Distinct Clinical Patterns Research Articles

Understanding Trauma in IPV: Distinguishing Complex PTSD, PTSD, and BPD in Victims and Offenders.

This work aims to shed light on the differential diagnosis of complex post-traumatic stress disorder (cPTSD), post-traumatic stress disorder (PTSD), and borderline personality disorder (BPD) within the context of intimate partner violence (IPV), which represents a highly innovative field of clinical research. To this end, a critical review of the literature was conducted to identify and compare the clinical patterns and symptomatic overlaps among cPTSD, PTSD, and BPD, with an emphasis on their manifestation in both IPV victims and offenders. The results show that despite some symptomatic similarities, cPTSD, PTSD, and BPD have distinct clinical patterns of interpersonal violence. Specifically, disturbances in self-organization (DSO) are more commonly found in offenders, while the diagnosis of cPTSD seems more aligned with the psychological functioning of victims. In addition, cPTSD and specific characteristics of BPD, such as fear of rejection and instability of identity, constitute risk factors for IPV victimization. cPTSD is shown as a predisposing factor not only for IPV victims but also for offenders, while PTSD emerges as a consequential factor. The specific pathways linking PTSD, cPTSD, and BPD with IPV have significant implications for clinical practice. Further research is needed to understand these profiles and the mechanisms linking trauma-related features to IPV, which is crucial for implementing effective violence prevention programs.

Revealing the distinct clinical patterns and relapse risk factors in seronegative IgG4-RD patients: A retrospective cohort study over a decade.

Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients. We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model. Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (p<0.0001), lower eosinophil count (p<0.0001), lower serum IgE levels (p<0.0001)), lower IgG4-RD responder index (RI) scores (p<0.0001), and fewer affected organ numbers (p<0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse. Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.

CMV-Related Anterior Uveitis in a Mediterranean European Population: Clinical Features, Prognosis, and Long-Term Treatment Outcomes

ABSTRACT Purpose To describe the spectrum of clinical features of cytomegalovirus-related anterior uveitis (CMV-AU) along with potential comorbidities, to calculate complication rates, and to determine risk factors and biomarkers affecting prognosis in a cohort of a Southern European Mediterranean population. Materials and methods It is a retrospective, multicenter case series of consecutive patients with persisting hypertensive AU, unresponsive to topical steroids therapy, and CMV-positive essays from two uveitis referral centers were collected and analyzed. Results Fifty-seven eyes of 53 patients with polymerase chain reaction-verified CMV-AU over a period of 8 years were included with a mean age of 48 ± 18. Four presentation patterns were identified: 26.3% as Posner–Schlossman-like, 31.6% as chronic AU, 19.3% as presumed herpetic uveitis, 12.3% as Fuchs uveitis syndrome-like, and 10.5% without specific initial classification. About 15.8% received oral valganciclovir, 22.8% received topical valganciclovir, and 61.4% received both, for a mean duration of treatment of 44 months. AU recurrences were observed in 23 eyes with a mean of 1.5 (±1.5) recurrences per year. The only finding significantly associated with recurrence was the presence of posterior synechiae (PS) (p = 0.034). Fewer keratic precipitates (KPs) were indicative for the need of longer treatment, and endotheliitis was strongly associated with the need for filtration surgery. Conclusion In this immunocompetent southern European population, four distinct clinical presentation patterns were further confirmed, and possible biomarkers such as PS, KPs, and endotheliitis were newly reported to influence treatment outcomes. Large-scale studies could provide a more effective customized treatment protocol.

A Treg-related riskscore model may improve the prognosis evaluation of colorectal cancer.

