Interval between prior SARS-CoV-2 infection and booster vaccination impacts magnitude and quality of antibody and B cell responses.

SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a 2-month period, we evaluated antibody and B cell responses to a third-dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies and memory B cells. Spike-specific B cell responses from recent infection (<180 days) were elevated at pre-boost but comparatively less so at 60 days post-boost compared with uninfected individuals, and these differences were linked to baseline frequencies of CD27lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B cell responses to booster vaccines are impeded by recent infection.

Immune responses to SARS-CoV-2 mRNA vaccination in people with idiopathic CD4 lymphopenia.

BACKGROUND: The immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines is variable in individuals with different inborn errors of immunity or acquired immune deficiencies and is yet unknown in people with idiopathic CD4 lymphopenia (ICL). OBJECTIVE: We sought to determine the immunogenicity of mRNA vaccines in patients with ICL with a broad range of CD4 T-cell counts. METHODS: Samples were collected from 25 patients with ICL and 23 age- and sex-matched healthy volunteers (HVs) after their second or third SARS-CoV-2 mRNA vaccine dose. Anti-spike and anti-receptor binding domain antibodies were measured. T-cell receptor sequencing and stimulation assays were performed to quantify SARS-CoV-2-specific T-cell responses. RESULTS: The median age of ICL participants was 51 years, and their median CD4 count was 150 cells/µL; 11 participants had CD4 counts ≤100 cells/µL. Anti-spike IgG antibody levels were greater in HVs than in patients with ICL after 2 and 3 doses of mRNA vaccine. There was no detectable significant difference, however, in anti-S IgG between HVs and participants with ICL and CD4 counts >100 cells/µL. The depth of spike-specific T-cell responses by T-cell receptor sequencing was lower in individuals with ICL. Activation-induced markers and cytokine production of spike-specific CD4 T cells in participants with ICL did not differ significantly compared with HVs after 2 or 3 vaccine doses. CONCLUSIONS: Patients with ICL and CD4 counts >100 cells/µL can mount vigorous humoral and cellular immune responses to SARS-CoV-2 vaccination; however, patients with more severe CD4 lymphopenia have blunted vaccine-induced immunity and may require additional vaccine doses and other risk mitigation strategies.

Application of 3D Printing in Cleft Lip and Palate Repair.

This manuscript reviews the transformative impact of 3-dimensional (3D) printing technologies in the treatment and management of cleft lip and palate (CLP), highlighting its application across presurgical planning, surgical training, implantable scaffolds, and postoperative care. By integrating patient-specific data through computer-aided design and manufacturing, 3D printing offers tailored solutions that improve surgical outcomes, reduce operation times, and enhance patient care. The review synthesizes current research findings, technical advancements, and clinical applications, illustrating the potential of 3D printing to revolutionize CLP treatment. Further, it discusses the future directions of combining 3D printing with other innovative technologies like artificial intelligence, 4D printing, and in situ bioprinting for more comprehensive care strategies. This paper underscores the necessity for multidisciplinary collaboration and further research to overcome existing challenges and fully utilize the capabilities of 3D printing in CLP repair.

Multicenter comparison using two AI stroke CT perfusion software packages for determining thrombectomy eligibility.

