Severe Course Research Articles

Modifiable factors for somatic symptom persistence in patients with somatic symptom disorder: study protocol for a longitudinal cohort with an embedded ecologically momentary assessment (SOMA.SSD)

IntroductionSomatic symptom disorder (SSD) is a distressing mental disorder characterised by the presence of at least one persistent somatic symptom and a significant psychological burden due to the symptom(s), as well as excessive thoughts, feelings or behaviours related to them or associated health concerns. The primary aim of our study is to deepen the understanding of risk factors and mechanisms for somatic symptom persistence. Specifically, we will investigate the role of patients’ expectations and somatic comorbidity regarding symptom persistence.Methods and analysisIn a prospective 12-month cohort study, n=240 patients with SSD will be recruited from the outpatient clinics of the Department of Psychosomatic Medicine and Psychotherapy at the University Medical Center Hamburg-Eppendorf. The roles of two hypothesised predictors (ie, expectations and comorbidity) will be analysed together with known predisposing and maintaining factors of persistent somatic symptoms. The study entails macrolevel and microlevel assessments to investigate symptom severity over different timespans. Assessments at the macrolevel take place at baseline, 6 and 12 months. At the microlevel, a 10-day ecological momentary assessment study will be implemented to elucidate patients’ dynamic experience with somatic symptoms in their natural environments. In order to elicit possible framing effects on the 10-day course of symptom severity, participants are randomised to either a positive or a negative expectation framing group. Cross-lagged panel models will be used to analyse data at the macrolevel. At the microlevel, multivariate latent growth curve models will be conducted to relate temporal changes in predictor and outcome variables to one another.Ethics and disseminationThe study was approved by the Ethics Committee of the Medical Associations Hamburg, Germany (2020-10197-BO-ff). The results will enable us to draw conclusions regarding the role of expectations for future targeted treatment options and regarding the utility of somatic comorbidity as a potential diagnostic specifier of SSD. Dissemination of our results will be achieved through scientific publications, and lay summaries for study participants, patient advocacy groups and the general public.Trial registration numberISRCTN36251388.

Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor and GAD65 Antibodies: Case Report and Potential Mechanisms.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder that can be associated with antibodies against surface antigens (glycine receptor (GlyR), dipeptidyl-peptidase-like-protein-6) and intracellular antigens (glutamate decarboxylase (GAD65), amphiphysin). We report clinico-pathologic findings of a PERM patient with coexisting GlyR and GAD65 antibodies. A 75-year-old man presented with myoclonus and pain of the legs, subsequently developed severe motor symptoms, hyperekplexia, a pronounced startle reflex, hallucinations, dysautonomia, and died 10 months after onset despite extensive immunotherapy, symptomatic treatment, and continuous intensive care support. Immunotherapy comprised corticosteroids, IVIG, plasmapheresis, immunoadsorption, cyclophosphamide, and bortezomib. Intensive care treatment and permanent isoflurane sedation was required for more than 20 weeks. CNS tissue revealed neuronal loss, astrogliosis and microgliosis, representing a pallido-nigro-dentato-bulbar-spinal degeneration pattern, specifically along GlyR and GAD expression sites. Neurons showed pSTAT1, MHC class I, and GRP78 upregulation. Inflammation was moderate and characterized by CD8+ T cells and single CD20+/CD79a+ B/plasma cells. Focal tau-positive thread-like deposits were detected in gliotic brainstem areas. In the spinal cord, GlyR, glycine transporter-2, and GAD67 expression were strongly reduced. A possible potentiating effect of pathogenic GlyR antibodies together with T cells directed against neurons may have led to the severe and progressive clinical course.

Wpływ polimorfizmu genetycznego na przebieg oraz ciężkość zakażenia wirusem SARS-CoV-2 oraz choroby COVID-19