Colorectal cancer (CRC) poses a significant health challenge. This study aims to investigate the prognostic value of a regulatory T cell (Treg)-related gene signature in CRC. We extracted the gene expression and clinical data on CRC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The gene module related to Treg was identified by weighted gene co-expression network analysis (WGCNA). The genes in the significant module were filtered by univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. A riskscore model was established in terms of the key Treg-related genes. The reliability of this riskscore model was validated using the external GEO dataset. The association of riskscore with clinical features, mutation patterns and signaling pathways was explored. Genes in the blue module showed the strongest association with Tregs. After a series of filtering cycles, seven Treg-related key genes, GDE1, GSR, HSPB1, AOC2, TBX19, TAMM41 and TIGD6, were selected to construct a riskscore model. This model performed well in evaluating the patients' survival in TCGA cohort, and was further affirmed by the GSE17536 validation cohort. For precise evaluation of the patients' survival, we established a nomogram in light of riskscore and clinical factors. Patients in different risk groups had distinct clinical features, mutation patterns and signaling pathway activities. The expression of five key genes was significantly associated with Treg infiltration in the CRC samples. We established a useful riskscore model in light of seven Treg-related genes. This model may contribute to the prognosis evaluation, direct tailored treatment, and hopefully improve clinical outcomes of the CRC patients.

Identification of Distinct Clinical Presentation Patterns of Food Allergies in Infancy: A Retrospective Cohort Study

Identification of Distinct Clinical Presentation Patterns of Food Allergies in Infancy: A Retrospective Cohort Study

Systemic Lupus Erythematosus Patients in the Qassim Region, Saudi Arabia: Insights on Peripheral Nervous System Involvements

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with diverse clinical manifestations. This study aimed to investigate the prevalence, clinical features, and risk factors associated with peripheral nervous system (PNS) involvement in SLE patients. Materials and Methods: This study encompassed a retrospective analysis involving 377 SLE patients diagnosed according to the European Alliance of Associations for Rheumatology/American College of Rheumatology criteria at Qassim region in Saudi Arabia, conducted through a meticulous chart review facilitated by proficient data collectors. A structured data collection form/checklist, incorporating explicit definitions and instructions, was utilized for extracting information from patient files, papers, and databases. Additionally, the SLE Quality of Life Questionnaire was employed to evaluate the quality of life among the participants. A multivariate logistic regression model was employed to identify independent predictors of PNS involvement. Results: Distinct clinical patterns were observed in SLE patients with PNS involvement, including a higher prevalence of nonscarring alopecia, acute cutaneous lesions, oral ulcers, and seizures. Diabetes and chronic kidney disease emerged as significant positive predictors for PNS complications. Hematological abnormalities, renal involvement, and vitamin deficiencies were prevalent, contributing to an overall poor quality of life among these patients. Conclusion: This study underscores the need for heightened clinical awareness of PNS complications in SLE, emphasizing the impact of diabetes and chronic kidney disease as significant risk factors. Early detection and targeted interventions are crucial to improving outcomes and enhancing the overall quality of life for SLE patients with PNS involvement.

Novel data-driven subtypes and stages of brain atrophy in the ALS–FTD spectrum

BackgroundTDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS–FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS–FTD spectrum.MethodsWe used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS–FTD patients with likely TDP-43. A Subtype and Stage Inference (SuStaIn) model was trained to identify subtypes of individuals along the ALS–FTD spectrum with distinct brain atrophy patterns, and we related subtypes and stages to clinical, genetic, and neuropathological features of disease.ResultsSuStaIn identified three novel subtypes: two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions, and a normal-appearing group without obvious brain atrophy. The limbic-predominant subtype tended to present with more impaired cognition, higher frequencies of pathogenic variants in TBK1 and TARDBP genes, and a higher proportion of TDP-43 types B, E and C. In contrast, the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A. The normal-appearing brain group showed higher frequency of ALS relative to ALS–FTD and bvFTD patients, higher cognitive capacity, higher proportion of lower motor neuron onset, milder motor symptoms, and lower frequencies of genetic pathogenic variants. The overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration, higher King’s stage, and cognitive decline. Additionally, SuStaIn stages differed across clinical phenotypes, genotypes and types of TDP-43 pathology.ConclusionsOur findings suggest distinct neurodegenerative subtypes of disease along the ALS–FTD spectrum that can be identified in vivo, each with distinct brain atrophy, clinical, genetic and pathological patterns.

