Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.

BACKGROUND: Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions. METHODS: This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses. RESULTS: Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2- + NO3-) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1ß (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population. CONCLUSIONS: Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.

Correlation of pre-existing comorbidities with disease severity in individuals infected with SARS-COV-2 virus.

Shortly after the first publication on the new disease called Coronavirus Disease 2019 (Covid-19), studies on the causal consequences of this disease began to emerge, initially focusing only on transmission methods, and later on its consequences analyzed in terms of gender, age, and the presence of comorbidities. The aim of our research is to determine which comorbidities have the greatest negative impact on the worsening of the disease, namely which comorbidities indicate a predisposition to severe Covid-19, and to understand the gender and age representation of participants and comorbidities. The results of our study show that the dominant gender is male at 54.4% and the age of 65 and older. The most common comorbidities are arterial hypertension, diabetes mellitus, and cardiovascular diseases. The dominant group is recovered participants aged 65 and older, with comorbidities most frequently present in this group. The highest correlation between patients with different severity of the disease was found with cardiovascular diseases, while the coefficient is slightly lower for the relationship between patients with different disease severity and urinary system diseases and hypertension. According to the regression analysis results, we showed that urinary system diseases have the greatest negative impact on the worsening of Covid-19, with the tested coefficient b being statistically significant as it is 0.030 < 0.05. An increase in cardiovascular diseases affects the worsening of Covid-19, with the tested coefficient b being statistically significant as it is 0.030 < 0.05. When it comes to arterial hypertension, it has a small impact on the worsening of Covid-19, but its tested coefficient b is not statistically significant as it is 0.169 > 0.05. The same applies to diabetes mellitus, which also has a small impact on the worsening of Covid-19, but its tested coefficient b is not statistically significant as it is 0.336 > 0.05. Our study has shown that comorbidities such as urinary system diseases and cardiovascular diseases tend to have a negative impact on Covid-19, leading to a poor outcome resulting in death, while diabetes mellitus and hypertension have an impact but without statistical significance.

Eye movement function captured via an electronic tablet informs on cognition and disease severity in Parkinson's disease.

Studying the oculomotor system provides a unique window to assess brain health and function in various clinical populations. Although the use of detailed oculomotor parameters in clinical research has been limited due to the scalability of the required equipment, the development of novel tablet-based technologies has created opportunities for fast, easy, cost-effective, and reliable eye tracking. Oculomotor measures captured via a mobile tablet-based technology have previously been shown to reliably discriminate between Parkinson's Disease (PD) patients and healthy controls. Here we further investigate the use of oculomotor measures from tablet-based eye-tracking to inform on various cognitive abilities and disease severity in PD patients. When combined using partial least square regression, the extracted oculomotor parameters can explain up to 71% of the variance in cognitive test scores (e.g. Trail Making Test). Moreover, using a receiver operating characteristics (ROC) analysis we show that eye-tracking parameters can be used in a support vector classifier to discriminate between individuals with mild PD from those with moderate PD (based on UPDRS cut-off scores) with an accuracy of 90%. Taken together, our findings highlight the potential usefulness of mobile tablet-based technology to rapidly scale eye-tracking use and usefulness in both research and clinical settings by informing on disease stage and cognitive outcomes.

Exploring the Correlation between Interleukin-17A Promoter Polymorphism at its -197 G/A and Rheumatoid Arthritis: Impact on Disease Severity and Activity.