COVID-19 is severe respiratory and systemic disease with complex pathogenesis and many clinical symptoms, including symptoms from respiratory system, immunology system, cardio-vascular system, haematopoietic system and neurological system. Severe character of the disease is associated with occurrence of respiratory failure, septic shock, multiple organ dysfunctions syndrome, which can lead to patients death due to cardiac arrest. Knowledge about interactions between the virus and human proteins as well as knowledge of immunological mechanisms against infection is a key to identifying the area of virus activity and severity factors of COVID-19. Multiple variants of genes encoding proteins involved in host cell invasion by SARS-CoV-2 virus have been identified: ACE2 i TMPRSS2, TMPRSS11A (HGNC:27954), ELANE (HGNC:3309) oraz CTSL (HGNC:2537), IL-6 rs1800795 variant associated with an increased risk of COVID-19, variant rs35705950:G>T located in the promoter of the MUC5B gene (11p15.5), encoding a protein that plays a key role in maintaining the proper function of the bronchoalveolar epithelium, having a protective effect against the form of the disease requiring hospitalization of the patient, as well as GC rs2282679 gene variant in the vitamin D binding protein associated with a more severe course of COVID-19. 48 of these variants were proved to be directly specific for some populations. Novel techniques of genome analysis enabled the research of the impact of specific polymorphism variants on the severity of various diseases including, COVID-19. Genetic factors analysis can permit understanding of disease pathogenesis, which is a chance to find effective treatment and prevention methods. Collected data from literature indicate that, in the case of COVID-19 disease, there are genes polymorphisms which affect the severity course.

Considerations in Paediatric and Adolescent Inflammatory Bowel Disease.

The incidence of inflammatory bowel disease [IBD] is rising most rapidly among children and adolescents. Paediatric-onset IBD is associated with a more extensive and severe disease course compared to adult-onset IBD. At a young age, screening for underlying genetic and immunological disorders is important and may impact treatment management. Early and effective treatment is crucial to reach disease remission and prevent complications of ongoing active disease. In children with Crohn's disease, exclusive enteral nutrition is an effective induction therapy. Other promising dietary therapies, such as the Crohn's disease exclusion diet, are emerging. Within paediatric IBD, anti-tumour necrosis factor therapy is the only approved biological thus far and additional treatment options are crucially needed. Other biological therapies, such as vedolizumab and ustekinumab, are currently prescribed off-label in this population. A specific challenge in paediatric IBD is the unacceptable and major delay in approval of drugs for children with IBD. A guided transfer period of paediatric patients to adult care is associated with improved disease outcomes and is required. Major knowledge gaps and challenges within paediatric IBD include the aetiology, diagnostics, and monitoring of disease, tailoring of treatment, and both understanding and coping with the physical and psychological consequences of living with IBD. Challenges and research gaps in paediatrics should be addressed without any delay in comparison with the adult field, in order to ensure a high quality of care for all patients with IBD, irrespective of the age of onset.

Risk factors for a severe course of COVID-19 in a hotspot clinic during the first and second wave of the SARS-CoV-2 pandemic in Germany

During the first wave of the SARS-CoV-2 pandemic, Weiden Hospital was a hotspot and was thus in an exceptional medical situation. This study deals with the question of whether the recognized risk factors for a severe course of COVID-19 also apply to the patients treated in Weiden Hospital during this time or whether other factors could have influenced patient outcomes. In a retrospective analysis, data on 669 patients of Weiden Hospital with proven SARS-CoV-2 infections in the first year of the pandemic were evaluated. Risk factors for a severe case of COVID-19 were determined from medical and demographic information in a univariate analysis and subjected to logistic regression. The logistic regression analysis was performed for the overall collective as well as separately for patients from Wave 1 (3-6/2020) and 2 (7-12/2020). Looking at all of 2020, significant risk factors for severe COVID-19 included being male, being a smoker, being 71 years or older, and a history of depression. All other commonly recognized risk factors were not applicable for the Weiden collective. When looking at both waves separately, in Wave 1 age was not a significant risk factor, whereas in Wave 2 an age of 61 years or older was associated with an increased risk of severe progression. For patients who were admitted to hospital in Wave 2, the risk of severe progression was reduced almost by half. It can be assumed that patient outcomes in Weiden's hotspot collective were predominantly determined by non-individual factors, like the difficult care situation in a hotspot clinic at the beginning of the pandemic. In preparation for future pandemics, provision of sufficient resources might significantly contribute to better patient outcomes.

Low Iron Diet Improves Clinical Arthritis in the Mouse Model of Collagen-Induced Arthritis.

