Clinical Manifestations Of Disease Research Articles

ЗНАЧЕНИЕ ПОЛИМЕРАЗНОЙ ЦЕПНОЙ РЕАКЦИИ В ВЫЯВЛЕНИИ ИНФЕКЦИОННЫХ АГЕНТОВ У КРУПНОГО РОГАТОГО СКОТА

The aim of our work was to identify bacterial and viral infectious agents in biological material from cows and calves with different clinical manifestations of diseases by PCR. Biological materials from animals were sent to the PCR laboratory from 23 agricultural organizations in the Ural Region. A total of 808 samples were studied, of which genomes of pathogens were found in 11.9 % of cases: Mycoplasma bovis DNA in 2.4 % of samples, Bovine virus diarrhoea RNA in 2.3 % of samples, Mycoplasma spp. and Chlamydia spp DNA in 2 % of samples, Mycoplasma bovigenitalium, Bovine herpesvirus (type 1), Chlamydophila abortus, Chlamydophila pecorum were found singly. Out of 80 samples in 36.2 % of biomaterials, specific DNA sites of Cl. difficile were found – 31.2 % of samples, Cl. perfringens – 20.0 % of samples, Cl. difficile + Cl. perfringens – 25.0 % of biosamples. Toxins were found in Cl. difficile: CDT toxin in 41.0 % of clostridia, toxin B in 6.0 % of pathogens, less often toxin A. In some cases, clostridia (Cl. perfringens, Cl. difficile B) were found in the biomaterial from dead calves, which confirmed the diagnosis – infectious anaerobic enterotoxemia of calves. Bacteria (E. coli, Salmonella enterica spp. entericaserogroup C (0:9, 2), Cl. perfringens and Cl. difficile CDT DNA) were detected in the biomaterial from dead cows, which confirmed the diagnosis of acute intestinal infection. All detected pathogens were presented in the form of monoinfection and singly in the form of mixed infections. Using PCR, it was possible to detect DNA and RNA of infectious agents in various clinical manifestations of diseases of bacterial and viral etiology in cattle herds in the Ural Region.

Modern Clinical Guidelines for the Management of Patients with Gaucher Disease

This article presents data on the epidemiology, pathogenesis, modern classification and the main clinical manifestations of Gaucher disease in children. The criteria for differential diagnosis with other diseases are given. It has been shown that the only effective method of treating Gaucher disease is pathogenetic enzyme replacement therapy, which relieves the main clinical manifestations of the disease, improving the quality of life of patients and without having pronounced side effects. The main errors of diagnosis and management of patients, as well as unjustified prescriptions for the treatment of this disease, are indicated.

Celiac Disease: A Transitional Point of View.

Celiac disease (CeD) is a chronic, lifelong, multifactorial, polygenic, and autoimmune disorder, characteristically triggered by exposure to the exogenous factor "gluten" in genetically predisposed individuals, with resulting duodenal inflammation and enteropathy, as well as heterogeneous multisystemic and extraintestinal manifestations. The immunopathogenesis of CeD is complex, favored by a peculiar human leukocyte antigen (HLA) genetic predisposition, leading to gluten presentation by antigen-presenting cells to CD4+ T helper (Th) cells, T cell-B cell interactions, and production of specific antibodies, resulting in the immune-mediated killing of enterocytes and, macroscopically, in duodenal inflammation. Here, the most relevant correlations between cellular and molecular aspects and clinical manifestations of this complex disease are reviewed, with final considerations on nutritional aspects for disease management.

Identification of Four New Mutations in the GLA Gene Associated with Anderson-Fabry Disease.

