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Matthew Silverman,1 Nicholas Zwolinski,1 Ethan Wang,2 Nishita Lockwood,1 Michael Ancuta,1 Evan Jin,1 Jinlei Li1 1Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA; 2Yale University School of Medicine, New Haven, CT, USACorrespondence: Jinlei Li, Yale University School of Medicine, Department of Anesthesiology, 333 Cedar Street, P.O. Box 208051, New Haven, CT, 06520-8051, USA, Email Jinlei.li@yale.eduIntroduction: With the current surge on peripheral nerve blocks in post-cesarean pain management and the historical lack of unequivocal evidence supporting its universal use, this review intended to re-examine the extended scope of literature on regional anesthesia and postoperative analgesia in low-transverse cesarean section.Methods: A literature search was conducted up to April 2023 using PubMed to identify articles relevant to our search words “cesarean section”, “neuraxial morphine”, “post-cesarean analgesia”, as well as the name of each individual nerve block. The literature search was ultimately narrowed to systematic reviews and randomized controlled trials published between 2012 and 2023. We define, describe, and discuss the evidence surrounding each individual regional anesthetic technique in the presence and absence of intrathecal morphine, which is used as the gold standard when appropriate.Results: In the absence of neuraxial morphine, all regional anesthetic techniques have some level of analgesic benefit in the post-cesarean analgesia. Transversus Abdominis Plane blocks continue to have the most studies in their use. Newer fascia plane blocks including the anterior Quadratus Lumborum, and Erector Spinae Plane blocks provide significant analgesia. In addition, direct comparison among peripheral nerve blocks consistently favors the more proximal, centralized techniques. Conversely, in the presence of neuraxial morphine, no peripheral anesthetic technique has reliably and reproducibly demonstrated an added analgesic benefit regardless of the peripheral nerve block technique or location of local anesthetic injection in the post-cesarean population.Conclusion: Neuraxial morphine continues to be the gold standard for post-cesarean section analgesia, the benefit of additional single injection regional anesthetic is currently not evidence supported. In cases where neuraxial opioids have not or cannot be given, there is overwhelming evidence that regional anesthetic techniques improve post-cesarean section analgesia and decrease post-operative opioid consumption. Even though there is no consensus on the optimal peripheral nerve block, emerging evidence suggests more centralized abdominal fascia plane block trends towards better analgesia.Keywords: cesarean section, peripheral nerve block, neuraxial morphine, erector spinae plane block, quadratus lumborum block, transversus abdominis plane block

We present an overview of the performance of the Neutralized Drift Compression Experiment-II (NDCX-II) accelerator at Berkeley Lab, and report on recent target experiments on beam-driven melting and transmission ion energy loss measurements with nanosecond and millimeter-scale ion beam pulses and thin tin foils. Bunches with around 1011 ions, 1 mm radius, and 2-30 ns full width at half maximum duration have been created with corresponding fluences in the range of 0.1-0.7 J/cm2. To achieve these short pulse durations and mm-scale focal spot radii, the 1.1 MeV [megaelectronvolt (106 eV)] He+ ion beam is neutralized in a drift compression section, which removes the space charge defocusing effect during final compression and focusing. The beam space charge and drift compression techniques resemble necessary beam conditions and manipulations in heavy ion inertial fusion accelerators. Quantitative comparison of detailed particle-in-cell simulations with the experiment plays an important role in optimizing accelerator performance.

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by the abrupt onset of significant obsessive-compulsive symptoms (OCS) and/or severe food restriction, together with other neuropsychiatric manifestations. An autoimmune pathogenesis triggered by infection has been proposed for at least a subset of PANS. The older diagnosis of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) describes rapid onset of OCD and/or tics associated with infection with Group A Streptococcus. The pathophysiology of PANS and PANDAS remains incompletely understood. We recently found serum antibodies from children with rigorously defined PANDAS to selectively bind to cholinergic interneurons (CINs) in the striatum. Here we examine this binding in children with relapsing and remitting PANS, a more heterogeneous condition, collected in a distinct clinical context from those examined in our previous work, from children with a clinical history of Streptococcus infection. IgG from PANS cases showed elevated binding to striatal CINs in both mouse and human brain. Patient plasma collected during symptom flare decreased a molecular marker of CIN activity, phospho-riboprotein S6, in ex vivo brain slices; control plasma did not. Neither elevated antibody binding to CINs nor diminished CIN activity was seen with plasma collected from the same children during remission. These findings replicate what we have seen previously in PANDAS and support the hypothesis that at least a subset of PANS cases have a neuroimmune pathogenesis. Given the critical role of CINs in modulating basal ganglia function, these findings confirm striatal CINs as a locus of interest in the pathophysiology of both PANS and PANDAS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Pittenger has served as a consultant and received research funding in the past year for Biohaven Pharmaceuticals, Transcend Therapeutics, Ceruvia Lifesciecnes, Freedom Biosciences, and Nobilis Therapeutics, and royalties from Oxford University Press, all for work unrelated to the current results. He is an inventor on a patent applications related to the use of neurofeedback and of psychedelic drugs for the treatment of OCD, also unrelated to this work. Dr. Che has received research funding from Duraviva Pharma for work unrealted to the current results. All other authors report no competing interests. The authors have declared that no conflict of interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population., Methods: We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 10 11 colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24., Results: A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction-based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; P = .0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; P = .0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups., Conclusions: CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (ClinicalTrials.gov, Number NCT03110133)., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Importance: In the US and Canada, women comprise approximately one-third of people who inject drugs (PWID); however, clinical characteristics and outcomes of injection drug use complications in women are poorly described., Objective: To identify clinical characteristics and outcomes of infective endocarditis (IE) among women who inject drugs (WWID)., Design, Setting, and Participants: This is a retrospective cohort study of PWID with definite IE (per 2023 Duke-International Society for Cardiovascular Infectious Diseases criteria) admitted from April 5, 2007, to March 15, 2018, at 5 tertiary-care hospitals in London, Ontario, and Regina, Saskatchewan, Canada. Data were analyzed from June 1, 2023, to