Constructing the brief diagnostic criteria for temporomandibular disorders (bDC/TMD) for field testing.

BACKGROUND: Despite advances in temporomandibular disorders' (TMDs) diagnosis, the diagnostic process continues to be problematic in non-specialist settings. OBJECTIVE: To complete a Delphi process to shorten the Diagnostic Criteria for TMD (DC/TMD) to a brief DC/TMD (bDC/TMD) for expedient clinical diagnosis and initial management. METHODS: An international Delphi panel was created with 23 clinicians representing major specialities, general dentistry and related fields. The process comprised a full day workshop, seven virtual meetings, six rounds of electronic discussion and finally an open consultation at a virtual international symposium. RESULTS: Within the physical axis (Axis 1), the self-report Symptom Questionnaire of the DC/TMD did not require shortening from 14 items for the bDC/TMD. The compulsory use of the TMD pain screener was removed reducing the total number of Axis 1 items by 18%. The DC/TMD Axis 1 10-section examination protocol (25 movements, up to 12 sets of bilateral palpations) was reduced to four sections in the bDC/TMD protocol involving three movements and three sets of palpations. Axis I then resulted in two groups of diagnoses: painful TMD (inclusive of secondary headache), and common joint-related TMD with functional implications. The psychosocial axis (Axis 2) was shortened to an ultra-brief 11 item assessment. CONCLUSION: The bDC/TMD represents a substantially reduced and likely expedited method to establish (grouping) diagnoses in TMDs. This may provide greater utility for settings requiring less granular diagnoses for the implementation of initial treatment, for example non-specialist general dental practice.

Evaluating the balance of benefits and harms in chronic pain clinical trials: prioritizing individual participants over individual outcomes.

BACKGROUND: Randomized clinical trials (RCTs) generally assess efficacy and safety separately, with the conclusion of whether a treatment is beneficial based solely on the efficacy endpoint. However, assessing and combining efficacy and safety domains, using a single composite outcome measure, can provide a more comprehensive assessment of the overall effect of a treatment. Furthermore, composite outcomes can incorporate information regarding the relationship between the individual outcomes. In fact, such outcomes have been suggested in the clinical trials literature for at least 15 years. OBJECTIVES: To (1) identify whether recent primary publications of chronic pain RCTs from major pain journals included a composite outcome measure of benefits and harms and (2) discuss the potential benefits of such outcomes in various stages of treatment development, including as outcome measures in RCTs, and to support decisions of Data and Safety Monitoring Boards and ordering of treatments in the context of treatment guidelines. EVIDENCE REVIEW: RCTs published in 6 major pain journals published between 2016 and 2021 that investigated interventions for chronic pain were reviewed. FINDINGS: Of 73 RCTs identified, only 2 included a composite outcome measure of benefits and harms. Both of these articles compared 2 active treatments. CONCLUSIONS: Composite outcomes of benefits and harms are underutilized in chronic pain RCTs. The advantages and challenges of using such outcomes are discussed.

Metabolic programs of T cell tissue residency empower tumour immunity.

Tissue resident memory CD8+ T (TRM) cells offer rapid and long-term protection at sites of reinfection1. Tumour-infiltrating lymphocytes with characteristics of TRM cells maintain enhanced effector functions, predict responses to immunotherapy and accompany better prognoses2,3. Thus, an improved understanding of the metabolic strategies that enable tissue residency by T cells could inform new approaches to empower immune responses in tissues and solid tumours. Here, to systematically define the basis for the metabolic reprogramming supporting TRM cell differentiation, survival and function, we leveraged in vivo functional genomics, untargeted metabolomics and transcriptomics of virus-specific memory CD8+ T cell populations. We found that memory CD8+ T cells deployed a range of adaptations to tissue residency, including reliance on non-steroidal products of the mevalonate-cholesterol pathway, such as coenzyme Q, driven by increased activity of the transcription factor SREBP2. This metabolic adaptation was most pronounced in the small intestine, where TRM cells interface with dietary cholesterol and maintain a heightened state of activation4, and was shared by functional tumour-infiltrating lymphocytes in diverse tumour types in mice and humans. Enforcing synthesis of coenzyme Q through deletion of Fdft1 or overexpression of PDSS2 promoted mitochondrial respiration, memory T cell formation following viral infection and enhanced antitumour immunity. In sum, through a systematic exploration of TRM cell metabolism, we reveal how these programs can be leveraged to fuel memory CD8+ T cell formation in the context of acute infections and enhance antitumour immunity.