BACKGROUND: Stroke AI platforms assess infarcted core and potentially salvageable tissue (penumbra) to identify patients suitable for mechanical thrombectomy. Few studies have compared outputs of these platforms, and none have been multicenter or considered NIHSS or scanner/protocol differences. Our objective was to compare volume estimates and thrombectomy eligibility from two widely used CT perfusion (CTP) packages, Viz.ai and RAPID.AI, in a large multicenter cohort. METHODS: We analyzed CTP data of acute stroke patients with large vessel occlusion (LVO) from four institutions. Core and penumbra volumes were estimated by each software and DEFUSE-3 thrombectomy eligibility assessed. Results between software packages were compared and categorized by NIHSS score, scanner manufacturer/model, and institution. RESULTS: Primary analysis of 362 cases found statistically significant differences in both software's volume estimations, with subgroup analysis showing these differences were driven by results from a single scanner model, the Canon Aquilion One. Viz.ai provided larger estimates with mean differences of 8cc and 18cc for core and penumbra, respectively (p<0.001). NIHSS subgroup analysis also showed systematically larger Viz.ai volumes (p<0.001). Despite volume differences, a significant difference in thrombectomy eligibility was not found. Additional subgroup analysis showed significant differences in penumbra volume for the Phillips Ingenuity scanner, and thrombectomy eligibility for the Canon Aquilion One scanner at one center (7 % increased eligibility with Viz.ai, p=0.03). CONCLUSIONS: Despite systematic differences in core and penumbra volume estimates between Viz.ai and RAPID.AI, DEFUSE-3 eligibility was not statistically different in primary or NIHSS subgroup analysis. A DEFUSE-3 eligibility difference, however, was seen on one scanner at one institution, suggesting scanner model and local CTP protocols can influence performance and cause discrepancies in thrombectomy eligibility. We thus recommend centers discuss optimal scanning protocols with software vendors and scanner manufacturers to maximize CTP accuracy.

Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment.

BACKGROUND: Nirmatrelvir/ritonavir, the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease inhibitor, reduces the risk of hospitalization and death by coronavirus disease 2019 (COVID-19) but has been associated with symptomatic rebound after therapy completion. METHODS: Six individuals with relapse of COVID-19 symptoms after treatment with nirmatrelvir/ritonavir, 2 individuals with rebound symptoms without prior antiviral therapy and 7 patients with acute Omicron infection (controls) were studied. Soluble biomarkers and serum SARS-CoV-2 nucleocapsid protein were measured. Nasal swabs positive for SARS-CoV-2 underwent viral isolation and targeted viral sequencing. SARS-CoV-2 anti-spike, anti-receptor-binding domain, and anti-nucleocapsid antibodies were measured. Surrogate viral neutralization tests against wild-type and Omicron spike protein, as well as T-cell stimulation assays, were performed. RESULTS: High levels of SARS-CoV-2 anti-spike immunoglobulin G (IgG) antibodies were found in all participants. Anti-nucleocapsid IgG and Omicron-specific neutralizing antibodies increased in patients with rebound. Robust SARS-CoV-2-specific T-cell responses were observed, higher in rebound compared with early acute COVID-19 patients. Inflammatory markers mostly decreased during rebound. Two patients sampled longitudinally demonstrated an increase in activated cytokine-producing CD4+ T cells against viral proteins. No characteristic resistance mutations were identified. SARS-CoV-2 was isolated by culture from 1 of 8 rebound patients; Polybrene addition increased this to 5 of 8. CONCLUSIONS: Nirmatrelvir/ritonavir treatment does not impede adaptive immune responses to SARS-CoV-2. Clinical rebound corresponds to development of a robust antibody and T-cell immune response, arguing against a high risk of disease progression. The presence of infectious virus supports the need for isolation and assessment of longer treatment courses. CLINICAL TRIALS REGISTRATION: NCT04401436.

Incidence of Infections, Explantations, and Displacements/Mechanical Complications of Spinal Cord Stimulation During the Past Eight Years.

OBJECTIVES: The overall awareness and potential of real-world data have drastically increased in the medical field, with potential implications for postmarket medical device surveillance. The goal of this study was to evaluate real-world data on incidence of infections, explantations, and displacements/mechanical complications of spinal cord stimulation (SCS) during the past eight years and to forecast point estimates for the upcoming three years on the basis of the identified patterns. MATERIALS AND METHODS: Based on electronic health records from 80 healthcare organizations within the TriNetX data base in the USA, data of 11,934 patients who received SCS as treatment for persistent spinal pain syndrome type 2 (PSPS T2) were extracted. Events of interest were explantations and displacements/mechanical complications of both the lead and implanted pulse generator (IPG), in addition to infection rates from 2015 to 2022. Mann-Kendall tests were performed to detect monotonic trends in the time series. Forecasts were conducted for the upcoming three years for every event of interest. RESULTS: Statistically significant increasing time trends were revealed for the annual incidence of IPG and lead displacements/mechanical complications in patients with PSPS T2 over the past eight years. These time trends were visible in both male and female patients and in smokers and nonsmokers. For annual incidence of explantations and infections, no significant time effect was observed. In 2025, the incidence of displacements/mechanical complications of the lead (3.07%) is predicted to be the highest, followed by explantations of the IPG (2.67%) and lead (2.02%). CONCLUSIONS: Based on real world data, device explantation was the most frequent event of interest, with negative peaks in the time series in 2016 and 2020, presumably due to the introduction of rechargeable pulse generators and to the COVID-19 pandemic, respectively.

