Clinical severity of enteric viruses detected using a quantitative molecular assay compared to conventional assays in the Global Enteric Multicenter Study.

BACKGROUND: Quantitative molecular assays are increasingly used for detection of enteric viruses. METHODS: We compared the clinical severity using modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIA] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (CT) cutoffs. RESULTS: Using conventional assays, the median (interquartile range) mVS was 10 (8, 11) for rotavirus, 9 (7, 11) for adenovirus 40/41, 8 (6, 10) for astrovirus, sapovirus, and norovirus GII, and 7 (6, 9) for norovirus GI. Compared to rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with CT<32.6 and 32.6≤CT<35, respectively (p-value<.0001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of CT cutoff. CONCLUSIONS: Quantitative molecular assays compared to conventional assays, such as EIA, may influence severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies.

The Index of Severity for Eosinophilic Esophagitis (I-SEE) Reflects Longitudinal Clinicopathologic Changes in Children.

BACKGROUND AND AIMS: The Index of Severity for Eosinophilic Esophagitis (I-SEE) was recently developed. We aimed to understand I-SEE scores in a longitudinal pediatric cohort and to determine the relationship between I-SEE and clinical features in children. METHODS: We performed a retrospective analysis on a prospectively enrolled cohort of children at a single center who were treated as part of routine clinical care. I-SEE was calculated at the diagnostic and follow-up endoscopies over a mean of 6.6 years. Scoring was 0 for inactive, 1-6 for mild, 7-14 for moderate, and ≥15 for severe eosinophilic esophagitis (EoE). We analyzed clinical, endoscopic, and histologic features at each instance. Symptoms were analyzed at the baseline, first follow-up, and last endoscopic instance. RESULTS: Of 67 children who met study criteria of at least 3 endoscopies over at least 2 years of follow-up time, 43%, 36%, and 21% had mild, moderate, and severe I-SEE scores at baseline, respectively. Between the first and second endoscopic instances, there was a decrease in the group mean I-SEE from 9.7 ± 7.2 to 6.1 ± 5.9 (P < .001). By the last instance, the overall I-SEE score dropped to 3.9 (P < .001). Body mass index <5% and poor feeding were more common in the children with severe I-SEE scores at baseline, and both improved by the last instance. Fibrosis was improved by the last instance biopsy (P < .01). CONCLUSIONS: I-SEE is a responsive severity metric in children treated long term during routine clinical care. Baseline low body mass index and poor feeding were more common in children with severe I-SEE scores.

Parental age effects and Rett syndrome.

Rett syndrome (RTT) is a progressive neurodevelopmental disorder, and pathogenic Methyl-CpG-binding Protein 2 (MECP2) variants are identified in >95% of individuals with typical RTT. Most of RTT-causing variants in MECP2 are de novo and usually on the paternally inherited X chromosome. While paternal age has been reported to be associated with increased risk of genetic disorders, it is unknown whether parental age contributes to the risk of the development of RTT. Clinical data including parental age, RTT diagnostic status, and clinical severity are collected from 1226 participants with RTT and confirmed MECP2 variants. Statistical analyses are performed using Student t-test, single factor analysis of variance (ANOVA), and multi-factor regression. No significant difference is observed in parental ages of RTT probands compared to that of the general population. A small increase in parental ages is observed in participants with missense variants compared to those with nonsense variants. When we evaluate the association between clinical severity and parental ages by multiple regression analysis, there is no clear association between clinical severity and parental ages. Advanced parental ages do not appear to be a risk factor for RTT, and do not contribute to the clinical severity in individuals with RTT.

The molecular epidemiology and clinical implication of methicillin-resistant Staphylococcus aureus (MRSA) sequence types in pediatric bacteremia: a restrospective observational study, 2016-2021.

