Clinical Manifestations Of Disease Research Articles

Ocular Behçet Disease—Clinical Manifestations, Treatments and Outcomes According to Age at Disease Onset

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (<18 years), adult (18-39 years) and late (≥40 years) disease onset. The study included 175 ocular BD patients (303 eyes) from Israel and Palestine: juvenile-onset (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar.

The study of antecedent clinical manifestations of hypertensive heart disease in cohort of hypertension.

Hypertensive heart disease presents increasing morbidity and mortality worldwide, however, the data about its epidemics and its specific symptoms in hypertension patients is scarce. To assess the frequency and correlated symptoms of hypertensive heart disease, 800 hypertension patients were randomly recruited for this study per the guidelines of the American College of Cardiology. The diagnosis of heart disease and its typical symptoms (palpitation and angina) were analyzed for the frequency of hypertensive heart disease in hypertension cohort. Cross-tabulation analysis was used to study the correlation between psychiatric indexes (annoy, amnesia, irritableness, depression, anxiety, and fear) and palpitation, the correlation between physical disorders (backache, lumbar debility, and numbness of limbs) and palpitation, and the correlation between symptoms (dizziness, daze, headache, and tinnitus) and palpitation presented in hypertensive patients. It was found that around half of patients suffered hypertensive heart disease, which correlated to certain physical and mental symptoms. Significant correlation exists between palpitation and annoy / amnesia. Significant correlation exists between palpitation and backache / lumbar debility / numbness of limbs; and significant correlation exists between palpitation and dizziness / daze / headache / tinnitus. These results provide clinical insights into the modifiable antecedent clinical conditions which are risk factors for hypertensive heart disease in elderly and will help improve early management of this disease.

БОЛЕЗНЬ ШЕГРЕНА И ОСТЕОПОРОЗ В ПРАКТИКЕ ВРАЧА-СТОМАТОЛОГА: КЛИНИЧЕСКИЙ СЛУЧАЙ

Subject. The subject of this research is Sjogren's syndrome.&#x0D; Objective. The objective of this research is to report a clinical case of Sjogren's syndrome associated with osteoporosis under hospital outpatient care provided by a dental therapist.&#x0D; Methodology. The research design includes description of one clinical case. The study is conducted by the Department of Preventive Dentistry and Propedeutics of Dental Disease, and the Department of Intermediate Level Therapy and Geriatrics of Ural State Medical University. This paper presents clinical observations of the patient developing main symptoms of Sjogren's syndrome, as well it explores somatic/dental status and describes the framework for supervision during dynamic observation.&#x0D; Conclusion. The case study allows to explore one of the multiple cases leading to development of chronic Sjogren's syndrome. The patient experiences a worsening of symptoms associated with menopausal transition and with new signs brought on by osteoporosis shows specific symptoms. Clinical manifestations of Sjogren's disease are highly variable, complicating the diagnostic process. This creates a risk of delayed treatment and provokes the development of severe complications, especially against the background of osteoporosis. Rational selection of appropriate modern medical treatment (active general drug therapy) and dynamic observation of a reumatologyst are specially important. However, being an interdisciplinary problem Sjogren's syndrome requires involvement of dental professionals, training in professional oral hygiene procedure which is the initial step of comprehensive maintenance treatment (based on clinical recommendations) and dynamic observation of patients; based on systemic manifestations, other specialists such as a reumatologyst, a gastroenterologist, an endocrinologist, an ophthalmologist may be involved.

НЕКОТОРЫЕ ОСОБЕННОСТИ СОСТОЯНИЯ ТВЕРДЫХ ТКАНЕЙ ЗУБОВ И ПАРОДОНТА У ПАЦИЕНТОВ С ВОСПАЛИТЕЛЬНЫМИ ЗАБОЛЕВАНИЯМИ КИШЕЧНИКА, ПРОЖИВАЮЩИХ В РЕСПУБЛИКЕ БАШКОРТОСТАН

