Chronic Course Research Articles

Efficient formation and maintenance of humoral and CD4 T-cell immunity targeting the viral capsid in acute-resolving hepatitis E infection

CD4 T cells shape the neutralizing antibody (nAb) response and facilitate viral clearance in various infections. Knowledge of their phenotype, specificity and dynamics in hepatitis E virus (HEV) infection is limited. HEV is enterically transmitted as a naked virus (nHEV) but acquires a host-derived quasi-envelope (eHEV) when budding from cells. While nHEV is composed of the open reading frame (ORF)-2-derived capsid, eHEV particles also contain ORF3-derived proteins. We aimed to longitudinally characterize the HEV-specific CD4 T cells targeting ORF1, 2 and 3 and antibodies against nHEV or eHEV in immunocompetent individuals with acute and resolved HEV infection. HEV-specific CD4 T cells were analyzed by intracellular cytokine staining after stimulation with in silico-predicted ORF1- and ORF2-derived epitopes and overlapping peptides spanning the ORF3 region. Exvivo multiparametric characterization of capsid-specific CD4 T cells was performed using customized MHC class II tetramers. Total and neutralizing antibodies targeting nHEV or eHEV particles were determined. HEV-specific CD4 T-cell frequencies and antibody titers are highest in individuals with acute infection and decline in a time-dependent process with an antigen hierarchy. HEV-specific CD4 T cells strongly target the ORF2-derived capsid and ORF3-specific CD4 T cells are hardly detectable. NAbs targeting nHEV are found in high titers while eHEV particles are less efficiently neutralized. Capsid-specific CD4 T cells undergo memory formation and stepwise contraction, accompanied by dynamic phenotypical and transcriptional changes over time. The viral capsid is the main target of HEV-specific CD4 T cells and antibodies in acute-resolving infection, correlating with efficient neutralization of nHEV. Capsid-specific immunity rapidly emerges followed by a stepwise contraction several years after infection. The interplay of CD4 T cells and neutralizing antibody responses is critical in the host defense against viral infections, yet little is known about their characteristics in hepatitis E virus (HEV) infection. We conducted a longitudinal study of immunocompetent individuals with acute and resolved HEV infection to understand the characteristics of HEV-specific CD4 T cells and neutralizing antibodies targeting different viral proteins and particles. We found that HEV-specific CD4 T cells mainly target capsid-derived epitopes. This correlates with efficient neutralization of naked virions while quasi-enveloped particles are less susceptible to neutralization. As individuals with pre-existing liver disease and immunocompromised individuals are at risk for fulminant or chronic courses of HEV infection, these individuals might benefit from the development of vaccination strategies which require a detailed knowledge of the composition and longevity of HEV-specific CD4 T-cell and antibody immunity.

SYNDROMAL APPROACH IN THE DIAGNOSIS OF HEREDITARY DISEASES (LECTURE)

The number of nosologic units of hereditary pathology is, according to Online Mendelian Inheritance in Man, about 16,000 syndromes (and their corresponding genes). Before starting diagnostics, it is necessary to make sure that the disease is genetically determined, using such signs as the familial and congenital nature of the pathology, progressive chronic course, multiplicity of pathological changes in organs and systems, resistance to known meth-ods of therapy. For effective diagnosis, it is necessary to use the assessment of minor and major developmental anomalies, as well as a syndromic approach. The syndromic approach is used to diagnose functional and anatomical syndromes that accompany hereditary diseases. This allows you to narrow the range of diseases to the use of labora-tory and instrumental research methods, and most accurately formulate a preliminary diagnosis for DNA diagnostics. Diagnosis of hereditary pathology is a rather complex problem because the number of nosologic forms is large, and the final diagnosis is determined using expensive DNA diagnostics. In this regard, the possibility of using a syn-dromic approach in clinical diagnosis comes to the fore

Tofacitinib Affects M1-like and M2-like Polarization and Tissue Factor Expression in Macrophages of Healthy Donors and IBD Patients.