T helper 17 (Th17) cells have been reported to be the most powerful factor in autoimmune disorder pathogenesis, which points to the Th17 master cytokine, interleukin (IL)-17A, as the crucial mediator. We aimed to determine the impact of IL-17A polymorphism in the -197 G/A promoter region on level of IL-17 and intensity of rheumatoid arthritis (RA) disease symptoms. This case-control study was conducted at the Department of Clinical Rheumatology of Aswan university Hospital and included 35 people suffering RA and 30 volunteer controls, matched for age and sex. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), serum IL-17, and C-reactive protein (CRP) were measured in the RA patient group. Restriction fragment length polymorphism (RFLP) was conducted by polymerase chain reaction (PCR) amplicon obtained by IL-17A -197 G /A primers. Of the 35 RA patients, RF was positive in 33 (94.29%) and anti-CCP antibodies in 25 (71.43%), CRP in 31 (88.57%). Of the 35 RA patients, 5 (14.29%) patients carried the G/G genotype, 18 (51.43%) G/A and 12 (34.29%) A/A. IL-17 serum level was significantly greater in the more active RA (DAS28 >5.1) group than the less active (DAS28 ≤5.1) group. Of the RA patients carrying wild type G/G genotype, 60% had more active disease (DAS 28> 5.1), as compared to those with lower activity (DAS 28 ≤5.1), 40% carried the wild type G/G genotype. In conclusion, the study findings imply that IL-17A gene polymorphism is connected to RA clinical severity rather than with RA susceptibility.

The role of C-reactive protein, procalcitonin, interleukin-6 and neutrophil / lymphocyte ratio as a laboratory biomarker in COVID-19.

Biomarkers such as Interleukin-6 (IL-6), Procalcitonin (PCT), C-reactive protein (CRP) and Neutrophil-Lymphocyte Ratio (NLR) have a role in the pathogenesis of severe coronavirus disease 2019 (COVID-19). The aim of this study was to explore the differences between serum levels of such biomarkers in severe and non-severe COVID-19 cases and compare them with normal people and to evaluate the sociodemographic variables and chronic diseases effect on the severity of COVID-19. The study included 160 subjects, divided into two groups, a case group of 80 patients, and a control group of 80 normal persons. The case group was divided into two subgroups: 40 severe COVID-19 patients and 40 patients with non-severe disease. Blood IL-6 was assessed by an enzyme-linked immunosorbent assay (ELISA), PCT by an immunoassay, CRP by an immunoturbidimetric assay and NLR from CBC. The levels of IL-6, PCT, CRP, and NLR were significantly higher in the case group than in control group (p= 0.001, for all). However, there was no difference between these biomarkers level in the non-severe COVID-19 subgroup and the control group (p>0.05 for all). The proportion of severe COVID-19 was significantly higher in patients aged >50 years, and in patients with chronic diseases (p=0.046 and p=0.001, respectively). We also found a strong correlation between such biomarkers and old age, and chronic diseases with the disease severity. There was a significant difference in the level of the three biomarkers (IL-6, PCT, CRP, and NLR) between patients' subgroups and the control group. In conclusion, since the levels of these biomarkers are correlated with the severity of the COVID-19 disease, and there was a difference in the levels between the groups with severe and non-severe symptoms, we suggest a role of these biomarkers in predicting the severity COVID-19 disease and its poor prognosis.

Impact of vaccination on COVID-19 severity during the second wave in Brunei Darussalam, 2021.

Objective: Coronavirus disease (COVID-19) vaccinations have been shown to prevent infection with efficacies ranging from 50% to 95%. This study assesses the impact of vaccination on the clinical severity of COVID-19 during the second wave in Brunei Darussalam in 2021, which was due to the Delta variant. Methods: Patients included in this study were randomly selected from those who were admitted with COVID-19 to the National Isolation Centre between 7 August and 6 October 2021. Cases were categorized as asymptomatic, mild (symptomatic without pneumonia), moderate (pneumonia), severe (needing supplemental oxygen therapy) or critical (needing mechanical ventilation) but for statistical analysis purposes were dichotomized into asymptomatic/mild or moderate/severe/critical cases. Univariate and multivariable analyses were conducted to identify risk factors associated with moderate/severe/critical disease. Propensity score-matched analysis was also performed to evaluate the impact of vaccination on disease severity. Results: The study cohort of 788 cases (mean age: 42.1 ± 14.6 years; 400 males) comprised 471 (59.8%) asymptomatic/mild and 317 (40.2%) moderate/severe/critical cases. Multivariable logistic regression analysis showed older age group (≥ 45 years), diabetes mellitus, overweight/obesity and vaccination status to be associated with increased severity of disease. In propensity score-matched analysis, the relative risk of developing moderate/severe/critical COVID-19 for fully vaccinated (two doses) and partially vaccinated (one dose) cases was 0.33 (95% confidence interval [CI]: 0.16-0.69) and 0.62 (95% CI: 0.46-0.82), respectively, compared with a control group of non-vaccinated cases. The corresponding relative risk reduction (RRR) values were 66.5% and 38.4%, respectively. Vaccination was also protective against moderate/severe/critical disease in a subgroup of overweight/obese patients (RRR: 37.2%, P = 0.007). Discussion: Among those who contracted COVID-19, older age, having diabetes, being overweight/obese and being unvaccinated were significant risk factors for moderate/severe/critical disease. Vaccination, even partial, was protective against moderate/severe/critical disease.