The work presents the results of assessing the spread of pathology of hard tissues of teeth and periodontal in patients with chronic inflammatory bowel diseases (IBD). Objective. Assessment of the intensity and spread of pathology of dental hard tissues and inflammatory periodontal diseases in patients with Crohn's disease (CD) and chronic ulcerative colitis (CUC). Materials and methods. A comprehensive clinical and dental examination of 70 patients with CD and CUC was carried out. The complex of dental examination included the analysis of complaints, anamnesis, assessment of the condition of hard tissues of teeth, periodontal tissues. Assessment of the intensity level of nociceptive pain was carried out using a visual analog scale (VAS). Results and discussion. As a result of the clinical examination, a high prevalence of caries (K02) was revealed in CD and CUC, respectively, in 97.2% and 91.4% of cases, high and very high intensity of the carious process according to the CP index ≥ 10. With CD, the symptom of hyperesthesia, increased erasure of mixed teeth and wedge-shaped defects were most often observed in 100, 77.14 and 60.0% of cases, in 68.57% chronic periodontitis prevails (K05.3), with CD, the symptom of hyperesthesia (K03.80) and increased tooth erasure (K03.0) were 1.2 times less common) (p &lt; 0.05), chronic gingivitis prevails in 62.85% (K05.10). The level of intensity of the pain symptom for patients with CD and CUC corresponds to the VAS scale from moderate to significant (p &lt; 0.001). Results. As a result of a comprehensive dental examination of patients with CD and CUC, a high prevalence and intensity of caries and non-carious dental hard tissue lesions, inflammatory periodontal diseases, the level of dental care in persons with CD and CUC is insufficient. Conclusion. The connection of dental status with clinical manifestations of chronic inflammatory bowel diseases is beyond doubt. The ambiguity of the etiology and pathogenesis of CD and CUC as well as the significant similarity of their clinical manifestations, dictate the need for an integrated approach to the development of methods for diagnosing pathology of hard tissues of teeth and periodontal and assessing their clinical features.

Ganmaidazao decoction alleviated cognitive impairment on Alzheimer's disease rats by regulating gut microbiota and their corresponding metabolites

Traditional Chinese medicine targeted at gut microbiota has good effects in relieving the clinical manifestation of Alzheimer's disease, and intestinal metabolites are considered as a bridge of communication between the brain-gut axis. In order to explore the molecular mechanism of Ganmaidazao decoction treatment, first, the model rats induced by Aβ25-35 and d-gal were used to test the therapy of Ganmaidazao extract using the Morris Water Maze, Western Blot and Elisa. Then the 16S rDNA gene sequencing of the gut microbiota as well as UPLC-QTOF/MS-based metabolomic analysis of feces were carried out. Last, the relationship between Alzheimer's disease, gut microbiota and metabolites was analyzed. Results showed that the abundance and diversity of gut microbiota were rescued and the changes of fecal metabolites in rats with Alzheimer's disease were reversed after Ganmaidazao decoction administration, which were mainly related to lipid metabolism, steroid hormone metabolism, energy metabolism, amino acid metabolism and bile acid metabolism. After associating with Spearman’s correlation analysis, we concluded that gut microbiota and metabolites were closely related and Ganmaidazao decoction could interfere with the balance of gut microbiota and their corresponding metabolites to exert anti- Alzheimer’s disease effect. Combined with PICRUSt2 functional prediction of gut microbiota and metabolomics results, phenylalanine metabolism has been focused as a key metabolic pathway, and Ganmaidazao decoction can reduce the abnormal accumulation of phenylalanine and phenylpyruvate and promote their metabolism by restoring the activity of phenylalanine hydroxylase. This integrated omics approach has potential roles in understanding the complex mechanisms of Ganmaidazao decoction in treating Alzheimer’s disease.