Anderson-Fabry disease is a hereditary, progressive, multisystemic lysosomal storage disorder caused by a functional deficiency of the enzyme α-galactosidase A (α-GalA). This defect is due to mutations in the GLA gene, located in the long arm of the X chromosome (Xq21-22). Functional deficiency of the α-GalA enzyme leads to reduced degradation and accumulation of its substrates, predominantly globotriaosylceramide (Gb3), which accumulate in the lysosomes of numerous cell types, giving rise to the symptomatology. Clinical diagnosis can still be difficult today due to the peculiarities of the disease, which presents with clinical manifestations that overlap with those of other pathologies and a wide possibility of differential diagnoses, which lead to missed diagnoses, misdiagnosis, or a diagnostic delay. Patients with clinical suspicion of Fabry disease undergo a diagnostic workup that includes an evaluation of α-GALA enzyme activity, genetic analysis of the GLA gene, and the measurement of blood Lyso-Gb3, a soluble derivative of Gb3. In this paper, we describe four novel mutations identified in the GLA gene which are associated with absent or reduced α-GalA activity, pathological accumulation of the specific substrate, and characteristic clinical manifestations of Fabry disease. We identified two mutations (c.583insGAATA and p.Y207X) that result in the formation of a premature translation stop codon, resulting in a truncated protein and thus a completely non-functional enzyme. The other two identified gene alterations (p.G261C and c.786G>T, which determine p.W262C) are missense mutations that cause reduced α-GALA activity, the accumulation of blood Lyso-Gb3, and symptoms consistent with Fabry disease, and therefore may be associated with this disorder. The identification of these new mutations in patients with symptoms attributable to Fabry disease increases the molecular knowledge of the GLA gene and provides important support to the clinician, for a more accurate and timely diagnosis of the pathology.

Influence of Weather on Sickle Cell Disease Vaso-Occlusive Episodes and Acute Chest Syndrome: A Nationwide Sample Analysis.

The clinical manifestations of sickle cell disease (SCD) result in significant morbidity and healthcare costs. The effect of weather as a risk factor for the development of vaso-occlusive episodes (VOEs) has been previously studied, although with variable results. The aim of our retrospective, nationwide study was to determine the association between weather patterns and pediatric VOE and acute chest syndrome (ACS). Demographic and clinical data were obtained between 2015 and 2022 from the Pediatric Health Information System and merged with weather data from the National Climatic Data Center. We observed a higher incidence of VOE and ACS admissions during the colder months. Results also revealed a negative association between VOE admissions and average temperature, whereas a positive association was found for ACS admissions. Medical providers should continue to counsel patients with SCD to take appropriate precautions during cold weather.

The effect of HLA genotype on disease onset and severity in CTLA-4 insufficiency.

Human Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency caused by heterozygous germline mutations in CTLA4 is a complex immune dysregulation and immunodeficiency syndrome presenting with reduced penetrance and variable disease expressivity, suggesting the presence of disease modifiers that trigger the disease onset and severity. Various genetic and non-genetic potential triggers have been analyzed in CTLA-4 insufficiency cohorts, however, none of them have revealed a clear association to the disease. Multiple HLA haplotypes have been positively or negatively associated with various autoimmune diseases and inborn errors of immunity (IEI) due to the relevance of MHC in the strength of the T cell responses. In this exploratory study, we investigated the association of disease onset, severity and clinical manifestations of CTLA-4 insufficiency with specific HLA class I (A, B and C) and class II (DRB1 and DQB1) alleles in forty-three individuals harboring heterozygous mutations in CTLA4. Twenty-six out of the 43 recruited individuals presented moderate or severe clinical symptoms whereas 17 were completely healthy. HLA frequency analysis, odds ratio analysis and genetic linkage analysis were used. The principal statistical analyses showed no positive association between the HLA genotypes analyzed with the disease onset or the disease severity. We found potential risk associations of HLA-DQB1*05:01 and HLA-DRB1*01:02 with respiratory tract involvement and HLA-C*05:01 with affection of the neurological system in the CTLA-4-insufficient patients. Additionally, wefound a potential protective association of HLA-DRB1*01:01 with gastrointestinal symptoms. Even though, our findings suggest that HLA-A, -B, -C, DRB1, and DQB1 do not contribute to the onset or severity of disease in CTLA-4 insufficiency, certain HLA-alleles may influence the manifestation of specific symptoms. We advocate for further investigation of specific class I and class II HLA alleles as potential disease modifiers in larger clinical cohorts of CTLA-4 insufficiency.

