Classic Syndrome Research Articles

OTULIN haploinsufficiency predisposes to environmentally directed inflammation.

Recently, OTULIN haploinsufficiency was linked to enhanced susceptibility to Staphylococcus aureus infections accompanied by local necrosis and systemic inflammation. The pathogenesis observed in haploinsufficient patients differs from the hyperinflammation seen in classical OTULIN-related autoinflammatory syndrome (ORAS) patients and is characterized by increased susceptibility of dermal fibroblasts to S. aureus alpha toxin-inflicted cytotoxic damage. Immunological abnormalities were not observed in OTULIN haploinsufficient patients, suggesting a non-hematopoietic basis. In this research report, we investigated an Otulin+/- mouse model after in vivo provocation with lipopolysaccharide (LPS) to explore the potential role of hematopoietic-driven inflammation in OTULIN haploinsufficiency. We observed a hyperinflammatory signature in LPS-provoked Otulin+/- mice, which was driven by CD64+ monocytes and macrophages. Bone marrow-derived macrophages (BMDMs) of Otulin+/- mice demonstrated higher proinflammatory cytokine secretion after in vitro stimulation with LPS or polyinosinic:polycytidylic acid (Poly(I:C)). Our experiments in full and mixed bone marrow chimeric mice suggest that, in contrast to humans, the observed inflammation was mainly driven by the hematopoietic compartment with cell-extrinsic effects likely contributing to inflammatory outcomes. Using an OTULIN haploinsufficient mouse model, we validated the role of OTULIN in the regulation of environmentally directed inflammation.

Notes on morphological characteristics and life history strategy of the genus Acanthopsis Harv. (Acanthaceae)

Background: Morphological characteristics and life history strategies are vital in the success of plants to inhabit specific areas. Until recently the genus Acanthopsis was taxonomically poorly understood, and a recent revision rectified this aspect. The group comprises 20 species, all confined to arid parts of South Africa and Namibia. Much regarding the life history and ecology of the genus was still unknown. Objectives: Members of the genus Acanthopsis adapted to harsh environmental conditions have evolved an array of functional traits to enhance their chances of survival. The present contribution focuses on a select few of these traits, with discussion centred around them. Methods: This paper gives an overview of some casual and anecdotal observations made on the morphological characteristics and life history strategy during the taxonomic study. Results: Significant adaptations include a perennial subshrub habit, spinous inflorescences/infructescences, and flowers exhibiting the classical syndrome for insect pollination, likely by insects possessing elongated proboscises. Additionally, the seeds are myxospermous and undergo dispersal solely when there is an ample supply of water for germination. Noteworthy is the prompt germination of seeds, occurring within 24 h. Conclusion: Certain observations may potentially serve as catalysts for further, more in-depth investigations into the ecological significance of specific morphological traits and how the species might respond to anticipated future changes in temperature and precipitation.

Heterozygous COL5A1 deletion in a cat with classical Ehlers-Danlos syndrome.

Heterozygous COL5A1 deletion in a cat with classical Ehlers-Danlos syndrome.

An audio-semantic multimodal model for automatic obstructive sleep Apnea-Hypopnea Syndrome classification via multi-feature analysis of snoring sounds.

Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) is a common sleep-related breathing disorder that significantly impacts the daily lives of patients. Currently, the diagnosis of OSAHS relies on various physiological signal monitoring devices, requiring a comprehensive Polysomnography (PSG). However, this invasive diagnostic method faces challenges such as data fluctuation and high costs. To address these challenges, we propose a novel data-driven Audio-Semantic Multi-Modal model for OSAHS severity classification (i.e., ASMM-OSA) based on patient snoring sound characteristics. In light of the correlation between the acoustic attributes of a patient's snoring patterns and their episodes of breathing disorders, we utilize the patient's sleep audio recordings as an initial screening modality. We analyze the audio features of snoring sounds during the night for subjects suspected of having OSAHS. Audio features were augmented via PubMedBERT to enrich their diversity and detail and subsequently classified for OSAHS severity using XGBoost based on the number of sleep apnea events. Experimental results using the OSAHS dataset from a collaborative university hospital demonstrate that our ASMM-OSA audio-semantic multimodal model achieves a diagnostic level in automatically identifying sleep apnea events and classifying the four-class severity (normal, mild, moderate, and severe) of OSAHS. Our proposed model promises new perspectives for non-invasive OSAHS diagnosis, potentially reducing costs and enhancing patient quality of life.