Clinical characteristics of probands with obsessive-compulsive disorder from simplex and multiplex families

Genetic and non-genetic factors contribute to obsessive-compulsive disorder (OCD), with strong evidence of familial clustering. Genomic studies in psychiatry have used the concepts of families that are "simplex" (one affected) versus "multiplex" (multiple affected). Our study compares demographic and clinical data from OCD probands in simplex and multiplex families to uncover potential differences. We analyzed 994 OCD probands (501 multiplex, 493 simplex) from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Clinicians administered the Structured Clinical Interview for DSM-IV (SCID-IV) to diagnose, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) to assess severity, and Dimensional Yale–Brown Obsessive-Compulsive Scale (DY-BOCS) to assess symptom dimensionality. Demographics, clinical history, and family data were collected. Compared to simplex probands, multiplex probands had earlier onset, higher sexual/religious and hoarding dimensions severity, increased comorbidity with other obsessive-compulsive-related disorders (OCRD), and higher family history of psychiatric disorders. These comparisons provide the first insights into demographic and clinical differences between Latin American simplex and multiplex families with OCD. Distinct clinical patterns may suggest diverse genetic and environmental influences. Further research is needed to clarify these differences, which have implications for symptom monitoring and management.

Evaluation of COVID-19 Pneumonia in Children According to the Original Strain, Alpha, Delta and Omicron Variants

Objective: As known, COVID-19, stemming from the SARS-CoV-2 virus, exhibits distinct clinical patterns across various variants. This research endeavors to comprehensively analyze the variations in clinical presentations between these variants and the original strain, particularly in pediatric COVID-19 pneumonia cases. Materials and Methods: Patients diagnosed with COVID-19 pneumonia who were admitted to Mersin City Research and Training Hospital between June 2020-2022, were included in the study. Clinical and laboratory data of the patients were evaluated according to their variant status. Results: 56% (n=62) of 110 pediatric patients were female, and their average age was 11±5.9 (median 13). 31%(n=34) of the patients were infected with the original strain, 20% (n=22) were alpha, 40% (n=44) were delta, and 9% (n=10) were omicron variant. 6% (n=7) of the patients were asymptomatic, 11% (n=12) were mildly symptomatic, 76% (n=83) were moderate (respiratory distress), and 7% (n=8) were severe clinical patients requiring mechanical ventilation. Fever and shortness of breath were most frequently seen in delta, and cough in alpha variant (p=0.0001;p=0.014;p=0.039,respectively). The most severe disease detected in omicron was alpha, delta and original virüs (p=0.001). No relationship detected between the laboratory values of the patients and the variant status (p&gt;0.05). When patients were compared based on radiological severity, no significant differences were found between the variants (p=0.214). However, when cases were classified according to pneumonia severity, regardless of the variant status, higher levels of ferritin (p=0.0001) and CRP (p=0.037) were observed, while lymphocyte count (p=0.009) decreased with increasing pneumonia severity. It's noteworthy that no patient fatalities occurred. Conclusion: In our study, the most severe clinical picture was shown in the omicron variant, followed by the alpha variant. But, omicron cases were limited, and it is important to examine variants in a larger population.

Co-existent Dowling–Degos disease, reticulate acropigmentation of Kitamura, and acropigmentation of Dohi in two generations: An overlap or concept of a single disease?

Reticulate pigmentary disorders (RPDs) are a group of rare autosomal dominant dermatoses with a distinctive clinical net-like pattern with specific arrangements and distributions in each entity. A forty-year-old female presented with asymptomatic, light and dark, macular lesions existing for over fifteen years with perioral scars and palmer pits and her twenty-year-old daughter beginning to develop similar lesions four years earlier. Cutaneous and histopathological examinations suggested a diagnosis of Dowling–Degos disease co-existent with reticulate acropigmentation of Kitamura in the mother and Dowling–Degos disease co-existent with acropigmentation of Dohi in the daughter. The co-existence of three infrequently encountered dermatoses with an irregular disease presentation within the family suggested the possibility of differing entities in the reticulate pigmentary group of disorders belonging to the diverse spectrums of the same disease. Key words: Reticulate pigmentary disorders, Dowling–Degos disease, Reticulate acropigmentation of Kitamura, Reticulate acropigmentation of Dohi

Application of Herbs and Dietary Supplements in ADHD Management.

Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder, which is characterised by a distinct clinical pattern of inattention, hyperactivity as well as impulsivity, which in turn interferes with the day-to-day activities of the affected individual. Although conventional allopathic medications have been found to provide symptomatic relief, they are accompanied by a plethora of side effects that overshadow and outweigh the potential therapeutic benefits. Hence, various alternative approaches in the management of Attention Deficit Hyperactivity Disorder (ADHD) are actively being investigated. Over the past few decades, numerous studies have been initiated and have delved into potential alternative strategies in the treatment and management of ADHD. The primary focus of this article is to discuss the etiology, pathophysiology coupled with a financial background as well as alternative strategies in the treatment and management of ADHD. A review of the literature on the clinical trialson alternative treatment approaches for ADHD showed that, plants and dietary supplements have beneficial effects on ADHD management. But in-depth studies still need to be conducted because the trials reported till now have a smaller sample size and need to be scaled up to get a broader understanding and knowledge of the potential impact of alternative forms of natural treatment on the patient population with ADHD. Also, the manufacturer of the alternative formulations needs to develop effective protocols and processes for the safe, effective, and robust manufacturing of such natural remedies, which fall in line with the expectation of the FDA to gain regulatory clearance for its manufacturing and sale, which can lead to better therapeutic outcomes in patients.

Gender differences in prevalence and associated factors of metabolic syndrome in first-treatment and drug-naïve schizophrenia patients

BackgroundMetabolic syndromes (MetS) are clinical syndromes involving multiple pathological states with distinct gender-specific clinical patterns. As a serious disorder associated with psychiatric conditions, the prevalence of MetS is significantly higher in the population with schizophrenia (Sch). The aim of this paper is to report gender differences in the prevalence, associated factors and severity-related factors of MetS in first-treatment and drug-naïve (FTDN) patients with Sch.MethodsA total of 668 patients with FTDN Sch were included in this study. We collected socio-demographic and general clinical information on the target population, measured and evaluated common metabolic parameters and routine biochemical indicators, and assessed the severity of psychiatric symptoms using Positive and Negative Symptom Scale (PANSS).ResultsIn the target group, the prevalence of MetS was significantly higher in women (13.44%, 57/424) than in men (6.56%, 16/244). In the males, waist circumference (WC), fasting blood glucose (FBG), diastolic blood pressure (DBP), and triglycerides (TG) were risk factors for MetS, while systolic blood pressure (SBP), TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and platelet (PLT) were risk factors for the females. More importantly, for the females, we found that age, LDL-C, PANSS scores and blood creatinine (CRE) were risk factors for higher MetS scores, while onset age and hemoglobin (HGB) were protective factors.ConclusionThere are significant gender differences in the prevalence of MetS and its factors among patients with FTDN Sch. The prevalence of MetS is higher and the factors that influence MetS are more numerous and extensive in females. The mechanisms of this difference need further research and clinical intervention strategies should be formulated with gender differences.

Randomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced or Metastatic Non-Small-Cell Lung Cancer.

To investigate the efficacy and safety of bevacizumab plus carboplatin and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer. In a phase II trial, 99 patients were randomly assigned to bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). Primary efficacy end points were time to disease progression and best confirmed response rate. On disease progression, patients in the control arm had the option to receive single-agent bevacizumab 15 mg/kg every 3 weeks. Compared with the control arm, treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5% v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest increase in survival (17.7 v 14.9 months). Of the 19 control patients that crossed over to single-agent bevacizumab, five experienced stable disease, and 1-year survival was 47%. Bleeding was the most prominent adverse event and was manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and major hemoptysis. Major hemoptysis was associated with squamous cell histology, tumor necrosis and cavitation, and disease location close to major blood vessels. Bevacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.