ПОВЫШЕНИЕ ЭФФЕКТИВНОСТИ МЕСТНОГО ЛЕЧЕНИЯ РЕЦИДИВИРУЮЩИХ АФТ ПОЛОСТИ РТА У ПАЦИЕНТОВ НА ФОНЕ КЛИНИЧЕСКИХ ПРОЯВЛЕНИЙ КЛАССИЧЕСКИХ И ОПОСРЕДОВАННЫХ ГИПЕРСЕКРЕТОРНЫХ ЗАБОЛЕВАНИЙ ЖЕЛУДОЧНО-КИШЕЧНОГО ТРАКТА

This work presents a comparative analysis of the effectiveness of local treatment of re-current aphtae in patients with clinical manifestations of hypersecretory diseases of the gastro-intestinal tract (GIT). Object. Evaluation of the effectiveness of the impact of a diode laser and applications of powdered platelet of autologous plasma relative to generally accepted methods of local treatment of recurrent oral aphtae. Materials and methods. 58 patients with clinical manifestations of K12.00 have been treated. Recurrent oral aphthae were at the age of 25 to 45 years. Depending on the method of local treatment, clinical subgroups – Ia and IIa (15 patients each) received the proposed complex of local treatment, Ib and IIb (14 patients each) treatment according to well-known methods. The effec-tiveness of local treatment was assessed by reducing the degree of inflammation, the intensity of the level of nociceptive pain and increasing the rate of epithelialization of aphtae. Results and discussion. The effectiveness of local treatment was assessed by reducing inflammation, pain and increasing the rate of epithelialization of aphtae. A more rapid reduction in pain and a decrease in the size of aft was observed in the Ia and IIa clinical subgroups during 3.0 ± 0.2 and 3.1 ± 0.2 days, complete epithelialization of aphtae and leveling of all complaints by 4.9 ± 0.4 and 4.7 ± 0.4 days, increased the remission period to 12 months. In patients Ib and IIb, pain reduction and reduction in aphtae size were observed by 3.5 ± 0.2 and 4.9 days, complete epithelialization and leveling of all complaints by 7.9 ± 0.2 and 7.5 ± 0.3 days, aft recurrence was observed by 6 and 12 months of dynamic observation. Conclusions. The in-clusion a diode laser in the local treatment regimen, applications of powdered autologous platelet plasma and maintenance therapy with a course frequency of 2 times a year is a highly effective method and helps to relieve nociceptive pain, inflammation, accelerate epithelializa-tion and regeneration of the mucous membrane and reduce relapses. Summary. The use a di-ode laser and applications of powdered autologous platelet plasma in combination with maintenance therapy is an effective method of local treatment of recurrent aphtae in patients against the background of basic and classical hypersecretory gastrointestinal diseases.

Vaccine-linked chemotherapy improves cardiac structure and function in a mouse model of chronic Chagas disease.

Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. We previously demonstrated in acute infection models that this strategy parasite specific immune responses, and reduced parasite burdens and cardiac pathology. Here, we tested our vaccine-linked chemotherapy strategy in a mouse model of chronic T. cruzi infection to evaluate the effect on cardiac function. Female BALB/c mice infected with 500 blood form T. cruzi H1 strain trypomastigotes were treated beginning 70 days after infection with a low dose of BNZ and either low or high dose of vaccine, in both sequential and concurrent treatments streams. Control mice were untreated, or administered only one treatment. Cardiac health was monitored throughout the course of treatment by echocardiography and electrocardiograms. Approximately 8 months after infection, endpoint histopathology was performed to measure cardiac fibrosis and cellular infiltration. Vaccine-linked chemotherapy improved cardiac function as evidenced by amelioration of altered left ventricular wall thickness, left ventricular diameter, as well as ejection fraction and fractional shortening by approximately 4 months of infection, corresponding to two months after treatment was initiated. At study endpoint, vaccine-linked chemotherapy reduced cardiac cellular infiltration, and induced significantly increased antigen specific IFN-γ and IL-10 release from splenocytes, as well as a trend toward increased IL-17A. These data suggest that vaccine-linked chemotherapy ameliorates changes in cardiac structure and function induced by infection with T. cruzi. Importantly, similar to our acute model, the vaccine-linked chemotherapy strategy induced durable antigen specific immune responses, suggesting the potential for a long lasting protective effect. Future studies will evaluate additional treatments that can further improve cardiac function during chronic infection.

Review on the application of imaging examination for brain injury in premature infants.

Brain injury is the main factor leading to the decline of the quality of life in premature infants. The clinical manifestations of such diseases are often diverse and complex, lacking obvious neurological symptoms and signs, and the disease progresses rapidly. Due to missed diagnosis, it is easy to miss the best treatment opportunity. Brain ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and other imaging methods can help clinicians diagnose and assess the type and extent of brain injury in premature infants to some extent, but the three methods have their own characteristics. This article briefly reviews the diagnostic value of these three methods for brain injury in premature infants.