Deep learning imaging phenotype can classify metabolic syndrome and is predictive of cardiometabolic disorders

BackgroundCardiometabolic disorders pose significant health risks globally. Metabolic syndrome, characterized by a cluster of potentially reversible metabolic abnormalities, is a known risk factor for these disorders. Early detection and intervention for individuals with metabolic abnormalities can help mitigate the risk of developing more serious cardiometabolic conditions. This study aimed to develop an image-derived phenotype (IDP) for metabolic abnormality from unenhanced abdominal computed tomography (CT) scans using deep learning. We used this IDP to classify individuals with metabolic syndrome and predict future occurrence of cardiometabolic disorders.MethodsA multi-stage deep learning approach was used to extract the IDP from the liver region of unenhanced abdominal CT scans. In a cohort of over 2,000 individuals the IDP was used to classify individuals with metabolic syndrome. In a subset of over 1,300 individuals, the IDP was used to predict future occurrence of hypertension, type II diabetes, and fatty liver disease.ResultsFor metabolic syndrome (MetS) classification, we compared the performance of the proposed IDP to liver attenuation and visceral adipose tissue area (VAT). The proposed IDP showed the strongest performance (AUC 0.82) compared to attenuation (AUC 0.70) and VAT (AUC 0.80). For disease prediction, we compared the performance of the IDP to baseline MetS diagnosis. The models including the IDP outperformed MetS for type II diabetes (AUCs 0.91 and 0.90) and fatty liver disease (AUCs 0.67 and 0.62) prediction and performed comparably for hypertension prediction (AUCs of 0.77).ConclusionsThis study demonstrated the superior performance of a deep learning IDP compared to traditional radiomic features to classify individuals with metabolic syndrome. Additionally, the IDP outperformed the clinical definition of metabolic syndrome in predicting future morbidities. Our findings underscore the utility of data-driven imaging phenotypes as valuable tools in the assessment and management of metabolic syndrome and cardiometabolic disorders.

Editorial: Application of genomics and epigenetics in disease and syndrome classification

Editorial: Application of genomics and epigenetics in disease and syndrome classification

Unilateral Genital Tract Obstruction with Ipsilateral Renal Anomaly Syndrome: Classification, Clinical Manifestations, and Precise Diagnose.

To recommend the classification of unilateral genital tract obstruction with ipsilateral renal anomaly (UGTOIRA) syndrome into five types based on the site of obstruction, and to analyze the clinical manifestations and precise diagnosis of the syndrome. The data, including demographic characteristics, symptoms, and precise diagnoses from 59 patients over the last decade, were retrospectively analyzed. Data analysis was conducted using the statistical software package SPSS 26.0. All 59 patients diagnosed with UGTOIRA syndrome were classified into five types based on the site of obstruction: Type I (vaginal obstruction) (45, 76.3%), Type II (cervicovaginal obstruction) (7, 11.9%), Type III (cervical obstruction) (3, 5.1%), Type IV (unilateral partial cervical aplasia) (3, 5.1%), and Type V (Unilateral isthmus atresia) (1, 1.7%). Of these cases, there were 34 cases (57.6%) with communication and 25 cases (42.4%) without communication between the left and right genital tracts. The chief complaints included dysmenorrhea alone in 28 cases (47.5%), dysmenorrhea accompanied by blood dripping after menstruation in 12 cases (20.3%), blood dripping after menstruation alone in 14 cases (23.7%), purulent vaginal secretions in one case (1.7%), vaginal pain in one case (1.7%), irregular menstruation in one case (l.7%), and infertility in two cases (3.4%). The precise diagnostic criteria include the affected side, abnormalities in the kidney and ureter, the site of obstruction, the location of blood accumulation, the size of the ipsilateral genital tract, whether there is communication and its site, the type based on the site of obstruction, and the presence and type of complications. This classification of UGTOIRA syndrome encompasses the anatomical features of all cases reported in our study. Only by fully understanding the anatomical characteristics of this syndrome and identifying its clinical manifestations can clinicians make precise diagnoses as early as possible and provide individualized management.