Tofacitinib, as inhibitor of Janus kinases (JAK), interrupts the transmission of numerous pro-inflammatory cytokines involved in the pathogenesis of inflammatory bowel diseases (IBD). Therefore, tofacitinib provides a potent option to treat ulcerative colitis (UC). Besides the anti-inflammatory potential, inhibition of widespread JAKs carries the risk of side effects. Macrophages are involved in the form of different subtypes in inflammation, wound healing, and even coagulation. This study aimed to explore the balanced use of tofacitinib in M1-like as well as M2-like macrophages of healthy donors and patients with IBD. Monocytes of healthy donors and patients with chronic courses of IBD were obtained from blood samples. Macrophage colony-stimulating factor (M-CSF)-derived macrophages were treated with tofacitinib (1 µM, 5 µM, 10 µM) and polarized with either lipopolysaccharide and interferon (IFN)-γ towards M1-like-phenotype or with interleukin (IL)-4 towards M2-like-phenotype. ELISA and flow cytometry were used to evaluate cytokine levels and surface molecules. Tofacitinib had a modulating effect on M1-like macrophages whereby the effect on pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12, IL-23) was less pronounced than the induction of anti-inflammatory IL-10. However, during M2-like polarization tofacitinib impaired the development of the corresponding phenotype becoming evident through decreased IL-10 levels and CD206 expression in treated macrophages. In both phenotypes, tofacitinib strongly downregulated the expression of immunostimulatory molecules (CD80, CD86, CD83, CD40). Furthermore, a dose-dependent correlation between treatment with tofacitinib and expressed tissue factor was noticed. Tofacitinib influences both polarizations (M1/M2) and the expression of tissue factor in a dose-dependent manner.

Risk Factors of Onset Time and Persistence of Atopic Dermatitis in Children Under Age 5 Years: A Cross-Sectional Study.

Background: The prevalence of atopic dermatitis (AD) is high among children, with development of AD occurring during early childhood in most affected children and some having a chronic disease course. Risk factors for AD in this group remain undefined. Objectives: We analyzed the medical records of children with AD under 5 years of age. We summarized characteristics of the natural course of AD in these children and explored relevant risk factors of AD in infancy and early childhood. Methods: Using a self-developed questionnaire, we investigated 716 children under 5 years of age who were treated for AD at the Dermatology Department of the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China. We conducted the study from October 2021 to September 2022 using telephone and on-site interviews with the children's parents. In parental interviews, data were gathered on neonatal diseases, comorbidities, parental allergy history, maternal history of tobacco and alcohol use, and basic infant information at birth. Some children were tested for serum total immunoglobulin E (IgE) before this study. Results: Neonatal hyperbilirubinemia, neonatal respiratory distress syndrome (NRDS), neonatal infection, and infection during childhood had a significant impact on persistent symptoms and the onset of first symptoms in children with AD (P < 0.05). Allergic diseases as common comorbidities with AD, which had earlier onset of AD related to more obvious disease activity (P < 0.05). Parental history of allergy was also significant in AD (P < 0.05). Serum total iIgE levels in children with AD showed an impact on the clinical course of AD; neonatal hyperbilirubinemia and NRDS may affect IgE levels (P < 0.05). Persistent AD had a significant effect on the physical growth of children with height/length for age Z score ≤3 and weight for height/length Z score ≤3 (P < 0.05). Conclusions: Early adverse events in infants, infection before onset, and susceptibility to infection may affect the onset and clinical course of childhood AD. Serum total IgE levels affect the progression of AD. Persistent AD in childhood may have a slight impact on children's physical growth.

Childhood interstitial lung disease: When to suspect and what to do

Childhood Interstitial lung Disease (chILD) is a heterogeneous group of more than 200 respiratory disorders characterized by the impairement of alveolar-capillary gas exchange and lung function. These disorders usually have a chronic course. Morbidity and mortality greatly vary depending on the disorder considered. Interstitial lung disease are associated with respiratory distress. During infancy the most common symptom to pay attention to is tachypnea, whilst in older children clinical presentation may be more insidious. When chILD is suspected, it is advisable to send the patient to a pediatric pulmonology center in order to set up a diagnostic work-up and an adequate treatment. A European protocol called the “Delphi method” has been standardizing empirical treatment since 2015.

Patients with Chronic Spinal Cord Injury Display a Progressive Alteration over the Years of the Activation Stages of the T Lymphocyte Compartment.