The Prevalence and Clinical Manifestations of Post-Tuberculosis Lung Disease in Immunocompetent HIV-Negative Individuals: A Scoping Review

The Prevalence and Clinical Manifestations of Post-Tuberculosis Lung Disease in Immunocompetent HIV-Negative Individuals: A Scoping Review

Domain-Specific Prediction of Clinical Progression in Parkinson's Disease Using the Mosaic Approach.

Due to the highly individualized clinical manifestation of Parkinson's disease (PD), personalized patient care may require domain-specific assessment of neurological disability. Evidence from magnetic resonance imaging (MRI) studies has proposed that heterogenous clinical manifestation corresponds to heterogeneous cortical disease burden, suggesting customized, high-resolution assessment of cortical pathology as a candidate biomarker for domain-specific assessment. Herein, we investigate the potential of the recently proposed Mosaic Approach (MAP), a normative framework for quantifying individual cortical disease burden with respect to a population-representative cohort, in predicting domain-specific clinical progression. Using MRI and clinical data from 135 recently diagnosed PD patients from the Parkinson's Progression Markers Initiative, we first defined an extremity-specific motor score. We then identified cortical regions corresponding to "extremity functions" and restricted MAP, respectively, and contrasted the explanatory power of the extremity-specific MAP to unrestricted MAP. As control conditions, domain-related but less specific general motor function and nondomain-specific cognitive scores were considered. We also tested the predictive power of the restricted MAP in predicting disease progression over 1 and 3 years using support vector machines. The restricted, extremity-specific MAP yielded higher explanatory power for extremity-specific motor function at baseline as opposed to the unrestricted, whole-brain MAP. On the contrary, for general motor function, the unrestricted, whole-brain MAP yielded higher power. No associations were found for cognitive function. The extremity-specific MAP predicted extremity-specific motor progression over 1 and 3 years above chance level. The MAP framework allows for domain-specific prediction of customized PD disease progression, which can inform machine learning, thereby contributing to personalized PD patient care.

Protein tyrosine phosphatase delta is a STAT3-phosphatase and suppressor of metabolic liver disease

ObjectiveImpaired hepatic expression of protein tyrosine phosphatase delta (PTPRD) is associated with increased STAT3 transcriptional activity and reduced survival from hepatocellular carcinoma in patients with chronic hepatitis C virus infection....

A20 haploinsufficiency diagnosis beyond systemic lupus erythematosus: A systematic review of the literature.

Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathophysiology remains incompletely understood, involving genetic and epigenetic factors. However, an increasing small subset of patients present with monogenic lupus, providing insight into the pathogenesis of the disease. This systematic review focuses on SLE associated with A20 haploinsufficiency (HA20), a monogenic disorder associated with tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3) variants. Besides the mainly auto-inflammatory phenotypic expression of HA20 mimicking Behçet's disease spectrum, some of its clinical and biological manifestations are part of the spectrum of autoimmune diseases, including glomerulonephritis as well as the frequent presence of antinuclear antibodies, sometimes with anti-DNA specificity. Among all the 191 HA20 patients reported in the literature, we identified 16 patients (8.4 %) with a compatible diagnosis of SLE. When estimable, the SLICC 2012 and EULAR/ACR 2019 classification criteria were positive for 92.9 % of them. A majority had multi-system involvement, mainly cutaneous (81.3 %), musculoskeletal (56.3 %), and/or renal (56.3 %) manifestations. They also seemed to exhibit differences compared to other SLE patients: higher prevalence of fever, chronic cutaneous lupus erythematosus, oral and genital ulcers, neuropsychiatric manifestations, autoimmune cytopenia, and elevated biologic inflammatory markers. This review highlights the necessity of considering TNFAIP3 variants in SLE patients with early-onset disease, familial history, and/or specific clinical manifestations suggestive of autoinflammatory diseases. Recognizing HA20-SLE patients may improve our understanding of SLE pathogenesis and lead to better therapeutic strategies for these patients.