Clinical Characteristics of Early-Onset Parkinson Disease in Mayo Clinic Population (P6-11.004)

<h3>Objective:</h3> To describe the demographic pattern and the clinical characteristics of the patients with Early Onset Parkinson’s Disease (EOPD) at the Mayo Clinic. <h3>Background:</h3> The causes of EOPD remain undefined; the clinical course and phenotypical characteristics of EOPD are different than those of late onset Parkinson disease. Unfortunately, there is still a gap of knowledge on EOPD. <h3>Design/Methods:</h3> We retrieved all the patients with EOPD that have visited the Mayo Clinic from 1990 to 2022 using Mayo Data Explorer (MDE). We included patients with a diagnosis of Parkinson’s disease (PD) at or before the age of 50 years old (according to the current Movement Disorder Society (MDS) recommendation on EOPD). In addition, we assessed the clinical features of those who were included. <h3>Results:</h3> A total of 838 (518 males and 320 females) patients with EOPD were included with a mean age at symptoms onset of 40.6 ± 6.7 years. Overall, 13.6% had a family history of PD, with only 4.5% with genetic testing. Resting tremor was reported in 84.8%, bradykinesia in 85.9%, rigidity in 81.3% and postural instability in 13.1%. Dyskinesias were documented in 44.4% with a mean time from PD diagnosis of 10.5 ± 6.2 years. Cognitive impairment was reported in 19.3% of patients with a mean time from PD diagnosis of 16.8 ± 14.3 years. <h3>Conclusions:</h3> We described the clinical characteristics of the EOPD in a large cohort. EOPD displays distinct clinical patterns regarding symptoms, progression, cognitive decline and response to medications. These differences may reflect multifactorial causes such as pathophysiological backgrounds and genetic, environmental, or age-related factors. <b>Disclosure:</b> Dr. Ghoniem has nothing to disclose. Dr. Jacobson has nothing to disclose. Aidan Mullan has nothing to disclose. Dr. Turcano has nothing to disclose. Dr. Camerucci has nothing to disclose. Mr. Stang has nothing to disclose. The institution of Dr. Bower has received research support from Abbvie. The institution of Dr. Savica has received research support from ACADIA Pharmaceuticals, Inc.

Clinical and microbiological profiles in post-chemotherapy neutropenic fever in hematological malignancy: exploration of clinical phenotype patterns by two-step cluster analysis

BackgroundEpidemiology of infectious diseases causing febrile illness varies geographically with human attributes. Periodic institutional surveillance of clinical and microbiological profiles in adding data to updating trends, modulating pharmatherapeutics, signifying possible excessive treatments and risk of drug resistance in post-chemotherapy neutropenic fever (NF) in hematological malignancy (HM) is limited. We aimed to review institutional clinical and microbiological data and explore clinical phenotype pattern groups among data.MethodsAvailable data from 372 NF episodes were included. Demographics, types of malignancies, laboratory data, antimicrobial treatments and febrile-related outcome data such as predominant pathogens and microbiological diagnosed infections (MDIs) were collected. Descriptive statistics, two-step cluster analysis and non-parametric tests were employed.ResultsThe occurrences of microbiological diagnosed bacterial infections (MDBIs; 20.2%) and microbiological diagnosed fungal infections (MDFIs; 19.9%) were almost equal. Gram-negative pathogens (11.8%) were comparable with gram-positive pathogens (9.9%), with gram-negative being slightly predominant. Death rate was 7.5%. Two-step cluster analysis yielded four distinct clinical phenotype pattern (cluster) groups: cluster 1 ‘lymphomas without MDIs’, cluster 2 ‘acute leukemias MDBIs’, cluster 3 ‘acute leukemias MDFIs’ and cluster 4 ‘acute leukemias without MDIs’. Considerable NF events with antibiotic prophylaxis being not identified as MDI might have cases in low-risk with non-infectious reasons causing febrile reactions that might possibly not require prophylaxis.ConclusionsRegular institutional surveillance with active parameter assessments to signify risk levels in the post-chemotherapy stage, even prior to the onset of fever, might be an evidence-based strategy in the management of NF in HM.

Identification of Three Different Phenotypes in Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis Patients: Implications for Prediction of Rapidly Progressive Interstitial Lung Disease.