Outcomes of Coronavirus Disease 2019 (COVID-19) Related Hospitalization Among People With Human Immunodeficiency Virus (HIV) in the ISARIC World Health Organization (WHO) Clinical Characterization Protocol (UK): A Prospective Observational Study.

BACKGROUND: Evidence is conflicting about how human immunodeficiency virus (HIV) modulates coronavirus disease 2019 (COVID-19). We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) World Health Organization (WHO) Clinical Characterization Protocol (CCP) study. METHODS: We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, 10 individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). RESULTS: Among 47 592 patients, 122 (0.26%) had confirmed HIV infection, and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 vs 74 years; P < .001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive versus HIV-negative groups (26.7% vs. 32.1%; P = .16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; P < .001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; P = .05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; P = .008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; P < .001). CONCLUSIONS: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19.

Hepatitis A and Hepatitis E: Clinical and Epidemiological Features, Diagnosis, Treatment, and Prevention.

Hepatitis A and E are both ancient diseases but have only been properly recognized as being caused by distinct pathogens in modern times. Despite significantly different genomic structures, both viruses employ remarkably similar strategies to avoid host detection and increase environmental transmission. There are millions of cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) each year, resulting in tens of thousands of deaths. The presentations can be clinically indistinguishable, but each virus also has a range of less common but more specific phenotypes. The epidemiology of HAV is complex, and is shifting in countries that are making improvements to public health and sanitation. HEV presents a significant public health challenge in resource-limited settings but has historically been incorrectly regarded as having little clinical relevance in industrialized countries.

CardioScape mapping the cardiovascular funding landscape in Europe.

Aims: The burden of cardiovascular disease is increasing worldwide, which has to be reflected by cardiovascular (CV) research in Europe. CardioScape, a FP7 funded project initiated by the European Society of Cardiology (ESC), identified where CV research is performed, how it is funded and by whom. It could be transformed into an on-line and up-to-date resource of great relevance for researchers, funding bodies and policymakers and could be a role model for mapping CV research funding in Europe and beyond. Methods and results: Relevant funding bodies in 28 European Union (EU) countries were identified by a multistep process involving experts in each country. Projects above a funding threshold of 100 k€ during the period 2010-2012 were included using a standard questionnaire. Results were classified by experts and an adaptive text analysis software to a CV-research taxonomy, integrating existing schemes from ESC journals and congresses. An on-line query portal was set up to allow different users to interrogate the database according to their specific viewpoints. Conclusion: CV-research funding varies strongly between different nations with the EU providing 37% of total available project funding and clear geographical gradients exist. Data allow in depth comparison of funding for different research areas and led to a number of recommendations by the consortium. CardioScape can support CV research by aiding researchers, funding agencies and policy makers in their strategic decisions thus improving research quality if CardioScape strategy and technology becomes the basis of a continuously updated and expanded European wide publicly accessible database.

Statistical Signal Properties of the Pressure-Reactivity Index (PRx).

