Differences In Clinical Manifestations Research Articles

Cluster analysis of clinical phenotypes in idiopathic inflammatory myopathy patients complicated with cardiac involvement.

This study aimed to classify idiopathic inflammatory myopathy (IIM) patients with cardiac involvement (IIM-CI) into different categories based on their clinical phenotypes via cluster analysis and to explore their differences in outcomes. IIM-CI patients admitted to Peking Union Medical College Hospital from January 2015 to June 2021 were retrieved. The clinical data, laboratory examinations, and treatment were retrospectively reviewed, and the outcome was traced. A second-order clustering method was employed for categorization. A total of 88 IIM-CI patients were enrolled in this study and were classified into two categories through cluster analysis. Category I consisted of patients who exhibited distinct cardiac structural and functional changes, such as enlargement of atriums and/or ventricles, along with the remarkable heart insufficiency biomarkers, whereas patients of category II displayed more widely systemic injuries and intensive skeletal muscle weakness. In comparison, pulmonary hypertension (58.8% vs 16.7%, p < 0.01), arrhythmia (82.4% vs 27.8%, p < 0.01), and positive serum anti-mitochondrial-M2 antibody (52.9% vs 5.6%, p < 0.01) were more prevalent in category I than in category II, and serum N-terminal pro-B-type natriuretic peptide levels (1703.5 pg/L vs 364.0 pg/L, p = 0.02) were significantly elevated in category I, whereas skeletal muscle weakness (50.0% vs 74.1%, p = 0.02), interstitial lung disease (20.6% vs 63.0%, p < 0.01), skin rash (11.8% vs 48.1%, p < 0.01), arthralgia (2.9% vs 27.8%, p < 0.01), fever (2.9% vs 27.8%, p < 0.01), and dysphagia (2.9% vs 22.2%, p < 0.01) were more common in category II patients. Heart failure was the primary cause of death in category I, but severe pneumonia was predominantly responsible for deaths in category II. Two categories of IIM-CI were identified based on clinical features with distinctive characteristics. Two categories exhibited differences in clinical manifestations, autoantibody profiles, and the primary cause of death.

Assessment and comparison of the 2023 ACR/EULAR APS criteria with the revised Sapporo criteria.

To analyze antiphospholipid antibody (aPL)-positive patients using the 2023 American College of Rheumatology/The European Alliance of Associations for Rheumatology (ACR/EULAR) antiphospholipid syndrome (APS) classification criteria and compare the revised Sapporo criteria and the 2023 ACR/EULAR criteria and evaluate whether the 2023 ACR/EULAR criteria provide added value over the revised Sapporo criteria. In this descriptive study, 94 aPL-positive patients (with or without APS diagnosis) were identified from two hospital-based registries (Gazi and Hacettepe University). Patients were classified into four groups to compare both criteria sets. These four groups are as follows: (1) patients classified with only the revised Sapporo criteria; (2) patients classified with only the 2023 ACR/EULAR APS criteria; (3) patients classified with both two criteria sets; and (4) patients classified with neither two criteria set. Of the 94 patients, 11 were classified with only the revised Sapporo criteria; one with only the 2023 ACR/EULAR APS criteria; 52 with both criteria sets; and 30 with neither set of criteria. For these 94 patients, the operating characteristics of the 2023 ACR/EULAR APS criteria, using the revised Sapporo criteria as the gold standard, the 2023 ACR/EULAR APS entry criteria demonstrated 100% sensitivity, and the 2023 ACR/EULAR APS classification criteria demonstrated 98% specificity and 82.5% sensitivity. The study emphasizes the importance of recognizing differences in clinical manifestations, such as early pregnancy loss without severe preeclampsia (PEC) and/or severe placental insufficiency (PI) and calls for a nuanced discussion on anticardiolipin (aCL) and anti-beta 2-glycoprotein-I (anti-β2GPI) immunoglobulin G (IgG) cutoff values.

Diagnostic accuracy of clinical visual assessment using endoscopic images for nasal cavity mass lesions.

