2 subsets: chronic spontaneous urticaria (CSU) with skin lesions occurring without a specific trigger and chronic inducible urticaria, which has an identified specific stimulus. The annual prevalence of chronic urticaria is 0.5% to 2.3% globally. The CSU is a self-limited disorder in most cases, with an average duration of 2 to 5 years, but symptoms persist beyond 5 years in up to 30% of patients. The first line of treatment is a daily nonsedating, second-generation H1-antihistamine. The CSU guidelines recommend using oral nonsedating antihistamines up to 4 fold in patients with CSU unresponsive to standard doses as the next step in treatment. A meta-analysis found that the rate of response in patients with CSU who responded to updosing was 63.2%. Therefore, approximately 40% of patients continue to have persistent hives and itching requiring treatment with the biologic omalizumab, based on evidence from randomized controlled trials. Although omalizumab has been shown to markedly relieve symptoms of CSU, omalizumab is not effective in all patients and has not been shown to induce long-term disease remission. Thus, there is an unmet need for more effective treatments that can lead to cure or long-term remission. In this review, we will provide an overview of new treatment targets and biologics that are under investigation for the treatment of CSU., Competing Interests: Disclosures Dr Saini reports receiving grant, research, and/or clinical trial support from the National Institutes of Health, Novartis, Sanofi, Regeneron, Amgen, Allakos, and Escient and served as a consultant or advisory boards to Allakos, Granular Therapeutics, Novartis, Aquestive, Regeneron, Escient, Innate, Celltrion, and Sanofi. Dr Min has no conflicts of interest to report., (Copyright © 2024. Published by Elsevier Inc.)

Background: The benefits and harms of adding antileukotrienes to H 1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear., Objective: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria., Methods: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/)., Results: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events., Conclusion: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain., Competing Interests: Disclosure statement This work was commissioned and funded by the American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) through the Joint Task Force on Practice Parameters to inform upcoming guidance on the management of CU. The task force contributed to defining the scope of the review but otherwise had no role in study design, data collection, data analysis, or data interpretation. The funder received a copy of the report before submission. The review team had the ability, but not the obligation, to consider the funders’ feedback. Disclosure of potential conflict of interest: M. Ben-Shoshan reports consulting fees from Sanofi/Regeneron and Novartis. S. Waserman reports consulting fees from Medexus Pharmaceuticals and Miravo Healthcare. S. K. Mathur reports consulting fees from Novartis. E. T. Oliver reports consulting fees from Novartis and Sanofi/Regeneron. R. N. Asiniwasis reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Medexus Pharmaceuticals. S. Eftekhari is employed by the Asthma and Allergy Foundation of America, a nonprofit patient organization, which has received grants for patient education and unbranded initiatives from AstraZeneca, Bayer, Johnson & Johnson, Merck, and Sanofi/Regeneron. T. Winders reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AstraZeneca, GlaxoSmithKline, Merek, Novartis, and Sanofi/Regeneron. J. Bernstein reports consulting fees from AstraZeneca, Merck, Sanofi/Regeneron, and Pfizer; and leadership role in the AAAAI and the US Hereditary Angioedema Association. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Reducing the burden of disease for patients and families requires being able to measure health status changes related to disease severity, control, and response to treatment over time. Patient-reported outcomes are patient perceptions of their health status. Such perceptions are critical to decision making. Some patient-reported outcome measures (PROMs) are extensive and often intended to be used only for detailed research assessments. Many PROMs, however, form critical components of valid, reliable, and responsive assessments in clinical research and routine clinical practice. The smallest score change in a PROM that would lead to different decision making by patients is called the minimally important difference. Using PROMs may also offer advantages over general questions or unvalidated tools. With the innovation of technology, the ability to chronicle disease symptoms using communication technology (mobile phone applications) has become increasingly available. Collection of real-world data in this capacity will be very useful for identifying more precise phenotypes/endotypes necessary for investigation of tailored therapies for chronic spontaneous and inducible urticaria, angioedema, and atopic dermatitis. Here, we provide an overview of PROMs that have been developed for the assessment of disease severity, control, and quality of life and that have been validated for the use of adults and children with these skin disorders., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Topical corticosteroids are widely used as a treatment for itch and wheals (urticaria), but their benefits and harms are unclear., Objective: To systematically synthesize the benefits and harms of topical corticosteroids for the treatment of urticaria., Methods: We searched MEDLINE, EMBASE, and CENTRAL from database inception to March 23, 2024, for randomized trials comparing topical corticosteroids with placebo for patients with urticaria (either chronic spontaneous or inducible urticaria or acute urticaria elicited from skin/intradermal allergy testing). Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects meta-analyses addressed urticaria severity, itch severity (numeric rating scale; range 0-10; higher is worse), and adverse events. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed certainty of evidence ratings. PROSPERO registration: CRD42023455182., Results: A total of 19 randomized controlled trials enrolled 379 participants with a median of mean age of 30.1 (range 21.1-44.0) years. Compared with placebo, topical corticosteroids may reduce wheal size (ratio of means 0.47, 95% CI 0.38-0.59; low certainty) and itch severity (mean difference -1.30, 95% CI -5.07 to 2.46; very low certainty). Topical corticosteroids result in little to no difference in overall adverse events (94 fewer patients per 1000, 95% credible intervals 172 fewer to 12 more; high certainty)., Conclusion: Compared with placebo, topical corticosteroids may result in a reduction of wheal size and little to no difference in overall adverse events. Topical corticosteroids may reduce itch severity, but the evidence is very uncertain. Future large, randomized trials addressing the use of topical corticosteroids would further support optimal urticaria management., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In chronic spontaneous urticaria (CSU), interleukin (IL)-4 and IL-13 may promote mast cell activation directly via IL-4 receptor expression, or indirectly via upregulated immunoglobulin E (IgE) production. Dupilumab significantly improved CSU signs and symptoms in the phase 3, randomized, placebo-controlled LIBERTY-CSU CUPID Study A. This analysis explores the impact of dupilumab on CSU signs and symptoms and serum IgE levels in patients from LIBERTY-CSU CUPID Study A with serum total IgE above and below 100 IU/mL at baseline., Methods: Patients with H1-antihistamine-refractory CSU received dupilumab (n = 70) or placebo (n = 68) for 24 weeks. Efficacy endpoints were change from baseline to weeks 12 and 24 in serum total IgE levels, Itch Severity Score over 7 days (ISS7), Urticaria Activity Score over 7 days (UAS7), and Hives Severity Score over 7 days (HSS7) in dupilumab- or placebo-treated patients with serum total IgE above and below 100 IU/mL at baseline., Results: Dupilumab treatment significantly reduced median (interquartile range) IgE levels at week 12 [dupilumab: -31.9% (-41.9; -22.6); placebo: -6.3% (-21.3; 14.9)] and week 24 [dupilumab: -48.2% (-56.8; - 39.5); placebo: - 6.3% (-34.5; 14.8)]. Similar IgE reductions relative to baseline were observed in dupilumab-treated patients regardless of baseline IgE level. Dupilumab treatment improved ISS7, UAS7, and HSS7 over 12 and 24 weeks, regardless of baseline serum IgE level (interaction p ≥ 0.59 for all treatment by subgroup comparisons), with weak correlations (r < 0.2) observed between IgE level changes and ISS7, UAS7, and HSS7 outcomes., Conclusions: Dupilumab significantly improved CSU signs and symptoms and reduced serum IgE, regardless of baseline IgE levels. In the current analysis, baseline total IgE had no predictive value as a dupilumab treatment response biomarker in CSU. Downregulation of IgE, a key mediator of mast cell activation and histamine release, may at least partially explain the effectiveness of dupilumab in reducing CSU signs and symptoms., Trial Registration: ClinicalTrials.gov Identifier: NCT04180488., (© 2024. The Author(s).)