Background: In response to inflammation, the absorption of nutritional iron is restricted. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal (51 mg/kg) or a low iron diet (5 mg/kg) starting four weeks before the first immunization. From day 4 after the second collagen booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. Concentrations of mouse anti-bovine and anti-mouse collagen type 2 IgG antibodies were measured by ELISA; blood cell counts were performed and mediators of inflammation, tissue matrix degradation, oxygenation and oxidative stress were measured in the mouse sera of both diet groups at the end of the experiment by bead-based multiplex assay. Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) were quantified in whole paw tissue by ELISA. Quantitative PCR was performed in the tissues for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to compare cross-sectional data. Nonlinear regression models were used for longitudinal data of the arthritis scores. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p < 0.001). The immune response against bovine and mouse type 2 collagen did not differ between the two diet groups. Mice fed a low iron diet exhibited significantly lower serum levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), a central regulator of inflammation and tissue matrix degradation (p < 0.05). In addition, a low iron diet led to a significant reduction in red blood cell indices, indicating restricted iron uptake and latent iron deficiency, but had no effect on hemoglobin concentrations or red blood cell counts. There were no differences between the dietary groups in Fe2+ or Fe3+ content in the paws. Based on calculation of the GSH/GSSG ratio and high MDA levels, high oxidative stress and lipid peroxidation were likewise detected in the paws of both diet groups of mice. Consequently, no differences associated with gene expression of key regulators of iron metabolism and ferroptosis could be detected between the paws of both diet groups. Conclusions: Restricted dietary iron intake alleviates immune-mediated inflammation in CIA without causing anemia. This finding suggests a promising option for dietary treatment of arthritis in inflammation. The underlying mechanism causing reduced arthritis may be linked to the complex regulatory network of TIMP-1 and appears to be independent from the local iron levels, oxidative stress and ferroptosis in the synovial tissues.

Redefining cardiovascular risk evaluation: employing the CaRi-Heart validated FAI-score in patients screened with SCORE2 and CAD-RADS 2.0 techniques

Abstract Background Cardiac computed tomography (CCT) has confirmed the fat attenuation index (FAI) as a trustworthy marker for coronary inflammation, notably in relation to plaque vulnerability and progression. The systematic coronary risk evaluation 2 (SCORE2) is a valuable instrument for forecasting the 10-year likelihood of initial cardiovascular disease (CVD) occurrence. This study aims to determine risk re-categorization using CaRi-Heart in comparison to SCORE2 and the coronary artery disease-reporting and data system (CAD-RADS 1.0/2.0). Methods We enrolled patients (INTEL-FAT study) undergoing CCT, who were aged 40-69 years and had no previous history of CVD or diabetes. SCORE2 classified very-high-risk regions as follows: low-moderate risk as &amp;lt;2.5% (&amp;lt;50 years) and &amp;lt;5% (50-69 years), high risk as 2.5 to &amp;lt;7.5% (&amp;lt;50 years) and 5 to &amp;lt;10% (50-69 years), and very-high risk as ≥7.5% (&amp;lt;50 years) and ≥10% (50-69 years). The CaRi-Heart risk assessment categorized low risk as FAI-score ≤75th percentile for the LAD or RCA and &amp;lt;95th percentile for the LCX; medium risk as falling between the 76th and 89th percentiles for LAD/RCA and ≥95th percentile for LCX; and high risk as ≥90th percentile for LAD/RCA. Results 203 patients were included, with a mean age of 58.7 ± 6.78; 143 (70.44%) were male. CaRi-Heart assessment redefined 71.13% (69/97) of individuals from high to low SCORE2 risk, and 40.0% (8/30) from low-moderate to high SCORE2 risk. The weighted Cohen's kappa analysis revealed minimal concordance between SCORE2 and CaRi-Heart (k=-0.043). 19.71% of patients categorized as CAD-RADS 1 in CCT were reassigned to high risk after CaRi-Heart evaluation, and 26.66% of those classified as CAD-RADS 4 were downgraded to low risk. Furthermore, of the CAD-RADS 1 P1/P2 group, 15.38% and of the P3/P4 group, 66.66% were upgraded to high risk. Conversely, 45.45% of CAD-RADS 4 P1/P2 and 15.78% of P3/P4 were reassigned to low CaRi-Heart risk. The Cohen's kappa analysis comparing CAD-RADS 1.0 and 2.0 with CaRi-Heart risk revealed a low concordance (k=0.067 and k=0.014). In comparing SCORE2 risk categories to CAD-RADS classifications, a significant association was found for low-moderate SCORE2 with CAD-RADS 2 (diagnostic odds ratio [DOR] of 11.26; 95% CI: 4.37-29.00; p&amp;lt;0.001), and for high SCORE2 with CAD-RADS 4 (DOR: 0.085; 95% CI: 0.036-0.20; p&amp;lt;0.001), indicating a strong predictive value of the SCORE2 system for certain CAD-RADS classifications. Conclusions The CaRi-Heart method significantly alters risk classifications in comparison to the SCORE2 risk assessment models or the anatomical CAD-RADS 1.0 and 2.0 diagnostic instruments. These results indicate the importance of integrating established scoring systems with additional markers, such as the FAI-score. This integration offers critical understanding into the severity and future course of CAD, assisting in risk stratification and informing therapeutic choices.SCORE2, CAD-RADS and CaRi-Heart risk.Interpretation of the CaRi-Heart® risk.