Association of CSF Total Protein with Clinical Heterogeneity, Disease Severity and Electrophysiological Pattern in GBS Patients.

Guillain-Barre Syndrome (GBS) is considered as an immune mediated inflammatory disease of peripheral nerves and nerve roots. The significance of CSF total protein (CSF-TP) in subtypes of Guillain-Barre syndrome has not been well established. This observational, cross sectional study's aim was to identify association of CSF total protein with clinical heterogeneity, disease severity and electrophysiological subtypes in GBS patients. This study was carried out in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from September 2017 to February 2019 on 50 (fifty) admitted GBS patients as per inclusion and exclusion criteria. About 3-5 ml of CSF was taken around 10±2 days from disease onset for detection CSF cell count and protein. Pattern of clinical presentation, disability status by Hughes scale and NCS findings of these patients was documented. Mean CSF-TP were substantially higher for Sensori-motor GBS (195.42 mg/dl) and GBS with cranial involvement (226.12 mg/dl) than that of GBS with motor (134.00 mg/dl) and autonomic involvement (155.21 mg/dl). Mean CSF total protein (CSF-MTP) in severely ill GBS patients (Grade-IV) was 217.04 mg/dl and very severely ill GBS patients (Grade-V) was 138.00mg/dl which was significantly higher than mean CSF total protein in mild GBS patients (CSF-MTP: 99.86mg/dl) and moderately ill GBS patients (CSF-MTP: 172.00 mg/dl). Mean CSF total protein is 245.00mg/dl in AIDP which is also higher than mean CSF total protein of AMAN (153.36 mg/dl) and AMSAN (165.17mg/dl). CSF-TP is thought to be a sensitive test for GBS in the second week after onset, but it may be a reliable predictor of clinical severity. There is a significant association of CSF-TP elevation with demyelinating electrophysiologic pattern.

Thrombocytopenia in Klebsiella pneumoniae liver abscess: a retrospective study on its correlation with disease severity and potential causes.

Objective: Thrombocytopenia is commonly associated with infectious diseases and serves as an indicator of disease severity. However, reports on its manifestation in conjunction with Klebsiella pneumoniae liver abscess (KPLA) are scarce. The present study sought to elucidate the correlation between thrombocytopenia and KPLA severity and delve into the etiological factors contributing to the incidence of thrombocytopenia. Materials and methods: A retrospective analysis of the clinical data from patients with KPLA admitted between June 2012 and June 2023 was performed. Baseline characteristics, biochemical assessments, therapeutic interventions, complications, and clinical outcomes were compared between patients with and without thrombocytopenia. To investigate the potential etiologies underlying thrombocytopenia, the association between platelet count reduction and thrombophlebitis was examined, with a particular focus on platelet consumption. Furthermore, bone marrow aspiration results were evaluated to assess platelet production anomalies. Results: A total of 361 KPLA patients were included in the study, among whom 60 (17%) had concurrent thrombocytopenia. Those in the thrombocytopenia group exhibited significantly higher rates of thrombophlebitis (p = 0.042), extrahepatic metastatic infection (p = 0.01), septic shock (p = 0.024), admissions to the intensive care unit (p = 0.002), and in-hospital mortality (p = 0.045). Multivariate analysis revealed that thrombocytopenia (odds ratio, 2.125; 95% confidence interval, 1.114-4.056; p = 0.022) was independently associated with thrombophlebitis. Among the thrombocytopenic patients, eight underwent bone marrow aspiration, and six (75%) had impaired medullar platelet production. After treatment, 88.6% of thrombocytopenic patients (n = 47) demonstrated recovery in their platelet counts with a median recovery time of five days (interquartile range, 3-6 days). Conclusions: Thrombocytopenia in patients with KPLA is indicative of increased disease severity. The underlying etiologies for thrombocytopenia may include impaired platelet production within the bone marrow and augmented peripheral platelet consumption as evidenced by the presence of thrombophlebitis.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Comparison of geographical and individual deprivation index to assess the risk of Sars-CoV-2 infection and disease severity: a retrospective cohort study.