A Review on the Immunological Response against Trypanosoma cruzi

Chagas disease is a chronic systemic infection transmitted by Trypanosoma cruzi. Its life cycle consists of different stages in vector insects and host mammals. Trypanosoma cruzi strains cause different clinical manifestations of Chagas disease alongside geographic differences in morbidity and mortality. Natural killer cells provide the cytokine interferon-gamma in the initial phases of T. cruzi infection. Phagocytes secrete cytokines that promote inflammation and activation of other cells involved in defence. Dendritic cells, monocytes and macrophages modulate the adaptive immune response, and B lymphocytes activate an effective humoral immune response to T. cruzi. This review focuses on the main immune mechanisms acting during T. cruzi infection, on the strategies activated by the pathogen against the host cells, on the processes involved in inflammasome and virulence factors and on the new strategies for preventing, controlling and treating this disease.

Seroprevalence of Hepatitis E virus in children and adolescents living in urban Bogotá: An explorative cross-sectional study.

The majority of Hepatitis E Virus (HEV)-related studies are carried out in adults whereas information about HEV seroprevalence, clinical disease manifestation, molecular epidemiology, and transmission patterns in children is limited. To estimate HEV seroprevalence among scholar children living in an urban setting and to analyze risk factors for an infection, we invited children aged 5-18 years from Bogotá (Colombia) for a cross-sectional survey. We collected self-reported data on demographics, social, clinical, and exposure variables in a structured interview. Venous blood samples were analyzed with two commercially available ELISAs for HEV-specific IgG antibodies. Among the 263 participants, we found three HEV IgG-reactive samples (1.1%) using both assays. We additionally characterized the samples for HEV IgM using a commercially available IgM ELISA and for HEV RNA. Here, we found one IgM-reactive sample, which was also reactive for IgG. In contrast, none of the IgM- and IgG-reactive sera samples showed detectable RNA levels indicating HEV exposure had not been recently. All participants reported access to drinking water and sanitary systems in their households and frequent hand washing routines (76-88%). Eighty percent of children reported no direct contact with pigs, but occasional pork consumption was common (90%). In contrast to the majority of studies performed in Colombian adults, we found a low unadjusted HEV seroprevalence of 1.1% (95% CI: 0.3-3.6%) for both HEV IgG ELISAs in our study population. While the majority of participants reported pork consumption, we speculate in the absence of viral RNA for genotyping in the affected individuals, that existing access to drinking water and sanitary systems within our study group contribute to the low HEV seroprevalence.

Systemic sclerosis gastrointestinal dysmotility: risk factors, pathophysiology, diagnosis and management.

Nearly all patients with systemic sclerosis (SSc) are negatively affected by dysfunction in the gastrointestinal tract, and the severity of gastrointestinal disease in SSc correlates with high mortality. The clinical complications of this dysfunction are heterogeneous and include gastro-oesophageal reflux disease, gastroparesis, small intestinal bacterial overgrowth, intestinal pseudo-obstruction, malabsorption and the requirement for total parenteral nutrition. The abnormal gastrointestinal physiology that promotes the clinical manifestations of SSc gastrointestinal disease throughout the gastrointestinal tract are diverse and present a range of therapeutic targets. Furthermore, the armamentarium of medications and non-pharmacological interventions that can benefit affected patients has substantially expanded in the past 10 years, and research is increasingly focused in this area. Here, we review the details of the gastrointestinal complications in SSc, tie physiological abnormalities to clinical manifestations, detail the roles of standard and novel therapies and lay a foundation for future investigative work.