The role of angiotensin II and endothelin receptor antibodies in COVID19 patients with HFpEF

Abstract Background The infection caused by the coronavirus SARS-COV-2, is associated with an unusual pattern of organ damage in comparison to other viral-induced pathologies. A theory of autoimmunity induced by ACE-2/SARS-COV-2 spike protein complex or its degradation products, was proposed as a possible explanation for the versatile and multiorgan damage in COVID-19. Aim The aim of the study is to determine whether antibodies against angiotensin II receptor type 1 (AT1R) or endothelin-1 receptor type A (ETAR) do exist in plasma of COVID -19 patients with heart failure with preserved ejection fraction and whether they correlate to the severity of the disease. Methods A total of 61 patients with COVID-19 and heart failure with preserved ejection fraction and 48 controls (free of COVID19) with heart failure with preserved ejection fraction were included. Patients were divided into two groups: patients with severe disease (admitted at the intensive care (n=30)), patients with milder clinical presentation that remained in the general therapeutical department (n=31). The plasma levels of IL-6 and auto-antibodies against AT1R or ETAR in peripheral blood were measured and compared between COVID19 patients with severe and milder disease and age matched controls. Clinical and standard laboratory parameters were also collected and their association with the research biomarkers was analysed. Results Auto-antibodies against AT1R were significantly increased in severe disease course (median 19.60 U/mL, IQR 4.8-34.75) compared to milder disease (median 10.95 U/mL, IQR 7.69 – 17.67, p=0.017) and the control group (median 6.79 U/mL, IQR 5.10 – 14.05, p&amp;lt; 0.001). ETAR antibody titers were also significantly increased in severe disease (median 14.52, IQR 6.76-32.94), compared to milder disease course (median 8.73 U/mL, IQR 6.59 –13.45, p=0.023) and to the control group (median 6.64, IQR 6.79 – 17.92, p &amp;lt;0.001). The same was the trend regarding IL-6 antibodies. Severe disease (median 12.11 U/mL, IQR 5.59–19.38); milder disease disease (median 8.64U/mL, IQR 1.84 – 14.13, p=0.039); control group (median 4.28U/mL, IQR 0.11–1.43, p&amp;lt;0.001).Both AT1R and ETAR correlated to IL-6 plasma levels. The results did not show association with the concomitant therapy. Conclusion In conclusion, we establishеd the presence of AT1R and ETAR autoantibodies in COVID-19 patients with heart failure with preserved ejection fraction. They correlated to IL-6 plasma levels (systemic inflammation) and are associated with severe form of the disease.

Lipid-associated GWAS loci as important markers of the risk, severity, and clinical course of peripheral artery disease

ABSTRACT Background This study investigated the relationship between lipid-associated loci identified through genome-wide association studies (GWAS) and the risk of peripheral artery disease (PAD), its severity, as well as clinical and laboratory features. Research design and methods A study included 1263 unrelated Russian subjects, consisting of 620 patients diagnosed with PAD and 643 healthy controls. Thirteen single nucleotide polymorphisms (SNP) were genotyped using the MassArray-4 system. Results Polymorphisms rs1689800, rs55730499 and rs881844 were found to be associated with an increased risk of PAD, whereas SNPs rs1883025, rs3136441, rs3764261 and rs6065906 showed protective effects against disease (Pperm ≤ 0.05). SNPs rs1689800, rs217406, rs1883025, and rs3136441 exhibited combined effects with cigarette smoking on the PAD risk (Pperm ≤ 0.05). Polymorphisms rs55730499 (beta = 0.124, Pperm = 0.04), rs9987289 (beta = 0.558, Pperm = 0.03), and rs881844 beta = −0.171, Pperm = 0.03) correlated with the ankle-brachial index. Multiple associations have been found between the SNPs and clinically significant characteristics, including disease severity, risk of gangrene, early disease onset, plasma procoagulant and atherogenic lipid changes (Pperm ≤ 0.05). Conclusions We identified novel genetic markers associated with PAD susceptibility and disease-related clinical and laboratory features. The identified biomarkers enhance the potential for predictive genetic testing related to the risk and progression of PAD, facilitating the integration of molecular diagnostics into clinical decision-making processes.

Effect of Statins and Renin-Angiotensin-Aldosterone System Inhibitors on IL-6 Levels in COVID-19 Patients.