BACKGROUND: It has been shown that COVID-19 affects people at socioeconomic disadvantage more strongly. Previous studies investigating the association between geographical deprivation and COVID-19 outcomes in Italy reported no differences in case-hospitalisation and case-fatality. The objective of this research was to compare the usefulness of the geographic and individual deprivation index (DI) in assessing the associations between individuals' deprivation and risk of Sars-CoV-2 infection and disease severity in the Apulia region from February to December 2020. METHODS: This was a retrospective cohort study. Participants included individuals tested for SARS-CoV-2 infection during the study period. The individual DI was calculated employing polychoric principal component analysis on four census variables. Multilevel logistic models were used to test associations between COVID-19 outcomes and individual DI, geographical DI, and their interaction. RESULTS: In the study period, 139,807 individuals were tested for COVID-19 and 56,475 (43.5%) tested positive. Among those positive, 7902 (14.0%) have been hospitalised and 2215 (4.2%) died. During the first epidemic wave, according the analysis done with the individual DI, there was a significant inversely proportional trend between the DI and the risk of testing positive. No associations were found between COVID-19 outcomes and geographic DI. During the second wave, associations were found between COVID-19 outcomes and individual DI. No associations were found between the geographic DI and the risk of hospitalisation and death. During both waves, there were no association between COVID-19 outcomes and the interaction between individual and geographical DI. CONCLUSIONS: Evidence from this study shows that COVID-19 pandemic has been experienced unequally with a greater burden among the most disadvantaged communities. The results of this study remind us to be cautious about using geographical DI as a proxy of individual social disadvantage because may lead to inaccurate assessments. The geographical DI is often used due to a lack of individual data. However, on the determinants of health and health inequalities, monitoring has to have a central focus. Health inequalities monitoring provides evidence on who is being left behind and informs equity-oriented policies, programmes and practices. Future research and data collection should focus on improving surveillance systems by integrating individual measures of inequalities into national health information systems.

Assessment of Red Blood Cell Aggregation in Preeclampsia by Microfluidic Image Flow Analysis-Impact of Oxidative Stress on Disease Severity.

Preeclampsia (PE) is a hypertensive disease characterized by proteinuria, endothelial dysfunction, and placental hypoxia. Reduced placental blood flow causes changes in red blood cell (RBC) rheological characteristics. Herein, we used microfluidics techniques and new image flow analysis to evaluate RBC aggregation in preeclamptic and normotensive pregnant women. The results demonstrate that RBC aggregation depends on the disease severity and was higher in patients with preterm birth and low birth weight. The RBC aggregation indices (EAI) at low shear rates were higher for non-severe (0.107 ± 0.01) and severe PE (0.149 ± 0.05) versus controls (0.085 ± 0.01; p < 0.05). The significantly more undispersed RBC aggregates were found at high shear rates for non-severe (18.1 ± 5.5) and severe PE (25.7 ± 5.8) versus controls (14.4 ± 4.1; p < 0.05). The model experiment with in-vitro-induced oxidative stress in RBCs demonstrated that the elevated aggregation in PE RBCs can be partially due to the effect of oxidation. The results revealed that RBCs from PE patients become significantly more adhesive, forming large, branched aggregates at a low shear rate. Significantly more undispersed RBC aggregates at high shear rates indicate the formation of stable RBC clusters, drastically more pronounced in patients with severe PE. Our findings demonstrate that altered RBC aggregation contributes to preeclampsia severity.