Temporal modeling and AT profiles in the early phase of Alzheimer's disease

Background Identifying markers that have predictive value for disease progression and clinical manifestations, such as mild cognitive impairment (MCI), is important to detect Alzheimer's disease (AD) early. Objective In this study, we combined biomarkers from amyloid and tau pathologies (AT profiles) with the prediction of diagnosis and the temporal evolution of clinical symptoms. Methods Multiple disease progression models were developed through supervised and unsupervised techniques via a two-stage data-driven approach. Models whose natural histories most closely resembled the diagnostic predictions were selected. Finally, various hypotheses regarding the progression of cognitive decline were tested using longitudinal patient data and AT profiles. Results At baseline, 22.5% of the cognitively unimpaired (CU) individuals and 46.2% of the CU converters (who progressed to MCI during the first four years) in the studied population had amyloid pathology (A+). Only a small subset of neuropsychological measures was used to predict cognitive decline and its timeline. The study revealed that amyloid pathology occurred approximately 5 years after cognitive decline in the population under investigation. Additionally, patients who were A+ at baseline experienced a more accelerated progression toward cognitive decline than those who were not (A−). Conclusions Based on the proposed natural histories and cross-sectional and longitudinal analysis of AD markers, the results indicate that only a single cerebrospinal fluid sample is necessary during the early phase of AD. The progression from CU to MCI and its timeline can be predicted exclusively through neuropsychological measures.

Evaluation of some biochemical changes and associated metabolic syndrome among pregnant women in Enugu Southeast of Nigeria

Objective: Metabolic syndrome is a global health problem which involves a cluster of conditions that increases the risk of heart disease, stroke and diabetes. Pregnancy induces significant physiological, hormonal and metabolic changes in a woman. The complex of metabolic and hormonal disorders is a risk factor for clinical manifestations of cardiovascular diseases, nephropathy and retinopathy. This study assessed some biochemical changes and associated metabolic syndrome among pregnant women in Enugu, Nigeria. Methods: A total of one hundred and thirty apparently healthy women consisting of seventy pregnant women as test group and sixty non-pregnant women as control group were recruited for this cross sectional study. Anthropometric parameters waist circumference (WC), height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP) were measured and body mass index (BMI) calculated. Five milliliters of fasting blood samples were collected and used for the determination of fasting plasma glucose (FPG) and lipid profile (TC, TG, HDL-C, LDL-C, VLDL-C) using enzymatic colorimetric methods. Metabolic Syndrome (MetS) prevalence was estimated using the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria. Data was analysed using the Statistical Package for the Social Sciences (SPSS) version 26. Results: The results showed a significant (P< 0.05) increase in BMI, WC, SBP, DBP, TG, VLDL-C and a decrease in HDL-C of pregnant women compared to non-pregnant women. Using the NCEP-ATP III criteria, it was found that about twenty-eight (40%) pregnant women had metabolic syndrome and only two (3.33%) non-pregnant woman had metabolic syndrome while the IDF criteria, presented about thirty (42.9%) pregnant women and ten (16.7%) non-pregnant women with metabolic syndrome. Conclusion: This study concludes that pregnancy predisposes women to higher risk of developing metabolic syndrome.

Clinical and Radiologic Predictors of Response to Teprotumumab: A 3D Volumetric Analysis of 35 Patients.

Teprotumumab, a novel human monoclonal antibody, has been shown to reverse the clinical manifestations of thyroid eye disease. Previous reports have suggested that it demonstrates disease-modifying properties through the reduction of orbital fat and muscle volumes. This study aims to analyze orbital volumetric change following treatment and to identify clinical and radiological predictors of response. This was a prospective longitudinal study with 35 consecutive patients who had available pre- and posttreatment orbital imaging. Three-dimensional volumetric calculations of orbital fat, extraocular muscles, and proptosis were measured using previously validated image processing software. This information was used with demographic data to create a multivariate regression model to review which baseline clinical or radiological factors were predictors of proptosis response. In the study orbit, 20 patients (57%) had a proptosis reduction of ≥2 mm. In the fellow orbit, 18 patients (51%) had a proptosis reduction of ≥2 mm. Regression modeling revealed that baseline proptosis and baseline muscle volumes were significant predictors of proptosis response (p < 0.01 and p < 0.05, respectively). Further, changes in muscle volume and fat volume were significantly associated with proptosis response (r = 0.5, p < 0.001 and r = 0.3, p = 0.012, respectively). Teprotumumab significantly reduces orbital fat and muscle volumes. This is manifested by a significant reduction in proptosis. Baseline proptosis and muscle volumes are significant predictors of proptosis response.