BACKGROUND: While there is a high burden of methicillin-resistant Staphylococcus aureus (MRSA) infections among pediatric patients, studies on the molecular epidemiology of MRSA infections in Korean children since the 2010s are lacking. This study aimed to investigate the molecular genotypes and clinical characteristics of MRSA isolates from children with MRSA bacteremia at Asan Medical Center Children's Hospital from 2016 to 2021. METHODS: Clinical data were retrospectively reviewed, and the molecular types of MRSA were determined using multilocus sequence typing (MLST) and Staphylococcal cassette chromosome mec (SCCmec) typing. RESULTS: The overall methicillin resistance rate of S. aureus bacteremia was 44.8% (77/172); 49.5% in the period 2016-2018 (period 1) and 37.3% in the period 2019-2021 (period 2) (P = 0.116). Community-acquired infections accounted for only 3.9% of cases. The predominant ST group was ST72 group (67.6%), followed by ST5 group (18.9%) and ST1 group (5.4%). The proportion of ST5 was significantly lower in period 2 compared to period 1 (P = 0.02). Compared to the ST5 and ST1 groups, the ST72 group exhibited lower overall antibiotic resistance and multidrug-resistant (MDR) rates (12.0% [6/50] in ST72 group vs. 100.0% [14/14] in ST5 group vs. 50.0% [2/4] in ST1 group; P < 0.001). In the multivariate analysis, the ST1 group was an independent risk factor for 30-day all-cause mortality (aOR, 44.12; 95% CI, 3.46-562.19). CONCLUSION: The ST72-MRSA strain remained the most frequently isolated genotype in Korean children, while the ST1 group emerged as an independent risk factor for 30-day all-cause mortality in pediatric MRSA bacteremia. Ongoing efforts to uncover the evolving epidemiology of MRSA are essential for developing effective strategies for prevention and treatment.

Amyloid and Tau as cerebrospinal fluid biomarkers in anti-N-Methyl-D-aspartate receptor encephalitis.

INTRODUCTION: Neuroinfection is associated with the deposition of amyloid-beta (Aß) peptides, and subsequent decrease in cerebrospinal fluid (CSF) amyloid levels. However, whether autoimmune encephalitis involves extracellular deposition of Aß peptides in the brain is unreported. METHODS: We examined CSF amyloid and tau values in adults with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E). Forty-two patients with NMDAR-E, 35 patients with viral and bacterial neuroinfections, and 16 controls were included. We measured CSF Aß1-42 (cAß1-42), Aß1-40 (cAß1-40), t-Tau (ct-Tau), and p-Tau181 (cp-Tau181) levels and assessed their efficacies regarding differential diagnosis and predicting prognosis. RESULTS: NMDAR-E patients had lower cAß1-42 levels; however, they were higher than those of patients with bacterial meningitis. ct-Tau levels in NMDAR-E patients were lower than those in patients with neuroinfections. No changes were observed in controls. cAß1-42 and ct-Tau were combined as an excellent marker to distinguish NMDAR-E from neuroinfections. cAß1-42 levels in NMDAR-E patients were positively correlated with Montreal Cognitive Assessment scores. We observed an inverse relationship between cAß1-42 levels and modified Rankin Scale scores. Patients with poor outcomes exhibited low cAß1-42 levels and high levels of several blood parameters. cAß1-42 was the highest quality biomarker for assessing NMDAR-E prognosis. Correlations were found between cAß1-42 and some inflammatory indicators. CONCLUSION: cAß1-42 was decreased in NMDAR-E patients. cAß1-42 levels indicated NMDAR-E severity and acted as a biomarker for its prognosis. Combining cAß1-42 and ct-Tau levels could serve as a novel differential diagnostic marker for NMDAR-E.

Epidemiological and clinical evolution of multisystem inflammatory syndrome in children throughout the SARS-CoV-2 pandemic in a tertiary Italian children's hospital.

Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening disease temporally linked to SARS-CoV-2 whose incidence and clinical presentation may have been altered by the different SARS-CoV-2 variants and by vaccination. METHODS: We retrospectively collected the data of all MIS-C cases admitted to the Gaslini Children's Hospital, the hub for SARS-CoV-2 related diseases in Liguria region, Italy, from 01 October 2020, to 30 November 2022, evaluating the ratio between MIS-C cases and (1) COVID-19 paediatric cases in our region, (2) emergency department admissions and (3) emergency department febrile patients. We also compared MIS-C incidence in pre- post-vaccination periods. RESULTS: We observed a significant global decline in the incidence of MIS-Cover the four variant periods and after the starting of vaccination whereas clinical features, therapeutic management and severity did not significantly vary. CONCLUSIONS: In our setting, we demonstrated a significant decrease of MIS-C incidence according to the predominant variant and including not vaccinated children. Regardless of variant type, the patients showed similar phenotypes and severity throughout the pandemic. SARS-CoV-2 variants as well as immune protection after previous infections and/or vaccination may have interacted by playing different roles and reducing the incidence of MIS-C.

Letter to editor: Clinical severity of aneurysmal subarachnoid hemorrhage over time: systematic review.