Background/Objectives: Severe clinical course and mortality from COVID-19 are mostly associated with increased concentrations of IL-6 and IL-10. Findings from clinical trials suggest that both statins and renin-angiotensin-aldosterone system inhibitors (RAASI) might have the potential to reduce unfavorable outcomes in patients with COVID-19. The aim of this study was to evaluate the effect of statins and RAASI on the cytokine concentrations in COVID-19 patients. Methods: SARS-CoV-2 infected patients were enrolled in this study, and demographic, clinical, and routine laboratory data were evaluated. Plasma cytokine levels were measured by multiplex assay. Results: COVID-19 patients with chronic cardiovascular diseases (CVD) had significantly lower median plasma IL-6 levels than COVID-19 patients with no co-morbidities (26 vs. 53 pg/mL, p = 0.021). COVID-19 patients with CVD who were taking statins had significantly lower median concentrations of IL-6 (21 vs. 44 pg/mL, p = 0.027), TNFα (21 vs. 39.5 pg/mL, p = 0.036), and IL-10 (19 vs. 25.5 pg/mL, p = 0.025) compared to COVID-19 patients with no CVD. In a binary logistic regression model, IL-6 was a significant variable, with an odds ratio value of 0.961 (95% CI 0.929-0.995). Regarding RAASI, only plasma IL-6 (22 vs. 44 pg/mL, p = 0.012) levels were found to be significantly lower in COVID-19 patients with CVD consuming these medications compared to patients who did not have any CVD. Conclusions: COVID-19 patients who had chronic cardiovascular co-morbidities and who were administered statins or RAASI had significantly lower concentrations of IL-6 than COVID-19 patients who did not have any co-morbidities. These findings suggest that the use of statins or RAASI may be of value in COVID-19 patients.

Intrathecal IgG and IgM synthesis correlates with neurodegeneration markers and corresponds to meningeal B cell presence in MS

Intrathecal synthesis of immunoglobulins (Igs) is a key hallmark of multiple sclerosis (MS). B cells are known to accumulate in the leptomeninges of MS patients and associate with pathology in the underlying cortex and a more severe disease course. However, the role of locally produced antibodies in MS brain pathology is poorly understood. Here, we quantified the protein levels of IgA, IgM, IgG and albumin in serum and cerebrospinal fluid (CSF) samples of 80 MS patients and 28 neurological controls to calculate Ig indices. In addition, we quantified presence of meningeal IgA+, IgM+ and IgG+ B cells in post-mortem brain tissue of 20 MS patients and 6 controls using immunostainings. IgM and IgG, but not IgA, indices were increased in CSF of MS patients compared to controls, with no observed differences between MS disease types. Both IgM and IgG indices correlated significantly with neurofilament light (NfL) levels in CSF, but not with clinical or radiological parameters of disease. Similarly, IgG+ and IgM+ B cells were increased in MS meninges compared to controls, whereas IgA+ B cells were not. Neuronal loss did not differ between sections with low or high IgA+, IgM+ and IgG+ B cells, but was increased in sections with high numbers of all CD19+ meningeal B cells. Similarly, high presence of CD19+ meningeal B cells and IgG+ meningeal B cells associated with increased microglial density in the underlying cortex. Taken together, intrathecal synthesis of IgG and IgM is elevated in MS, which corresponds to an increased number of IgG+ and IgM+ B cells in MS meninges. The significant correlation between intrathecal IgG and IgM production and NfL levels, and increased microglial activation in cortical areas adjacent to meningeal infiltrates with high levels of IgG+ B cells indicate a role for intrathecal IgM- and IgG-producing B cells in neuroinflammatory and degenerative processes in MS.

Indicators of the cytokine profile and standard immunogram in the controlled and uncontrolled course of bronchial asthma in children