SIGNIFICANCE OF NEUTROPHIL-LYMPHOCYTE RATIO AND PLATELET-LYMPHOCYTE RATIO AS PROGNOSTIC MARKERS OF DISEASE SEVERITY IN SYSTEMIC LUPUS ERYTHEMATOSUS.

Managing systemic lupus erythematosus (SLE) is challenging because of its diverse symptoms, relapses, and issues related to immunosuppressive therapy. Hence, the management of autoimmune disorder has become a hot topic in this era. Thus, the study aims to predict disease severity in SLE cases by assessing the value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. In this study, we included a total of 80 patients, of which 40 were controls and 40 were experimental group. We gathered the demographic data and each patient provided informed consent. Furthermore, the clinical examinations were done, and results were noted. The study compared 40 SLE patients with 40 controls. SLE patients had lower complement levels, higher rates of LN and encephalopathy, and elevated Hs-CRP and ESR. They also showed lower WBC, neutrophil, lymphocyte, and platelet counts, along with higher NLR and PLR. Higher SLEDAI scores correlated with elevated Hs-CRP and ESR, and lower C3. Neutrophils positively correlated with NLR, while lymphocytes negatively correlated with SLEDAI scores, NLR, and PLR. Platelets did not significantly correlate with these markers. SLE patients showed higher rates of LNand encephalopathy, elevated inflammatory markers, and altered blood cell counts. Lower SLEDAI scores correlated with less inflammation and higher C3 levels, potentially indicating disease severity. Neutrophils were closely linked to disease activity, while lymphocytes showed a strong negative correlation. Platelet count was not a significant marker. Understanding these aspects could improve diagnosis and management.

Online Questionnaire with Fibromyalgia Patients Shows Negative Correlations between Disease Severity and Adherence to Mediterranean Diet.

Fibromyalgia (FM) is a multidimensional disorder in which intense chronic pain is accompanied by a variety of psychophysical symptoms that impose a burden on the patients' quality of life. Despite the efforts and the recent advancement in research, FM pathogenesis and effective treatment remain unknown. Recently, the possible role of dietary patterns and/or components has been gaining attention. The current study aimed to investigate a potential correlation between adherence to the Mediterranean diet (MedDiet) and FM severity in a sample of Italian FM patients. An online survey was designed, composed of customized questions and validated questionnaires with the aim of investigating the intensity and type of pain, the presence of other psychophysical symptoms, the overall impact of FM, general food and lifestyle habits, and adherence to the MedDiet. The collected responses were analyzed for descriptive statistics, linear regression, and propensity score analyses. The results show that, despite considerable use of pharmaceuticals and supplements, FM participants suffered from a high-severity grade disease. However, those with good adherence to the MedDiet experienced a lower pain intensity and overall FM impact. A propensity score analysis indicates a positive influence of the MedDiet against FM severity, thus unveiling the need for well-designed intervention studies to evaluate the therapeutic potential of different dietary patterns.

Patients' and physicians' awareness of clinical symptoms and disease severity in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare inherited disease with the potential to affect virtually every organ system. Clinical presentation is age- and partly sex-dependent and varies broadly with respect to disease manifestations including treatment-refractory epilepsy, intellectual disability and TSC-associated neuropsychiatric disorders, chronic kidney disease or progressive lung function decline. Given the complexity of this disease, multidisciplinary care in specialized TSC centres is recommended. We aimed to elucidate the state of knowledge of patients/caregivers and physicians on individual disease manifestations. We further examined whether the association to a TSC centre has an impact on the comprehensive consideration of potential disease manifestations. Therefore, a survey was performed in a cohort of German TSC patients and their physicians. Complete information was available for 94 patients with a median age of 18 years [range 1-55] and a sex distribution of 53.2% (male): 48.8% (female). Using almost identical questionnaires for patients/caregivers and their respective physician, there was a good correlation for disease assessments associated with relevant morbidity and mortality like epilepsy, renal angiomyolipoma, cardiac rhabdomyomas or intellectual disability. Correlation was moderate for several neuropsychiatric disorders and only poor for hypomelanotic macules, dental pits or retinal achromic patches. Estimation of overall disease severity using a numeric rating scale correlated highly significantly (Pearson correlation coefficient = 0.767; p < 0.001) between patients/caregivers and physicians. In general, physicians more likely quoted items as 'unknown' than patients (822 answers vs. 435 answers in the respective groups). Questionnaires completed by physicians who were associated with a specialized TSC centre declared a significantly lower proportion of items as unknown (mean 8.7% vs. 20.5%; p < 0.001). These findings indicate that patients treated by specialized TSC centres seem to obtain a more comprehensive surveillance. Furthermore, it shows that there were reasonable surveillance strategies in general and sufficient patient/caregiver interaction and education in the examined cohort. However, for the most prominent disease characteristics there was a good awareness within both the patients/caregivers and the physicians group.