August 2, 2024. Descriptive analyses were conducted for baseline characteristics at index hospitalization and stratified by sex., Main Outcomes and Measures: The primary outcome was the difference in 5-year survival between female and male PWID with IE. The secondary outcome was 1-year survival. Multivariable time-dependent Cox proportional hazards regression analyses were conducted for variables of clinical importance to evaluate 5-year mortality., Results: Of 430 PWID with IE, 220 (51.2%) were women; of 332 non-PWID with IE, 101 (30.4%) were women. WWID with IE were younger than men (median [IQR] age, 31.5 [27.0-38.5] vs 38.5 [31.0-49.0] years), and 11 of 220 (5.0%) were pregnant at index hospitalization, although only 12 of 220 (5.5%) had contraceptive use documented. Women had a larger proportion of right-sided IE than men (158 of 220 women [71.8%] vs 113 of 210 men [53.8%]). WWID living in urban areas had higher mortality than WWID in rural areas (adjusted hazard ratio [aHR], 2.70; 95% CI, 1.15-6.34; P = .02). Overall mortality was lower among PWID referred for substance use disorder counseling in centers with inpatient services compared with centers with only outpatient referrals (aHR, 0.29; 95% CI, 0.17-0.51; P < .001). Overall mortality was lower with right-sided heart disease for both women (aHR, 0.44; 95% CI, 0.27-0.71; P < .001) and men (aHR, 0.22; 95% CI, 0.10-0.50; P < .001) and was higher with congestive heart failure for both women (aHR, 2.32; 95% CI, 1.29-4.18; P = .005) and men (aHR, 1.73; 95% CI, 1.07-2.79; P = .02)., Conclusions and Relevance: In this cohort of PWID with IE, women were overrepresented. Reasons for women's disproportionately high IE incidence need further study. Inpatient substance use disorder services, contraception counseling, and enhanced social support for WWID living in urban areas need to be prioritized.

A public health approach to suicide prevention recognises the powerful influence of social determinants. In this paper-the fifth in a Series on a public health approach to suicide prevention-we consider four major risk factors for suicide (alcohol use, gambling, domestic violence and abuse, and suicide bereavement) and examine how their influence on suicide is socially determined. Cultural factors and societal responses have an important role in all four risk factors. In the case of alcohol use and gambling, commercial entities are culpable. This Series paper describes a range of universal, selective, and indicated interventions that might address these risk factors, and focuses particularly on key universal interventions that are likely to yield substantial population-level benefits., Competing Interests: Declaration of interests JP holds a National Health and Medical Research Council Investigator Grant (number 1173126) that provides salary support and research costs. She is also Scientific Adviser to Australia's National Suicide Prevention Office, which is developing the new National Suicide Prevention Strategy. DK declares salary support and research costs from the Wellcome Trust, the Centre for Pesticide Suicide Prevention, and the American Foundation for Suicide Prevention and research costs from the National Institute of Health Research. JR holds a National Health and Medical Research Council Investigator Grant (number 2008460) that provides salary support and research costs. She is a member of the Expert Advisory Group to Australia's National Suicide Prevention Office, which is developing the new National Suicide Prevention Strategy. She is also a member of Meta's suicide and self-injury global advisory group. KH is a member of the National Suicide Prevention Strategy for England Advisory Group. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Economic circumstances and related factors, including unemployment and poverty, can have substantial effects on suicide rates. This relationship applies in all countries, irrespective of their World Bank income status or level of development. Therefore, means of mitigating such influences are essential components of strategies to reduce suicides. In this Series paper, we consider examples of such initiatives, including national policies to try to reduce the effect of economic downturns, efforts to maintain employment and avoid damaging austerity measures, maintenance of reasonable minimum wage levels, and specific policies to assist those most affected by poverty. We also highlight upstream measures such as investment in transport infrastructure, industries, and retraining programmes. Positive public health messaging that encourages coping, together with discouragement of media stories with messages that could contribute to hopelessness in those experiencing economic difficulties, can also be important components of strategies to try to reduce the effect of economic downturn on suicide., Competing Interests: Declaration of interests MSin receives research salary support from the University of Toronto and Sunnybrook Health Sciences Centre. MSil has received payment for expert testimony not related to any of the topics covered in this manuscript and has participated on advisory boards not related to any of the topics covered in this manuscript. JP holds a National Health and Medical Research Council Investigator Grant (1173126), which provides salary suport and research costs; and is scientific adviser to Australia's National Suicide Prevention Office, which is developing the new National Suicide Prevention Strategy. KH is a member of the National Suicide Prevention Strategy for England Advisory Group., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Suicide is prevalent in all countries and is largely preventable. The causes of suicide are multiple and varied. Social determinants of suicide are crucial, but to date these have received insufficient policy attention. This paper, which is the first in a Series on taking a public health approach to suicide prevention, argues for a major change in the way we think about suicide and its prevention. This Series paper presents a public health model that emphasises the broad social determinants of suicide and describes a framework through which these might be addressed. We argue for a policy reset that would take national suicide prevention strategies to the next level. Such policies would become whole-of-government endeavours that tackle major social determinants of suicide at their source. We also argue that high-quality data and methodologically rigorous evaluation are integral to this public health approach., Competing Interests: Declaration of interests JP holds a National Health and Medical Research Council Investigator grant (number 1173126), which provides salary support and research costs. She is also scientific adviser to Australia's National Suicide Prevention Office, which is developing the new National Suicide Prevention Strategy. MS has received payment for expert testimony not related to any of the topics covered in this manuscript and has participated on advisory boards not related to any of the topics covered in this manuscript. KH is a member of the National Suicide Prevention Strategy for England Advisory Group. RD and MK declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI., Objective, Design, and Patients: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities., Methods: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24., Results: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression., Conclusions: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients., Trial Registration: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141., (© 2024. The Author(s).)