OBJECTIVES: The pressure-reactivity index (PRx) is defined in terms of the moving correlation coefficient between intracranial pressure (ICP) and mean arterial pressure (MAP) and is a measure of cerebral autoregulation ability. Plots of PRx against cerebral perfusion pressure (CPP) show a U-shaped behaviour: the minimum reflecting optimal cerebral autoregulation (CPPopt). However U-shaped behaviour may also occur by chance. To date there has been no evaluation of the statistical properties of these signals. MATERIALS AND METHODS: We simulated PRx/CPP distributions using synthetic ICP and MAP signals from Gaussian noise with known cross-correlation and calculated the statistical distribution of extrema in the PRx/CPP relationship. RESULTS: The calculation of PRx on random data is statistically biased to show a U-shaped behaviour when the signals are positively cross-correlated (equivalent to PRx > 0). For PRx < 0, the bias is towards an inverse U-shaped behaviour. We demonstrate that this bias is eliminated by Fisher transforming the PRx data before CPPopt analysis. CONCLUSIONS: Cross-correlated signals are biased to show a U-shaped distribution. A CPPopt-like behaviour will be observed more often than not even from random ICP and MAP signals that do not exhibit autoregulation, unless PRx is Fisher transformed. Care must be taken in interpreting CPPopt in terms of physiology calculated from untransformed data.

Can we give culturally competent care?

Sophie Kelly, currently studying for MA Nursing (children and young people), University of Salford, reflects on the challenges of providing care for families with differing cultural backgrounds.

The power of inspiration on a paediatriac oncology unit.

Sophie Kelly, Third Year Student, MA Nursing, Children and Young People, University of Salford, looks back at what she learned from a placement she was initially apprehensive about.

Economics of chronic diseases protocol: cost-effectiveness modelling and the future burden of non-communicable disease in Europe.

BACKGROUND: The majority of chronic disease is caused by risk factors which are mostly preventable. Effective interventions to reduce these risks are known and proven to be applicable to a variety of settings. Chronic disease is generally developed long before the fatal outcome, meaning that a lot of people spend a number of years in poor health. Effective prevention measures can prolong lives of individuals and significantly improve their quality of life. However, the methods to measure cost-effectiveness are a subject to much debate. The Economics of Chronic Diseases project aims to establish the best possible methods of measuring cost-effectiveness as well as develop micro-simulation models apt at projecting future burden of chronic diseases, their costs and potential savings after implementation of cost-effective interventions. METHOD: This research project will involve eight European countries: Bulgaria, Finland, Greece, Lithuania, The Netherlands, Poland, Portugal and the United Kingdom (UK). A literature review will be conducted to identify scientific articles which critically review the methods of cost-effectiveness. Contact will be made health economists to inform and enrich this review. This evidence will be used as a springboard for discussion at a meeting with key European stakeholders and experts with the aim of reaching a consensus on recommendations for cost-effectiveness methodology. Epidemiological data for coronary heart disease, chronic kidney disease, type 2 diabetes and chronic obstructive pulmonary disease will be collected along with data on time trends in three major risk factors related to these diseases, specifically tobacco consumption, blood pressure and body mass index. Economic and epidemiological micro-simulation models will be developed to asses the future distributions of risks, disease outcomes, healthcare costs and the cost-effectiveness of interventions to reduce the burden of chronic diseases in Europe. DISCUSSION: This work will help to establish the best methods of measuring cost-effectiveness of health interventions as well as test a variety of scenarios to reduce the risk factors associated with selected chronic diseases. The modelling projections could be used to inform decisions and policies that will implement the best course of action to curb the rising incidence of chronic diseases.

The K9-Teen Pandemic: When Good Boy Goes Bad. The Epidemiology, Management and Public Health Ramifications of Facial Dog Bite Injuries: Newcastle, Australia, Experience.

The purpose of this study was to investigate the epidemiology, pattern of injury and management of facial dog bite injuries. Methods: The authors conducted a retrospective cohort study over a 5-year period of patients who sustained a facial dog bite injury. The study setting was an Oral and Maxillofacial Surgery Department at a level 1 trauma centre, servicing an estimated catchment population in excess of 950,000 people. Results: In total, 171 patients were managed in the designated period from January 2017 to January 2022. The median age was 9 years (range 11 months to 77 years), with the highest incidence of a single age 4 years. The frequency was slightly greater amongst males (n = 93) than females (n = 78). The most common responsible breed were Pitbull types (n = 26). Overall, bites most often resulted from the family dog (n = 87), in the victim's own home (n = 84) and whilst playing with the dog (n = 64). The primary sites involved were the lips (n = 70), cheek (n = 53) and nose, representing the so called 'target area'. In 53 cases, the injuries were classified as severe. 138 patients required hospital admission, and of these, 130 required surgical management under general anaesthesia. Conclusions: Facial dog bite injuries present a significant burden on the healthcare system and result in physical, functional and/or emotional distress for the patient. As the rates of dog ownership continue to rise, a consequential increase in these injuries is also likely. Further, public health intervention is essential, particularly as the most susceptible demographic remains young male children.