Objectives: Discrimination of nasal cavity lesions using nasal endoscopy is challenging because of the differences in clinical manifestations and treatment strategies. We aimed to investigate the diagnostic accuracy of clinical visual assessment (CVA) of nasal cavity masses using endoscopic images and determine whether there is a difference according to pathologic class and the examiners' experience. Methods: We collected pathologically confirmed endoscopic images of normal findings, nasal polyp (NP), benign tumor, and malignant tumor (each class contained 100 images) randomly selected. Eighteen otolaryngologists, including six junior residents, six senior residents, and six board-certified rhinologists classified the test set images into four classes of lesions by CVA. Diagnostic performance according to the pathologic class and the examiner's experience level was evaluated based on overall accuracy, F1-score, confusion matrix, and area under the receiver operating characteristic curve (AUC). Results: Diagnostic performance was significantly different according to the pathological class of nasal cavity mass lesions with the overall accuracy reported high in the order of normal, NP, benign tumor, and malignant tumor (0.926 ± 0.100; 0.819 ± 0.135; 0.580 ± 0.112; 0.478 ± 0.187, respectively), F1 score (0.937 ± 0.076; 0.730 ± 0.093; 0.549 ± 0.080; 0.554 ± 0.146, respectively) and AUC value (0.96 ± 0.06; 0.84 ± 0.07; 0.70 ± 0.05; 0.71 ± 0.08, respectively). The expert rhinologist group achieved higher overall accuracy than the resident group (0.756 ± 0.157 vs. 0.680 ± 0.239, p < .05). Conclusion: CVA for nasal cavity mass was highly dependent on the pathologic class and examiner's experience. The overall accuracy was reliably high for normal findings, but low in classifying benign and malignant tumors. Differential diagnosis of lesions solely based on nasal endoscopic evaluation is challenging. Therefore, clinicians should consider further clinical evaluation for suspicious cases.

Insights into the diagnosis and management of sarcoid uveitis: A review.

Sarcoidosis is a leading cause of non-infectious uveitis that commonly affects middle-aged individuals and has a female preponderance. The disease demonstrates age, sex and ethnic differences in clinical manifestations. A diagnosis of sarcoidosis is made based on a compatible clinical presentation, supporting investigations and histologic evidence of non-caseating granulomas, although biopsy is not always possible. Multimodal imaging with widefield fundus photography, optical coherence tomography and angiography can help in the diagnosis of sarcoid uveitis and in the monitoring of treatment response. Corticosteroid remains the mainstay of treatment; chronic inflammation requires steroid-sparing immunosuppression. Features on multimodal imaging such as vascular leakage may provide prognostic indicators of outcome. Female gender, prolonged and severe uveitis, and posterior involving uveitis are associated with poorer visual outcomes.

Comparison of clinical features and outcomes between two age groups of cryptorchidism testicular torsion in children: a retrospective study in single center.

The purpose of this study was to compare the clinical characteristics and outcomes of children with cryptorchidism testicular torsion between the younger age group and the older age group. We collected the clinical data of children with cryptorchidism complicated with testicular torsion in our hospital from January 1, 2013 to January 1, 2023. The patients were divided into two groups: the younger age group (1month∼4 years old, n = 7) and the older age group (4∼18 years old, n = 7). The differences of clinical manifestations and surgical results between the two groups were compared. A total of 14 patients with unilateral cryptorchidism testicular torsion were included in this study, including 9 on the left side and 5 on the right side. The main clinical manifestations were pain /swelling of groin. The rate of crying in the younger age group was significantly higher than those in the older age group [(5,71.4%) vs. (0,0.0%), P < 0.05]. The median duration of symptoms of the younger group was less than the older group [42(7,96) h vs. 70(24, 96) h, P > 0.05]. The ipsilateral testicular salvage rate in the younger age group was 14.3% (1/7), which was lower than the older age group 57.1% [(4/7), P > 0.05]. The degree of testicular torsion in younger age group was more severe than the older age group [720(360, 1,080)° vs. 360(270, 360)°, P > 0.05]. The overall salvage rate of cryptorchidism testicular torsion is low. Although the duration of symptoms in the older age group was longer, the salvage rate of the older age group seemed to be higher than that in the younger age group. In addition, physical and imaging examination of the reproductive system should be carried out in time to identify the children with cryptorchidism testicular torsion in the early stage.

Psoriatic Arthritis Involving TMJ: A Review on Pathogenesis and Consideration on Eventual Gender Differences.