Covariate Adjustment in Chronic Pain Trials: An Oft-Missed Opportunity.

Self-reported pain intensity, frequently used as an outcome in randomized clinical trials (RCTs) of chronic pain, is often highly variable and could be associated with multiple baseline factors. Thus, the assay sensitivity of pain trials (ie, the ability of the trial to detect a true treatment effect) could be improved by including prespecified baseline factors in the primary statistical model. The objective of this focus article was to characterize the baseline factors included in statistical analyses of chronic pain RCTs. Seventy-three RCTs published between 2016 and 2021 that investigated interventions for chronic pain were included. The majority of trials identified a single primary analysis (72.6%; n = 53). Of these, 60.4% (n = 32) included one or more covariates in the primary statistical model, most commonly baseline value of the primary outcome, study site, sex, and age. Only one of the trials reported information regarding associations between covariates and outcomes (ie, information that could inform prioritization of covariates for prespecification in future analyses). These findings demonstrate inconsistent use of covariates in the statistical models in chronic pain clinical trials. Prespecified adjustments for baseline covariates that could increase precision and assay sensitivity should be considered in future clinical trials of chronic pain treatments. PERSPECTIVE: This review demonstrates inconsistent inclusion and potential underutilization of covariate adjustment in analyses of chronic pain RCTs. This article highlights areas for possible improvement in design and reporting related to covariate adjustment to improve efficiency in future RCTs.

Diagnostic criteria for temporomandibular disorders-INfORM recommendations: Comprehensive and short-form adaptations for adolescents.

BACKGROUND: The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for use in adults is in use worldwide. Until now, no version of this instrument for use in adolescents has been proposed. OBJECTIVE: To present comprehensive and short-form adaptations of the adult version of DC/TMD that are appropriate for use with adolescents in clinical and research settings. METHODS: International experts in TMDs and experts in pain psychology participated in a Delphi process to identify ways of adapting the DC/TMD protocol for physical and psychosocial assessment of adolescents. RESULTS: The proposed adaptation defines adolescence as ages 10-19 years. Changes in the physical diagnosis (Axis I) include (i) adapting the language of the Demographics and the Symptom Questionnaires to be developmentally appropriate for adolescents, (ii) adding two general health questionnaires, one for the adolescent patient and one for their caregivers and (iii) replacing the TMD Pain Screener with the 3Q/TMD questionnaire. Changes in the psychosocial assessment (Axis II) include (i) adapting the language of the Graded Chronic Pain Scale to be developmentally appropriate for adolescents, (ii) adding anxiety and depression assessment that have been validated for adolescents and (iii) adding three constructs (stress, catastrophizing and sleep disorders) to assess psychosocial functioning in adolescents. CONCLUSION: The recommended DC/TMD, including Axis I and Axis II for adolescents, is appropriate to use in clinical and research settings. This adapted first version for adolescents includes changes in Axis I and Axis II requiring reliability and validity testing in international settings. Official translations of the comprehensive and short-form to different languages according to INfORM requirements will enable a worldwide dissemination and implementation.

Human papillomavirus E5 suppresses immunity via inhibition of the immunoproteasome and STING pathway.