The letter to the editor titled "Clinical severity of aneurysmal subarachnoid hemorrhage over time: systematic review" provides a comprehensive and systematic examination of the changing clinical landscape of aSAH, emphasizing the importance of advancements in medical technology and treatment protocols. The review's methodological rigor ensures reliable findings, highlighting the positive trends in clinical outcomes due to improved diagnostic tools and early interventions. However, potential publication bias and the need for a more detailed analysis of specific medical innovations and regional variations are notable limitations. Despite these, the letter is a valuable contribution, offering insights that could guide future research and improve patient outcomes.

Endovenous glue ablation for chronic venous insufficiency: A comprehensive 5-year assessment of clinical and hemodynamic outcomes.

OBJECTIVES: Chronic venous insufficiency is mainly caused by reflux, obstruction, or both. Endovenous glue ablation has become one of the widely used methods for treating reflux in recent years. Duplex ultrasonography is the most commonly used method for diagnosing and evaluating treatment. However, there is important information that plethysmographic venous hemodynamics provides, which Duplex USG cannot provide. This retrospective study aimed to evaluate the 5-year clinical, anatomical, and hemodynamic results of endovenous glue ablation in the treatment of chronic venous insufficience, accompanied by the data from the plethysmographic study. PATIENTS AND METHOD: Between January 2018 and August 2018, 133 patients with symptomatic CEAP 2-6 varicose veins with reflux of the great saphenous vein lasting longer than 0.5 seconds and a diameter of 5.5 mm in the standing great saphenous vein underwent EVGA. CEAP, VCSS, CIVIQ 20, Doppler USG, GSV diameters and insufficiency times, and hemodynamically Venous Refilling Time and Venous Half-Value Time measurements were performed before the procedure. In the same way, measurements were made at the 1st, 3rd, 6th, 12th, 24th, and 60th months of the patients who were called and came to the postoperative follow-up. RESULTS: Procedural success was 100%, and complete occlusion was observed %93 after treatment, at the 60 month. The improvement in VCSS (from 4.4 ± 1.3 to 1.7 ± 0.9), CIVIQ20 (from 8.5 ± 3.1 to 4.7 ± 2.0), VRT (from 20.3 ± 5.0 to 131.1 ± 4.0), and TH (from 2.8 ± 0.3 to 2.4 ± 0.2) was significant (p < .001 was for all). CONCLUSION: Endovenous glue ablation is a preferred method for the treatment of great saphenous vein insufficiency due to its ease of use and the comfort it provides to patients, as well as its effectiveness and safety. In particular, it can be considered an effective method for improving venous hemodynamics and relieving associated symptoms.

The place of B-mode ultrasonography, shear-wave elastography, and superb microvascular imaging in the diagnosis of De Quervain tenosynovitis.

PURPOSE: Superb microvascular imaging (SMI) and Shear wave elastography (SWE) are newly developed ultrasonographic diagnostic tools used to support the diagnosis of De Quervain tenosynovitis (DQT). The aim of this study was to examine the capacity to differentiate between the wrist with DQT and the healthy wrist, as well as the potential for predicting the disease's severity using B-mode ultrasonography, SWE, and SMI. METHODS: A total of 19 cases with unilateral clinical DQT were included in the prospective study. The wrists of these cases without DQT clinic constituted the control group. RESULTS: The SWE parameters of m/s and kPa cutoff values were ≤5.225 and ≤ 77.65, respectively, in the wrists with DQT compared to the wrists not diagnosed with DQT (p < 0.001). Regarding SMI findings no microvascularity was determined in the abductor pollicis longus (APL) and extensor pollicis brevis (EPB) tendon sheaths of the wrists without DQT, and a significant increase was observed in the degree of microvascularity as the clinical severity of DQT increased. CONCLUSION: SWE results can differentiate between the presence and absence of DQT. SMI grading of the APL and EPB tendon sheaths may be helpful to the clinician in deciding the clinical severity of DQT.

[Relationship between the lung ultrasound and the clinical severity of the patient with seasonal flu]. / Lien entre l'aspect échographique du poumon et la sévérité́ clinique du patient atteint d'une grippe saisonnière.