Spinal cord injury (SCI) is a serious medical condition associated with severe morbidities and disability. Chronic SCI patients present an enhanced susceptibility to infections and comorbidities with inflammatory pathogenesis. Chronic SCI appears to be associated with a systemic dysfunction of the immune system. We investigated the alteration of the pivotal CD4+ and CD8+ T lymphocytes in patients with chronic SCI at different years of evolution. A clinically homogenous population of 105 patients with chronic SCI (31 with time of evolution less than 5 years (SCI SP); 32 early chronic (SCI ECP) with time of evolution between 5 and 15 years; and 42 late chronic (SCI LCP) with time of evolution more than 15 years) and 38 healthy controls were enrolled. SCI ECP and SCI LCP patients showed significant CD4+ and CD8+ T lymphopenia, ascribed to a reduction in naïve and CM subsets. Furthermore, SCI ECP and SCI LCP patients showed a significant reduction in the expression of CD28 on CD8+ T lymphocytes. The expression of CCR6 by CD4+ T lymphocytes was decreased during the evolution of chronic SCI, but on CD8+ T lymphocytes, it was observed during the first 15 years of evolution. In conclusion, the chronic SCI course with severe damage to T lymphocytes mainly worsens over the years of disease evolution.

Clinical and psychopathological characteristics of patients with pulmonar y tuberculosis and anxiety-depressive disorders treated in a phthisiological hospital

The aim of the research was to study the clinical and psychopathological characteristics of patients with pulmonary tuberculosis in the active phase and identified anxiety and depressive disorders. The study included 145 patients with anxiety-depressive disorders: 85 patients with a diagnosis of pulmonary tuberculosis who were being treated in a phthisiological hospital (the main group) and 60 patients with anxiety-depressive disorders without a history of tuberculosis, who were under follow-up and treatment in a psychoneurological dispensary (comparison group). In addition, in the main clinical group, two subgroups were identified depending on the length of hospital stay: with hospital stays of up to 2 months (44 patients) and over 2 months (41 patients). The study assessed the level of anxiety-depressive disorders, asthenia, the nature and intensity of psychosomatic complaints, and signs of vegetative changes. The study showed the presence of more intense psychosomatic complaints, asthenic disorders, and signs of autonomic disorders among the patients with pulmonary tuberculosis compared to those without tuberculosis. Furthermore, in the main clinical group, there was an increase in anxiety-depressive symptoms, asthenic manifestations, and signs of vegetative changes during a longer stay in the phthisiological hospital. The obtained results are presented in the context of the concept of «psychosomatic proportion», implying the ratio of subjective and objective components of patients» psychosomatic status (intensity and structure of psychosomatic complaints and objectively detectable somatovegetative changes in the body). It is concluded that tuberculosis determines a more severe course of affective spectrum disorders and negatively affects the general psychosomatic state of patients, while a long stay in a phthisiological hospital contributes to the chronic course and aggravation of anxiety-depressive disorders, which indicates the need for timely detection and treatment of affective pathology, as well as taking into account predictors of its development in order to elaborate an integrated approach to the therapy of tuberculosis and concomitant mental disorders.

Тубулоинтерстициальный нефрит с увеитом: серия клинических наблюдений

Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare autoimmune disease that develops predominantly in young people and is characterized by variable clinical manifestations and an uncertain prognosis. A single-center retrospective observational study included 3 pediatric patients (a girl and two boys) with clinically and morphologically confirmed TINU. Age of onset, clinical symptoms, gender-age-height-standardized blood pressure (BP), proteinuria (g/l), excretion level of β2-microglobulin, glucose, phosphorus in urine, blood pH and bicarbonate levels, Bedside Schwartz equation estimated glomerular filtration rate (eGFR, ml/min/1.73 m2, norm≥90 ml/min/1.73 m2), ophthalmoscopy data and the therapy were analyzed at the time of disease manifestation and during the follow-up. The duration of follow-up ranged from 3 to 7 years. The disease debuted at the age of 10 to 14 y/o with severe symptoms of intoxication, inflammatory activity, acute kidney damage (eGFR=22 to 35 ml/min/1.73 m2) and the development of Fanconi syndrome. Anterior uveitis had manifested in 1 to 5 months after the kidney disease. The TINU diagnosis was established after 6 to 9 months from the onset of the disease. All children received systemic steroid therapy coupled with the local treatment for uveitis. A significant decrease in blood creatinine levels and urine β2-microglobulin excretion with partial restoration of renal filtration function was noted by the sixth month of the therapy. All children developed chronic kidney disease (CKD) stages 2 to 3 over time. Stable remission of uveitis was achieved in 2 children after 3 to 10 months of treatment without complications; and in one patient a subacute uveitis led to the secondary changes in the cornea and decreased visual acuity. Conclusion: children with TINU have a high risk of developing CKD as a result of acute kidney disease; uveitis is characterized by a chronic course and, in the absence of remission, can lead to the development of ophthalmological complications.