Urticaria, also known as hives, is a common condition thought to affect up to 20% of individuals worldwide in their lifetime. This skin condition is characterized by the appearance of pruritic, erythematous papules or plaques with superficial swelling of the dermis. The major complaint is the symptom of pruritus. Angioedema, which involves a deeper swelling of dermal or mucosal tissues, may accompany urticaria. Urticaria can be classified by both time course of symptoms and the underlying etiology., Competing Interests: Disclosure E.T. Oliver: Grant Support: National Institutes of Health, United States (K23AI139394), Robert Meyerhoff Professorship Advisory Board/Consultant: Novartis, Regeneron/Sanofi. S.S. Saini: Grant Support: Novartis, Switzerland, Sanofi, France, Regeneron, United States, National Institutes of Health, United States, Allakos, Escient Advisory Board/Consultant: Allakos, Granular Therapeutics, Novartis, Aquestive, Regeneron, Escient, Evommune, Innate, Celltrion, Sanofi., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear., Objective: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids., Methods: We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach., Results: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty)., Conclusions: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by recurrent pruritic wheals (hives) and/or angioedema. Patients with CSU could remain symptomatic despite standard-of-care H 1 antihistamines (H1-AH) or anti-IgE (omalizumab) treatment. Dupilumab blocks IL-4/IL-13 signaling and is approved for multiple type 2/atopic indications., Objective: We conducted two phase 3, randomized, placebo-controlled, double-blind trials comparing dupilumab with placebo in patients with symptomatic CSU despite H1-AH., Methods: In LIBERTY-CSU CUPID Study A, patients were omalizumab-naive (n = 138, aged ≥6 years). In Study B, patients were omalizumab-intolerant/incomplete responders (n = 108, aged ≥12 years). The primary end point was either change from baseline over 7 days in the Urticaria Activity Score (UAS7) or Itch Severity Score (ISS7) at week 24, with the other as a key secondary end point, depending on regional regulatory requirements. Studies were pooled for safety assessment., Results: In Study A, UAS7 and ISS7 improved with dupilumab versus placebo (difference -8.5 [95% CI, -13.2 to -3.9; P = .0003] and -4.2 [95% CI, -6.6 to -1.8; P = .0005]). In Study B, tested at α = 0.043 after interim analysis, UAS7 improved (difference -5.8 [95% CI, -11.4 to -0.3; P = .0390]), with a numerical trend in ISS7 (difference -2.9 [95% CI, -5.7 to -0.07; nominal P = .0449, not significant]). Pooled safety data were consistent between dupilumab and placebo and with the known dupilumab safety profile., Conclusions: Dupilumab reduced urticaria activity by reducing itch and hives severity in omalizumab-naive patients with CSU uncontrolled with H1-AH. Although the primary end point for Study B was not met, dupilumab effects were small in patients who were omalizumab-intolerant/incomplete responders., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives The coronavirus disease 2019 (COVID-19) pandemic has impacted public health systems and individuals' behaviour, with decreasing survival rates among out-of-hospital cardiac arrest (OHCA) patients. Bystander cardiopulmonary resuscitation (CPR) improves OHCA outcomes, which may have been affected by COVID-19. We sought to understand the impacts of COVID-19 on bystanders' willingness to administer CPR in three Canadian provinces. Methods Participants ≥ 18 years of age were surveyed online about their current and recalled pre-pandemic attitudes toward CPR and perceived transmission risk. We compared mean willingness to perform various CPR actions before and during the pandemic using paired t-tests. Differences in willingness across three provinces were assessed using analysis of variance (ANOVA) and Tukey's Honestly Significant Difference (HSD) test. We also conducted Chi-square tests to assess changes in willingness to perform CPR on children and older adults. Results Five hundred thirty-five participants were surveyed from October 1 to November 15, 2021. The mean age was 42.7 years (SD 14.5), and 60.2% were female. Participants reported less willingness to perform chest compressions on strangers during the pandemic compared to their recollections before the pandemic (mean willingness 86.2% vs. 94.3% prior, p<0.001). With personal protective equipment (PPE) available, particularly masks, willingness recovered to 91.3% (p<0.001). Willingness was higher in Nova Scotia (NS) than in British Columbia (BC) or Ontario (ON). Reluctance to assist older adults increased from 6.6% to 12.0% (p=0.020). Conclusions This study highlights changes in CPR willingness during the COVID-19 pandemic, underscoring the importance of PPE and offering insights into public health strategies pertaining to CPR during a pandemic., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Ethics Board of the University of British Columbia issued approval H21-02624. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: John Sapp declare(s) a grant and personal fees from Abbott, Johnson and Johnson, Medtronic, Varian. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shadarevian et al.)

Competing Interests: Declaration of competing interest The other authors have no conflicts of interest to disclose.

Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder that manifests with itchy wheals, angioedema, or both for more than 6 weeks. Mast cells and basophils are the key pathogenic drivers of CSU; their activation results in histamine and cytokine release with subsequent dermal inflammation. Two overlapping mechanisms of mast cell and basophil activation have been proposed in CSU: type I autoimmunity, also called autoallergy, which is mediated via IgE against various autoallergens, and type IIb autoimmunity, which is mediated predominantly via IgG directed against the IgE receptor FcεRI or FcεRI-bound IgE. Both mechanisms involve cross-linking of FcεRI and activation of downstream signaling pathways, and they may co-occur in the same patient. In addition, B-cell receptor signaling has been postulated to play a key role in CSU by generating autoreactive B cells and autoantibody production. A cornerstone of FcεRI and B-cell receptor signaling is Bruton tyrosine kinase (BTK), making BTK inhibition a clear therapeutic target in CSU. The potential application of early-generation BTK inhibitors, including ibrutinib, in allergic and autoimmune diseases is limited owing to their unfavorable benefit-risk profile. However, novel BTK inhibitors with improved selectivity and safety profiles have been developed and are under clinical investigation in autoimmune diseases, including CSU. In phase 2 trials, the BTK inhibitors remibrutinib and fenebrutinib have demonstrated rapid and sustained improvements in CSU disease activity. With phase 3 studies of remibrutinib ongoing, it is hoped that BTK inhibitors will present an effective, well-tolerated option for patients with antihistamine-refractory CSU, a phenotype that presents a considerable clinical challenge., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Prostaglandin inhibitors are used for the treatment of patent ductus arteriosus (PDA) and they often transiently decrease the urine output (UO) due to prostaglandin inhibition in the renal vasculature. We hypothesized that preterm infants whose renal vasculature shows greater sensitivity to prostaglandin inhibitors are likely to have ductal tissue with greater sensitivity to the same. Our objective was to determine whether the decrease in UO following treatment of PDA with a prostaglandin inhibitor is associated with a higher probability of PDA closure., Study Design: In a prospective, proof-of-concept, cohort study, we enrolled 40 preterm neonates with hemodynamically significant PDA (hsPDA), being treated with a prostaglandin inhibitor. The key predictor, UO, was measured at baseline and daily until 72 hours. We repeated echocardiography daily until PDA closure or the end of treatment. The key outcome was PDA closure. We compared "PDA-closed" ( n  = 28) and "PDA-open" ( n  = 12) groups for change in UO from baseline., Results: The median (Q1, Q3) percent decrease in UO (figures rounded off to integers) was greater in the "PDA-closed" versus "PDA-open" group: from baseline to 0 to 24 hours [-45% (-55%, +0.04%) vs. -15% (-28%, +49%)]; baseline to 24 to 48 hours [-41% (-53%, +14%) vs. -3% (-25%, +62%), p  = 0.03] and baseline to 48 to 72 hours [-33% (-49%, +32%) vs. +21% (-7%, +98%), p  = 0.02]. Decrease in UO preceded PDA closure. The "PDA-closed" group had significantly greater weight loss, despite a greater decrease in UO. A decrease in UO of 27 and 17% by 24 to 48 hours and 48 to 72 hours, respectively, best predicted PDA closure., Conclusion: A decrease in UO after treating hsPDA with a prostaglandin inhibitor is associated with successful closure of PDA., Key Points: · Prostaglandin inhibition causes both decrease in urine output and PDA closure following medical treatment. · The association between drug-induced decrease in urine output and PDA closure has been inadequately studied.. · Decrease in urine output after treatment with prostaglandin inhibitors increases the chances of PDA closure.., Competing Interests: None declared., (Thieme. All rights reserved.)

Global climate change (GCC) is posing a serious threat to organisms, particularly plants, which are sessile. Drought, salinity, and the accumulation of heavy metals alter soil composition and have detrimental effects on crops and wild plants. The hormone auxin plays a pivotal role in the response to stress conditions through the fine regulation of plant growth. Hence, rapid, tight, and coordinated regulation of its concentration is achieved by auxin modulation at multiple levels. Beyond the structural enzymes involved in auxin biosynthesis, transport, and signal transduction, transcription factors (TFs) can finely and rapidly drive auxin response in specific tissues. Auxin Response Factors (ARFs) such as the ARF4, 7, 8, 19 and many other TF families, such as WRKY and MADS, have been identified to play a role in modulating various auxin-mediated responses in recent times. Here, we review the most relevant and recent literature on TFs associated with the regulation of the biosynthetic, transport, and signalling auxin pathways and miRNA-related feedback loops in response to major abiotic stresses. Knowledge of the specific role of TFs may be of utmost importance in counteracting the effects of GCC on future agriculture and may pave the way for increased plant resilience., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Marzi, Brunetti, Saini, Yadav, Puglia and Dello Ioio.)

Antifreeze glycoproteins (AFGPs) are produced by extremophiles to defend against tissue damage in freezing climates. Cumbersome isolation from polar fish has limited probing AFGP molecular mechanisms of action and limited development of bioinspired cryoprotectants for application in agriculture, foods, coatings, and biomedicine. Here, we present a rapid, scalable, and tunable route to synthetic AFGPs (sAFGPs) using N -carboxyanhydride polymerization. Our materials are the first mimics to harness the molecular size, chemical motifs, and long-range conformation of native AFGPs. We found that ice-binding activity increases with chain length, Ala is a key residue, and the native protein sequence is not required. The glycan structure had only minor effects, and all glycans examined displayed antifreeze activity. The sAFGPs are biodegradable, nontoxic, internalized into endocytosing cells, and bystanders in cryopreservation of human red blood cells. Overall, our sAFGPs functioned as surrogates for bona fide AFGPs, solving a long-standing challenge in accessing natural antifreeze materials.