Crosstalk between miR-146a and pro-inflammatory cytokines in patients with systemic lupus erythematosus.

microRNA-146a (miR-146a) plays an essential role in immune anomalies and organ injury of systemic lupus erythematosus (SLE) by regulating the disease's inflammation and complications. Here, we analyzed the expression of miR-146a in SLE and a panel of pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-17, and TNF-α). Association between all measured parameters and the disease's clinical manifestation and response to treatment was monitored. Our study populations were 113 SLE patients and 104 healthy volunteers. miR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured by quantitative real-time PCR (RT-qPCR). The content of the plasma cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, miR-146a expression was significantly increased (p < 0.05) in lupus patients. The analysis of the receiver operator characteristic curve (ROC) of miR-146a showed 91% sensitivity and 70% specificity. IL-1β, IL-6, and IL-17 cytokines were significantly increased (p < 0.001), while IL-8 and TNF-α were significantly decreased (p < 0.001) in SLE patients against controls. The expression of miR-146a and TNF-α was upregulated considerably in SLE patients with severe disease activity. miR-146a expression was positively correlated with IL-6. Our results pointed to the elevation of miR-146a as a trade marker of SLE patients. Reduction of IL-8 and TNF-α in combination with an elevation of IL-1β, IL-6, and IL-17 might refer to miR-146a's dual effect in controlling inflammation in lupus. Although we shed some light on the role of miR-146a in SLE, further study is recommended to improve our results.

Kimura's disease

The analysis of published clinical observations on the diagnosis and treatment of patients with Kimura's disease, which is a rather rare chronic inflammatory disease of human soft tissues of unknown etiology, is presented. The onset of Kimura's illness is hardly noticeable. The disease proceeds sluggishly, with a varied clinical picture, most often with the formation of single or multiple subcutaneous nodules or tubercles and swelling in the head and neck on one or both sides. Other localizations of lesions are also described: limbs, orbit, eyelids, palate, pharynx, armpit, chest, inguinal region. The affected areas gradually increase in size over many months or years. Other clinical manifestations of Kimura's disease are presented in the form of edema of the extraocular muscle, juvenile temporal arteritis, sleep apnea in cases of damage to the larynx, and life-threatening coronary artery spasm in children. There are reports of other rare systemic clinical signs of Kimura's disease in the form of pruritus, eczema and rash. The disease is often associated with regional lymphadenopathy and/or salivary gland involvement, eosinophilia, and an increase in serum immunoglobulin E from 800 to 35,000 IU/mL. The disease may be accompanied by kidney damage in the form of glomerulonephritis and nephrotic syndrome. Most reported cases of Kimura's disease occur in young Asian men in their 20s and 30s, sporadically the disease is diagnosed in Europeans, North Americans, Caucasians, and Africans. Diagnosis of Kimura's disease is often clinically difficult. It is primarily based on excisional biopsy of the lesion or regional lymph nodes, and the histopathological findings are consistent regardless of the location of the lesion. Morphologically, Kimura's disease is characterized by the presence in biopsy specimens of such histological features as reactive follicular hyperplasia with prominent follicles surrounded by fibrous tissue. Interfollicular infiltrates are rich in plasma cells and eosinophils, which form diffuse eosinophilic microabscesses associated with granulomatous inflammation. The vessels are numerous, with an increase in postcapillary venules. At the same time, the blood vessels remain thin-walled, with cuboidal endothelial cells. Treatment issues are highlighted, and differences between Kimura's disease and angiolymphoid hyperplasia with eosinophilia are presented.

Different relationships between epilepsy syndromes and autoimmune diseases.

Our objective was to study the relationship between epilepsy and autoimmune diseases in two different types of epilepsy: idiopathic generalized epilepsies (IGEs) and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). The contribution of the human leukocyte antigen (HLA) system to this relationship was analysed. Adult patients with IGEs and MTLE-HS at a tertiary epilepsy centre were consecutively enrolled between January 2016 and December 2020. A total of 664 patients, 422 with IGEs and 242 with MTLE-HS, were included. Patients with IGEs were 15 years younger, on average, than patients with MTLE-HS (p<0.001). The frequency of autoimmune diseases was 5.5% (n=23) and 4.5% (n=11), in patients with IGEs and MTLE-HS, respectively (p=0.716). The mean age of autoimmune disease onset was 20±15.6 years in patients with IGEs and 36.7±16.5 years in patients with MTLE-HS (p<0.05). Clinical manifestations of autoimmune diseases preceded epilepsy onset in 30.4% of patients with IGEs (i.e., in early childhood); in the other patients, epilepsy appeared before autoimmune disease onset. In all but one patient with MTLE-HS and autoimmune diseases, the autoimmune diseases appeared after epilepsy onset, from adolescence onwards. Our study indicates two relationship patterns: a bidirectional association between IGEs and autoimmune diseases and a unidirectional relationship between MTLE-HS and autoimmune diseases. The involvement of genetic susceptibility factors (such as the HLA system), autoinflammatory mechanisms, female sex, and antiseizure medications in these relationships are discussed.