Ninoa T. cruzi Strain Modifies the Expression of microRNAs in Cardiac Tissue and Plasma During Chagas Disease Infection.

Background: Chronic chagasic cardiomyopathy is the most severe clinical manifestation of Chagas disease, which affects approximately seven million people worldwide. Latin American countries bear the highest burden, with the greatest morbidity and mortality rates. Currently, diagnostic methods do not provide information on the risk of progression to severe stages of the disease. Recently, microRNAs (miRNAs) have been proposed as promising tools for monitoring the progression of Chagas disease. This study aimed to analyze the expression profiles of the miRNAs miR-1, miR-16, miR-208, and miR-208b in cardiac tissue, plasma, and plasma extracellular vesicles from Ninoa TcI-infected mice during the acute and indeterminate phases of Chagas disease. Methods: The cardiac-specific miRNAs and miR-16 levels were examined in all samples using RT-qPCR. Additionally, pathway analysis was performed to investigate the impact of potential miRNA target genes across various databases. Results: Elevated miR-208b expression was observed in cardiac tissue and plasma during the acute phase. Bioinformatic analysis identified three pathways implicated in disease progression: phosphatidylinositol 3-kinase signaling, Fc gamma receptor-mediated phagocytosis, and leukocyte transendothelial migration, as well as cholinergic synapse pathways. Conclusions: MiR-208b was upregulated during the acute phase and downregulated in the indeterminate phase, suggesting it may play a crucial role in disease progression.

Central lumbar stenosis. Recommendations of the Russian Association for the Study of Pain (RASP)

Narrowing of the central spinal canal in the lumbar spine (central lumbar stenosis, CLS) is one of the most common causes of lumbar pain, disability and spinal surgery in the elderly. The most common is acquired degenerative CLS, in which the main role play lumen-narrowing medial intervertebral disc herniating with ossification phenomena and marginal bone proliferation on the sides of the vertebral bodies – osteophytes, hypertrophy of the facet joints with their medial displacement, hypertrophy of the yellow ligament. The development of CLS can also be a consequence of spondylolisthesis, postoperative changes, rheumatic diseases and other causes. Both the compression of the cauda equine roots due to narrowing of the spinal canal and their ischemia, caused by compression of the radicular vessels and venous congestion play an important role in the pathogenesis of CLS. CLS develops in elderly age and occurs predominantly in men. The main clinical manifestation of CLS is neurogenic (caudogenic) intermittent claudication, which manifests as pain, numbness and weakness in the legs when the patient walks or stands for a long time but subsides when the patient sits or stands and bends forwards (flexion in the lumbar spine). The diagnosis of CLS is confirmed by magnetic resonance imaging (MRI), which shows a narrowing of the spinal canal and makes it possible to rule out specific causes of lumbar pain. It is important to note that, according to MRI, CLS often occurs at an older age, so its detection in the absence of clinical manifestations does not require an immediate discussion of the prospects of surgical treatment. Pain in patients with CLS according to MRI may be musculoskeletal in nature. Therefore, the diagnosis of CLS should include specific clinical manifestations and stenosis on MRI. In patients without clinical manifestations of CLS, osteoporosis and severe concomitant somatic diseases, only conservative therapy is recommended. Modern conservative treatment of CLS includes an educational program, therapeutic exercises (kinesiotherapy), psychological therapy methods for emotional disorders (cognitive-behavioral therapy), manual therapy and pharmacotherapy. Complex conservative treatment of CLS can reduce pain, improve the patient's condition and in some cases increase the patient's walking distance.