Objectives : This quality improvement (QI) project was to lean the process for managing critical high and low glucose levels in the hospice unit and to simplify the pharmacologic options for hypoglycemic management for nursing staff. Methods : The process for developing and refining the recommendations involved a modified Delphi approach with a team of key stakeholders with overlapping expertise in hospice care practice. Recommendations were based on literature review, judgement of experts, and clinical experience. Stakeholders ranked six potential solutions and two were prioritized within the scope of this project. Results : From 1/1/21 - 12/31/21, there were 48 veterans with insulin sliding scale orders in the hospice unit, of which there were six critical values acted on. A standard operating procedure (SOP) for the management of critical glucose values in hospice was developed based on updated processes. In addition, hospice patient specific insulin sliding scale order sets were created and endorsed for utilization and dissemination. Following implementation on 3/1/22, no critical values were found in the hospice unit from 3/1/22 - 6/1/22 during the sustainment period. Conclusions : The implementation of hospice insulin sliding scale order sets and SOP on the management of critical glucose values in hospice reduced the number of critical glucose values., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Docusate sodium's efficacy is widely debated. Several studies on opioid induced constipation (OIC) concluded that docusate sodium vs either placebo or in combination with sennosides provided no benefit., Objective: This medication use evaluation aimed to investigate constipation treatment trends within the West Palm Beach VA Healthcare System Community Living Center, and to assess the therapeutic effectiveness of docusate sodium., Methods: This was a retrospective review of data extracted from April 1, 2022, to September 30, 2022. Patients were included if they had oral orders for docusate sodium, sennosides, lactulose, and/or polyethylene glycol. Patients without active bowel regimen medications were excluded. Requirements for rescue constipation medication was evaluated., Results: A total of 98 patients were reviewed. Docusate sodium was used in 43% (n = 42/98) of patients. Rescue medications were needed in 58% (n = 22/38) of patients receiving oral docusate sodium. 52% (n = 29/56) of patients without docusate sodium required rescue medications. For OIC treatment, when docusate sodium was added to other bowel regimens, 59% (n = 17/29) of patients needed a rescue medication, while 66% (n = 19/29) of patients without docusate sodium required a rescue medication. Patients on morphine were given the greatest quantity of rescue constipation medications (73%, n = 16/22)., Conclusion: Oral docusate sodium did not reduce the requirement for rescue constipation medications in the WPB VAHCS CLC population. When evaluating constipation treatment, docusate sodium may supply minimal benefit and could be identified as nonessential for deprescribing efforts. Morphine was the most constipating opioid used in this patient population, requiring more aggressive bowel regimens., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: A significant proportion of patients with advanced heart failure present with dilated left ventricles and functional mitral regurgitation. These patients currently have limited treatment options. The MitraClip device (Abbott) has benefited only patients with smaller left ventricles (end-diastolic dimension <70 mm), whereas those with larger left ventricles did not benefit. A possible explanation is correcting functional mitral regurgitation alone may not adequately reduce the wall stresses of a dilated left ventricle. We have developed a beating-heart device that not only approximates the papillary muscles to reduce functional mitral regurgitation but also modifies the left ventricle size and shape to reduce wall stress., Methods: Yorkshire swine (n = 16) had a myocardial infarction induced by permanent occlusion of the left circumflex with intracoronary ethanol. Three months later, the animals developed heart failure and moderate or greater functional mitral regurgitation. Through a transapical approach, the new device was implanted under echocardiography guidance to reshape the left ventricle and correct functional mitral regurgitation. The acute impact of this approach on the mitral valve and left ventricle was assessed with echocardiography and invasive hemodynamics., Results: After reshaping, echocardiography showed a decrease in end-diastolic volume by 36.3 ± 30.5 mL (P < .001), a decrease in sphericity index by 0.143 ± 0.087 (P < .001), and an increase in ejection fraction of 5.90% ± 6.38% (P < .01). Mitral valve tenting area was reduced by 39.29 ± 33.66 mm 2 (P < .001), coaptation length was increased by 2.12 ± 1.02 mm (P < .001), and posterior excursion angle was improved by 9.07° ± 9.14° (P < .01), resulting in functional mitral regurgitation reduction., Conclusions: Correction of functional mitral regurgitation with favorable changes in mitral valve geometry and reduction in left ventricle geometry is possible with the proposed device., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate 131 I-apamistamab with conventional care., Methods: SIERRA (ClinicalTrials.gov identifier: NCT02665065) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an 131 I-apamistamab-led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the 131 I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131 I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population., Results: The ITT population included 153 patients ( 131 I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131 I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131 I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring 131 I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131 I-apamistamab and conventional care groups, respectively., Conclusion: The 131 I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131 I-apamistamab was well tolerated and could address an unmet need in this population.