Psoriatic arthritis is defined as chronic inflammatory arthritis associated with psoriasis. The current data regarding gender differences in clinical manifestation and therapeutic outcomes of psoriatic arthritis are limited. Generally, men show a peripheral disease manifestation, while women have an axial distribution of the lesions. If we look at temporomandibular joint (TMJ) involvement, epidemiological data on the involvement of the TMJ are hard to find. Few studies on therapeutic management and the related impact on the quality of life are reported in the literature. Given the morpho-functional peculiarities of the TMJ and the different pain burdens between male and female genders, when manifestation of psoriatic arthritis occurs, clinicians should face it using a multidisciplinary approach for a correct diagnosis and successful treatment. This review aims to examine the diagnostic signs of psoriatic arthritis in the TMJ, the eventual variations of this disease in male and female patients, and the therapeutical strategies. The coordination of different specialties is fundamental to the remission of clinical symptoms and lesion regression.

Cognition and Cognitive Reserve.

Cognition is a mental process that provides the ability to think, know, and learn. Though cognitive skills are necessary to do daily tasks and activities, cognitive aging causes changes in various cognitive functions. Cognitive abilities that are preserved and strengthened by experience can be kept as a reserve and utilized when necessary. The concept of reserving cognition was found when people with Alzheimer's disease had differences in clinical manifestations and cognitive functions. The cognitive reserve builds resilience against cognitive decline and improves the quality of life. Also, several lines of studies have found that the plasticity between neurons has a significant impact on cognitive reserve and acts against cognitive decline. To extend the findings, the present study provides a comprehensive understanding of cognitive reserve and the variables that are involved in maintaining cognition. The study also considers reading as one of the cognitive proxies that develops and maintains cognitive reserve.

Molecular-genetic foundations of energy exchange and physical qualities of man. Research perspectives

Human physical qualities represent a complex trait influenced by environmental and genetic factors, with most traits being polygenic in nature. The study of the relationship between molecular genetic data, physical characteristics and metabolic individuality (regulation of biogenesis, energy balance, lipid metabolism, glucose homeostasis, etc.) is a promising vector of research, both in the population as a whole and in various nosologies, primarily for hereditary and metabolic diseases characterized by impaired physical development and metabolic balance, including cystic fibrosis (CF), obesity, diabetes mellitus. The first studies were devoted to the study of these parameters in athletes. The genotype-phenotype study in CF has been actively studied for the past few years. It has been shown that environmental factors can determine clinical polymorphism in CF, which account for nearly 50% of lung function variability in this disease. However, CF patients with similar molecular genetic variants of the CFTR gene and in a single habitat (for example, in siblings) can have highly variable clinical manifestations. Genes whose products provide cell energy exchange (PPARA, PPARG, PPARD, PGC-1, UCP2, UCP3, ACTN, ACE) can also be “modifiers” and have an effect on the phenotype, the difference in clinical manifestations of the disease of patients with CF, the relationship of which in this category of patients has not been studied. The world has seen a steady increase in obesity and its complications. Patients with CF from the category of persons with nutritional deficiency in recent decades began to move into the category of overweight patients, which requires study. This review summarizes the recent achievements of studying genes whose products provide energy exchange of the cell, discusses the development of the relationship both with the physical characteristics of individuals and with pathological changes in the body as a result of the appearance of metabolic products in excess or with altered physicochemical properties and functional activity parameters leading to various diseases.

Clinical characteristics and outcomes of patients with mpox during the 2022 mpox outbreak compared with those before the outbreak: A systematic review and meta-analysis.