Multiple Red Flags of Cardiac Amyloidosis in a Single Patient: Clinical Manifestations of an Underdiagnosed Disease.

Cardiac transthyretin amyloidosis is an underdiagnosed disorder with significant diagnostic difficulties due to its non-specific clinical manifestations. It is caused by the deposition of protein aggregates with an abnormal tertiary structure in the extracellular matrix. Their accumulation leads to the development of hypertrophic and restrictive cardiomyopathy and, at a later stage, heart failure with preserved ejection fraction syndrome. Depending on the pathogenesis, there are different types of the disease-hereditary and age-related wild-type transthyretin amyloidosis. We present the case of an 85-year-old woman who was referred to the department with a two-month history of exertional dyspnea in New York Heart Association functional class II. After reviewing the initial findings, several red flags for cardiac amyloidosis (CA) were identified. Following the diagnostic algorithm, scintigraphy was performed and showed significant radioisotope accumulation in the myocardium, confirming the suspected disease. In this manuscript, we present the current recommendations and diagnostic pathway, discussing in detail both available and emerging treatment options. As early diagnosis is essential to prevent the development of serious complications, we would like to highlight the pitfalls in diagnosing CA and emphasize the need to be aware of its variable clinical presentation and red flags.

Complex Death Associated with Intra-Hospital Adverse Events and SARS-CoV-2 Pneumonia: Court-Appointed Medico-Legal Evaluation

Background: Among the deaths recorded during the COVID-19 pandemic, some were caused by clinical manifestations of venous thromboembolic disease, mainly pulmonary embolism. Several litigations were settled worldwide for professional malpractice associated with COVID-19 and anticoagulant therapy management. The authors aimed to discuss, as court-appointed consultants in civil court, a case settled for compensation against a healthcare facility associated with SARS-CoV-2 infection. Case report: We described the case of an old patient in therapy with a direct oral anticoagulant for thrombotic diathesis, hospitalized for COVID-19 pneumonia, who died after two intra-hospital adverse events influencing coagulation imbalance. Discussion: Two health professionals’ malpractice hypotheses were discussed related to the adverse events’ occurrence: one related to the administration of an enema, resulting in rectal perforation, and the other related to proper anticoagulant prophylaxis and comprehensive coagulation imbalance management after the rectal perforation in a patient at high risk of venous thromboembolic disease. Intra-hospital adverse events complicated the hospitalization and then significantly reduced the concrete possibility, even uncertain in terms of time and extent, of the patient’s living longer, representing the damage of reduced possibilities of survival, also called loss-of-chance damage. Conclusions: The case discussed as court advisors, characterized by clinical and legal complexity, together with SARS-CoV-2 infection, underscores the vital role of forensic examiners in cause-of-death ascertainment and as interpreters of statistical-probabilistic data according to naturalistic, logical, and scientific criteria.

Radiological assessment of extremity bone involvement in Erdheim-Chester disease: a systematic review of case reports.

To describe the clinical presentations and radiological manifestations of Erdheim-Chester disease (ECD) in the extremities, with particular emphasis on radiologic findings, as radiographs are typically the initial imaging modality used in clinical practice. Following the PRISMA guidelines, a comprehensive systematic search was performed across Scopus, PubMed, Web of Science, and Embase databases, covering case reports from inception until August 1, 2024. Included were studies with pathologically confirmed ECD (CD68 positive and CD1a negative) that were evaluated with at least one imaging modality and provided detailed descriptions of radiological findings. Out of 401 identified articles, 20 articles comprising 20 histologically confirmed cases of ECD met the inclusion criteria following screening and full-text review. Pathological reports were assessed for the presence of lipid-laden cells and Touton giant cells, which were identified in 84.2% and 75% of cases, respectively. Upper extremities were affected in 65% of cases and lower extremities in all cases. Symmetric involvement was observed in 84.6% of upper extremity cases and 84.2% of lower extremity cases. Radiological findings were categorized as pure sclerosis (53.3%) and cortical thickening (42.8%) identified as the most common findings. Clinical manifestations were assessed, with pain and swelling in the extremities being the most common symptoms, occurring in 70% of cases. The hallmark of ECD is bilateral, symmetric diaphyseal and/or metaphyseal osteosclerosis in the long tubular bones of the lower extremities. Epiphyseal sparing is observed in more than half of the patients.