Atopic Dermatitis in the Elderly Population.

Atopic dermatitis is a common inflammatory disease with a chronic and relapsing course. Although considered a childhood disease, it is now evident that atopic dermatitis is also common in adulthood and in the elderly population. Atopic dermatitis typically manifests with bilateral and symmetrical eczematous lesions on the face, trunk and skin folds. Itch is invariably present and may be very severe, markedly affecting daily life and sleep. In older adults, atopic dermatitis may have a high level of impact on quality of life, frequently burdening an already complex comorbid situation. The full assessment of disease burden (localizations, itch severity, sleep alterations, impact on quality of life, disease history, comorbidities) is crucial to identify the most appropriate treatment. In many cases, moderate-to-severe atopic dermatitis in the elderly population can be successfully and safely treated with biological agents inhibiting the interleukin-4/-13 pathway, whereas the use of Janus kinase inhibitors may pose concerns about the safety profile.

Historical and current aspects of angiovisualization methods in CАD (a literature review)

The aim of the work. To summarize and expand knowledge about current methods used for visualization of coronary arteries, their evolution, capabilities, effectiveness, indications for use, safety for patients, guided by the principles of evidence-based medicine. Coronary artery disease (CАD) is an extremely common clinical cardiovascular disease, which is caused by atherosclerosis of the subepicardial coronary arteries (CAs) and can have both acute and chronic course. The incidence of CАD is increasing every year and getting younger. CАD has not only a high morbidity rate, but also a high mortality rate. In Ukraine, mortality from CАD is the main cause of population mortality. Without timely diagnosis and effective treatment, myocardial infarction or sudden cardiac death may develop. It is possible to ascertain the etiological cause of myocardial ischemia only after visualization of the СAs. A practicing physician is able to visualize the СAs using X-ray contrast coronary angiography or contrast-enhanced computed tomography of the chest. СA visualization methods have been used in clinical practice for more than half a century. The hardware and software are constantly upgraded, the diagnostic options of these methods are improved and expanded, and recommendations regarding their use in general clinical practice are updated. The main task for clinicians is to confirm or rule out the presence of a СA atherosclerotic lesion, as well as to determine its localization, extent, degree of stenosis and its significance for coronary blood flow, the presence of СA calcification, collateral pathways, plaque composition and its internal structure. Only after identifying the anatomical and physiological aspects of the atherosclerotic process in СA, it is possible to choose the right strategy for the treatment of patients by a multidisciplinary heart team including pharmacological therapy, a method of cardiac revascularization, and measures for primary or secondary prevention. Conclusions. CАD is a common disease worldwide. Today, two methods of the CА visualization are available – invasive coronary angiography and non-invasive coronary CT angiography. Further research is needed on the efficacy and safety of different СA imaging methods in CAD. Better results of the diagnostic search depend on both the capabilities of the clinic hardware component and on the optimal sequence for diagnostic processes rationally constructed by physicians.

Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature

BackgroundNon-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.Case presentationA 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.ConclusionsSuppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

Rare diseases in Germany - Developments in the status of medical care.

Rare diseases are a heterogeneous group of complex clinical patterns, which more often than not run a chronic course. The fact that they are rare complicates the provision of medical care for the specific diseases. In the field of action titled 'Care, Centres, Networks' of its National Action Plan, the National Action League for People with Rare Diseases recommends the formation of a three-level, interconnected centre model. This form of care was investigated in two large research projects. It was shown that the time to diagnosis was markedly reduced. Commissioned by the Federal Ministry of Health, the expert report on the health status of people with rare diseases in Germany issued in 2023 concludes that the medical care provided to this group of people has improved markedly since the National Action Plan was introduced. The establishment of the Centres for Rare Diseases (ZSE, Zentren für Seltene Erkrankungen) is seen as the most important development. However, it is noted that there is still a lack of coordinated care provision pathways for referring patients to the appropriate facilities. The provision of care to people with rare diseases has improved upon the implementation of the measures from the National Action Plan. In a next step, care provision pathways must be established across sector boundaries. Challenges remain in the area of psychosocial care and the long-term securing of funding for these structures.