On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that caused the outbreak was classified as clade IIb, which belongs to the West African clade. However, the relationship between MPXV clades and symptoms, as well as the severity of mpox outcomes, is not fully understood. Thus, we aimed to investigate the global mpox prevalence and the differences in clinical manifestations and outcomes among patients with mpox between pre-outbreak (2003-2021) and the current mpox outbreak. In this systematic review and meta-analysis, PubMed/MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were searched using the keyword "monkeypox" and "mpox" up to 13 October 2022. A random effects model was used to obtain the pooled prevalence and 95% confidence intervals. This study included 27 articles, and 5698 patients with mpox with 19 distinctive features from 19 countries across five continents were assessed. Patients with mpox during the 2022 mpox outbreak showed mild clinical manifestations and outcomes compared with those before the 2022 mpox outbreak: mild rash (relative ratio [RR]: 5.09, 95% confidence interval [CI]: 1.52-17.08), fever (0.68, 0.49-0.94), pruritus (0.25, 0.19-0.32), myalgia (0.50, 0.31-0.81), headache (0.56, 0.35-0.88), skin ulcer (0.32, 0.17-0.59), abdominal symptom (0.29, 0.20-0.42), pharyngitis (0.32, 0.18-0.58), nausea or vomiting (0.15, 0.02-0.93), conjunctivitis (0.11, 0.03-0.38), concomitant infection with HIV (1.70, 0.95-3 0.04), and death (0.02, 0.001-0.31). MPXV clade IIb exhibited higher infectivity but may cause mild disease symptoms and low mortality rate. It is important to consider MPXV infection in patients with mpox-related features and/or a history of sexual transmission to prevent the spread of the disease and recognise the current pandemic threat.

The Differences in Clinical Manifestations and Prognosis of Infective Endocarditis Patients With Positive Serology to Antineutrophilic Cytoplasmic Antibody Compared to Negative Serology.

Previous studies have established a relationship between bacterial proteins and autoimmune diseases through several mechanisms. Infective endocarditis is known for its immunological phenomena, and the presence of antineutrophil cytoplasmic antibodies (ANCA) antibodies has been previously demonstrated in several infectious diseases. This retrospective, comparative, and descriptive study examined the relationship between infective endocarditis and the presence of ANCA antibodies. Ninety infective endocarditis cases were included in the study and tested for ANCA antibodies. The prevalence of ANCA positivity was determined, along with the differences in characteristics and prognosis between infective endocarditis patients with positive and negative serology for ANCA antibodies. The results showed that the characteristics of endocarditis patients who underwent ANCA serology testing were similar to those who did not, except for a higher prevalence of central line and chronic kidney disease in patients with ANCA serology (6.7% compared to 1.1% and 25.6% compared to 12.9%, respectively). Of the 90 endocarditis patients tested for ANCA serology, 18% were ANCA-positive, consistent with other prospective studies. There were no statistically significant differences in the primary outcome, six-month and one-year mortality, between patients with positive and negative ANCA serology. Similarly, in the secondary outcomes of acute kidney injury, heart surgery, and days of hospitalization, there were no statistically significant differences between patients with positive and negative ANCA serology. However, there were statistically significant differences in certain characteristics between the two groups. Patients with positive ANCA serology were found to have a higher prevalence of Enterococcus involvement (29.4% compared to 9.6% with P-value 0.046) and Q fever (23.5% compared to 4.1% P-value 0.02%). In contrast, patients with negative ANCA serology had a higher prevalence of fever (73% compared to 41% P-value 0.033).

Emergency department evaluation of transplanted children with COVID-19

BackgroundChildren usually have an asymptomatic or mild course of SARS-CoV-2 infection, studies in immunocompromised patients have shown a different evolution. The aim of this study was to describe the clinical, laboratory, and radiologic manifestations of pediatric solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients testing positive for SARS-CoV-2. MethodsA multicenter retrospective, observational descriptive study was conducted in 3 tertiary hospitals in Madrid (Spain) between March 2020 and December 2022. Consecutive patients aged 0–18 attending the corresponding pediatric emergency departments with a positive result in the real-time polymerase chain reaction test or antigenic test to detect SARS-CoV-2 in the nasopharyngeal sample were included. ResultsA total of 31 children were included in the study. Sixteen (51.6%) were patients with HSCT and 15 (48.3) were patients with SOT. The median time from transplantation to COVID-19 was 1.2 years (IQR:0.5–5.1). The SOT cohort included liver (n = 4, 12.9%), kidney (n = 4, 12.9%), heart (n = 3, 9.7%), multivisceral (n = 3, 9.7%), and lung (n = 1, 3.2%). Of the 31 patients, only one was asymptomatic. The most common symptom on presentation was fever (76.7%). Abnormalities were seen on chest X-ray in 8 (66.6%) of the 12 patients. There was no significant difference in clinical manifestations, lymphopenia and radiological findings regardless of the type of transplantation or immunosuppression status. Thirteen patients (41.9%) were hospitalized. There were no patient deaths. ConclusionsIn our study, we found that the clinical course and outcome of SOT and HSCT pediatric patients with COVID-19 were generally favorable.