Background: Unnecessary antibiotic prescriptions in primary care are common and contribute to antimicrobial resistance in the population. Audit and feedback (A&F) on antibiotic prescribing to primary care can improve the appropriateness of antibiotic prescribing, but the optimal approach is uncertain. We performed two pragmatic randomized controlled trials of different approaches to audit and feedback. The trial results showed that A&F was associated with significantly reducing antibiotic prescribing. Still, the effect size was small, and the modifications to the A&F interventions tested in the trials were not associated with any change. Herein, we report a theory-informed qualitative process evaluation to explore potential mechanisms underlying the observed effects., Methods: Ontario family physicians in the intervention arms of both trials who were sent A&F letters were invited for one-on-one interviews. Purposive sampling was used to seek variation across interested participants in personal and practice characteristics. Qualitative analysis utilized inductive and deductive techniques informed by the Clinical Performance Feedback Intervention Theory., Results: Modifications to the intervention design tested in the trial did not alter prescribing patterns beyond the changes made in response to the A&F overall for various reasons. Change in antibiotic prescribing in response to A&F depended on whether it led to the formation of specific intentions and whether those intentions translated to particular behaviours. Those without intentions to change tended to feel that their unique clinical context was not represented in the A&F. Those with intentions but without specific actions taken tended to express a lack of self-efficacy for avoiding a prescription in contexts with time constraints and/or without an ongoing patient relationship. Many participants noted that compared to overall prescribing, A&F on antibiotic prescription duration was perceived as new information and easily actionable., Conclusion: Our findings indicate that contextual factors, including the types of patients and the setting where they are seen, affect how clinicians react to audit and feedback. These results suggest a need to test tailored feedback reports that reflect the context of how, where, and why physicians prescribe antibiotics so that they might be perceived as more personal and more actionable., Trial Registration: Clinical Trial registration IDs: NCT04594200, NCT05044052., (© 2024. The Author(s).)

Objectives: Portable oxygen concentrators (POCs) are medical devices that use filters to selectively remove nitrogen from ambient air to produce concentrated, medical-grade oxygen. This is the first study to evaluate a ruggedized POC's performance during simulated polytrauma intubation., Methods: Twenty-seven swine were intubated and anesthetized with ketamine. At T  = 0, animals were extubated, received a chest wall injury, a tibia fracture, and 20% total blood volume controlled hemorrhage was initiated. At T  = 10 min, the swine were pre-oxygenated using a bag-valve mask connected to one of three randomized oxygen sources: (1) a ruggedized POC, (2) a M-15 oxygen cylinder, or (3) room air (control). At T  = 12 min, animals were re-intubated to simulate polytrauma intubation and connected to the test oxygen source for the remainder of the experiment. Surviving animals entered a 2-h period where partial pressure of oxygen (PaO 2 ), oxygen saturation (SpO 2 ), and regional oxygen saturation (rSO 2 ) were monitored. Groups were compared using analysis of variance (ANOVA), Fisher's exact, log-rank analysis, or mixed-effects model as appropriate., Results: All animals survived except one in the POC group. Mixed-effects models revealed differences between groups with regards to PaO 2 ( p  < 0.0001) and SpO 2 ( p  = 0.006). Based on post hoc analysis, oxygen cylinder PaO 2 was superior to both POC and control, but there were no differences between POC and control PaO 2 . There were statistically and clinically significant differences in SpO 2 during periods of pre-oxygenation ( T  = 10‒12 min), intubation ( T  = 12‒14 min), and immediately after intubation ( T  = 14‒20 min). The POC battery was consumed in 43 ± 13 min., Conclusion: In our swine model, a single, ruggedized POC provided inferior amounts of oxygen supplementation compared to an oxygen cylinder and performed no better than room air., Competing Interests: The views expressed are those of the authors and do not reflect the official views or policy of the Department of Defense or its Components. The experiments reported herein were conducted according to the principles set forth in the National Research Council's Guide for the Care and Use of Laboratory Animals (8th ed.), and the Animal Welfare Act of 1966 as amended. The views of the manufacturers are not necessarily the official views of, or endorsed by, the U.S. Government, the Department of Defense, or the Department of the Air Force. No Federal endorsement of the manufacturer is intended., (© 2024 The Author(s). Journal of the American College of Emergency Physicians Open published by Wiley Periodicals, Inc. on behalf of American College of Emergency Physicians.)