There is substantial heterogeneity among the phenotypes of patients with anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis (DM), hindering disease assessment and management. This study aimed to identify distinct phenotype groups in patients with anti-MDA5+ DM and to determine the utility of these phenotypes in predicting patient outcomes. A total of 265 patients with anti-MDA5+ DM were retrospectively enrolled in the study. An unsupervised hierarchical cluster analysis was performed to characterize the different phenotypes. Patients were stratified into 3 clusters characterized by markedly different features and outcomes. Cluster 1 (n=108 patients) was characterized by mild risk of rapidly progressive interstitial lung disease (RPILD), with the cumulative incidence of non-RPILD being 85.2%. Cluster 2 (n=72 patients) was characterized by moderate risk of RPILD, with the cumulative incidence of non-RPILPD being 73.6%. Patients in cluster 3 (n=85 patients), which was characterized by a high risk of RPILD and a cumulative non-RPILD incidence of 32.9%, were more likely than patients in the other 2 subgroups to have anti-Ro 52 antibodies in conjunction with high titers of anti-MDA5 antibodies. All-cause mortality rates of 60%, 9.7%, and 3.7% were determined for clusters 3, 2, and 1, respectively (P < 0.0001). Decision tree analysis led to the development of a simple algorithm for anti-MDA5+ DM patient classification that included the following 8 variables: age >50 years, disease course of <3 months, myasthenia (proximal muscle weakness), arthritis, C-reactive protein level, creatine kinase level, anti-Ro 52 antibody titer, and anti-MDA5 antibody titer. This algorithm placed patients in the appropriate cluster with 78.5% accuracy in the development cohort and 70.0% accuracy in the external validation cohort. Cluster analysis identified 3 distinct clinical patterns and outcomes in our large cohort of anti-MDA5+ DM patients. Classification of DM patients into phenotype subgroups with prognostic values may help physicians improve the efficacy of clinical decision-making.

Clustering and prediction of long-term functional recovery patterns in first-time stroke patients.

The purpose of this study was to cluster long-term multifaceted functional recovery patterns and to establish prediction models for functional outcome in first-time stroke patients using unsupervised machine learning. This study is an interim analysis of the dataset from the Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO), a long-term, prospective, multicenter cohort study of first-time stroke patients. The KOSCO screened 10,636 first-time stroke patients admitted to nine representative hospitals in Korea during a three-year recruitment period, and 7,858 patients agreed to enroll. Early clinical and demographic features of stroke patients and six multifaceted functional assessment scores measured from 7 days to 24 months after stroke onset were used as input variables. K-means clustering analysis was performed, and prediction models were generated and validated using machine learning. A total of 5,534 stroke patients (4,388 ischemic and 1,146 hemorrhagic; mean age 63·31 ± 12·86; 3,253 [58.78%] male) completed functional assessments 24 months after stroke onset. Through K-means clustering, ischemic stroke (IS) patients were clustered into five groups and hemorrhagic stroke (HS) patients into four groups. Each cluster had distinct clinical characteristics and functional recovery patterns. The final prediction models for IS and HS patients achieved relatively high prediction accuracies of 0.926 and 0.887, respectively. The longitudinal, multi-dimensional, functional assessment data of first-time stroke patients were successfully clustered, and the prediction models showed relatively good accuracies. Early identification and prediction of long-term functional outcomes will help clinicians develop customized treatment strategies.

Distinct clinical pattern of colorectal cancer patients with POLE mutations: A retrospective study on real-world data.