Stress and skin diseases. Overview using acne vulgaris as an example

Stress is defined as the activation of complex physiological and psychological response mechanisms in situations that threaten physical as well as mental human homeostasis. Skin diseases and associated skin lesions can become a source of stress and psychological burden. Acne vulgaris affects appearance, which plays an important role in self-esteem, a person’s functioning in society, his or her psychological state, and quality of life. Stress is one of many factors considered in the etiopathogenesis of this dermatosis. Chronic stress hurts the condition of the skin because cortisol levels are increased, which inhibits the synthesis of collagen and proteins the skin’s building blocks. This study aimed to review the literature on the significance of stress in the onset and course of skin diseases, using acne vulgaris as an example. Due to the recurrent and chronic course of acne, treatment should be interdisciplinary, complemented by appropriate psychological care and effective methods of stress management, to increase the efficiency of dermatological therapy.

Risk factors of chronic course of anxiety and depressive disorders: a 3-year longitudinal study in the general population.

Risk factors of a chronic course of anxiety and depressive disorders were previously studied using a limited definition of recovery, i.e. remission of the index disorder. However, frequently, other mental disorders are present at follow-up. Thus, the course of anxiety and depressive disorders was represented too rosy and the identified determinants may not apply when using a broader, more realistic definition. Additionally, physical health risk factors have often been ignored. Data were used from two waves of the Netherlands Mental Health Survey and Incidence Study-2 including 509 respondents with 12-month anxiety disorder (panic disorder, social phobia, agoraphobia or generalized anxiety disorder) or/and major depressive disorder at baseline. Chronic course was defined as (1) presence of index disorder; and (2) presence of any anxiety, mood or substance use disorder (overall course) during the subsequent three years. Regression models were built with sociodemographic, clinical, and lifestyle/physical health indicators. Predictive accuracy was evaluated with area under the curve (AUC). Chronic course of the index disorder was present among 24.8% of cases, whereas 38.7% had a chronic overall course. The accuracy of prediction of chronic course of the index disorder was suboptimal (AUC = 0.68) compared to prediction of overall course (AUC = 0.75). The main risk factors were baseline number of mental disorders, neuroticism, childhood abuse, parental psychopathology and alcohol use. Lifestyle and physical health indicators were marginally relevant. Transdiagnostic risk factors are important in predicting overall course of anxiety and depressive disorders but cannot accurately predict chronic course of the index disorder.

Real-World Evidence of Avatrombopag for the Treatment of Immune Thrombocytopenia Intolerant or Ineffective to Eltrombopag/Hetrombopag

Abstract Objectives: Thrombopoietin receptor agonists (TPO-RA) have dramatically changed the treatment landscape for immune thrombocytopenia (ITP). Although avatrombopag has been confirmed to achieve platelet response for chronic ITP in clinical trials, and it has no hepatotoxicity unlike eltrombopag or hetrombopag, there is still a lack of real-world research on the application of avatrombopag in Chinese ITP patients. Here, we aimed to evaluate the effect and safety of avatrombopag in ITP treatment in a real-world clinical practice. Methods: In this retrospective analysis, we enrolled consecutive cohorts of 50 adult ITP patients who received avatrombopag in two centers from January 2021 to March 2023. The median duration of follow-up of these patients was 16.5 months (range from 3.8 to 25.4 months). Results: The median age of patients was 44 years when they received the treatment of avatrombopag, and 42% of them were males. Most patients (n=45) had a persistent (3-12 months) or chronic course (more than 12 months) of ITP. The patients in our study were heavily treated, who received a median of 4 kinds of ITP treatment prior to avatrombopag. The baseline TPO levels was 88.1 (110.2±84.5) pg/ml. Based on the reasons for choosing avatrombopag, these patients were divided into eltrombopag/hetrombopag intolerance group (IG, n=14) and eltrombopag/hetrombopag unresponsive group (UG, n=36). The reasons for choosing avatrombopag in IG included active hepatitis B (n=4), hepatic insufficiency before using TPO-RA (n= 6), autoimmune hepatitis (n=1), hepatic lesion after using eltrombopag (n=2), and myelofibrosis after using eltrombopag (n=1). Compared with UG, more patients had a history of liver disease (active Hepatitis B and autoimmune liver diseases, P=0.003). The median platelet count before avatrombopag was 9 × 10 9/L. The median duration of avatrombopag treatment was 12 weeks and the median weekly dose of avatrombopag was 140 mg. Among the total cohort, platelet response (platelet count ≥30 × 10 9 /L) was achieved in 44/50 (88%) and complete platelet response (platelet count ≥100 × 10 9 /L) was seen in 35/50 patients (70%) after using avatrombopag. The median time of platelets rising above 30 × 10 9 /L was 7 days, while it was 8 days when platelet count exceeded 50 × 10 9 /L. Nearly half patients (47%) were able to discontinue more than 1 concomitant ITP medication after avatrombopag treatment. Besides, most patients (74%) in our study tapered off or withdrew steroids. There were no significant differences in baseline platelet count, 30-day response rate, the maximum effective dose of avatrombopag and duration of avatrombopag between IG and UG. So far, 19 patients achieved platelet response were still taking avatrombopag, and 58% of them maintained platelet count above 100× 10 9 /L. Meanwhile, 31 patients discontinued avatrombopag.The reasons for withdrawal of drug included adverse events (n=2), sustained remission in ITP (n=8), no/lose response to avatrombopag (n=10), and unablity to afford the cost consistently (n=11). Avatrombopag was well tolerated in most patients, even those suffered from hepatic insufficiency and/or myelofibrosis after other TPO-RA. However, two cases had thrombosis and two patients reported mild fatigue. Conclusion: In the ITP population, avatrombopag was effective and safe, especially for those intolerant or ineffective to eltrombopag/hetrombopag. However, most patients with ITP were not able to afford the long-term usage of avatrombopag in China.