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.

New Paradigms in the Clinical Management of Li-Fraumeni Syndrome.

Approximately 8.5%-16.2% of childhood cancers are associated with a pathogenic/likely pathogenic germline variant-a prevalence that is likely to rise with improvements in phenotype recognition, sequencing, and variant validation. One highly informative, classical hereditary cancer predisposition syndrome is Li-Fraumeni syndrome (LFS), associated with germline variants in the TP53 tumor suppressor gene, and a >90% cumulative lifetime cancer risk. In seeking to improve outcomes for young LFS patients, we must improve the specificity and sensitivity of existing cancer surveillance programs and explore how to complement early detection strategies with pharmacology-based risk-reduction interventions. Here, we describe novel precision screening technologies and clinical strategies for cancer risk reduction. In particular, we summarize the biomarkers for early diagnosis and risk stratification of LFS patients from birth, noninvasive and machine learning-based cancer screening, and drugs that have shown the potential to be repurposed for cancer prevention.

CELIAC DISEASE AND CARDIOVASCULAR DISEASES

Background: Celiac disease, an immune-mediated enteropathy that occurs in susceptible individuals after gluten ingestion, has clinical manifestations that go beyond the classical malabsorption syndrome and can affect other systems. Objective: To review the current literature for cardiovascular changes described in patients with celiac disease. Method: We conducted a search in the PubMed database and selected articles based on their relevance to the objective. Results: Celiac patients have a 1.2 times higher risk of cardiovascular events compared to non-celiac patients. The most common cardiovascular manifestations include atherosclerosis, cardiac arrhythmias (especially atrial fibrillation), myocarditis, coronary artery disease, dilated cardiomyopathy, impaired aortic function, and cerebrovascular diseases. There are several possible explanations for this relationship, including: prothrombotic changes, accelerated atherosclerosis compared to patients without celiac disease, associated comorbidities, such as antiphospholipid syndrome and Type 1 Diabetes mellitus, subclinical chronic inflammation and genetic factors. Celiac disease patients have a 38% higher risk of developing atrial fibrillation and a 19% higher risk of coronary artery disease. Furthermore, celiac patients have a 22% higher risk of coronary artery disease-related death, regardless of small intestine histopathology. Patients with celiac disease also show an increased prevalence of dilated cardiomyopathy (5.7%) and a 73% higher risk of developing dilated cardiomyopathy, particularly within the first year of celiac disease diagnosis. Conclusion: Celiac disease may be associated with cardiovascular changes, especially in newly diagnosed patients who have not adhered to a gluten-free diet. Therefore, cardiovascular assessment should be considered as part of the initial assessment and follow-up of individuals with celiac disease.

Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. We evaluated obesity and longitudinal growth among children (1-18years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.

Epileptic spasms relapse is associated with response latency but not conventional attributes of post-treatment EEG.