Genetic Polymorphisms of NOD2 and ATG16L1 in Different Types of Digestive Tract Inflammation.

Inflammatory bowel diseases (IBD) result from genetic and environmental factors. The two clinical manifestations of inflammatory bowel disease are ulcerative colitis and Crohn's disease (IBD). Numerous studies have demonstrated a link between immune system molecules' single nucleotide polymorphisms (SNPs) and the incidence of IBD. The study aimed to examine the potential impact of the SNPs NOD2 rs2066844 and ATG16L1 rs2241880 in a group sample of Iraqi IBD patients. The AG genotype for rs2241880 was associated with an increased risk for CD (P=0.1) and a negative association with UC, whereas the AA genotype presents less in CD patients and a negative association with UC (P=0.89). For this SNP, the G allele was associated with the risk of CD but not for UC. For the rs2066844, there were no significant differences for NOD2 in both CD and UC, and associations between variation and diseases were not observed.

Comparative effectiveness and complications of intravenous ceftriaxone compared with oral doxycycline in Lyme meningitis in children: a multicentre prospective cohort study

IntroductionLyme disease is the most common vectorborne disease in the Northern hemisphere with more than 400 000 new cases in the USA annually. Lyme meningitis is an uncommon but potentially...

Clinical outcomes among young patients with Fabry disease who initiated agalsidase beta treatment before 30 years of age: An analysis from the Fabry Registry.

Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5-30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742, sponsor: Sanofi). Reported GLA variants were predicted to be associated with the classic phenotype or not classified in fabry-database.org. Linear mixed models were conducted to assess changes over ≥2-year follow-up in the estimated glomerular filtration rate (eGFR) stratified by low (LRI) and high (HRI) renal involvement (defined by proteinuria/albuminuria levels), and changes in interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) Z-scores stratified by median age at first treatment. Self-reports ('yes'/'no') of abdominal pain, diarrhea, chronic peripheral pain (denoting neuropathic pain), and acute pain crises at baseline were compared with reports after ≥0.5-year and ≥2.5-year follow-up using McNemar's test. Male (n = 117) and female patients (n = 59) with LRI initiated treatment at a median age of 19.9 and 23.6 years, respectively, and were followed for a median of 6.3 and 5.0 years, respectively. The eGFR slopes were -1.18 (Pfrom 0 <0.001) and -0.92 mL/min/1.73 m2/year (Pfrom 0 = 0.040), respectively. Males with HRI (n = 23, median UPCR 1.0 g/g), who started treatment at a median age of 26.7 years, had an eGFR slope of -2.39 mL/min/1.73 m2/year (Pfrom 0 <0.001; Pdifference = 0.055, as compared with the slope of -1.18 mL/min/1.73 m2/year for LRI males) during a median follow-up of 5.6 years. Echocardiographic variables were stable among males, regardless of age, and among young females (median follow-up >5.5 years and ≥4.5 years, respectively). Older females (treatment initiation at median age 27.5 years) had a slope of LVPWT Z-scores of 0.18/year (n = 12, Pfrom 0 = 0.028), whereas IVST Z-scores remained stable (n = 13, 0.10/year, Pfrom 0 = 0.304) during a median follow-up of ≥3.7 years. These slopes did not significantly differ from slopes of younger females. Reports of chronic peripheral pain and acute pain crises by males, and of diarrhea and acute pain crises by females, significantly reduced after a median follow-up of ≥4.0 years. After a median follow-up of ≥5.4 years, reports of all four symptoms significantly decreased among males, whereas among females only reports of abdominal pain significantly decreased. During sustained treatment with agalsidase beta in young Fabry patients with a predicted classic phenotype or with unclassified GLA variants with similar characteristics, the decline in eGFR was modest among male and female patients with LRI. The greater decline in eGFR among older, proteinuric (i.e., HRI) males may suggest a benefit of earlier treatment. Overall, echocardiographic variables remained stable, particularly among males and younger females. Significant reductions in symptom reports occurred primarily among males after longer follow-up and were less noticeable among females. These observed trends are suggestive of an overall improvement after treatment in young patients, but warrant larger longitudinal studies.