Objective: To observe the laryngeal CT and strobe laryngoscopy signs of unilateral vocal fold hypomobility (UVFHM) in patients with well-closed glottises in the horizontal plane., Methods: A retrospective analysis was performed on 18 subjects with well-closed glottises in the horizontal plane using strobe laryngoscopy, 9 patients diagnosed with unilateral vocal fold hypomobility with an unknown etiology were enrolled in the UVFHM group, and 9 healthy matched subjects with symmetrical bilateral vocal fold movement were enrolled in the control group. Vertical plane distances of bilateral vocal folds and three-dimensional structural parameters of vocal folds were measured through laryngeal CT. Glottic insufficiency in the vertical plane and reflux findings scores (RFS) were assessed under laryngeal CT and strobe laryngoscopy. Reflux symptom index (RSI) were collected. SPSS25.0 software was used for statistical analysis., Results: The height differences in vertical plane and thicknesses of bilateral vocal folds in the UVFHM group were larger than those in the control (P < 0.05), while the length, width and subglottic convergence angle of the vocal folds were not statistically significant between the two groups (P > 0.05). In the UVFHM group, laryngeal CT showed that 77.78% of patients (7/9) had glottic insufficiency in the vertical plane, with height differences ranging from 0.3 to 1.9 mm and a mean of 0.76mm. However, strobe laryngoscopy showed that 33.33% (3/9) had glottic insufficiency in the vertical plane. The proportion of patients with glottic insufficiency in vertical plane in the UVFHM group was significantly higher than that in the control group (P < 0.05). RSI and RFS scores of the UVFHM group were higher than those of the control group (P < 0.05)., Conclusion: Glottic insufficiency in the vertical plane often occurred in patients with UVFHM with an unknown cause of hoarseness, so the presence of glottic insufficiency in the vertical plane should be considered when hoarseness is detected by clinicians. Laryngeal dynamic CT can enhance the diagnostic rate compared to strobe laryngoscopy. Unexplained UVFHM patients have higher RSI and RFS compared to control subjects, warranting further research about the relationship between UVFHM and laryngopharyngeal reflux., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We report the use of IV dalbavancin in Canadian patients using data captured by the national CLEAR registry., Methods: The CLEAR registry uses the web-based data management program, REDCap™ (online survey https://rcsurvey.radyfhs.umanitoba.ca/surveys/?s=TPMWJX98HL) to facilitate clinicians entering details associated with their clinical experiences using IV dalbavancin., Results: Data were available for 40 patients. The most common infections treated were acute bacterial skin and skin structure infection (ABSSSI) (62.5% of patients), bone/joint infection (22.5%), bloodstream/vascular infection (7.5%) and endocarditis (5.0%). Dalbavancin was used as directed (75.0%) and empiric therapy (25.0%). MRSA was the most common identified pathogen (70.0%). Dalbavancin was used both in outpatient (e.g., emergency department) (65.0%), and inpatient treatment settings (e.g., hospital ward) (35.0%). Dalbavancin was used due to the convenience of a single dose treatment (77.5%) as well as to facilitate hospital discharge (7.5%). Dalbavancin was primarily used alone (90.0%), and most commonly using a single 1500 mg dose (77.5%). Microbiological success (pathogen eradicated or presumed eradicated) occurred in 88.2% of known cases, while clinical success (cure and/or improvement) occurred in 93.3% of known cases. No adverse events were reported., Conclusions: In Canada, IV dalbavancin is used as both directed and empiric therapy to treat ABSSSI as well as off-label (bone/joint, bacteremia/vascular, endocarditis, device-related) infections. It is used in both outpatient and inpatient settings due primarily to its convenience as a single-dose treatment regimen and to facilitate early hospital discharge. Dalbavancin use is associated with high microbiological and clinical cure rates along with an excellent safety profile., Competing Interests: Conflict of interests GZ has received research funding from Paladin Labs., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: A3 adenosine receptor (A3AR) is overexpressed in the skin and peripheral blood mononuclear cells of psoriasis patients. We investigated the efficacy/safety of piclidenoson (CF101), an orally bioavailable A3AR agonist that inhibits IL‐17 and IL‐23 production in keratinocytes, in moderate‐to‐severe plaque psoriasis. Methods: The randomized, placebo‐ and active‐controlled, double‐blind phase 3 COMFORT‐1 trial randomized patients (3:3:3:2) to piclidenoson 2 mg BID, piclidenoson 3 mg BID, apremilast 30 mg BID or placebo. At Week 16, patients in the placebo arm were re‐randomized (1:1:1) to piclidenoson 2 mg BID, piclidenoson 3 mg BID or apremilast 30 mg BID. The primary end point was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI‐75) at Week 16 versus placebo. Results: A total of 529 patients were randomized and received ≥1 dose of study medication (safety population). The efficacy analysis population for the primary end point included 426 patients (piclidenoson 2 mg BID, 127; piclidenoson 3 mg BID, 103; apremilast, 118; placebo, 78). Piclidenoson at 2 and 3 mg BID exhibited similar efficacy. The primary end point was met with the 3 mg BID dose: PASI 75 rate of 9.7% versus 2.6% for piclidenoson versus placebo, p = 0.037. The PASI responses with piclidenoson continued to increase throughout the study period in a linear manner. At week 32, analysis in the per‐protocol population showed that a greater proportion of patients in the piclidenoson 3 mg BID arm (51/88, 58.0%) achieved improvement from baseline in Psoriasis Disability Index (PDI) compared to apremilast (59/108, 55.1%), and the test for noninferiority trended towards significance (p = 0.072). The safety/tolerability profile of piclidenoson was excellent and superior to apremilast. Conclusions: Piclidenoson demonstrated efficacy responses that increased over time alongside a favourable safety profile. These findings support its continued clinical development as a psoriasis treatment (ClinicalTrials.gov identifier: NCT03168256). [ABSTRACT FROM AUTHOR]

We present an overview of the performance of the Neutralized DriftCompression Experiment-II (NDCX-II) accelerator at Berkeley Lab, and summarizerecent studies of material properties created with nanosecond andmillimeter-scale ion beam pulses. The scientific topics being explored includethe dynamics of ion induced damage in materials, materials synthesis far fromequilibrium, warm dense matter and intense beam-plasma physics. We summarizethe improved accelerator performance, diagnostics and results of beam-inducedirradiation of thin samples of, e.g., tin and silicon. Bunches with over3x10^10 ions, 1- mm radius, and 2-30 ns FWHM duration have been created. Toachieve these short pulse durations and mm-scale focal spot radii, the 1.2 MeVHe+ ion beam is neutralized in a drift compression section which removes thespace charge defocusing effect during final compression and focusing.Quantitative comparison of detailed particle-in-cell simulations with theexperiment play an important role in optimizing accelerator performance; thesekeep pace with the accelerator repetition rate of ~1/minute.