A patient with a PTPN11 gene variant complicated with Chiari I malformation and syringomyelia and a review of literatures.

According to previous literature reports, PTPN11 gene variants account for approximately 50% of Noonan syndrome (NS) cases and 85% of Leopard syndrome (LS) cases. Several patients who were diagnosed with NS or LS complicated with Chiari I malformation (CIM) and/or syringomyelia have been reported to have a PTPN11 variant. However, it is not always clear whether the association between CIM and/or syringomyelia and PTPN11 variants is real or random. We try to explain this phenomenon by reporting a clinical case and making a mini-review. We retrospectively described a clinical case in detail and made a genetic test on the proband and her family members using whole-exome sequencing. And made a review of the related literatures. The patient was manifesting progressive abnormal gait and muscle weakness for more than 2 years before she was admitted to our hospital at the age of 5 years and 2 months. On examination, she looked frail and slender. She had short stature, mild intellectual disability, decreased muscle strength in the left limb, thinner left limb, left hollow foot and foot drop, weakened left knee and Achilles tendon reflexes and a positive left Babinski sign. She looked timid and had very little expressive language. MRI of the brain and spine revealed CIM and syringomyelia with hydrops. Cardiac ultrasonography revealed an ostium secundum defect. ECG examination showed no abnormalities. She received a spinal cavity subarachnoid shunt; the symptoms were relieved to some extent, and the cavity in the lumbar vertebrae was significantly reduced after the surgery. Genetic testing found a variant, c. 922A>G (p. Asn308Asp) in the PTPN11 gene. Both parents were wild-type at this locus. A literature review found that 31 patients with NS or LS were complicated with CIM, syringomyelia or both. Together with our patient, a total of six patients in this group had the PTPN11 gene variant. Among them, four were complicated with both CIM and syringomyelia, and two were complicated with CIM only. We report another case with a PTPN11 variant that was complicated with both CIM and syringomyelia. It suggests that CIM and syringomyelia may be clinical manifestations of PTPN11 variation-related diseases. This phenomenon may be underrated due to limitations of genetic diagnostic methods in the past. We strongly suggest routine craniocerebral and spinal MRI scans and genetic testing for patients suspected of having NS or LS.

Interplay between platelets and coagulation: from protective haemostasis to pathological arterial thrombosis

Abstract Haemostasis refers to the physiological process aimed at repairing vessel injury and preventing bleeding. It involves four interlinked stages culminating in the formation of a platelet–fibrin haemostatic plug that is eventually dissolved once the vessel heals. In contrast, arterial thrombosis is a pathological condition resulting from atheroma exposure, triggering the formation of a platelet-rich thrombus that may obstruct blood flow, leading to the clinical manifestations of ischaemic cardiovascular disease. The following review will provide a comprehensive overview of the finely regulated endogenous antithrombotic mechanisms responsible for maintaining the haemostatic balance and preventing intravascular thrombosis. Thereafter, it will further detail the different stages and mechanisms governing the intricate interplay between the vessel, platelets, and the coagulation cascade in haemostasis, highlighting the most recent advances in platelet biology and function, to further elucidate the differential traits and players contributing to pathological arterial thrombus growth. The review will also delve into the impact of emerging cardiovascular risk factors on tilting the haemostatic balance towards a pro-thrombotic state, thereby increasing the patient’s vulnerability to thrombotic events. Finally, it will underscore the importance of early screening for subclinical atherosclerosis through advanced imaging technologies capable of quantifying plaque burden and metabolic activity since they may set the stage for an increased thrombotic risk. Implementing proactive interventions to halt atherosclerosis progression or inducing its regression at early stages is crucial for preserving haemostasis and reducing the likelihood of ischaemic atherothrombotic disease.