Relapse of epileptic spasms after initial treatment of infantile epileptic spasms syndrome (IESS) is common. However, past studies of small cohorts have inconsistently linked relapse risk to etiology, treatment modality, and EEG features upon response. Using a large single-center IESS cohort, we set out to quantify the risk of epileptic spasms relapse and identify specific risk factors. We identified all children with epileptic spasms at our center using a clinical EEG database. Using the electronic medical record, we confirmed IESS syndrome classification and ascertained treatment, response, time to relapse, etiology, EEG features, and other demographic factors. Relapse-free survival analysis was carried out using Cox proportional hazards regression. Among 599 children with IESS, 197 specifically responded to hormonal therapy and/or vigabatrin (as opposed to surgery or other second-line treatments). In this study, 41 (21%) subjects exhibited relapse of epileptic spasms within 12 months of response. Longer duration of IESS prior to response (>3 months) was strongly associated with shorter latency to relapse (hazard ratio = 3.11; 95% CI 1.59-6.10; p = 0.001). Relapse was not associated with etiology, developmental status, or any post-treatment EEG feature. This study suggests that long duration of IESS before response is the single largest clinical predictor of relapse risk, and therefore underscores the importance of prompt and successful initial treatment. Further study is needed to evaluate candidate biomarkers of epileptic spasms relapse and identify treatments to mitigate this risk. Relapse of infantile spasms is common after initially successful treatment. With study of a large group of children with infantile spasms, we determined that relapse is linked to long duration of infantile spasms. In contrast, relapse was not associated with the cause of infantile spasms, developmental measures, or EEG features at the time of initial response. Further study is needed to identify tools to predict impending relapse of infantile spasms.

Graph Node Classification to Predict Autism Risk in Genes.

This study explores the genetic risk associations with autism spectrum disorder (ASD) using graph neural networks (GNNs), leveraging the Sfari dataset and protein interaction network (PIN) data. We built a gene network with genes as nodes, chromosome band location as node features, and gene interactions as edges. Graph models were employed to classify the autism risk associated with newly introduced genes (test set). Three classification tasks were undertaken to test the ability of our models: binary risk association, multi-class risk association, and syndromic gene association. We tested graph convolutional networks, Graph Sage, graph transformer, and Multi-Layer Perceptron (Baseline) architectures on this problem. The Graph Sage model consistently outperformed the other models, showcasing its utility in classifying ASD-related genes. Our ablation studies show that the chromosome band location and protein interactions contain useful information for this problem. The models achieved 85.80% accuracy on the binary risk classification, 81.68% accuracy on the multi-class risk classification, and 90.22% on the syndromic classification.

Carcinoid Heart Disease Associated with Primary Ovarian Carcinoid Tumor: A Rare Presentation

Primary ovarian carcinoid tumors, an extremely rare subset of ovarian malignancies (&lt;0.1% of cases), typically manifest with abdominal pain and bloating. The occurrence of carcinoid heart disease (CHD) without classic carcinoid syndrome features is exceptionally uncommon. We report a 54-year-old female presenting with dyspnea and edema over months, lacking typical carcinoid syndrome signs. Initial assessments diagnosed heart failure, supported by elevated NT-Pro BNP, echocardiographic right ventricular dilation, and pulmonary/tricuspid valve regurgitation (normal left ventricular function). Right heart catheterization showed normal pulmonary/right ventricular pressures. Subsequent investigations (computed tomography thorax abdomen pelvis, 5-hydroxyindole acetic acid levels) strongly suggested carcinoid disease, confirmed by an octreotide scan revealing an octreotide-secreting ovarian carcinoid tumor. Surgical intervention included tricuspid and pulmonary valve repair, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. Primary ovarian carcinoid tumors, though rare, may lead to unexpected complications like CHD. Timely diagnosis and intervention are pivotal for optimizing patient outcomes in such cases.

Estrogen Receptor Expression in DICER1-related Lesions is Associated With the Presence of Cystic Components.