Interaction between Chronic Influenza and COVID-19: Novel Aspects of Immune System Combat

This abstract provides an overview of two highly contagious viruses - influenza viruses and the COVID-19 virus, causing severe acute respiratory illness. The paper examines common and unique characteristics of the viruses, their structure, transmission mechanisms, and pathogenesis. Special attention is given to differences in clinical manifestations, spread dynamics, and strategies to combat each of them. The consequences of epidemics and public health measures aimed at preventing virus spread are analyzed. This abstract offers a comprehensive overview of key aspects of influenza and COVID-19 virology, contributing to a contemporary understanding and fight against infectious diseases.

2661. Characterization of Mpox in Southeast Michigan

Abstract Background More than 30,000 cases of mpox have been identified in the United States. Data suggest that about 40% of affected persons are co-infected with HIV. Although most cases are self-limiting, patients with low CD4 counts are at increased risk of developing severe clinical manifestations and dying. Methods Retrospective case-control study comparing mpox cases among people with HIV (PWH) and HIV-uninfected persons from July to Dec 2022, at Henry Ford Health in Southeast Michigan. Demographic data, clinical characteristics, treatment, and outcomes were evaluated. Results 54 patients were diagnosed with mpox. Overall, 42 (78%) were MSM or bisexual men, 36 (67%) Black, and 34 (63%) PWH; median age was 34.5 years (Table 1). The majority (63%) had prior sexually transmitted infections (STIs), which were more common in PWH (82% vs 30%, p&amp;lt; 0.001). About one-third had multiple sexual partners; more than half engaged in insertive or receptive anal intercourse. 32 (94%) of PWH were on ART, 26 (76%) had CD4 counts &amp;gt;200 and 19 (60%) had undetectable viral load; mean CD4 count was 602 and viral load 7942. Of the HIV-uninfected persons, 5 (25%) were on PrEP. Receipt of mpox vaccine was uncommon in either group. All patients presented with rash that was disseminated in 35%. Fever/chills, lymphadenopathy, headache, proctitis and pharyngitis were the most common manifestations and did not differ among the two groups. Concomitant STIs were present in 22 (48%) of 46 persons tested; syphilis co-infection was more prevalent among PWH (35% vs 25%, p&amp;lt; 0.006). Hospitalization and receipt of tecovirimat were similar between the two groups; no patients died. Demographics, Risk Factors, Clinical Manifestations and Outcomes of Mpox Patients Conclusion Overall, there were no significant differences in clinical manifestations or outcomes between PWH and HIV-uninfected persons with mpox except for syphilis co-infection. Most of our PWH cohort was on ART and virally suppressed with high CD4 count. Hence, efforts should focus on rapid treatment of PWH with effective ART to achieve virological suppression and immunological recovery to minimize clinical complications and severe outcomes associated with opportunistic pathogens. Vaccinating all high-risk individuals, early mpox recognition and testing, and screening for additional STIs should be prioritized. Disclosures Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria

Clinical particulars of acute coronary syndrome course in patients with COVID-19

Background: Cardiovascular complications of COVID-19 result in challenges for differential diagnosis, patients referral and treatment, which negatively affect the outcomes.&#x0D; Aim: To identify clinical particulars of various types acute coronary syndrome course in patients with COVID-19.&#x0D; Materials and methods: This retrospective cross-sectional study included 202 patients with COVID-19 and acute coronary syndrome (ACS) admitted to a primary vascular medicine center from September to December 2020. Their medical records were used for the analysis of ACS and COVID-19 clinical course, including physical and history data, laboratory and instrumental work-up. For the analysis, the patient sampling was divided into three study groups: 50 patients with unstable angina (UA), 107 patients with acute myocardial infarction with ST segment elevation (STEMI), and 45 patients with acute myocardial infarction without ST segment elevation (non-STEMI).&#x0D; Results: There were no differences in clinical manifestations of ACS in the study groups. As far as clinical manifestations of coronavirus infections are concerned, the patients differed significantly as per prevalence of fever and dry cough. Fever was present in 22 (44%) UA patients, 18 (17%) of STEMI patients and in 10 (22%) of non-STEMI patients (p 0.001 for comparison of 3 groups, Kruskall-Wallis test), whereas dry cough was present in 18 (36%), 19 (18%), and 14 (31%) patients, respectively (p = 0.029). Paired comparison (Mann-Whitney test with Bonferroni adjustment) showed significant differences between US and STEMI groups for both symptoms. The number of involved vessels (median [25%; 75%]) in UA patients was 0 [0; 2], in STEMI and non-STEMI patients 2 [1; 3] (p 0.001). A left coronary artery stenosis was detected in 2 (6%) of the UA patients, 13 (14%) of the STEMI and 4 (13%) of the non-STEMI patients (p = 0.452); left anterior descending artery stenosis, in 12 (36%), 67 (72%) and 23 (72%) patients, respectively (p 0.001). In the pairwise comparison, there were differences between UA and STEMI groups and between UA and non-STEMI groups. A left circumflex artery stenosis was found in 7 (21%) of the UA patients, 45 (48%) of the STEMI and 18 (56%) of the non-STEMI patients (p = 0.008); the pairwise comparisons showed the difference between UA and non-STEMI study groups. A right coronary artery stenosis was identified in 9 (27%), 64 (69%) and 18 (56%) of the study patients, respectively (p 0.001); in the pairwise comparison the difference was found between the UA and STEMI group. There were significant differences in the percentage of the right descendent and right coronary artery stenosis: the right descending artery stenosis was 70% [45; 80] in the UA patients, 90% [70; 100] in the STEMI and 95% [70; 100] in the non-STEMI patients (p = 0.013), whereas the right coronary artery stenosis was 50% [45; 80], 90% [70; 100], 90% [60; 100], respectively (p = 0.018). In the pairwise comparison, the differences were found between the UA and STEMI patients in both arteries. The STEMI patients had higher TIMI thrombus grade scores than those with non-STEMI: 3 [0; 5] vs 0 [0; 4] (p = 0.023). The rates of successful percutaneous coronary intervention and achievement of TIMI flow grade 3 between them was not significantly different (p = 0.170).&#x0D; Conclusion: The ACS patients with ACS and COVID-19 have high thrombotic load according to coronary angiography and TIMI score in the case of STEMI and more frequent absence of hemodynamically significant stenosis in those with UA and non-STEMI. The absence of any difference in clinical manifestations of ACS and viral infection between the study groups (except fever and dry cough difference between the UA and STEMI patients) indicates that specific characteristics of the ACS course in COVID-19 patients can be identified only by coronaroangiography.

Sex-related differences in patient characteristics, and efficacy and safety of advanced therapies in randomised clinical trials in psoriatic arthritis: a systematic literature review and meta-analysis