Exploring measurement tools used to assess knowledge, attitudes, and perceptions of pregnant women toward prenatal screening: A systematic review.

There is a lack of standardized measurement tools globally to assess knowledge, attitudes, and perceptions of expecting women toward prenatal screening. The purpose of this systematic review was to identify reasons women pursue or decline prenatal screening and compare the strengths and limitations of available measurement tools used to assess pregnant women's perceptions, knowledge, and attitudes toward prenatal screening. This review followed the five-step York methodology by Arksey and O'Malley and incorporated recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist for the extraction, analysis, and presentation of results. The five steps consisted of: (1) identification of the research questions; (2) searching for relevant studies; (3) selection of studies relevant to the research questions; (4) data charting; and (5) collation, summarization, and reporting of results. Four online databases (PubMed, Embase, Web of Science, and Cochrane Library) were selected after the librarian's development of a detailed search strategy. The Rayyan platform was used between June 2023 and August 2023 to epitomize the articles produced from our search. A total of 68 eligible studies were included in the analysis. The top five major reasons for declining prenatal screening uptake included (1) being unsure of the risk of prenatal screening and harm to the baby or miscarriage (n = 15), (2) not considering action such as termination of pregnancy for prenatal screening to be considered as necessary (n = 14), (3) high cost (n = 12), (4) lack of knowledge about testing procedures and being anxious about the test (n = 10), and (5) being worried about probability of false negative or false positive results (n = 6). Only 32 studies utilized scientifically validated instruments. Difficulties in capturing representative, adequately sized samples inclusive of diverse ethnicities and demographics were pervasive. Findings highlight the need for rigorous validation of research measurement methodologies to ensure the accuracy and applicability of resulting data regarding the assessment of prenatal screening perceptions, knowledge, and attitudes across diverse female populations.Registration: N/A.

Measurement tools used to assess knowledge, attitudes, and perceptions of pregnant women toward prenatal screeningThe following systematic review provides a comprehensive summary and quality evaluation of measurement tools used globally to assess the role of knowledge, attitudes, and perceptions of pregnant women in seeking prenatal tests.

A rhPDGF-BB/bovine type I collagen/ß-TCP mixture for the treatment of critically sized non-union tibial defects: An in vivo study in rabbits.

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/ß-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.

Choroid plexus tumors: A spectrum from benign to malignant.

Choroid plexus tumors (CPT) are believed to originate from outgrowths of the choroid plexus. Despite their broad spectrum of symptoms, invasive nature, and prognosis, most CPTs typically exhibit similar presentations due to their relationship with the cerebral ventricles, as well as the mechanical obstruction and mass effect associated with their growth. In addition, these tumors mainly affect the pediatric population, further complicating the differentiation between benign and malignant subtypes. The World Health Organization classifies CPTs into three grades, namely, grades I, II, or III, based on their mitotic activity, which determine the benign or malignant nature of the tumors. CPTs classified by the World Health Organization (WHO) include choroid plexus papillomas (CPP), atypical CPPs (aCPP), and malignant choroid plexus carcinomas (CPC). Choroid plexus adenomas represent an additional category of benign CPTs not officially classified by the WHO. Despite the variations in histology, immunohistochemistry, imaging, treatment, and prognosis, CPTs cannot be reliably distinguished based solely on clinical presentation. Therefore, in this review, we aim to provide a comprehensive overview of each tumor subtype, along with the current management approach and emerging treatments.

Perceptions of pain in aging females undergoing spinal cord stimulation.