Delineating immune variation between adult and children COVID-19 cases and associations with disease severity.

The SARS-CoV-2 pandemic has emphasized the need to explore how variations in the immune system relate to the severity of the disease. This study aimed to explore inter-individual variation in response to SARS-CoV-2 infection by comparing T cell, B cell, and innate cell immune subsets among primary infected children and adults (i.e., those who had never experienced SARS-CoV-2 infection nor received vaccination previously), with varying disease severity after infection. We also examined immune subset kinetics in convalescent individuals compared to those with persistent infection to identify possible markers of immune dysfunction. Distinct immune subset differences were observed between infected adults and children, as well as among adult cases with mild, moderate, and severe disease. IgM memory B cells were absent in moderate and severe cases whereas frequencies of B cells with a lack of surface immunoglobulin expression were significantly higher in severe cases. Interestingly, these immune subsets remained stable during recovery implying that these subsets could be associated with underlying baseline immune variation. Our results offer insights into the potential immune markers associated with severe COVID-19 and provide a foundation for future research in this area.

Correlation of serum and local CXCL13 levels with disease severity in patients with non-traumatic osteonecrosis of femoral head.

OBJECTIVE: The primary aim of the present study was to explore the potential correlation of serum / local CXCL13 expressions and disease severity in non-traumatic osteonecrosis of the femoral head (NT-ONFH). METHODS: In total, NT-ONFH patients (n = 130) together with healthy controls (HCs, n = 130) were included in this investigation. Radiographic progression was evaluated based on the imaging criteria outlined in the ARCO classification system. To assess the diagnostic value of serum CXCL13 in relation to radiographic progression, Receiver operating characteristic (ROC) curve analysis was conducted. Serum CXCL13 levels were quantified utilizing ELISA in all participants. Furthermore, local protein/mRNA expressions of CXCL13 were examined employing immunohistochemistry, western blot, as well as RT-PCR techniques. Clinical severity was appraised using the visual analogue scale (VAS), Harris Hip Score (HHS), and Western Ontario as well as McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The findings revealed a significant reduction in serum CXCL13 levels among NT-ONFH patients in contrast with HCs. Moreover, both mRNA and protein expressions of CXCL13 were markedly decreased in the necrotic area (NA) than the non-necrotic area (NNA) as well as the healthy femoral head tissues. Additionally, serum CXCL13 levels were substantially lower among patients classified as ARCO stage 4 than those at ARCO stage 3. The concentrations of CXCL13 in stage 3 patients were notably diminished relative to those at ARCO stage 2. Notably, serum CXCL13 levels demonstrated a negative association with ARCO grade. Furthermore, these levels were also inversely linked to VAS scores as well as WOMAC scores while displaying a positive association with HHS scores. The findings of ROC curve suggested that reduced serum CXCL13 levels could be an underlying indicator for ARCO stage. CONCLUSIONS: The reduced levels of either serum CXCL13 or local CXCL13 were intricately linked to disease severity for patients with NT-ONFH.

Serum ACE2 and S19P gene polymorphism in Egyptian patients with COVID-19 infection: correlation with disease severity.