The authors examined the prevalence of abnormal amplitude integrated electroencephalography (aEEG) patterns in neonates diagnosed with sepsis-associated encephalopathy (SAE). They recorded 36626 min of aEEG in 75 study neonates. Encephalopathy was defined by the Brighton Collaboration Neonatal Encephalopathy criteria. Neonates with primary outcome [either non-survivors or survivors with abnormal neurological examination at discharge using Amiel-Tison assessment tool, n = 58, (77%)] were compared with 17 survivors having normal neurological examination at discharge. Severely abnormal aEEG patterns (isoelectric voltage, continuous low voltage, burst suppression) collectively represented 31% of total 36626 min aEEG tracings. Neonates experiencing primary outcome had significantly higher Burdjalov scores than survivors with normal neurological exam (p value 0.01). After adjusting for gestational age, birth weight, and invasive ventilation, severely abnormal aEEG (aOR 5.8, 95% CI 1.7-19.5, p value 0.005) and Burdjalov score (aOR 0.77, 95% CI 0.63-0.95, p value 0.01) were independently associated with death or abnormal neurological examination at discharge., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objective Doppler velocimetry provides a sensitive, non-invasive, and safe method of surveillance of fetal hemodynamics and fetomaternal circulation. Cerebroplacental ratio (CPR) is an indicator of placental function and fetal maladaptation to placental insufficiency. Cerebroplacental ratio (CPR) is becoming a significant indicator of unfavorable pregnancy outcomes, which has implications for the assessment of fetal well-being. This study aimed to determine the cut-off value of the cerebroplacental ratio (CPR) in appropriate for gestational age (AGA) fetuses in high-risk mothers to predict adverse perinatal outcomes. We also compared the efficacy of CPR, umbilical artery pulsatility index (UmA PI), and middle cerebral artery pulsatility index (MCA PI) for predicting adverse perinatal outcomes. Design and setting This was a prospective observational study conducted at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Methods A total of 100 women with singleton high-risk pregnancies were included in this prospective observational study. Obstetric ultrasound was performed at the time of recruitment, and fetal weight and CPR were noted. Based on fetal weight, patients were divided into AGA and fetal growth restriction (FGR) groups; CPR was measured; patients were followed up fortnightly; and outcomes were noted. Main outcome The effectiveness of CPR, UmA PI, and MCA PI for predicting poor perinatal outcomes and identifying the cut-off value of CPR in appropriate for gestational age (AGA) fetuses in high-risk mothers was assessed. Result The values of MCA PI, UmA PI, and CPR were statistically significant between AGA and FGR (p-value =.023, .002 and .0001), respectively. The cut-off value for CPR-detecting adverse outcomes in AGA was 1.49. It has sensitivity, specificity, positive predictive value, and negative predictive value of 67.5%, 68%, 71.69%, and 70.21%, respectively. Conclusion Cerebroplacental ratio (CPR) reflects both circulatory insufficiency of the placenta and adaptive changes of the middle cerebral artery, indicating an important non-invasive surveillance modality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kumar et al.)

Iron deficiency anemia is considered the leading cause of anemia during pregnancy; however, there is a lack of comprehensive studies on the etiological factors of anemia in pregnant women. The objective of this study was to systematically investigate the causes of anemia in pregnancy. Five hundred women with hemoglobin levels < 11 g/dl between 6 and 40 weeks of pregnancy underwent a complete hemogram, iron studies, serum folate, serum B12, serum copper, and serum zinc level assessments using standard methods. The median age of the patients was 26 years (range 24-29 years). The majority of patients were in the third trimester (449/500, 89.8%). Among the patients, 325 (65%) had vitamin B12 deficiency, with 159 (31.8%) having isolated B12 deficiency and 142 (28.4%) having combined B12 and iron deficiency. Isolated iron deficiency anemia was present in 74 patients (14.8%). Additionally, 28 patients (5.6%) had beta-thalassemia minor, and anemia of chronic disease was found in 17.2% (86) of the patients. Vitamin B12 deficiency was the most common cause of anemia, followed by combined B12 and iron deficiency. Further studies in diverse populations are warranted as they have broader implications for nutrient supplementation during pregnancy., Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01682-x., Competing Interests: Conflict of interestNone., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: To investigate the barriers and facilitators involved in the back-referral process of newborns from a tertiary care centre to district Special Newborn Care Units (SNCUs) for step-down care., Methods: The study employed mixed methods, including feedback questionnaires for parents of back-referred neonates, in-depth interviews with doctors and nurses from six SNCUs, and focused group discussions with medical staff at a tertiary-level institute. The study was conducted over a period of seven and a half months in a north Indian tertiary care centre., Results: The back-referral process received positive acceptance from parents and healthcare personnel. Notable barriers included the lack of Retinopathy of Prematurity (ROP) screening services in some SNCUs, inadequate free transport facilities for back-referral, and deficiencies in two-way communication. Parents provided valuable feedback for improvement, suggesting back-referral to the SNCU nearest to their home, daytime back-referral with adequate prior notice, and the availability of post-partum obstetric care at SNCUs for the mother. Inadequate environmental hygiene and limited availability of ROP services were identified as concerns. Facilitators included effective communication, proximity-based back-referral, and ongoing mentoring of SNCUs by tertiary centres., Conclusions: Establishing efficient two-way communication between tertiary centres and district SNCUs, provision of essential facilities at SNCUs, and ensuring a seamless continuum of care are pivotal for successful back-referral of convalescent neonates. Addressing these factors can contribute to improving the back-referral process, level 3 bed availability at the tertiary centres and neonatal health outcomes., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: Traumatic birth experience is an unaddressed arena, especially in Asian women, with several societal stigmas lingering around., Aim: A study was undertaken to simultaneously assess the post-partum mental and physical health follow-up of maternal near-miss (MNM) women and compare it with women of uneventful deliveries., Materials and Methods: The prospective cohort study enrolled 88 MNM women (case cohort) and 80 women with an uneventful peri-partum period (control cohort) at the same time. The participants were followed up with Edinburgh Postnatal Depression Scale (EDPS), PTSD Checklist - Civilian Version (PLC-C), and a 36-item short-form-survey form over 6 months after the delivery., Results: The case group had higher mean EPDS and PLC-C scores, with poor quality of life (QOL) performance, compared to the control group at 6 weeks and 3 months, and 6 months follow-up ( P < 0.05). At the sixth-week follow-up visit, the study observed that 28 (31.8%) women from the case group required a psychiatry consultation compared to the control group with only two (2.5%) participants ( P < 0.001). At 3 months, an evident difference was noted on various QOL parameters, such as limitations due to physical health and emotional problems, energy fatigue, general health, and health change parameters between the two groups ( P < 0.05). The difference persisted at 6-month follow-up as well for limitations due to physical health, energy fatigue, and general health parameters only ( P < 0.05)., Conclusion: There is an urgent need for a multi-departmental collaborative approach at the hospital level and policy-making decisions at higher levels for the mental health of Asian women facing MNM events., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