DICER1 tumor predisposition syndrome results from pathogenic variants in DICER1 and is associated with a variety of benign and malignant lesions, typically involving kidney, lung, and female reproductive system. Over 70% of sarcomas in DICER1 tumor predisposition syndrome occur in females. Notably, pediatric cystic nephroma (pCN), a classic DICER1 tumor predisposition syndrome lesion, shows estrogen receptor (ER) expression in stromal cells. There are also renal, hepatic, and pancreatic lesions unassociated with DICER1 tumor predisposition syndrome that have an adult female predominance and are characterized/defined by ER-positive stromal cells. Except for pCN, the expression of ER in DICER1-associated lesions remains uninvestigated. In the present study, ER expression was assessed by immunohistochemistry in 89 cases of DICER1-related lesions and 44 lesions lacking DICER1 pathogenic variants. Expression was seen in stromal cells in pCN and pleuropulmonary blastoma (PPB) types I and Ir, whereas anaplastic sarcoma of kidney and PPB types II and III were typically negative, as were other solid tumors of non-Müllerian origin. ER expression was unrelated to the sex or age of the patient. Expression of ER showed an inverse relationship to preferentially expressed antigen in melanoma (PRAME) expression; as lesions progressed from cystic to solid (pCN/anaplastic sarcoma of kidney, and PPB types I to III), ER expression was lost and (PRAME) expression increased. Thus, in DICER1 tumor predisposition syndrome, there is no evidence that non-Müllerian tumors are hormonally driven and antiestrogen therapy is not predicted to be beneficial. Lesions not associated with DICER1 pathogenic variants also showed ER-positive stromal cells, including cystic pulmonary airway malformations, cystic renal dysplasia, and simple renal cysts in adult kidneys. ER expression in stromal cells is not a feature of DICER1 perturbation but rather is related to the presence of cystic components.

Relevance of obesity-related organ damage and metabolic syndrome classification in cardiovascular and renal risk stratification in patients with essential hypertension.

Hypertension is a relevant cardiovascular comorbidity. Adipose tissue represents a metabolically active tissue involved in the regulation of blood pressure and metabolic alterations. In recent decades, several classifications for the metabolic syndrome (MS) have been proposed. Recently, a new syndrome called the "Cardiovascular-kidney-metabolic" (CKM) syndrome was identified, to determine patients at high cardiovascular and metabolic risk. The aim of the study was to compare different classifications in a large population of hypertensive patients. Between September 2022 and August 2023, we consecutively enrolled 772 hypertensive patients (407 men; 365 women; mean age 52.2 ± 15.1 years), evaluating anthropometric, biochemical, and instrumental parameters (transthoracic echocardiogram, carotid echo-Doppler, 24-h ambulatory blood pressure monitoring, fundus oculi). Using different classifications we found MS prevalence: Adult Treatment Panel III (ATP-III) 28.8%, International Diabetes Federation (IDF) 31.5%, CKM 40.7%. CKM Classes 3 and 4 showed higher body mass index and waist circumference compared with other groups. Compared with ATP-III and IDF, CKM Class 4 showed higher 24-h systolic blood pressure, lower percentage of controlled hypertension, increased interventricular septum and posterior wall, reduced ejection fraction, and greater prevalence of hypertensive arterial retinal damage. Visceral obesity and MS are frequent conditions with healthy impact, becoming an important trigger for the development of cardiovascular and metabolic complications. The different MS classifications allow the early identification of patients at high risk of cardiometabolic complications. The new CKM syndrome proves useful to identify individuals at high risk for CKM morbidity and mortality.

An Interpretable Machine Learning Framework for Rare Disease: A Case Study to Stratify Infection Risk in Pediatric Leukemia.

Background: Datasets on rare diseases, like pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), have small sample sizes that hinder machine learning (ML). The objective was to develop an interpretable ML framework to elucidate actionable insights from small tabular rare disease datasets. Methods: The comprehensive framework employed optimized data imputation and sampling, supervised and unsupervised learning, and literature-based discovery (LBD). The framework was deployed to assess treatment-related infection in pediatric AML and ALL. Results: An interpretable decision tree classified the risk of infection as either "high risk" or "low risk" in pediatric ALL (n = 580) and AML (n = 132) with accuracy of ∼79%. Interpretable regression models predicted the discrete number of developed infections with a mean absolute error (MAE) of 2.26 for bacterial infections and an MAE of 1.29 for viral infections. Features that best explained the development of infection were the chemotherapy regimen, cancer cells in the central nervous system at initial diagnosis, chemotherapy course, leukemia type, Down syndrome, race, and National Cancer Institute risk classification. Finally, SemNet 2.0, an open-source LBD software that links relationships from 33+ million PubMed articles, identified additional features for the prediction of infection, like glucose, iron, neutropenia-reducing growth factors, and systemic lupus erythematosus (SLE). Conclusions: The developed ML framework enabled state-of-the-art, interpretable predictions using rare disease tabular datasets. ML model performance baselines were successfully produced to predict infection in pediatric AML and ALL.