Red flags to diagnose infiltrative cardiomyopathies

Infiltrative cardiomyopathies are a group of diseases characterized by the deposition of abnormal substances in heart tissues, which leads to thickening of the walls or dilation of chambers with a secondary decrease in wall thickness and the development of diastolic, less often systolic, ventricular dysfunction. Most often, these are progressive diseases that, in the absence of adequate therapy, have an unfavorable prognosis. Clinical manifestations of infiltrative cardiac diseases are variable, which often leads to diagnostic difficulties and errors. In most cases, specific laboratory and morphological tests are required to confirm or clarify the diagnosis. Early diagnosis is critical to initiating therapy and improving patient prognosis. This article provides characteristic signs and symptoms, the so-called "red flags", making it possible to suspect infiltrative cardiomyopathies, diagnose them at an early stage and start life-saving therapy.

Management of patients with inflammatory bowel diseases and extra-intestinal skin manifestations

Introduction. Clinical manifestations of inflammatory bowel diseases (IBD) are limited not only by the gastrointestinal tract syndromes, but also by a wide range of extra-intestinal manifestations, which include skin manifestations. Skin lesions in IBD occur in different forms. Some of them are associated with the activity of the main process, for example, gangrenous pyoderma. Others, such as psoriasis, are combined with pathogenetic factors common to IBD. Materials and methods. Three clinical observations of patients with IBD and extra-intestinal manifestations are presented: gangrenous pyoderma (case 1) and psoriasis (cases 2, 3). The stages of differential diagnostic search and treatment are described. The interleukin 12/23 inhibitor ustekinumab is prescribed to both bionaive patients (observations 1, 2), and to the patient who (observation 3) had high activity of the inflammatory process in the intestine and had received early treatment with GEBD. The extension of indications for use ustekinumab (ulcerative colitis, Crohn’s disease, psoriasis, psoriatic arthritis) of allows for its wider use in the treatment of patients. Conclusion. The interleukin 12/23 inhibitor ustekinumab has broad indications for use; its use allows to achieve a positive clinical, laboratory and endoscopic effect at the early stages of use. This effect has spread to skin manifestations, the reduction of which occurs in parallel with the healing of the intestinal mucosa.

Impaired kynurenine metabolism in patients with primary Sjögren’s syndrome

ObjectivesPrimary Sjögren’s syndrome (pSS) is an autoinflammatory disease characterized by inflammation of the exocrine glands. Elevated inflammation causes an increase in kynurenine pathway (KP) metabolite levels by activating indoleamine 2,3-dioxygenase (IDO). The aim of this study was to measure serum KP metabolite concentrations in patients with pSS and to evaluate the relationship between these metabolites with disease activity score and clinical manifestations. Design & MethodsA total of 80 patients with pSS and 80 healthy controls were enrolled in this study. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QUIN) concentrations were quantified with liquid chromatography with tandem mass spectrometry (LC-MS/MS). Demographic characteristics, clinical manifestations and disease activity score (ESSDAI) of the participants were recorded. ResultsThe serum level of KYN and QUIN were significantly higher in patients with pSS with low and moderate activity compared those healthy controls, while the serum level of TRP, KYNA/KYN and 3HK/KYN were lower. In addition, the significant difference for the serum level of KYNA was only in patients with moderate activity from healthy controls, and the difference was higher in favor of pSS patients. Moreover, the KYN/TRP levels were significantly increased with disease activity. The ESSDAI score was positively correlated with KYN/TRP ratio, but negatively correlated with KYNA/KYN ratio. ConclusionsThese findings indicated that KP metabolites may play a role in the etiopathogenesis, activation and progression of pSS.