Objectives: This study characterizes cerebral spinal fluid (CSF) indices including total protein, the albumin quotient, IgG index and oligoclonal bands in patients followed at a single center for pediatric acute-neuropsychiatric syndrome (PANS) and other psychiatric/behavioral deteriorations., Methods: In a retrospective chart review of 471 consecutive subjects evaluated for PANS at a single center, navigational keyword search of the electronic medical record was used to identify patients who underwent lumbar puncture (LP) as part of the evaluation of a severe or atypical psychiatric deterioration. Psychiatric symptom data was ascertained from parent questionnaires and clinical psychiatric evaluations. Inclusion criteria required that subjects presented with psychiatric deterioration at the time of first clinical visit and had a lumbar puncture completed as part of their evaluation. Subjects were categorized into three subgroups based on diagnosis: PANS (acute-onset of severe obsessive compulsive disorder (OCD) and/or eating restriction plus two other neuropsychiatric symptoms), autoimmune encephalitis (AE), and "other neuropsychiatric deterioration" (subacute onset of severe OCD, eating restriction, behavioral regression, psychosis, etc; not meeting criteria for PANS or AE)., Results: 71/471 (15.0 %) of patients underwent LP. At least one CSF abnormality was seen in 29% of patients with PANS, 45% of patients with "other neuropsychiatric deterioration", and 40% of patients who met criteria for autoimmune encephalitis. The most common findings included elevated CSF protein and/or albumin quotient. Elevated IgG index and IgG oligoclonal bands were rare in all three groups., Conclusion: Elevation of CSF protein and albumin quotient were found in pediatric patients undergoing LP for evaluation of severe psychiatric deteriorations (PANS, AE, and other neuropsychiatric deteriorations). Further studies are warranted to investigate blood brain barrier integrity at the onset of the neuropsychiatric deterioration and explore inflammatory mechanisms., 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., (Copyright © 2024 Pooni, Zheng, Ma, Silverman, Xie, Farhadian, Thienemann, Mellins and Frankovich.)

Purpose: Supporting psychological well-being in persons with aphasia (PWA) can improve social and health outcomes; however, PWA and their care partners (CPs) are often not receiving mental health support. Previous research explores this from the perspective of health care professionals., Aims: The aim of this study was to examine knowledge, beliefs, and experiences related to mental health services directly from PWA and CPs., Method: The study included 11 PWA and 11 CPs. Participants completed a guided survey (virtual) with opportunities for elaboration related to the knowledge, beliefs, and experiences of mental health., Results: There was variability in personal preferences for referrals, types of coping strategies, and confidants for general thoughts and feelings and those specific to aphasia. PWA identified health care professionals as people to share thoughts and feelings, whereas CPs chose family and friends more often. Both CPs and PWA reported communication difficulty and finding a counselor as "sometimes" preventing access to services but cited fear and trust as "always" preventing access., Conclusions: Knowledge, beliefs, and experience with help-seeking and mental health services are personal and variable. Assessing barriers unique to living with aphasia, such as communication challenges and locating a suitable counselor, must also be considered within more complex and personal barriers of fear and trust that are consistently reported in the general public. Health professionals across the continuum of aphasia care need to understand the communication challenges of living with aphasia in tandem with understanding individual differences to personalize approaches to mental health services and help-seeking.