Calcium-sensing receptor protein as a prognostic predictor of asthma formation and exacerbation in young children

Asthma remains the most common non-communicable disease among children, which often has a chronic course and leads to disability. Particular attention should be paid to the diagnosis of asthma in young children. To date, the calcium-sensing receptor (CaSR) is considered to be one of the specific markers in the development of bronchial obstructive diseases. Purpose - to assess the level of CaSR protein and its significance in preschool children with asthma. Materials and methods. The study included 37 patients divided into 3 groups. The Group 1 - children with mild persistent asthma (n=20), the Group 2 - children with moderate persistent asthma (n=17), the Group 3 - almost healthy children (n=20). The study of CaSR protein levels in the blood serum of patients with asthma was performed twice - in the first 2 days of clinical manifestations of the disease and when remission was achieved. The level of CaSR protein in the blood serum was analyzed by enzyme-linked immunosorbent assay (ELISA). All statistical analyses were performed using StatSoft STATISTICA version 8.0 (Tulsa, Oklahoma) and MedCalc version 17.2 statistical software. Results. There was no significant difference in CaSR protein levels between the Group 1 and the Group 2. The level of CaSR protein was significantly lower in the Group 1 and the Group 2 both in the period of acute and remission than in the control group. The level of the marker in the period of disease flare-up in the Group 1 and the Group 2 was significantly lower than in children of the same groups in the period of remission. Conclusions. In all patients with asthma, the level of CaSR protein at the acute stage of the disease is lower than at the remission stage, which is obviously associated with its redistribution from the peripheral blood to the smooth muscle of the lungs. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Chronic limping in childhood, what else other than juvenile idiopathic arthritis: a case series

BackgroundLimping is a common clinical symptom in childhood; different clinical conditions may lead to limping and the diagnosis of the underlying cause may often be a challenge for the pediatrician.Case presentationWe describe the clinical manifestations, radiological pictures and disease course of other causes of limping in childhood, through a case series of seven cases and a brief discussion of each disease.Conclusionsalthough trauma is the most common cause of acute limping, when there is no history of traumatic events and the limping has a chronic course, Juvenile Idiopathic Arthritis is usually the most likely clinical diagnosis. However, other some rare conditions should be taken into account if JIA is not confirmed or if it presents with atypical clinical picture.

Contextual factors in persistent severe back pain: A longitudinal analysis among German employees.