India is committed to achieve a single-digit neonatal mortality rate (NMR) and stillbirth rate (SBR) by 2030 through India Newborn Action Plan (INAP) 2014. However, the current rate of decline is not enough to achieve the target neonatal mortality rate. Course correction and renewed efforts are required. This review outlines the current scenario and proposed scale-up of services included during labour, childbirth, and the immediate newborn period. The article summarises the challenges and bottlenecks in achieving a reduction in neonatal mortality rate and INAP targets. India has achieved over 80% coverage of three of the four ENAP coverage targets, but antenatal care coverage is still poor. There are concerns about the quality and completeness of antenatal care visits and other program interventions. The ongoing quality assurance should be strengthened through continuous supportive supervision by involving the medical colleges in a hub and spoke model and other key stakeholders. There is a need for effective and strategic engagement of the private sector in these initiatives. The states need to systematically assess the gaps as per population requirements and find effective solutions to overcome them quickly. The state and district-wise data maps show immense variations in coverage between states and within states, mirroring the variations in NMR. This indicates the need to ensure contextual micro-plans and provides an opportunity for the districts and states to learn from each other. The recent initiatives to strengthen primary healthcare should be used as a platform for all stillbirth and neonatal mortality prevention interventions in India., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: Doxycycline (DX) is the first-line therapeutic agent for scrub typhus. Macrolides, especially azithromycin (AZ), have been found to be equally efficacious as DX for treating scrub typhus in adults. We conducted this study to compare the efficacy of AZ versus DX in pediatric scrub typhus., Study Design: Open-label randomized controlled trial., Methods: Children 1-14 years of age suffering from acute febrile illness of ≥5 days and with a positive scrub IgM serology were randomized to receive either DX (2.2 mg/kg/dose twice daily in <40 kg; 100 mg BD in >40 kg for 7 days) or AZ (10 mg/kg/day for 5 days). The primary outcome was defervescence within 7 days of DX or 5 days of AZ., Results: We had 75 children randomized and analyzed using an intention-to-treat approach and 60 children analyzed via per-protocol analysis. The proportion of children achieving defervescence was comparable in 2 groups [per-protocol analysis: 90.9% in the DX group vs. 96.3% in the AZ group, RR: 0.94 (95% CI: 0.83-1.08)]. On Kaplan-Meier curves, AZ showed a significantly higher probability of defervescence at any time point during treatment as compared with DX (log-rank test P value 0.035)., Conclusion: AZ and DX had comparable rates of defervescence among children with scrub typhus. Trial registration No.: CTRI/2020/01/022991., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The present study assessed whether applying enhanced recovery after surgery (ERAS) guidelines for cesarean delivery is feasible in the tertiary care setting with an add-on objective to identify barriers to successful implementation. The cross-sectional study included women undergoing elective CS and willing to participate. The study attempted to understand barriers to ERAS implementation through timely interviewing study participants. Sixty-two patients participated in the study. Antenatal and fetal complications were observed in 39(63%) and 32(51%) participants. The study observed that at least 80% of the proposed components could be applied to 71% of the study population. All 15 components could be applied to 7(11.2%) patients, and at least 50% could be applied to 58(94%) patients. The least applied component was minimizing starvation by taking clear liquids until 2 hrs before surgery in 26(42%) patients due to waiting hours outside the operation-theater (OT). When fitness-for-discharge was assessed against the percent components of ERAS implemented, the area under the curve (AUC) value was 0.75, with a specificity value of 95.65% and a positive predictive value of 94.12%. In the postoperative ERAS bundle, fitness-for-discharge on day-two was statistically associated with early and frequent breastfeeding ( p  = 0.000) and prevention of intra-op hypotension ( p  = 0.03). In conclusion, the primary barriers to implementing ERAS were resource limitations in the form of single functional OT and limited doctors.