A Revised Classification of Primary Iron Overload Syndromes.

The clinical introduction of hepcidin25 (Hep25) has led to a more detailed understanding of its relationship with ferroportin (FP) and divalent metal transporter1 in primary iron overload syndromes (PIOSs). In 2012, we proposed a classification of PIOSs based on the Hep25/FP system, which consists of prehepatic aceruloplasminemia, hepatic hemochromatosis (HC), and posthepatic FP disease (FP-D). However, in consideration of accumulated evidence on PIOSs, we aimed to renew the classification. We reviewed the 2012 classification and retrospectively renewed it according to new information on PIOSs. Iron-loading anemia was included in PIOSs as a prehepatic form because of the newly discovered erythroferrone-induced suppression of Hep25, and the state of traditional FP-D was remodeled as the BIOIRON proposal. The key molecules responsible for prehepatic PIOSs are low transferrin saturation in aceruloplasminemia and increased erythroferrone production by erythroblasts in iron-loading anemia. Hepatic PIOSs comprise four genotypes of HC, in each of which the synthesis of Hep25 is inappropriately reduced in the liver. Hepatic Hep25 synthesis is adequate in posthepatic PIOSs; however, two mutant FP molecules may resist Hep25 differently, resulting in SLC40A1-HC and FP-D, respectively. PIOS phenotypes are diagnosed using laboratory tests, including circulating Hep25, followed by suitable treatments. Direct sequencing of the candidate genes may be outsourced to gene centers when needed. Laboratory kits for the prevalent mutations, such as C282Y, may be the first choice for a genetic analysis of HC in Caucasians. The revised classification may be useful worldwide.

Primary ciliary dyskinesia (Kartagener syndrome): a case of late diagnosis and follow-up

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease that develops as a result of an ultrastructural defect of the cilia and flagella. The symptoms are non-specific, especially in childhood, and are characterized by recurrent rhinitis and bronchitis, often with obstruction. Half of the patients with PCD are diagnosed with such clear clinical manifestation as Kartagener’s syndrome (chronic bronchitis, chronic sinusitis, reverse position of internal organs (situs inversus), but even in these cases the diagnosis can be difficult.The aim of this paper was to demonstrate a clinical case of late diagnosis of PCD in a child with classic Kartagener syndrome and concomitant atopy, and the results of 11 years of follow-up and microbiological monitoring. The stages of the diagnostic search are presented in detail and typical errors on the way to diagnosis are analyzed.Conclusion. This clinical observation demonstrates the difficulties of diagnosing PCD in a patient with concomitant atopy. It is noted that appropriate continued monitoring and timely therapy are crucial for children with PCD. The need to standardize approaches to the diagnosis and management of patients with PCD, including continuity during transfer to the adult healthcare network, is emphasized.

Diagnosis and Management of Catastrophic Antiphospholipid Syndrome and the Potential Impact of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria.

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening condition characterized by the persistence of antiphospholipid antibodies and occurrence of multiple vascular occlusive events. CAPS currently remains a diagnostic challenge and requires urgent treatment. The diagnosis of CAPS is made difficult by classification criteria used as diagnostic criteria in clinical practice, knowledge derived from retrospective data and case reports, confounding clinical and biological features, and its rapid onset and mortality. The absence of prospective studies of CAPS limits the strength of evidence for guideline treatment protocols. This comprehensive review summarizes the current understanding of the disease, and discusses how the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria impact the definition and therapeutic management of CAPS, which is considered the most severe form of APS. The correct integration of 2023 ACR/EULAR APS classification criteria is poised to facilitate CAPS diagnosis, particularly in critical situations, offering a promising avenue for improved outcomes.