Bronchial asthma in children is a multifactorial disease, but it is based on atopic inflammation, which is the focus of the main methods of research and therapy of this pathology. However, if we evaluate not only the fact of the appearance of bronchial asthma in a particular patient, but also consider its course in more detail, and especially the possibility of achieving control over the disease, then indicators of not only atopic inflammation, but also local inflammation in general, acquire great influence, which is one of the reasons for the continuing high percentage of uncontrolled and partially controlled course bronchial asthma in children. The purpose of this work is to identify changes in cytokine status indicators and immunograms – markers of the risk of uncontrolled bronchial asthma. 167 patients with bronchial asthma were examined, who, based on a standard clinical and instrumental examination, according to the criteria of clinical recommendations, were divided into two groups – controlled (70 people) and partially controlled and uncontrolled (97 children). All of them had their cytokines and IgA, IgM, IgG, IgE levels determined, in blood serum by ELISA, subpopulations of lymphocytes by flow cytometry, indicators of neutrophilic phagocytosis by light microscopy. In the group with uncontrolled asthma, the following significant differences were noted: a decrease in the level of IL-7, IL-9 and an increase in IL-8, there is also a higher level of B lymphocytes, IgE and IgM, and a lower level of IgA, similar changes, but less pronounced, were previously detected in other studies when comparing patients with bronchial asthma and conditionally healthy, as well as mild and severe course diseases. There were no significant differences in the other studied indicators. It is noteworthy that the greater influence on the control of the disease in bronchial asthma is not exerted by atopic cytokines responsible for the very fact of atopic inflammation, but by cytokines of general inflammation, such as IL-7, IL-8, IL-9, regulating the severity of inflammation in general, the role of IL-8 as a cytokine of granulocyte chemotaxis regulating local inflammation is especially interesting.

Оценка нутритивного статуса и рисков его нарушения у детей с болезнью Крона: одномоментное исследование

Children with Crohn's disease (CD) are at high risk for developing nutritional deficiencies. According to studies in adult patients with CD, loss of lean and skeletal muscle mass and decreased bone mineral density (BMD) are unfavorable prognostic factors for the course of the disease; among children, the prevalence of these changes has not been sufficiently studied as yet. The purpose of this research was to study the frequency and correlation between disorders of body composition and decreased bone mineral density in children with CD. Materials and methods used: medical records of 163 aged 5 to 17 y/o with a confirmed CD diagnosis were assessed for the risk of nutritional deficiency using STRONGkids screening tool, anthropometric parameters, body composition with bioimpedance measurements as well as the disease activity index with PCDAI and endoscopic activity with SES-CD. BMD was assessed in 145 using densitometry. Results: depending on the degree of risk of malnutrition, children were divided into 2 groups as follows: G1 with high and G2 with moderate risks for malnutrition. G1 patients had significantly lower values of both anthropometric indices (Z-scores BMI/age, mid-upper arm circumference/age) and lean and skeletal muscle mass (p&lt;0.001) along with more severe course of CD according to PCDAI (p&lt;0.001). According to bioimpedansometry data, a significant increase in catabolic processes was found in G1 children as a decrease in Z-scores for both the phase angle (p&lt;0.001) and the active cell mass (p&lt;0.001). A decrease in BMD was detected in 9 (37%) of G1 and 26 (21.4%) of G2. A correlation was found between Z-scores lean body mass/age and BMD/age (p&lt;0.001, Rs=0.612). Among children with reduced BMD values, the indicators for BMI, lean, skeletal muscle and active cell mass according to bioimpedance measurements were significantly lower (p&lt;0.001). Conclusion: the data obtained during the study proposes high incidence of decreased bone mineral density along with pathological changes in body composition in children with CD. The use of STRONGkids tool to identify children at high risk of developing malnutrition, especially in the absence of the technical ability to conduct a detailed assessment of nutritional status with determination of body composition and BMD indicators, makes it possible to timely identify patients requiring individual nutritional support aiming to optimizing diets and, if necessary, prescribing addition of specialized food supplements.

Attitudes towards air quality during outdoor exercise amongst habitual exercisers.

The effects of air pollution on health outcomes are well-established. However, little is known about perceptions of air pollution and how it may influence exercise behaviours. The aim of this study was to understand the perceived importance of air pollution during planned exercise, and where relevant, explore how those perceptions may differ between those living in different locations. A questionnaire was disseminated to several running and cycling clubs in the United Kingdom, covering population characteristics to determine urban, rural or coastal residents and exercisers, self-reported asthma, perceptions of air quality during active travel, planned exercise and attitudes towards learning more about the topic. Anonymised responses were gained from 381 adult participants (≥18years and 60% female), 119 of whom answered questions related to active travel. More than half (54%) of all respondents think about the air quality they are exposed to during exercise and how it may affect their health. More urban than rural respondents (59% vs. 47% and p=0.03) think about air quality and the impact it may have on their health when exercising. There were insufficient coastal respondents for direct comparison. Most survey respondents (57%) state that they would take the most severe course of action regarding exercise behaviour by avoiding it altogether during periods ofheavy road traffic. Individuals with self-reported asthma (n=60), irrespective of place of residence, are the most likely to be conscious of the potential effects of air pollution on their health and exercise performance compared to counterparts without self-reported asthma.

Feeding Intolerance-A Key Factor in the Management of Acute Pancreatitis: A Review.

Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, which in 20% of cases can turn into a severe form, with mortality reaching up to 30%. One of the cornerstones of AP treatment is early nutritional treatment. Feeding intolerance (FI) occurs in up to 25% of patients with AP and is associated with a more severe disease course and poorer clinical outcome. Feeding intolerance can have a multifaceted clinical presentation. The early identification of FI risk factors and appropriately conducted nutritional treatment are critical to the course of the disease. In this review, we summarize the current knowledge of feeding intolerance in AP, its pathomechanisms and risk factors, and its impact on disease progression. We also present suggestions for the management of feeding intolerance.

Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis

RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age. Although viewed primarily as a childhood disease, the majority of infections affect adults. Patients with chronic respiratory diseases are at a higher risk for severe clinical course of pertussis infection. It has therefore been recommended that all adults should get a pertussis booster with their next scheduled tetanus vaccination, given as a combination vaccine (Tdap). For risk groups (healthcare personnel, community facilities) a booster vaccination every 10 years is recommended. Herpes Zoster (shingles) is caused by the varicella-zoster virus, and reactivations can lead to painful skin lesions and potential complications such as herpes zoster oticus, meningitis, or postherpetic neuralgia. People with chronic lung diseases such as COPD or asthma are at increased risk of herpes zoster-related complications. A recombinant adjuvanted inactivated vaccine was approved in 2018 and offers robust protection against herpes zoster and its complications. The vaccine is recommended for all people over 60 years of age and for certain risk groups over 50 years of age.

Respiratory sarcopenia: aspects of pathogenesis, approaches to diagnosis

The severe course of infectious and inflammatory diseases of the respiratory system, high rates of morbidity and mortality among the elderly and senile aged people may be associated with respiratory sarcopenia, a new nosological form that describes age-related changes in the strength and structure of the respiratory muscles. The aim of the review is to update the data of open access scientific sources on aspects of pathogenesis and diagnostic approaches to respiratory sarcopenia. Foreign and domestic scientific publications on this topic were analyzed from 2019 to the present. The mechanisms of respiratory sarcopenia pahogenesis were assessed in the light of its relationship with whole body sarcopenia, age-related mechanisms of aging of the respiratory system as a whole, risk factors and lifestyle aspects of the elderly. The currently proposed diagnostic algorithm for respiratory sarcopenia is considered in detail. Conclusion. Age-related changes in muscle tissue also affect the respiratory muscles. Whole-body sarcopenia, according to some authors, may be accompanied by respiratory sarcopenia. The proposed terminology and algorithm for diagnosing this pathology require additional data accumulation and further discussion.

The Role of Quantitative PCR in Evaluating the Clinical Significance of Human Bocavirus Detection in Children.

Human bocavirus (HBoV) has emerged as a significant pathogen primarily associated with respiratory infections in children. This study aimed to evaluate the clinical relevance of HBoV infection by quantifying viral loads in nasopharyngeal swabs from hospitalized children with acute respiratory infections (ARIs) and investigating correlations with clinical outcomes. A total of 957 children were tested, with HBoV detected in 73 cases (7.6%), either as a sole infection or co-infection with other respiratory viruses. Quantitative polymerase chain reaction (qPCR) was employed to measure viral load, and a threshold of 104 copies/mL was used to differentiate high and low viral concentrations. Results have shown that children with lower respiratory tract infections (LRTIs) had significantly higher viral loads, most notably in cases where HBoV was the sole pathogen. Additionally, children with pre-existing health conditions were more likely to have elevated HBoV concentrations compared to those who were previously healthy. Children with higher viral loads were more likely to require oxygen supplementation and receive empirical antibiotic therapy, indicating a more severe clinical course. This study underscores the importance of considering HBoV viral load in clinical diagnostics, as higher concentrations were associated with more severe presentations, including the need for oxygen support. Future research should focus on refining diagnostic thresholds and exploring HBoV's role in co-infections to enhance patient care strategies.

Acute Quetiapine Intoxication: Relationship Between Ingested Dose, Serum Concentration and Clinical Presentation-Structured Literature Review and Analysis.