The role that human papillomavirus (HPV) oncogenes play in suppressing responses to immunotherapy in cancer deserves further investigation. In particular, the effects of HPV E5 remain poorly understood relative to E6 and E7. Here, we demonstrate that HPV E5 is a negative regulator of anti-viral interferon (IFN) response pathways, antigen processing, and antigen presentation. Using head and neck cancer as a model, we identify that E5 decreases expression and function of the immunoproteasome and that the immunoproteasome, but not the constitutive proteasome, is associated with improved overall survival in patients. Moreover, immunopeptidome analysis reveals that HPV E5 restricts the repertoire of antigens presented on the cell surface, likely contributing to immune escape. Mechanistically, we discover a direct interaction between E5 and stimulator of interferon genes (STING), which suppresses downstream IFN signaling. Taken together, these findings identify a powerful molecular mechanism by which HPV E5 limits immune detection and mediates resistance to immunotherapy.

A rapidly spreading deleterious aphid endosymbiont that uses horizontal as well as vertical transmission.

Endosymbiotic bacteria that live inside the cells of insects are typically only transmitted maternally and can spread by increasing host fitness and/or modifying reproduction in sexual hosts. Transinfections of Wolbachia endosymbionts are now being used to introduce useful phenotypes into sexual host populations, but there has been limited progress on applications using other endosymbionts and in asexual populations. Here, we develop a unique pathway to application in aphids by transferring the endosymbiont Rickettsiella viridis to the major crop pest Myzus persicae. Rickettsiella infection greatly reduced aphid fecundity, decreased heat tolerance, and modified aphid body color, from light to dark green. Despite inducing host fitness costs, Rickettsiella spread rapidly through caged aphid populations via plant-mediated horizontal transmission. The phenotypic effects of Rickettsiella were sensitive to temperature, with spread only occurring at 19 °C and not 25 °C. Body color modification was also lost at high temperatures despite Rickettsiella maintaining a high density. Rickettsiella shows the potential to spread through natural M. persicae populations by horizontal transmission and subsequent vertical transmission. Establishment of Rickettsiella in natural populations could reduce crop damage by modifying population age structure, reducing population growth and providing context-dependent effects on host fitness. Our results highlight the importance of plant-mediated horizontal transmission and interactions with temperature as drivers of endosymbiont spread in asexual insect populations.

Physicochemical, mechanical, dielectric, and biological properties of sintered hydroxyapatite/barium titanate nanocomposites for bone regeneration.

Bone implants fabricated using nanocomposites containing hydroxyapatite (HA) and barium titanate (BT) show osteoconductive, osteoinductive, osteointegration, and piezoelectricity properties for bone regeneration applications. In our present study, HA and BT nanopowders were synthesized using high-energy ball-milling-assisted solid-state reaction with precursors of calcium carbonate and ammonium dihydrogen phosphate, and barium carbonate and titanium oxide powder mixtures, respectively. Hexagonal HA and tetragonal BT phases were formed after calcination at 700 and 1000 °C, respectively. Subsequently, hydroxyapatite/barium titanate (HA/BT) nanocomposites with different weight percentages of HA and BT were prepared by ball-milling, then compacted and sintered at two different temperatures to endow these bioceramics with better mechanical, dielectric, and biological properties for bone regeneration. Microstructure, crystal phases, and molecular structure characterizations of these sintered HA/BT nanocomposite compacts (SHBNCs) were performed using field-emission scanning electron microscopy, x-ray diffraction, and Fourier-transform infrared spectroscopy, respectively. Bulk density was evaluated using the Archimedes method. HA/BT nanocomposites with increased BT content showed enhanced dielectric properties, and the dielectric constant (ϵr) value for 5HA/95BT was ∼182 at 100 Hz. Mechanical properties such as Vicker's hardness, fracture toughness, yield strength, and diametral tensile strength were also investigated. The hemolysis assay of SHBNCs exhibited hemocompatibility. The effect of these SHBNCs as implants on thein vitrocytocompatibility and cell viability of MG-63 osteoblast-like cells was assessed by MTT assay and live/dead staining, respectively. 15HA/85BT showed increased metabolic activity with a higher number of live cells than BT after the culture period. Overall, the SHBNCs can be used as orthopedic implants for bone regeneration applications.