Chronic back pain in employees compromises participation in social and daily activities, as well as work. To examine the severity of back pain after 2 years and identify factors predicting stagnation at this level of pain. Data were derived from a prospective cohort study with randomized sampling of insurants in the German Pension Insurance using a questionnaire at baseline and follow-up after 2 years. The sample consisted of middle-aged employees (45-59 years) with strong limitations due to back pain (Chronic Pain Grade III or IV), who had not applied for disability pension and did not use medical rehabilitation in the previous 4 years before baseline. Stepwise multivariable logistic regression models with backwards selection were used to identify relevant contextual factors in the stagnation of severe back pain. Of 1208 persons with severe back pain at baseline, 48% had stagnated at that pain level after 2 years. Predictors of persistent severe back pain were older age, poorer general health, more additional disabling conditions, more depressive symptoms, caregiving burden, less pain-related self-efficacy and more fear avoidance beliefs. In a high-risk subgroup with several co-existing conditions, this analysis highlights (mental) health, social and personal (contextual) factors associated with long-term unfavourable back pain progression. Back pain is a condition that often has a chronic or recurrent course, threatening participation in many areas of life. In this study it was found that the unfavourable condition of severe back pain can remain stable for long periods of time in a significant proportion of sufferers. Contextual factors (self-efficacy, fear-avoidance beliefs, caregiving burden) as well as additional health problems should be considered when identifying persons with stagnating pain courses.

Health-related Quality of Life During the First 4 Years After Non–Muscle-invasive Bladder Cancer Diagnosis: Results of a Large Multicentre Prospective Cohort

BackgroundThe health-related quality of life (HRQoL) of patients with non–muscle-invasive bladder cancer (NMIBC) may be impaired due to the chronic and burdensome disease course, but longitudinal data are limited. ObjectiveTo evaluate HRQoL outcomes during the first 4 yr after NMIBC diagnosis, and to compare HRQoL across patient characteristics and with a normative population. Design, setting, and participantsPatients with NMIBC (n = 1019) were included from the multicentre prospective cohort UroLife. Data were collected at 6 wk (baseline), and 3, 15, and 51 mo after diagnosis. Longitudinal reference data were obtained from an age- and sex-matched normative population (n = 490). Outcome measurements and statistical analysisCancer- and NMIBC-specific HRQoL outcomes (range 0–100) were evaluated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-NMIBC24 questionnaires, respectively. Linear mixed modelling was used to analyse within-group changes and between-group differences. Results and limitationsThe majority of HRQoL outcomes remained stable over time. Observed changes were only of small clinical relevance. Improvements were noted in insomnia, social functioning, and three NMIBC-specific symptoms, while minor deteriorations in appetite and diarrhoea lasted until 51 mo. HRQoL in some domains was worse for high-grade NMIBC, high European Association of Urology (EAU) risk group, initial Bacillus Calmette-Guérin (BCG) treatment, being female, and being younger (<65 yr); yet differences were few, small, and temporary. No differences were observed across recurrence status. Compared with a normative population, clinically relevant worse scores were observed for six of 15 outcomes, which mostly recovered at 51 mo, except for minor symptoms of appetite loss and diarrhoea. ConclusionsNo remarkable changes in HRQoL were observed during the first 4 yr after NMIBC diagnosis. Grade, EAU risk group, initial treatment, recurrence, sex, and age did not importantly affect HRQoL. HRQoL was largely comparable with that of the general population, especially after 4 yr. Patient summaryQuality of life is not largely affected during the first 4 yr after non–muscle-invasive bladder cancer diagnosis.

Structural integrity of grey and white matter in schizophrenic patients by diffusion tensor imaging

BackgroundSchizophrenia is a chronic disabling mental illness. A novel magnetic resonance imaging (MRI) technique known as diffusion tensor imaging (DTI) is a non-invasive and does not need external contrast materials. It is capable of identifying anomalies in the white matter micro-structure of the brain. This work conducted the DTI in schizophrenic patients to evaluate altered structural integrity in grey and white matter.MethodsThis prospective case control study was conducted on 25 schizophrenic patients selected from neuropsychiatric department, and 25 age/sex-matched healthy controls.ResultsSchizophrenic patients showed diminished fractional anisotropy in fornix, corpus callosum, right cingulum, right superior and inferior occipito-frontal fasciculi. Increased mean diffusivity in right inferior occipito-frontal fasciculus, corpus callosum, right thalamus and right basal ganglia were noted in schizophrenic patients. Fractional anisotropy and mean diffusivity had a predictive value for detection of schizophrenic patients.ConclusionsDTI of white and grey matter tracts is considered a promising tool for diagnosis of schizophrenic patients which usually have prolonged illness, chronic course and poor outcome.