The expression of ACE2 is linked to disease severity in COVID-19 patients. The ACE2 receptor gene polymorphisms are considered determinants for SARS-CoV-2 infection and its outcome. In our study, serum ACE2 and its genetic variant S19P rs73635825 polymorphism were investigated in 114 SARS-CoV-2 patients. The results were compared with 120 control subjects. ELISA technique and allele discrimination assay were used for measuring serum ACE2 and genotype analysis of ACE2 rs73635825. Our results revealed that serum ACE2 was significantly lower in SARS-CoV-2 patients (p = 0.0001), particularly in cases with hypertension or diabetes mellitus. There was a significant difference in the genotype distributions of ACE2 rs73635825 A > G between COVID-19 patients and controls (p-value = 0.001). A higher frequency of the heterozygous AG genotype (65.8%) was reported in COVID-19 patients. The G allele was significantly more common in COVID-19 patients (p < 0.0001). The AG and GG genotypes were associated with COVID-19 severity as they were correlated with abnormal laboratory findings, GGO, CXR, and total severity scores with p < 0.05. Our results revealed that the ACE2 S19P gene variant is correlated with the incidence of infection and its severity, suggesting the usefulness of this work in identifying the susceptible population groups for better disease control.

Comparison of Disease Severity, Anxiety and Depression in Obsessive-Compulsive Disorder Patients with Different Insight.

BACKGROUND: Significant individual differences exist in the insight of patients with obsessive-compulsive disorder (OCD), and the clinical characteristics of OCD patients with varying levels of insight are not entirely uniform. This study aims to investigate disparities in disease severity, anxiety, and depression status among OCD patients with differing levels of insight, with the goal of generating novel treatment strategies for OCD. METHODS: A total of 114 patients diagnosed with OCD were recruited from the Department of Psychology at Affiliated Mental Health Center & Hangzhou Seventh People's Hospital to participate in this research. Based on their Total Insight and Treatment Attitude Questionnaire (ITAQ) scores, the patients were divided into two groups: Group OCD with high insight (referred to as Group OCD-HI, ITAQ score ≥20 points, n = 80) and Group OCD with low insight (referred to as Group OCD-LI, ITAQ score <20 points, n = 34). Subsequently, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were compared between the two groups. All questionnaires for this study were completed by experienced psychiatrists. RESULTS: The Y-BOCS scores for YB1, YB2, YB4, YB5, YB6, YB9, and the total Y-BOCS scores in Group OCD-HI were significantly higher than those in Group OCD-LI (p < 0.05). Conversely, Group OCD-HI exhibited significantly lower HAMA and HAMD scores compared to Group OCD-LI (p < 0.05). Furthermore, the total ITAQ score displayed a significant negative correlation with the total Y-BOCS, HAMA, and HAMD scores (p < 0.05). CONCLUSIONS: This study revealed that certain OCD patients exhibit incomplete insight, and this lack of insight is strongly associated with increased disease severity and heightened levels of anxiety and depression. It is hoped that by enhancing the insight of OCD patients, the goal of ameliorating disease symptoms and alleviating negative emotions can be attained.

No association between disease severity and respiratory syncytial virus subtypes RSV-A and RSV-B in hospitalized young children in Norway.

OBJECTIVE: There is conflicting evidence whether subtypes of Respiratory syncytial virus have different seasonality or are differentially associated with clinical severity. We aimed to explore the associations between disease severity and RSV subtypes RSV-A and RSV-B and to describe the circulation of RSV subtypes pattern by season and age. METHODS: Active prospective hospital surveillance for RSV-A and RSV-B in children <59 months of age was conducted during 2015-2018. All febrile children 12-59 months of age were enrolled, whereas children <12 months were eligible if presenting with fever or respiratory symptoms. Risk factors and upper and lower respiratory tract infection was identified by linkage to national registry data and analyzed using penalized maximum likelihood logistic regression. RESULTS: Both RSV-A and B were found to co-circulate throughout all three study seasons, and no clear seasonal pattern was identified. Likewise, we found no association between sex or measures of severity with RSV-A or RSV-B. There was significantly more RSV-A than RSV-B among children with comorbidities. CONCLUSIONS: No association was found between disease severity or sex and RSV subtypes RSV-A and RSV-B in hospitalized young children in Norway.