A rose by another name? Characteristics that distinguish headache secondary to temporomandibular disorder from headache that is comorbid with temporomandibular disorder.

ABSTRACT: Co-occurring pain conditions that affect overlapping body regions are complicated by the distinction between primary vs secondary pain conditions. We investigate the occurrence of headache and painful temporomandibular disorder (TMD) in a community-based, cross-sectional study of US adults in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA-II) study. A specific goal was to determine whether headache attributed to TMD is separable from primary headache. Using DC/TMD and International Classification of Headache Disorders-third edition criteria, 3 groups of individuals were created: (a) headache without TMD; (b) headache comorbid with TMD; and (c) headache attributed to TMD. Regression models compared study groups according to demographic and comorbid characteristics, and post hoc contrasts tested for differences. Descriptive statistics and Cohen d effect size were computed, by group, for each predictor variable. Differences in continuous predictors were analyzed using one-way analysis of variance. Nearly all demographic and comorbid variables distinguished the combined headache and TMD groups from the group with headache alone. Relative to the reference group with primary headache alone, markers related to headache, TMD, somatic pain processing, psychosocial, and health conditions were substantially greater in both headache comorbid with TMD and headache attributed to TMD, attesting to their qualitative similarities. However, effect sizes relative to the reference group were large for headache comorbid with TMD and larger again for headache attributed to TMD, attesting to their separability in quantitative terms. In summary, the presence of overlapping painful TMD and headache adds substantially to the biopsychosocial burden of headache and points to the importance of comprehensive assessment and differential management.

A New Instrument for Assessing Work-Related Body Mechanics and Strain in the General Population.

Clinical pain is often linked to poor body mechanics, with individuals sometimes presenting multiple painful disorders. Such disorders may be influenced by behaviors that affect the general resiliency and health of the musculoskeletal system. We aimed to develop a self-reported scale using the Malmö Diet and Cancer Study questions on work-related body mechanical exposures. An expert panel identified 41 variables having content validity for musculoskeletal problems. Exploratory factor analysis was conducted on a random selection of 50% of the cohort (n = 6,789 adults); the remaining was reserved for confirmatory factor analyses (CFA), item response theory (IRT) item calibration, and differential item functioning investigations. Supported by standard measure development methods and fit criteria, the final unidimensional item bank contains 13 items. Overall CFA statistics (root mean square error of approximation = .09; comparative fit index = .96; Tucker-Lewis index = .96; standardized root mean residuals = .05) indicated excellent single-factor model fit and appropriateness of IRT modeling and calibration. Expert review and item information values (score-precision) guided selection of an 8-item short form with acceptable score-level reliabilities (≥.70) for T-scores = 39-80+. This measure provides reliable assessment of body mechanics strain in adults and can be useful when evaluating different contributions to musculoskeletal problems affecting pain-treatment success in future clinical research. PERSPECTIVE: This article presents the development and psychometric properties of a new measure, "Work-related Body Mechanics and Strain Scale (WR-BMSS)." The scale has 13-items or alternatively an 8-item short form. This measure could potentially help clinicians who seek to assess how musculoskeletal problems may contribute to patient pain and disability.

Exploration of anticancer potential of Lantadenes from weed Lantana camara: Synthesis, in silico, in vitro and in vivo studies.