Objective: Studies have demonstrated an association between somatic POLE exonuclease domain mutations (EDMs) and the prognosis of colorectal cancer (CRC). However, the prognostic value of POLE non-EDMs remains unclear. This retrospective study aimed to explore the possible relationships between POLE mutation subtypes and CRC prognosis. Methods: The 272 CRC patients from the First Affiliated Hospital of Zhengzhou University (ZZ cohort) and 499 CRC patients from The Cancer Genome Atlas database (TCGA cohort) were retrospectively collected. The cases were divided into subgroups based on POLE mutation sites and microsatellite instability (MSI) status. The continuous variables were compared among three subgroups with Kruskal-Wallis tests. Pairwise comparisons between three groups were performed by Bonferroni correction method, and adjusted p < 0.05 was considered statistically significant. The categorical variables were compared with Chi-square test and Fisher's exact test. The Kaplan-Meier curves and Cox regression models were conducted to evaluate prognostic values of POLE mutations. Results: In the ZZ cohort, POLE EDMs (2.6%) were significantly associated with younger age (p = 0.018) and localized in the left colon (p = 0.001). POLE non-EDMs were significantly associated with MSI-high status (p < 0.001) and localization in the right colon (p = 0.001). In the TCGA cohort, the tumor mutation burden (TMB) of both POLE EDM tumors (p < 0.001) and POLE non-EDM tumors (p < 0.001) was significantly higher than that of POLE wild-type (WT) tumors. A similar trend was observed in the ZZ cohort, although there were no significant differences. In the ZZ cohort, the POLE EDM group had higher progression-free survival (PFS) (p = 0.002) and overall survival (OS) (p = 0.042) than the POLE non-EDM group and POLE WT group. We also report one CRC patient harboring a germline POLE mutation who received camrelizumab and exhibited long-term stable disease. Conclusion: Both POLE-EDMs and POLE non-EDMs were associated with significantly increased TMB in CRC and may be biomarkers for CRC treatment and prognosis. Current evidence does not support an effect of POLE non-EDMs on PFS and OS. A significant association between POLE EDMs and improved PFS and OS may exist, but future studies with larger sample sizes are needed. Entire coding region of the POLE gene should be screened.

Molecular subtypes identified by pyroptosis-related genes are associated with tumor microenvironment cell infiltration in colon cancer.

The important role of pyroptosis in tumor progression has been well characterized in recent years. However, little is known about the impact of tumor pyroptosis characteristics on patient prognosis and tumor microenvironment (TME) as well as efficacy of immunotherapy. In this study, we successfully classified colon cancer samples into three pyroptosis characterizations with different prognosis and TME cell infiltration patterns based on the expression of pyroptosis-related genes. Cluster 2, with the characterizations of immunosuppression, was classified as immune-desert cell infiltration patterns. Cluster 3, with the patterns of immune-inflamed cell infiltration, had the feature of an activated innate and adaptive immunity and significant prolonged survival. The activation of stromal pathways including EMT, angiogenesis and TGF-β in cluster 1 may mediate the impaired immune penetration of this cluster, which was classified as immune-excluded cell infiltration patterns. Our results demonstrated the PyroSig signature was a robust and independent biomarker for predicting patient prognosis. Patients with low PyroSig signature was confirmed to be correlated with treatment advantages and significant prolonged survival in two anti-checkpoint immunotherapy cohorts. This study identified three pyroptosis-related subtypes with distinct molecular features, clinical and microenvironment cell infiltration patterns in colon cancer, which could promote individualized immunotherapy for colon cancer.

Rhinitis symptom in patients with self-reported allergic rhinitis is influenced by sensitization pattern: A cross-sectional study of China.

Allergic rhinitis (AR) is characterized by distinct clinical heterogeneity and allergic sensitization patterns. We aimed to quantify rhinitis symptoms in patients with self-reported allergic rhinitis according to the potential sensitization patterns for relevant allergens in China. We used latent class analysis (LCA; a subset of structural equation modeling) to independently cluster patients into different patterns of atopic sensitization in an unsupervised manner, based on specific immunoglobulin E tests. AR symptom severity was assessed by the visual analogue scale. We evaluated the association between the severity of AR and the allergen sensitization patterns. LCA revealed four phenotypes of atopic sensitization among 967 patients with self-report AR. We labeled latent classes as: Class 1, weed pollens and indoor sensitization (n = 74 [7.7%]); Class 2, weed pollen with low indoor sensitization (n = 275 [28.4%]); Class 3, low or no sensitization (n = 350 [36.2%]); and Class 4, house dust mite-dominated sensitization (n = 268 [27.7%]). AR was more severe in Class 2 compared to the other 3 classes, indicating that upper respiratory symptoms are more severe among patients with isolated seasonal rhinitis. We have identified four sensitization patterns in patients with self-reported AR, which were associated with different clinical symptoms and comorbidities.