Over the past decade, quetiapine has become one of the most commonly used psychotropic drugs in acute intoxication events worldwide. A structured literature review and analysis were conducted to assess the relationship between the kinetic and dynamic profiles in acute quetiapine intoxication. The correlation between dose and peak serum concentration (cmax) was determined using Pearson's correlation coefficient. Binary logistic regression was used to evaluate dose and cmax as predictors of the most common clinical events, signs and symptoms. One hundred and thirty-four cases of acute quetiapine ingestion were included in the analysis, with a median ingested dose of 10 g and a median cmax of 4 mg/L. The typical half-life was estimated to be 16.5 h, significantly longer than at therapeutic doses. For the immediate-release formulation, a biphasic disposition could not be excluded. Dose and cmax demonstrated a weak but significant correlation (r = 0.256; N = 63; p = 0.043). Central nervous system depression and tachycardia were the most common clinical signs. Higher doses and concentrations increased the risk of severe intoxication and were good predictors of intubation, tachycardia, hypotension, QTc prolongation and seizures, but not QRS prolongation, arrhythmia, heart block, hypokalaemia or acidosis. The thresholds for dose and cmax that increased the risk for individual signs and symptoms varied widely. However, doses > 3 g or cmax > 2 mg/L can be considered as alert levels that represent a high risk for severe clinical course of acute quetiapine intoxication.

FUNCTIONAL STATE OF RENAL PARENCHYMA IN CHILDREN WITH DYSMETABOLIC NEPHROPATHY

Abstract. Metabolic nephropathy in children is a relevant issue in our time, as the prevalence of this disease is increasing. Negative consequences of metabolic nephropathy include a gradual deterioration of kidney function. A significant aspect is the fact that metabolic nephropathy can lead to the development of chronic kidney disease in children. Chronicity requires continuous medical monitoring and treatment to support kidney function and prevent further complications, such as renal insufficiency and other metabolic disorders. There is no doubt that one of the leading pathogenetic factors in kidney dysfunction is hypoxia. It can be caused by both hemodynamic disturbances associated with renal pathology and tissue respiration disorders in congenital dysplasia of the kidney's connective tissue, which arises in the embryo under the influence of epigenetic factors in utero and is further exacerbated by various epigenetic factors in postnatal life. Purpose of the work to investigate the functional state of kidney parenchyma in children with dysmetabolic nephropathy. Materials and methods. Two groups of children were examined: those with a complicated course of dysmetabolic nephropathy, a history of inflammatory episodes of the urinary system organs (Group I - UN, 52 children), and dysmetabolic nephropathy with persistent crystalluria (Group II - DN, 56 children). A control group consisted of 65 healthy children. Tubular reabsorption, as a partial function of the proximal segment of the nephrons, was assessed based on urinolysis test data, specifically the levels of excretion of inorganic phosphates, proteinuria, amino acids, reduced sugars (maltose, sucrose, fructose by Benedict's test), glucose (by Gaines's test), and calcium (by Sulcovitch's test). The level of creatinine and glycosaminoglycan (GAG) excretion in daily urine in children with dysmetabolic nephropathy was determined and compared with data from healthy children in the control group. Research results. In children from both observation groups, a significantly high frequency of hyperphosphaturia (94.23% and 96.42%), calciuria (94.23% and 89.28%), glucosuria (78.85% and 73.21%), increased excretion of amino acids in the urine (40.38% and 37.5%), microproteinuria (32.69% and 28.57%), and increased excretion of reduced sugars (28.85% and 26.79%) were observed. The daily excretion of creatinine, glycosaminoglycans, and oxypyrrolidine in the urine of children with dysmetabolic nephropathy indicates a significantly reduced level of creatinine in the daily urine in the majority of children in Group I (0.56±0.19 g/L, 80.77% of those examined) and more than half of the children in Group II (0.83±0.08 g/L, 57.14% of those examined), compared to the data from healthy children in the control group (1.25±0.75 g/L, 0.0%). Conclusions. The analysis of the functional state of the kidney tissue in oxalate dysmetabolic nephropathy in children allows us to testify to the presence of tubular and glomerular partial renal tissue failure. Significant decreases in creatinine excretion and increased excretion of glycosoaminoglycans in the urine and significantly higher levels of oxyproline in the urine indicate the presence of glomerular type partial renal failure in oxalate dysmetabolic nephropathy in children and the presence of undifferentiated dysplasia of the renal connective tissue with the onset of its sclerosis with subsequent transition to interstitial nephritis. The presence of these changes in the vast majority of children with complicated course of oxalate dysmetabolic nephropathy in the period of clinical and laboratory remission of the inflammatory process indicates the priority of renal connective tissue dysplasia and paucity of renal failure in the pathogenesis of dysmetabolic nephropathy and its severity in children. Indicators of oxyproline creatinine, glycosoaminoglycans and oxyproline excretion can be used as epigenetic markers of susceptibility to dysmetabolic nephropathy in general and its more severe course in particular. Keywords: dysmetabolic nephropathy, functional state, kidney parenchyma, nephron.