Naturally occurring pentacyclic triterpenoids and their semisynthetic analogues have engrossed increasing attention for their anticancer potential and exhibiting promising role in discovery of new anticancer agents. Present study include the semi synthetic modifications of Lantadenes from the weed Lantana carama and their structures delineation by FT-IR, 1H-NMR, 13C-NMR & mass spectroscopy. All the compounds were scrutinized for in vitro cytotoxicity, ligand receptor interaction and in vivo anticancer studies. Most of the novel analogues displayed potent antiproliferative activity against A375 & A431 cancer cell lines and found superior to parent Lantadenes. In particular, 3ß-(4-Methoxybenzoyloxy)-22ß-senecioyloxy-olean-12-en-28-oic acid was found to be most suitable compound, with IC50 value of 3.027 µM aganist A375 cell line having least docking score (-69.40 kcal/mol). Promising anticancer potential of the lead was further indicated by significant reduction in tumor volume and burden in two stage carcinoma model. These findings suggests that the Lantadene derivatives may hold promising potential for the intervention of skin cancers.

Diagnostic criteria for temporomandibular disorders-INfORM recommendations: Comprehensive and short-form adaptations for children.

BACKGROUND: The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) are used worldwide in adults. Until now, no adaptation for use in children has been proposed. OBJECTIVE: The aim of this study was to present comprehensive and short-form adaptations of Axis I and Axis II of the DC/TMD for adults that are appropriate for use with children in clinical and research settings. METHODS: Global Delphi studies with experts in TMDs and in pain psychology identified ways of adapting the DC/TMD for children. RESULTS: The proposed adaptation is suitable for children aged 6-9 years. Proposed changes in Axis I include (i) adapting the language of the Demographics and the Symptom Questionnaires to be developmentally appropriate for children, (ii) adding a general health questionnaire for children and one for their parents, (iii) replacing the TMD Pain Screener with the 3Q/TMD questionnaire and (iv) modifying the clinical examination protocol. Proposed changes in Axis II include (i) for the Graded Chronic Pain Scale, to be developmentally appropriate for children, (ii) adding anxiety and depression assessments that have been validated in children and (iii) adding three constructs (stress, catastrophising and sleep disorders) to assess psychosocial functioning in children. CONCLUSION: The recommended DC/TMD, including Axis I and Axis II, for children aged 6-9 years, is appropriate for use in clinical and research settings. This adapted the first version for children includes changes in Axis I and Axis II changes requiring reliability and validity testing in international settings. Official translations to different languages according to INfORM requirements will enable a worldwide dissemination and implementation.

Infantile Galactosialidosis with Novel Mutation: An Early Presentation.

Galactosialidosis (GS) is a rare lysosomal storage disorder. We reported here, the case of a 29-day-old boy who had increased body swelling, difficulty breathing, and petechiae on the trunk since birth. The antenatal history was unremarkable. Clinical laboratory findings included coarse facies, hepatosplenomegaly, gross ascites, thrombocytopenia, nephrotic range proteinuria, and bilateral hydronephrosis. The diagnostic challenge was resolved after genetic testing, which revealed GS with a novel homozygous c.1158dupA mutation.

National Control Laboratory Assessment of Quality of Rituximab Biosimilars in India.

In past few years many rituximab (RTX) biosimilars have been launched in India. Biosimilars are products that are similar in terms of quality, safety, and efficacy to its innovator product and are expected to offer improved affordability. The less clinical examination is a significant source of reduction in the cost of development of a biosimilar. However, this clinical relief is predicated on the assumption that there is analytical similarity between the biosimilar and the innovator product. Therefore, the role of National Control Laboratory become very important to ensure the quality of these drugs by carrying out analytical characterization at the point of drug product release level as when referred by National Regulatory Authority for quality evaluation. To assess the similarity between innovator and biosimilars, different physicochemical and biological quality attributes were assessed. A multitude of state-of-the-art analysis of N = 3 RTX biosimilars marketed in India revealed that the impurity profiles of these biosimilars measured by charge variant analysis (cation exchange chromatography-high performance liquid chromatography [HPLC], capillary zone electrophoresis, and capillary isoelectric focusing), aggregates profiling (size exclusion chromatography-HPLC), fragments analysis (capillary electrophoresis-sodium dodecyl sulfate) were found to be significantly varying as compared with the innovator product. There were significant variations in acidic variants (p = 0.023) and basic variants (p = 0.0005), isoelectric point value (p < 0.0001), aggregates (p = 0.0231), and fragments (p < 0.0001) of biosimilars were found as that of innovator product. However, these differences were not affecting the biological activity in the cell-based potency analysis by complement-dependent cytotoxicity (CDC) assay (p = 0.1026), antibody-dependent cell-mediated cytotoxicity (ADCC) (p = 0.3736), and binding assay by flow cytometer fluorescence-activated cell sorting (p = 0.4005) of these biosimilars as compared with the innovator product.