Background: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy., Objective: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination., Methods: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters., Results: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions., Conclusions: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Sepsis is a leading cause of neonatal mortality worldwide, with a disproportionately high burden in low-income and middle-income countries. There is limited prospective data on microorganism profiles and antimicrobial resistance (AMR) in outborn newborns referred to pediatric emergency in developing countries. We aimed to assess the pathogen profile and AMR patterns in outborn neonates referred to the pediatric emergency at a tertiary care center., Methods: In this prospective cohort study, we enrolled neonates with suspected sepsis and sent blood or cerebrospinal fluid cultures. Neonates were followed up daily until discharge or death. The isolated organisms were identified and tested for antimicrobial susceptibility. Standard definitions were used to define multidrug resistance., Results: Between January 1, 2020, and December 31, 2020, 1072 outborn neonates with suspected sepsis were enrolled. The rate of proven sepsis was 223.6 (95% CI:198.7-248.4) per 1000 infants. Gram-negative sepsis was the most common (n = 107,10%), followed by gram-positive sepsis (n = 81,7.6%) and fungal sepsis (n = 67,6.3%). Coagulase-negative staphylococci (n = 69), Candida spp. (n = 68), Klebsiella spp. (n = 55), Acinetobacter spp . (n = 31) and Escherichia coli (n = 9) were the most common pathogens. Over two-thirds (68.6%) of pathogens were multidrug resistance, with an alarming prevalence in Klebsiella spp. (33/53, 62%), Acinetobacter spp. (25/30, 83%) and coagulase-negative staphylococci (54/66, 82%). In total, 124 (11.6%) neonates died in the hospital (13.3% of proven cases and 11.1% of culture-negative sepsis cases)., Conclusions: High sepsis burden and alarming AMR among neonates referred to tertiary care centers warrant urgent attention toward coordinated implementation of rigorous sepsis prevention measures and antimicrobial stewardship across all healthcare levels., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To compare blood pressures (BP) between neonates with culture-proven sepsis and clinical sepsis in the first 120 h of sepsis onset and to examine association between BP and in-hospital mortality., Methods: In this cohort study, consecutively enrolled neonates with 'culture-proven' sepsis [growth in blood/ cerebrospinal fluid (CSF) within 48 h] and clinical sepsis (sepsis workup negative, cultures sterile) were analyzed. Their BP was recorded every 3-hourly for initial 120 h and averaged in 20 time-epochs of 6 h each (0-6 h to 115-120 h). BP Z-scores were compared between neonates with culture-proven vs. clinical sepsis and survivors vs. non-survivors., Results: Two hundred twenty eight neonates (102-culture-proven and 126-clinical sepsis) were enrolled. Both groups had comparable BP Z-scores except significantly lower diastolic BP (DBP) and mean BP (MBP) in 0-6 and 13-18 time-epochs in culture-proven sepsis group. Fifty-four neonates (24%) died during their hospital stay. BP Z-scores in the initial 54 h of sepsis were independently associated with mortality [systolic BP (SBP) Z-scores in first 54 h, DBP Z-scores in first 24 h, and MBP Z-scores in first 24 h] after adjusting for gestational age, birth weight, cesarean delivery, and 5-min Apgar score. On receiver operating characteristic curves, SBP Z-scores showed better discriminative ability than DBP and MBP to identify non-survivors., Conclusions: Neonates with culture-proven and clinical sepsis had comparable BP Z-scores except low DBP and MBP in the initial few hours in culture-proven sepsis. BP in initial 54 h of sepsis was significantly associated with in-hospital mortality. SBP discriminated non-survivors better than DBP and MBP., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Aim: (i) To compare perfusion index (PI) and plethysmography variability index (PVI) between neonates with proven or probable sepsis versus no-sepsis, (ii) to examine an association of PI and PVI with in-hospital mortality., Methods: We enrolled neonates with clinically presumed sepsis. Culture-proven or probable sepsis were categorised as 'cases' and no-sepsis as 'controls'. PI and PVI were recorded hourly for 120 h and averaged in 20-time epochs (0-6 h to 115-120 h)., Results: We analysed 148 neonates with sepsis (proven sepsis = 77, probable sepsis = 71) and 126 with no-sepsis. Neonates with proven/probable sepsis and no-sepsis had comparable PI and PVI values. Among 148 neonates with sepsis, 43 (29%) died. Non-survivors had significantly lower PI values than survivors (mean difference 0.21 [95% CI 0.14-0.29], p-value <0.001). PI had a significant but modest discriminative ability to identify non-survivors. However, PI did not independently predict mortality., Conclusion: Neonates with proven/probable sepsis and no-sepsis had comparable PI and PVI values in the first 120 h of sepsis. PI but not PVI values were significantly lower in non-survivors than survivors. PI did not independently predict in-hospital mortality. Due to modest discriminative ability, PI should be interpreted along with other vital signs to take clinical decisions., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to allergen-induced skin reactions supports that skin mast cell IgE receptor activation is also involved in CSU. Accumulating evidence also supports a role for blood basophils in disease expression. Blood basopenia is noted in active CSU disease with the recruitment of blood basophils to skin lesion sites. Blood basophils further display altered IgE receptor mediated degranulation patterns in two phenotypes that improve in remission. In active CSU subjects, changes in IgE receptor signaling molecule expression levels accompany the altered degranulation function in blood basophils. The success of therapies targeting IgE in CSU patients have also shown that altered blood basophil phenotypes and enumeration have potential use as a disease biomarker., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Apart from aerosols, contaminated surfaces with SARS-CoV-2 virus are the significant carriers of virus transmission. The disinfection and sanitization of the indoor and outdoor places are one among the powerful and effective strategies to avoid the surface-to-human transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) through frequent touch and physical contact. Electrostatic spraying is one of the effective and efficient methods to apply the liquid-based sprays on surfaces to be disinfected or sanitized. This technique covers the directly exposed and obscured surfaces uniformly and reaches to hidden areas of the target. In this paper, the design and performance parameters of a motorized pressure-nozzle based handheld electrostatic disinfection device were optimized and the chargeability of ethanol (C2H5OH), formaldehyde (CH2O), glutaraldehyde (C5H8O2), hydrogen peroxide (H2O2), phenol (C6H5OH) and sodium hypochlorite (NaClO) has been critically investigated. The chargeability indicator for disinfectants was presented in terms of the charge-to-mass ratio. The significant value of the charge-to-mass ratio of 1.82 mC/kg was achieved at an applied voltage of 2.0 kV, the liquid flow rate and pressure of 28 ml/min and 5 MPa, respectively. The experimental results are well aligned to the proposed theoretical context., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chauhan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with workers' compensation (WC) insurance claims are often shown to experience inferior patient-reported outcomes (PROs) after an orthopaedic surgical intervention compared with patients without WC claims., Purpose: To compare the postoperative PROs of patients with WC claims (WC patients) versus those without WC claims (non-WC patients) after proximal hamstring repair (PHR)., Study Design: Cohort study; Level of evidence, 3., Methods: WC patients who underwent PHR between November 2011 and to September 2020 were propensity score matched at a 1:2 ratio to non-WC patients according to age, sex, and body mass index. Comorbidity data were collected as well as minimum 1-year postoperative PRO scores for the Lower Extremity Functional Scale (LEFS), the Hip Outcome Score (HOS), and the 12-Item Short From Health Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS). The type of work was characterized according to national WC insurance guidelines as light (maximum 20 lbs [9.1 kg]), medium (maximum 50 lbs [22.7 kg]), or heavy (≥50 lbs) [>/=22.7 kg]., Results: A total of 30 patients (10 WC and 20 non-WC) were included. The work type and baseline demographic characteristics of patients did not differ between groups. There were no significant between-group differences in postoperative PRO scores as measured by the LEFS ( P = .488), HOS ( P = .233), or SF-12 PCS ( P = .521). However, the WC cohort showed inferior SF-12 MCS scores compared with the non-WC group (49.28 ± 9.97 vs 54.26 ± 9.69, respectively; P = .032). The WC status was also associated with an increased time needed for patients to return to full-duty work capacity (21 ± 9 vs 9 ± 8 weeks; P = .005)., Conclusion: Our findings suggest that WC and non-WC patients who undergo PHR have comparable outcomes. Differences in SF-12 MCS scores and return to work time for full-duty capacity warrant further investigation., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: S.S.S. has received grant support from Arthrex and education payments from Kairos Surgical, Liberty Surgical, and Smith & Nephew. S.L.M. has received education payments from Arthrex and Kairos Surgical and has an ownership or investment interest in Anika Therapeutics. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

A 56-year-old man with well-controlled human immunodeficiency virus, anxiety, depression, and hypercholesterolemia developed acute urticaria, lip angioedema, and respiratory distress after consumption of a cheeseburger, French fries, lemonade, and ibuprofen. He was evaluated in the emergency department and, during admission, developed asystole, diaphoresis, pallor, and a brief episode of posturing that was treated with two doses of epinephrine. Results of the initial workup with electrocardiogram, troponin, complete blood cell count, and comprehensive metabolic panel were normal. He was subsequently evaluated by an allergist for further recommendations.