Aim: Effects of age and sex on chronic pain outcomes following spinal cord stimulation (SCS) have not yet been assessed. Methods: We retrospectively reviewed 1 year outcomes from a database of patients receiving thoracic SCS. Subjects were divided into four cohorts: pre-menopausal and post-menopausal females, and aged-matched males. Improvement using the numerical rating scale, Oswestry Disability Index (ODI), Beck's Depression Inventory (BDI), McGill Pain Questionnaire and Pain Catastrophizing Scale (PCS) was assessed. Results: Older females were notably different from males and females under 60 as they had greater improvements in ODI, BDI and PCS. Further, females ≥60 had greater improvement in PCS compared with males ≥60. Conclusion: Our findings suggest greater improvement with 1 year SCS treatment in post-menopausal females, compared with age-matched males.

Spinal cord stimulation (SCS) has been shown to be an effective treatment for chronic pain that does not respond to other therapies. It is well recognized that men and women differ in how they perceive pain and how they respond to pain treatments. However, whether women who are over 60 years old and thus presumed to be menopausal respond differently to SCS has not been evaluated. We looked at our database which collected outcomes related to pain, measured before patients had SCS and 1 year after SCS. We found that women over 60 responded better to SCS treatment. They experienced significantly greater improvements in the disability, depression and catastrophizing associated with their pain than did women under 60. Further SCS resulted in more improvements in catastrophizing in women over 60 than in men over 60. Taken together, our hope is that these data help physicians to determine the best patients for SCS and to counsel their patients appropriately. To the best of our knowledge, this study is the first to show the impact of sex-specific aging on response to spinal cord stimulation. While we used age as a surrogate for menopause, menopausal status should be documented in the future to confirm that it effects response.

Dynamics of SARS-CoV-2 Seroprevalence in a Large US population Over a Period of 12 Months.

Due to a combination of asymptomatic or undiagnosed infections, the proportion of the United States population infected with SARS-CoV-2 was unclear from the beginning of the pandemic. We previously established a platform to screen for SARS-CoV-2 positivity across a representative proportion of the US population, from which we reported that almost 17 million Americans were estimated to have had undocumented infections in the Spring of 2020. Since then, vaccine rollout and prevalence of different SARS-CoV-2 variants have further altered seropositivity trends within the United States population. To explore the longitudinal impacts of the pandemic and vaccine responses on seropositivity, we re-enrolled participants from our baseline study in a 6- and 12- month follow-up study to develop a longitudinal antibody profile capable of representing seropositivity within the United States during a critical period just prior to and during the initiation of vaccine rollout. Initial measurements showed that, since July 2020, seropositivity elevated within this population from 4.8% at baseline to 36.2% and 89.3% at 6 and 12 months, respectively. We also evaluated nucleocapsid seropositivity and compared to spike seropositivity to identify trends in infection versus vaccination relative to baseline. These data serve as a window into a critical timeframe within the COVID-19 pandemic response and serve as a resource that could be used in subsequent respiratory illness outbreaks.

Characterization of the antispike IgG immune response to COVID-19 vaccines in people with a wide variety of immunodeficiencies.

Research on coronavirus disease 2019 vaccination in immune-deficient/disordered people (IDP) has focused on cancer and organ transplantation populations. In a prospective cohort of 195 IDP and 35 healthy volunteers (HV), antispike immunoglobulin G (IgG) was detected in 88% of IDP after dose 2, increasing to 93% by 6 months after dose 3. Despite high seroconversion, median IgG levels for IDP never surpassed one-third that of HV. IgG binding to Omicron BA.1 was lowest among variants. Angiotensin-converting enzyme 2 pseudo-neutralization only modestly correlated with antispike IgG concentration. IgG levels were not significantly altered by receipt of different messenger RNA-based vaccines, immunomodulating treatments, and prior severe acute respiratory syndrome coronavirus 2 infections. While our data show that three doses of coronavirus disease 2019 vaccinations induce antispike IgG in most IDP, additional doses are needed to increase protection. Because of the notably reduced IgG response to Omicron BA.1, the efficacy of additional vaccinations, including bivalent vaccines, should be studied in this population.