Adynamic bone disease: Revisited.

The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.

Results of fusional vergence therapy in managing consecutive esotropia: A case series.

Purpose: To analyze the efficacy of fusional vergence therapy (FVT) in management of consecutive esotropia with diplopia after intermittent exotropia (IXT) surgery. The current study is carried on how FVT affects the duration of treatment, sensory fusion, and exotropic drift. Methods: This was a retrospective study for the medical record of 11 patients with consecutive esotropia after IXT surgery of 543 patients over the period of 5 year, with mean surgery age of 9.5 (range: 4-33 y). FVT was planned after minimum 6 weeks of surgery and was considered for maximum 24 weeks. Patients underwent a combination of office-based and home-based FVT. Successful outcome of therapy was considered where diplopia resolves in free space and achieves sensory fusion, stereopsis with no manifest deviation. Results: Record of 543 patients who had horizontal muscle surgery for IXT were identified and reviewed. Records of 11 patients who showed consecutive esotropia of 10 prism diopter (PD) or more with normal retinal correspondence, with or without diplopia complaint, after 6 week of surgery and had undergone vision therapy management were reviewed. A successful outcome of binocular single vision with good sensory and motor fusion with no manifest deviation or prism requirement was achieved with in the mean duration of 4.8 month of therapy. With a mean duration of 4 weeks of therapy, the mean angle of deviation reduced by 53% for distance (17 PD to 8 PD) and 27% for near (11 PD to 8 PD) and mean stereopsis improvement by 80% with 94% patients demonstrating sensory fusion on Bagolini test and 94% of patients having no symptoms of diplopia or squint. Conclusion: With nonsurgical management involving refractive error correction, FVT, and prism, consecutive esotropia was resolved in 74% cases. Management of consecutive esotropia with FVT can result in satisfactory sensory fusion and successful motor alignment.

Correlation of Nuclear Morphometry with Clinicopathologic Parameters in Malignant Breast Aspirates.

Shilpa GargBackground Nuclear size, shape, chromatin pattern, and nucleolar size and number have all been reported to change in breast cancer. Aim The aim of the study was to quantify nuclear changes on malignant breast aspirates using morphometry and to correlate the morphometric parameters with clinicopathologic features such as cytologic grade, tumor size, lymph node status, mitotic index, and histopathologic grade. Materials and Methods Forty-five cases of carcinoma breast diagnosed on cytology were included in this study. Cytologic grading was performed as per the Robinson's cytologic grading system. Nuclear morphometry was done on Papanicolaou stained smears. One hundred nonoverlapping cells per case were evaluated. Both geometrical and textural parameters were evaluated. Results Comparison of cytologic grades with most morphometric features (nuclear area, perimeter, shape, long axis, short axis, intensity, total run length, and TI homogeneity) was highly significant on statistical analysis. Correlation with tumor size yielded significant results for nuclear area, perimeter, long and short axes, and intensity with p < 0.05. The study of lymph node status and morphometry showed a highly significant statistical association with all the parameters. Mitotic count was significantly associated with all the geometric parameters and one textural parameter (total run length). On correlation of ductal carcinoma in situ and histopathological Grades 1 to 3 with morphometry, it was found that all the parameters except long-run emphasis were highly significant with p < 0.001. Conclusion Morphometry as a technique holds immense promise in prognostication in breast carcinoma.