Sex-related differences in clinical manifestations and disease outcomes exist in psoriatic arthritis, however, there is limited information on sex-related differences in randomised controlled trials of psoriatic arthritis. We aimed to compare patient characteristics and efficacy and safety of advanced therapies (including biological and targeted synthetic therapies) between male and female patients with psoriatic arthritis participating in randomised controlled trials. In this systematic review and meta-analysis, we searched Medline, Embase, and Central databases, and conference abstract archives, from their inception to June 10, 2022, for randomised controlled trials that assessed the efficacy of advanced therapies in psoriatic arthritis. Two reviewers extracted information on participants' characteristics and rates of American College of Rheumatology (ACR) 20 and ACR50 response and minimal disease activity (MDA) by sex. Random-effects models were used to calculate pooled effects of ACR20, ACR50, and MDA in male versus female patients by drug class. We included 54 trials (11 514 [50·9%] of 22 621 participants were female and 11 107 [49·1%] were male). Sex-disaggregated results were reported in a minority of studies (nine [17%] of 54 reported baseline characteristics by sex, 18 [33%] reported efficacy by sex, and two [4%] reported safety endpoints by sex). At baseline, male patients had lower baseline tender joint count (mean difference -3·01 [95% CI -3·83 to -2·18], health assessment questionnaire scores (-0·28 [-0·33 to -0·24]), pain scores (-4·58 [-6·86 to -2·30]), patient global assessment (-3·22 [-5·27 to -1·17]), and physician global assessment (-1·34 [-2·08 to -0·08]) than did female patients. Male patients had higher baseline psoriasis area and severity index scores (mean difference 1·95 [95% CI 0·78 to 3·11]) and C-reactive protein concentrations (2·57 [0·40 to 4·74]) than did female patients. ACR20 response by sex varied across drug classes, with higher rates in males than females with interleukin (IL)-17 inhibitors (odds ratio [OR] 1·70 [95% CI 1·38-2·11]), IL-23 inhibitor (1·46 [1·20-1·78]), IL-12 and IL-23 inhibitor (2·67 [1·39-5·09]), and tumour necrosis factor (TNF) inhibitors (1·55 [1·11-2·18]), but no difference with JAK and TYK2 inhibitors (1·10 [0·87-1·38]). Similarly, ACR50 response rates were higher in male patients versus female patients in all drug classes, with exception of JAK and TYK2 inhibitors (TNF inhibitors, OR 2·17 [95% CI 1·62-2·90]; IL-17 inhibitors, 1·93 [1·56-2·38]; IL-23 inhibitor, 1·71 [1·25-2·34]; IL-12 and 23 inhibitor, 2·43 [1·14-5·20]; and JAK and TYK2 inhibitors, 1·09 [0·73-1·62]). Male patients were more likely to reach MDA with most drug classes, including IL-17 inhibitors (OR 1·99 [95% CI 1·50-2·63]), IL-23 inhibitors (1·79 [1·29-2·50]), TNF inhibitors (2·62 [1·54-4·44]), and JAK and TYK2 inhibitors (1·77 [1·15-2·73]). Risk of bias was low for most studies. Biological sex of patients with psoriatic arthritis influences their response to advanced therapies, but the effect varies by drug class. Selective reporting might have influenced these results. Future trials should report baseline characteristics and endpoint results by sex. Canadian Rheumatology Association.

Genotype-phenotype spectrum and prognosis of early-onset Marfan syndrome

BackgroundMarfan syndrome is a genetic connective tissue disorder affecting skeletal, ocular, and cardiovascular organ systems. Previous research found that pathogenic variants clustered in exons 24–32 of fibrillin-1 (FBN1) gene result in more severe clinical phenotypes. Furthermore, genotype-phenotype correlation studies suggested that more severe cardiovascular phenotypes were related to variants held responsible for haploinsufficiency. Our objective was to analyze the differences in clinical manifestations and genotypes of individuals with early-onset Marfan syndrome and to assess their impact on management strategies.MethodsWe analyzed clinical and genetic data of a new patient with early-onset Marfan syndrome together with 51 previously reported ones in the PubMed database between 1991 and 2022.ResultsAnalysis showed 94% (49/52) of pathogenic variants clustered in exons 24–32 of the FBN1. The most common skeletal features were arachnodactyly (98%), reduced elbow extension (48%), pectus deformity (40%), and scoliosis (39%). Haploinsufficiency variants were reported as having poor outcome in 87.5% of the cases. Among patients carrying variants that substitute a cysteine for another amino acid and those that do not change cysteine content, cardiac intervention was found to be associated with a better outcome (p = 0.035 vs. p = 0.002). Variants that create an extra cysteine residue were found to be associated with a higher risk of ectopia lentis. Additionally, children up to 36-months-old were more often reported as still alive at the time of publication compared to newborns (p < 0.01).ConclusionsOur findings have implications for prognosis, because different genotype groups and their resulting phenotype may require personalized care and management.

Implications of combined NOD2 and other gene mutations in autoinflammatory diseases.