An ultrasound assisted solid phase extraction method using rotating cigarette filter is developed herein to preconcentrate and determine trace amount of bisphenol in source and drinking water. Qualitative and quantitative measurements were performed using high-performance liquid chromatography coupled with ultra violet detector. Sorbent-analyte interactions were thoroughly investigated computationally and experimentally using molecular dynamics simulations; and attenuated total reflectance Fourier transform infrared spectroscopy, and Raman spectroscopy, respectively. Various extraction parameters were investigated and optimized. Under the optimal conditions, the results were linear in a low scale range of 0.01-55 ng/mL with correlation coefficient of 0.9941 and a low limit of detection (0.04 ng/mL, signal/noise = 3:1). A good precision (intra-day relative standard deviation ≤ 6.05%, inter-day relative standard deviation ≤ 7.12%) and recovery (intra-day ≥ 98.41%, inter-day ≥ 98.04%)) are obtained. Finally, the proposed solid phase extraction method offered a low cost, simple, fast, and sensitive analytical method to determine trace amount of bisphenol A in source and drinking water samples with chromatographic detection., (© 2023. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Computationally and spectroscopically assisted analytical comparative investigation into the extraction of bisphenol A using three cyclodextrins, that is, α, β, and γ respectively, were performed. A simple, self-tailored μ-solid-phase extraction podium was used to extract bisphenol A from water samples, and high-performance liquid chromatography-ultraviolet was used for the qualitative and quantitative analysis of bisphenol A. Density functional theory first principle calculations, attenuated total reflectance Fourier-transform infrared spectroscopy and Fourier-transform Raman spectroscopy data supports the analytical selection of β-cyclodextrin as the adsorbent for bisphenol A extraction. Analytical optimization of various parameters including sample volume, sample pH, eluting solvent and its volume was performed to discover the most proper conditions for maximum extraction. Under the optimized conditions, a limit of detection value of 0.70 ng/ml and a limit of quantification value of 2.31 ng/ml was achieved with β-cyclodextrin, with recovery (%) values over 98.40-102.50 in real source water samples. Overall, well assisted by comprehensive computational and spectroscopic studies, a novel, simple, sensitive and economic analytical method was developed for the extraction of bisphenol A from source water using cyclodextrin., (© 2023 Wiley-VCH GmbH.)

We aimed to assess the risk factors, clinical features and microbial profiles of meningitis in neonates with suspected sepsis referred to a pediatric emergency. Over 13 months, 191 neonates were enrolled, of whom 64 (33.5%) had meningitis. There were no significant differences in risk factors or clinical features between infants with and without meningitis. Ninety-three neonates (49%) had culture-positive sepsis (109 isolates). Candida spp. (n = 29), coagulase-negative staphylococci (n = 28) and Klebsiella pneumoniae (n = 23) were the most common pathogens. Forty-one (53%) bacteria were multidrug resistant., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To validate Grobman's nomogram for prediction of trial of labour after caesarean section (TOLAC) success in the Indian population., Methods: A prospective observational study of women with previous lower segment caesarean sections (LSCS) who were admitted for TOLAC between January 2019 and June 2020 at a tertiary care hospital We compared the Grobman's predicted VBAC success probability to the observed VBAC rate in the study population and devised a receiver-operator characteristics (ROC) curve for the nomogram., Results: Among the 124 women with prior LSCS who chose TOLAC and were included in the study, 68 (54.8%) had a successful VBAC and 56 (45.2%) had a failed TOLAC. The mean Grobman's predicted success probability for the cohort was 76.7%, significantly higher in VBAC women versus CS women (80.6% vs. 72.1%; p 0.001). The VBAC rate was 69.1% with a predicted probability of > 75% and only 42.9% with a probability of 50%. Women in the > 75% probability group had a nearly similar observed and predicted VBAC rate (69.1% vs. 86.3%; p = 0.002), and a greater number of women in the 50% probability group had successful VBAC than predicted (42.9% vs. 39.5%; p = 0.018). The area under the ROC curve for the study was 0.703 (95% CI 0.609-0.797; p 0.001). Grobman's nomogram had a sensitivity of 57.35%, a specificity of 82.14%, a positive predictive value (PPV) of 79.59%, and a negative predictive value (NPV) of 61.33% at a predicted probability cut-off of 82.5%., Conclusions: Women who had a higher Grobman's predicted probability had greater VBAC success rates than those with low predicted probability scores. The prediction ability of the nomogram was highly accurate at higher predicted probabilities, and even at lower predicted probabilities, women did have good odds of delivering vaginally., Competing Interests: No conflict of interest., (© 2023 The Authors.)

Protein aggregation is an obstacle for the development of new biopharmaceuticals, presenting challenges in shipping and storage of vital therapies. Though a variety of materials and methods have been explored, the need remains for a simple material that is biodegradable, nontoxic, and highly efficient at stabilizing protein therapeutics. In this work, we investigated zwitterionic polypeptides prepared using a rapid and scalable polymerization technique and conjugated to a supramolecular macrocycle host, cucurbit[7]uril, for the ability to inhibit aggregation of model protein therapeutics insulin and calcitonin. The polypeptides are based on the natural amino acid methionine, and zwitterion sulfonium modifications were compared to analogous cationic and neutral structures. Each polymer was end-modified with a single cucurbit[7]uril macrocycle to afford supramolecular recognition and binding to terminal aromatic amino acids on proteins. Only conjugates prepared from zwitterionic structures of sufficient chain lengths were efficient inhibitors of insulin aggregation and could also inhibit aggregation of calcitonin. This polypeptide exhibited no cytotoxicity in human cells even at concentrations that were five-fold of the intended therapeutic regime. We explored treatment of the zwitterionic polypeptides with a panel of natural proteases and found steady biodegradation as expected, supporting eventual clearance when used as a protein formulation additive.

Background: This study sought to determine whether range of motion (ROM) of the ankle and subtalar joint complex (STJ) is correlated with ankle injuries in National Basketball Association (NBA) G-league and collegiate basketball players to identify an at-risk population that may benefit from participation in an ankle injury prevention program., Methods: This prospective cohort study encompassed 103 player-seasons (68 collegiate, 35 NBA G-League). Patient demographics, passive ankle and STJ range of motion measurements, anterior drawer, and talar tilt tests were collected at preseason physicals along with plain radiographs. Subtalar eversion and inversion measurements were added to assess the Combination Motion (CM) of the STJ and subtracted to calculate the Subtalar Difference (SD). We defined the ratio of CM to SD as Subtalar Mobility Index (SMI=CM/SD)., Results: Twenty-one ankle injuries occurred with 10 405 player exposures yielding an incidence of 2.11/1000 exposures, resulting in 113 days of missed playing time. No direct measures of ankle, subtalar, or combined motion were associated with risk of injury, rejecting our original hypothesis that increased STJ ROM would predispose to ankle injuries. However, we did find that athletes with CM >16 degrees in combination with either SD <6 degrees ( P = .025) or SMI >3.75 ( P = .032) were nearly 3 times more likely to have an ankle injury (3.14 vs 2.97, respectively)., Conclusion: Using the predictive subtalar mobility thresholds found in this study may help identify at-risk players that may benefit from targeted ankle injury prevention programs., Level of Evidence: Level II, prospective cohort study.