Demographic and clinical characteristics associated with variations in antibody response to BNT162b2 COVID-19 vaccination among healthcare workers at an academic medical centre: a longitudinal cohort analysis.

OBJECTIVES: We sought to understand the demographic and clinical factors associated with variations in longitudinal antibody response following completion of two-dose regiment of BNT162b2 vaccination. DESIGN: This study is a 10-month longitudinal cohort study of healthcare workers and serially measured anti-spike protein IgG (IgG-S) antibody levels using mixed linear models to examine their associations with participant characteristics. SETTING: A large, multisite academic medical centre in Southern California, USA. PARTICIPANTS: A total of 843 healthcare workers met inclusion criteria including completion of an initial two-dose course of BNT162b2 vaccination, complete clinical history and at least two blood samples for analysis. Patients had an average age of 45±13 years, were 70% female and 7% with prior SARS-CoV-2 infection. RESULTS: Vaccine-induced IgG-S levels remained in the positive range for 99.6% of individuals up to 10 months after initial two-dose vaccination. Prior SARS-CoV-2 infection was the primary correlate of sustained higher postvaccination IgG-S levels (partial R2=0.133), with a 1.74±0.11 SD higher IgG-S response (p<0.001). Female sex (beta 0.27±0.06, p<0.001), younger age (0.01±0.00, p<0.001) and absence of hypertension (0.17±0.08, p=0.003) were also associated with persistently higher IgG-S responses. Notably, prior SARS-CoV-2 infection augmented the associations of sex (-0.42 for male sex, p=0.08) and modified the associations of hypertension (1.17, p=0.001), such that infection-naïve individuals with hypertension had persistently lower IgG-S levels whereas prior infected individuals with hypertension exhibited higher IgG-S levels that remained augmented over time. CONCLUSIONS: While the IgG-S antibody response remains in the positive range for up to 10 months following initial mRNA vaccination in most adults, determinants of sustained higher antibody levels include prior SARS-CoV-2 infection, female sex, younger age and absence of hypertension. Certain determinants of the longitudinal antibody response appear significantly modified by prior infection status. These findings offer insights regarding factors that may influence the 'hybrid' immunity conferred by natural infection combined with vaccination.

Clinical efficacy of mycophenolate mofetil versus levamisole therapy in frequently relapsing and steroid dependent childhood nephrotic syndrome - A retrospective comparative analysis.

BACKGROUND: Children with frequently relapsing (FR) or steroid dependent (SD) nephrotic syndrome (NS) often develop side effects of corticosteroids. Various steroid-sparing agents are in practice, but only a few studies exist so far which have compared the safety and efficacy of these two commonly used agents. METHODS: We did a retrospective medical records review of children with FRNS or SDNS who had levamisole or mycophenolate mofetil (MMF) as a steroid-sparing agent with a minimum follow-up period of 12 months. The aim was to compare the course of our patients on MMF and levamisole. Our primary objective was to determine the number of children in sustained remission and those with the infrequently relapsing course on levamisole and MMF and, the median time to relapse in months in the two groups. The secondary objective was to compare time to first relapse and number of relapses in FRNS and SDNS group children on MMF and levamisole. RESULTS: A total of 88 children (34% female) with diagnosis FR/SDNS (44 each) were included in the study. Thirty-nine patients took levamisole, while 49 received MMF therapy. The median age of presentation at the relapsing course was 4.2 years. The proportion of children with sustained remission or infrequent relapsing (IFR) course on MMF was 73.6%, compared to 48.71% on levamisole (p-value .015). In addition, the median time to first relapse was 12 months (24, 1.5) and 4.5 months (24, 1) on respective medications. CONCLUSION: Clinical outcome was superior in the MMF group than levamisole, especially in SDNS patients, and also MMF was more efficacious in maintaining sustained remission.