A remarkably high rate of post-transplant relapse in patients with TP53-mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT (N = 38) versus non-HSCT (N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs. 72) while patients in the non-HSCT cohort more commonly had complex karyotype with chromosome 17 aberrancy and 5q deletion (p < .01). A total of 69 TP53 variants including 64 pathogenic variants, and 5 variants of undetermined significance were detected. Nine patients (4 in HSCT and 5 in non-HSCT) had multi-hit TP53 variants. After induction: 57.9% versus 56.6% in the HSCT versus non-HSCT cohort achieved morphologic complete remission. Median time to HSCT was 6 months and median follow-up was 15.1 months for HSCT and 5.7 months for non-HSCT. Median disease-free survival (DFS) and overall survival (OS) were 11.7 and 15.9 months for HSCT, and 4.1 and 5.7 months for non-HSCT cohorts, respectively. Non-relapse mortality at 12 months was 22% versus 44% for HSCT versus non-HSCT. In the HSCT cohort, the rate of grade II-IV acute and chronic graft-versus-host disease (GVHD) was 55% and 18%, respectively. None of the patients from the non-HSCT cohort were alive while four patients from the HSCT cohort were alive, in remission, and without GVHD (GRFS) at the time of abstraction. Better treatment strategies for patients with TP53-mutated MDS/AML remain an area of unmet clinical need., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Importance: Epidemiologic studies indicate a high rate of autoimmune conditions among patients with obsessive-complusive disorder and other psychiatric conditions. Furthering the understanding of the inflammatory diatheses of psychiatric conditions may open doors to new treatment paradigms for psychiatric disorders., Objectives: To evaluate whether pediatric acute-onset neuropsychiatric syndrome (PANS) is associated with an inflammatory diathesis by assessing signs of immune activation and vasculopathy during a psychiatric symptom exacerbation (flare), estimating the risk of developing arthritis and other autoimmune diseases, and characterizing subtypes of arthritis., Design, Setting, and Participants: This retrospective cohort study used longitudinal clinical data on 193 consecutive patients with PANS followed up within the Stanford Immune Behavioral Health Clinic from September 1, 2012, to December 31, 2021., Main Outcomes and Measures: Medical records were reviewed, and a predefined set of immune markers that were measured during a flare and the features and imaging findings of arthritis and other autoimmune diseases were collected. Immune activation markers included (1) autoimmunity signs (antinuclear antibody, antihistone antibody, antithyroglobulin antibody, C1q binding assay, and complement levels [C3 and C4]); (2) immune dysregulation or inflammation signs (leukopenia, thrombocytosis, C-reactive protein, and erythrocyte sedimentation rate); and (3) vasculopathy signs (livedo reticularis, periungual redness and swelling, abnormally prominent onychodermal band, palatal petechiae, high von Willebrand factor antigen, and high d-dimer). Last, the cumulative risk of developing arthritis and autoimmune diseases was estimated using product limit (Kaplan-Meier) survival probability., Results: The study included data from 193 children (112 boys [58.0%]) who had PANS at a mean (SD) age of 7.5 (3.5) years. They were followed up for a mean (SD) of 4.0 (2.1) years. Among those tested for immune activation markers, 54.2% (97 of 179) had nonspecific markers of autoimmunity, 12.0% (22 of 184) had nonspecific signs of immune dysregulation or inflammation, and 35.8% (69 of 193) had signs of vasculopathy. By 14 years of age, the estimated cumulative incidence of arthritis was 28.3% (95% CI, 20.8%-36.3%), and the estimated cumulative incidence of another autoimmune disease was 7.5% (95% CI, 4.0%-12.4%). Novel findings in the subgroup with arthritis include joint capsule thickening (55.0% [22 of 40]), distal interphalangeal joint tenderness (81.8% [45 of 55]), and spinous process tenderness (80.0% [44 of 55]). Among the 55 patients with arthritis, the most common subtypes of arthritis included enthesitis-related arthritis (37 [67.3%]), spondyloarthritis (27 [49.1%]), and psoriatic arthritis (10 [18.2%])., Conclusions and Relevance: This study found that patients with PANS show signs of immune activation and vasculopathy during psychiatric symptom flares and have an increased risk of developing arthritis and other autoimmune diseases compared with the general pediatric population. The most common arthritis subtype was enthesitis-related arthritis. These findings suggest that PANS may be part of a multisystem inflammatory condition rather than an isolated psychiatric or neuroinflammatory disorder.

Background: Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. New-onset post-operative AF may signal an elevated risk of AF and associated outcomes in long-term follow-up. We aimed to estimate the rate of AF recurrence as detected by an implantable loop recorder (ILR) in patients experiencing post-operative AF within 30 days after cardiac surgery., Methods: We searched MEDLINE, Embase and Cochrane CENTRAL to April 2023 for studies of adults who did not have known AF, experienced new-onset AF within 30 days of cardiac surgery and received an ILR. We pooled individual participant data on timing of AF recurrence using a random-effects model with a frailty model applied to a Cox proportional hazard analysis., Results: From 8671 citations, 8 single-centre prospective cohort studies met eligibility criteria. Data were available from 185 participants in 7 studies, with a median follow-up of 1.7 (IQR: 1.3-2.8) years. All included studies were at a low risk of bias. Pooled AF recurrence rates following 30 post-operative days were 17.8% (95% CI 11.9%-23.2%) at 3 months, 24.4% (17.7%-30.6%) at 6 months, 30.1% (22.8%-36.7%) at 12 months and 35.3% (27.6%-42.2%) at 18 months., Conclusions: In patients who experience new-onset post-operative AF after cardiac surgery, AF recurrence lasting at least 30 s occurs in approximately 1 in 3 in the first year after surgery. The optimal frequency and modality to use for monitoring for AF recurrence in this population remain uncertain., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Ischemic mitral regurgitation (IMR) imposes volume overload on the left ventricle (LV), accelerating adverse LV remodeling. In this study, we sought to investigate the impact of volume overload due to IMR on regional myocardial contractile mechanics., Methods: Ten Yorkshire swine were induced with myocardial infarction (MI) by occluding the left circumflex coronary artery (LCx). Cardiac MRI was performed at baseline (BL) and 2.5 months (2.5M) post-MI. IMR was quantified with epicardial echocardiography 3 months post-MI. The animals were then assigned to 2 groups: no/mild MR (nmMR, n  = 4) and moderate/severe MR (msMR, n  = 6). MRI images were analyzed to assess infarction size, end-diastolic and end-systolic volume (EDV and ESV, respectively), ejection fraction (EF), longitudinal strain (LS), circumferential strain (CS), and systolic dyssynchrony index (SDI). The myocardial region was divided into infarction, border, and remote zones based on the LCx-supplied region., Results: There was no difference in the infarction size. Group-wise comparison of LS and CS between BL and 2.5M demonstrated that LS and CS in the infarction zone and the border zone decreased at 2.5M in both groups. However, LS and CS in the remote zone were elevated only in the msMR group (LS: -9.81 ± 3.96 vs. -12.58 ± 5.07, p  < 0.01; CS; -12.78 ± 3.81 vs. -16.09 ± 3.33, p  < 0.01) at 2.5M compared to BL. The SDI of CS was significantly elevated in the msMR group (0.1255 vs. 0.0974, p  = 0.015) at 2.5M compared to BL., Conclusions: Elevated LS and CS in the remote zone were observed in moderate/severe MR and ventricular dyssynchrony. These elevated cardiac strains, coupled with ventricular dyssynchrony, may contribute to the progression of MR, thereby accelerating heart failure., Competing Interests: MP reports stock ownership, board directorship and employment in Nyra Medical Inc. MP also received personal consulting fees from Heart Repair Technologies, and research grants from Heart Repair Technologies. MP led this work when he was at Emory University. DO received personal consulting fees from Nyra Medical Inc. The remaining 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., (© 2024 Kikuchi, Onohara, Silverman, King, Tom, Govin, Guyton and Padala.)