Background: There are no established clinical or laboratory markers of preload adequacy and fluid responsiveness in management of neonatal shock. Functional echocardiographic preload markers are evaluated in children and adults, but there is no data in neonatal septic shock. We evaluated five functional echocardiographic preload markers during intravenous volume resuscitation in neonatal septic shock., Objective: (1) To compare baseline functional echocardiographic preload markers between neonates with septic shock and their "matched" healthy controls. (2) To compare echocardiographic preload markers before and after intravenous volume resuscitation., Methods: In this cohort study, we enrolled neonates with septic shock (cases) and recorded five preload markers - inferior vena cava collapsibility index (IVC-CI), left ventricular end-diastolic (LVEDV) & end-systolic volume (LVESV) and their indices (LVEDVI, LVESVI) - before initiation of intravenous fluid resuscitation (baseline evaluation). An equal number of "matched hemodynamically stable" controls were recruited, who underwent functional echocardiographic assessment once. In neonates with shock, we recorded these markers again after volume resuscitation., Results: We analyzed 46 neonates (23 cases and 23 controls). Neonates with shock had significantly elevated baseline IVC-CI as compared to controls [53% (21, 100) vs. 20% (15, 24) respectively, p -value = .01). Rest 4 echocardiographic markers (LVEDV, LVESV, LVEDVI, and LVESVI) were comparable between cases and controls. Sixteen neonates (70% of 23) received intravenous fluid resuscitation and rest 7 (30%) were started directly on vasoactive drugs. None of the preload markers changed significantly after volume resuscitation as compared to the baseline values including IVC-CI, which was almost significant [74% (33, 100) at baseline to 48% (13, 93) after 10 mL/kg and 50% (40, 69) after 20 mL/kg, ( p  = .05). All preload markers were comparable between survivors and non-survivors., Conclusion: Neonates with septic shock had significantly elevated IVC-CI at baseline as compared to hemodynamically stable neonates. None of the preload markers changed significantly after volume resuscitation as compared to the baseline values including IVC-CI, which was almost significant.

Treatment of chronic spontaneous urticaria (CSU) is responsive to H1 antihistamines administered up to four times the recommended US Food and Drug Administration dose in approximately 50% of patients. However, when patients do not respond to these first-line agents, evidence-based guidelines using Grading of Recommendations, Assessment, Development, and Evaluations methodology have provided direction for second- and third-line treatments that can effectively treat patients with CSU. Some patients remain refractory to these advanced treatments; therefore, alternative treatments with a lower certainty of evidence may be necessary. Regardless of the therapies used to treat CSU patients, it is essential for clinicians to be knowledgeable about the mechanism of action, efficacy, and safety and monitoring recommendations of the treatments prescribed. This review provides a comprehensive review of the adverse effects and monitoring recommendations for agents in use for CSU treatment as well as those currently undergoing investigation for CSU treatment., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: CT-P39 is being developed as a biosimilar of reference omalizumab. This study aimed to assess the pharmacokinetic equivalence of CT-P39 to European Union-approved and United States-licensed reference omalizumab (EU- and US-omalizumab, respectively)., Methods: This two-part, randomised, parallel-group, double-blind Phase 1 trial (NCT04018313) was conducted in healthy individuals with a total immunoglobulin E (IgE) level ≤100  international units (IU)/ml at screening. In part 2, described herein, participants were randomised (1:1:1) to receive a single 150 mg subcutaneous dose of CT-P39, EU-omalizumab, or US-omalizumab. The primary endpoint was pharmacokinetic equivalence in terms of area under the concentration-time curve (AUC) from time zero to the last quantifiable concentration (AUC 0-last ), AUC from time zero to infinity (AUC 0-inf ), and maximum serum concentration (C max ). Equivalence was concluded if 90% confidence intervals (CIs) of the geometric least-squares means ratios were contained within the predefined 80%-125% equivalence margin. Additional pharmacokinetic parameters, pharmacodynamics, safety, and immunogenicity were also evaluated., Results: Overall, 146 participants were randomised (CT-P39, N = 47; EU-omalizumab, N = 49; US-omalizumab, N = 50). For all primary pharmacokinetic parameters, 90% CIs for pairwise treatment comparisons were within the 80%-125% equivalence margin, demonstrating pharmacokinetic equivalence. Decreases in free IgE and increases in total IgE serum concentrations were comparable across groups. CT-P39 was well tolerated. Safety endpoints were comparable across groups: there were no treatment-related serious adverse events, deaths, or discontinuations due to treatment-emergent adverse events., Conclusions: CT-P39 was well tolerated and demonstrated pharmacokinetic equivalence with EU-omalizumab and US-omalizumab following administration of a single dose in healthy individuals., (© 2022 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Total anomalous pulmonary venous connection (TAPVC) is an uncommonly encountered cyanotic congenital heart disease characterized by anomalous drainage of the pulmonary veins. Concomitant venous anomalies are rarely found in these patients. We present a case of an infra-cardiac TAPVC with an intrahepatic portosystemic shunt, where a vascular channel was seen between the middle hepatic vein and the left branch of the portal vein with fusiform dilatation of the latter, diagnosed on computed tomography angiography., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Pediatric Cardiology.)

Introduction: This study aims at observing placental pathologies in COVID-19 infected women, and analyzing its impact on pregnancy outcome., Method: This is a descriptive-analytical study done at a tertiary centre of Northern India. All COVID-19 positive pregnant women with gestational age ≥20 weeks, with placental histopathological reporting, were included in this study. A total of 173 COVID-19 pregnant women were included in the study., Results: Placental abnormalities were noticed in 49·16% of total 179 placentae examined. Maternal vascular malperfusion (27·93%) was the most observed placental pathology followed by villous fibrin deposits (22·90%), fetal vasculopathy (16·75%), and acute inflammation (6·70%). Stillbirths were 22 and NICU admissions were seen in 50 neonates. Abnormal placental abnormalities led to higher stillbirths (p value 0·011) and lower Apgar scores at 1 and 5 min (p-value 0·028; p-value 0·002, respectively). Intervillous fibrin deposits had higher risk associated with lower Apgar score at 1 and 5 min [RR 2·05 (95% CI 1·21-3·48, p-value 0·010) and RR 5·52 (95% CI 2·58-11·81, p-value <0·001), respectively]. RP clot/hemorrhage was also associated with lower Apgar score at 1 and 5 min [RR 2·61 (95% CI 1·52-4·49, p-value 0·002) and RR 3.54 (95% CI 1·66-7·55, p-value 0·001), respectively]., Discussion: Placental abnormalities in COVID-19 infection were associated with significant higher incidence of unexplained stillbirths, and lower Apgar scores. Although, this is the largest descriptive-analytical study done so far, comparative studies are required to draw a clear conclusion regarding the impact of COVID-19 infection on human placenta and its effect on pregnancy outcomes., Competing Interests: Declaration of competing interest We declare no conflict of interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)