NOD-like receptors (NLRs) are intracellular sensors associated with systemic autoinflammatory diseases (SAIDs). We investigated the largest monocentric cohort of patients with adult-onset SAIDs for coinheritance of low frequency and rare mutations in NOD2 and other autoinflammatory genes. Sixty-three patients underwent molecular testing for SAID gene panels after extensive clinical workups. Whole exome sequencing data from the large Atherosclerosis Risk in Communities (ARIC) study of individuals of European-American ancestry were used as control. Of 63 patients, 44 (69.8%) were found to carry combined gene variants in NOD2 and another gene (Group 1), and 19 (30.2%) were carriers only for NOD2 variants (Group 2). The genetic variant combinations in SAID patients were digenic in 66% (NOD2/MEFV, NOD2/NLRP12, NOD2/NLRP3, and NOD2/TNFRSF1A) and oligogenic in 34% of cases. These variant combinations were either absent or significantly less frequent in the control population. By phenotype-genotype correlation, approximately 40% of patients met diagnostic criteria for a specific SAID, and 60% had mixed diagnoses. There were no statistically significant differences in clinical manifestations between the two patient groups except for chest pain. Due to overlapping phenotypes and mixed genotypes, we have suggested a new term, "Mixed NLR-associated Autoinflammatory Disease ", to describe this disease scenario. Gene variant combinations are significant in patients with SAIDs primarily presenting with mixed clinical phenotypes. Our data support the proposition that immunological disease expression is modified by genetic background and environmental exposure. We provide a preliminary framework in diagnosis, management, and interpretation of the clinical scenario.

Age-related genes USP2 and ARG2 are involved in the reduction of immune cell infiltration in elderly patients with rheumatoid arthritis.

There are large differences in clinical manifestations and biological markers between elderly patients with rheumatoid arthritis (EPRA, age >60) and younger patients with RA (YPRA, age ≤60), partly owing to variations in the immune system of different age groups. Here, we focused on the changes of immune cell infiltration in YPRA and EPRA. The R packages "ssGSEA" and "GSEA" were used to identify the changes in immune cell infiltration and immune-related pathways between the two groups. The R packages "WGCNA" and "DEseq2" were used to screen and verify age-related differentially expressed genes (DEGs). Hub genes were identified using Cytoscape and cytoHubba. Spearman correlation coefficient was conducted to evaluate correlations between hub age-related genes and immune cells. Compared with 54 established YPRA, several immune cells and immune-related pathways were markedly decreased in 29 EPRA synovial tissues. Moreover, 78 age-related DEGs related to amino acid and glycosphingolipid synthesis and metabolism were identified. USP2 and ARG2 were verified to be upregulated in EPRA, signifying that these two genes could effectively distinguish YPRA and EPRA and have potential as biomarkers. In addition, we found that USP2 was significantly negatively correlated with B cells and monocytes, while there was a significant negative association between ARG2 and T cells. In conclusion, this study is the first to systematically analyze changes in immune cell infiltration between YPRA and EPRA patients and obtain hub age-related genes, which may provide the basis for illuminating the pathogenesis of EPRA and informing treatment strategies.

Molecular characterization of Streptococcus pneumoniae causing disease among children in Nigeria during the introduction of PCV10 (GSK).

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (n=189) and Abuja (n=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, n=35), 6B (16 %, n=31), 1 (9 %, n=17), 5 (9 %, n=17) and 6A (9 %, n=17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance.

A hospital-based retrospective study: early recognition of neuronal surface antibodies by clinical manifestations and CSF inflammation indicators in patients with unexplained epilepsy

Background There is a lack of actual and comprehensive data on the detection rate of neuronal surface antibodies in patients with unexplained epilepsy in China. Thus, we attempted to analyze the differences in clinical manifestations, cerebrospinal fluid (CSF) characteristics, seizure types and other aspects of antibody-positive and negative patients, to identify suspected antibody-positive epilepsy patients. Methods In total, 137 inpatients with unexplained epilepsy were consecutively included, and neuronal surface antibodies (NSAbs) were detected by serological and/or CSF evaluations. The clinical features and seizure characteristics were analyzed between the NSAb-positive and negative patients. In addition, patients were divided into four groups based on CSF and blood antibody titers. CSF cell count and protein content were analyzed in relation to antibody titers. Results There were 45 (32.8%) patients tested positive for antibodies. Multivariate analyses revealed that age, mental status changes or memory deterioration, CSF protein, CSF cell count, treatment, days of hospitalization, outcome, duration of symptoms before hospitalization, status epilepticus, and number of antiepileptic drugs were significantly associated with the NSAb-positive group and changes in inflammatory indicators in routine CSF analysis were associated with antibody titers. Conclusions A relatively high proportion of patients with unexplained epilepsy have positive NSAbs. Patients with the above clinical characteristics need to be highly suspected of NSAbs positivity and should be tested for antibodies in time to assist treatment. The decrease of CSF cell count and protein content has suggestive value for the decrease of antibody titer, which should be evaluated in the follow-up.