Methotrexate (MTX) doses on days +1, +3, +6, and +11 after match unrelated donor allogeneic stem cell transplant (MUD HSCT) is a common graft-versus-host disease (GVHD) prophylaxis regimen. However, the overlapping toxicity of MTX with conditioning chemotherapy sometimes warrants the omission of the fourth dose of MTX. Prior single-institution studies showed conflicting results comparing the outcomes of patients who received three versus four doses of MTX, but to our knowledge, the effect of concomitant antithymocyte globulin (ATG) has not been reported. Charts of patients who underwent MUD HSCT between 2009 and 2023 were reviewed. Patients received rabbit ATG (Thymoglobulin), given at 0.5 mg/kg on day -3, 2 mg/kg on day -2, and 2.5 mg/kg on day -1. MTX is given at 15 mg/m 2 on day +1 and 10 mg/m 2 on days +3, +6, and +11. Severe mucositis was the most common indication for day +11 MTX omission (82%). We identified 292 patients (116 in 3 dose cohort and 176 in 4 dose cohort). Median follow-up was 23 months (range 1-151). Patients in the 4 doses cohort were more frequently male (68% vs. 50%, p  < 0.01), received a reduced intensity conditioning regimen (38.0% vs. 22%, p  < 0.01), were older (median 58 vs. 54 years, p  = 0.02), and received a transplant in the earlier era (median HSCT year 2014 vs. 2018, p  < 0.01). A statistically significant difference was not evidenced between the cohorts for the following outcomes: acute GVHD (aGVHD) (HR 1.1, 95% CI 0.9-1.5), chronic GVHD (cGVHD) (HR 1.3, 95% CI 0.8-1.6), relapse-free survival (RFS) (HR 1.0, 95% CI 0.6-1.5), non-relapse mortality (NRM) (HR 1.4, 95% CI 0.9-2.2), and overall survival (OS) (HR 1.2, 95% CI 0.9-1.7). Both cohorts had similar median time to neutrophil engraftment at 14 days. When ATG is incorporated, omission of day +11 MTX does not significantly impact the rate of engraftment or cumulative incidence of aGVHD, cGVHD, RFS, NRM, and OS., Competing Interests: All authors declare no conflict of interest pertinent to this manuscript., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Several interventional therapies are in development to treat functional tricuspid regurgitation. Most have failed to achieve adequate efficacy, as animal models of this lesion are lacking. We developed a new image-guided technique in swine, by tethering the tricuspid valve chordae using echo-guided chordal encircling snares. Five swine underwent baseline echocardiographic assessment of tricuspid valve function, followed by echo-guided placement of snares that encircle the chordae inserting into the anterior and posterior tricuspid valve leaflets. Tethering these snares and stabilizing them on the right ventricle caused the regurgitant fraction to increase from 8.48±5.38% to 48.76±12.5%, and the valve tenting area to increase from 60.26±52.19 to 160.9±86.92 mm 2 . Image-guided chordal encircling snares could reproducibly induce clinically significant levels of functional tricuspid regurgitation and create a valve geometry like that seen in patients, providing a new animal model for use to study novel interventional devices., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS ( N  = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS ( r  = 0.81) and PANS Total and GIS ( r  = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.

Introduction: Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL) is a relatively poorly understood entity which has been suggested to be very common in asymptomatic adults and possibly related to infectious complications despite not progressing to CLL., Methods: We describe the first case of Progressive Multifocal Leukoencephalopathy (PML) presenting in a 72-year-old man with LC-MBL but no other immunocompromising conditions., Results: A diagnosis of PML was confirmed with classic MRI findings in association with a high CSF John Cunningham polyomavirus (JCV) viral load (4.09' 10 5 copies/mL). An extensive search for underlying immunocompromising conditions only demonstrated LC-MBL representing approximately 4% of total leukocytes (0.2' 10 9 /L)., Discussion: This is the first report of PML in association with LC-MBL. Careful review of peripheral blood flow cytometry results is necessary to identify this disorder. Further study of the epidemiology and infectious complications of LC-MBL are warranted., Competing Interests: The authors have nothing to disclose., (© Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada), 2024.)