INTRODUCTION: The seasonal flu is a very important reason for consultation every winter. Symptoms can quickly progress to severe pneumonia. Currently, few tools exist to assess the clinical severity of patients. The aim of this study is to demonstrate the role of lung ultrasound as a marker of severity in patients with influenza. METHODS: 79 patients who arrived at the emergency department with flu-like symptoms were included. A pulmonary ultrasound looking for an interstitial syndrome or consolidation was performed. The qSOFA, the SOFA, the saturation, the PaO2/FiO2 ratio, the oxygen needs, the destination of the patient made it possible to establish the seriousness of the pathology of the patient. Ultrasound was then compared to these different tools. RESULTS: The more the ultrasound became pathological, the more we observed a proportion of qSOFA (p = 0.001) and pathological SOFA (p = 0.009). Most patients with acute respiratory distress syndrome have pathological ultrasound (p < 0.001). The average admission saturation is 89.2 % in the "pathological ultrasound" group compared to 95.8 % in the "normal ultrasound" group (p < 0.001). Patients who required invasive therapies had pathological ultrasound (p < 0.001). Of the 28 patients with pathological ultrasound, 24 required hospitalization (p < 0.001). CONCLUSION: Lung ultrasound is a major asset for assessing the severity of the patient with seasonal flu. In addition, ultrasound allows better monitoring of the patient by being able to influence the destination of the latter towards a return home or monitoring in intensive care.

INTRODUCTION: La grippe saisonnière représente chaque hiver un motif de consultation très important. La symptomatologie peut rapidement évoluer vers une pneumonie sévère. Actuellement, peu d'outils existent pour évaluer la sévérité clinique des patients. Le but de cette étude est de démontrer le rôle de l'échographie pulmonaire comme marqueur de sévérité́ chez les patients atteints d'une grippe. Méthodes : L'étude a comporté 79 patients arrivés aux urgences pour grippe. Une échographie pulmonaire a été réalisée à la recherche d'un syndrome interstitiel ou d'une consolidation. Le qSOFA, le SOFA, la saturation, le rapport PaO2/FiO2, les besoins en oxygène, la destination du patient ont permis d'établir la gravité de la pathologie du patient. L'échographie a alors été comparée à ces différents outils. Résultats : Plus l'échographie devient pathologique, plus on observe une proportion de qSOFA (p = 0,001) et de SOFA pathologiques (p = 0,009). La majorité́ des patients ayant un syndrome de détresse respiratoire aiguë ont une échographie pathologique (p < 0,001). La moyenne des saturations d'admission est de 89,2 % dans le groupe «échographie pathologique¼ contre 95,8 % dans le groupe «échographie normale¼ (p < 0,001). Les patients ayant eu recours à des thérapies invasives ont une échographie pathologique (p < 0,001). Sur les 28 patients ayant une échographie pathologique, 24 ont nécessité́ une hospitalisation (p < 0,001). CONCLUSION: L'échographie pulmonaire est un atout majeur pour l'évaluation de la sévérité du patient atteint d'une grippe saisonnière. De plus, l'échographie permet une meilleure surveillance du patient en pouvant influencer la destination de celui-ci vers un retour à̀ domicile ou une surveillance aux soins intensifs.

Alpha to Omicron: Disease Severity and Clinical Outcomes of Major SARS-CoV-2 Variants.

BACKGROUND: Four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants predominated in the United States since 2021. Understanding disease severity related to different SARS-CoV-2 variants remains limited. METHOD: Viral genome analysis was performed on SARS-CoV-2 clinical isolates circulating March 2021 through March 2022 in Cleveland, Ohio. Major variants were correlated with disease severity and patient outcomes. RESULTS: In total 2779 patients identified with either Alpha (n 1153), Gamma (n 122), Delta (n 808), or Omicron variants (n 696) were selected for analysis. No difference in frequency of hospitalization, intensive care unit (ICU) admission, and death were found among Alpha, Gamma, and Delta variants. However, patients with Omicron infection were significantly less likely to be admitted to the hospital, require oxygen, or admission to the ICU (2 12.8, P .001; 2 21.6, P .002; 2 9.6, P .01, respectively). In patients whose vaccination status was known, a substantial number had breakthrough infections with Delta or Omicron variants (218/808 [26.9] and 513/696 [73.7], respectively). In breakthrough infections, hospitalization rate was similar regardless of variant by multivariate analysis. No difference in disease severity was identified between Omicron subvariants BA.1 and BA.2. CONCLUSIONS: Disease severity associated with Alpha, Gamma, and Delta variants is comparable while Omicron infections are significantly less severe. Breakthrough disease is significantly more common in patients with Omicron infection.

Short-term exposure to ambient air pollution and COVID-19 severity during SARS-CoV-2 Delta and Omicron waves: A multicenter study.

Air pollution may affect the clinical course of respiratory diseases, including COVID-19. This study aimed to evaluate the relationship between exposure of adult patients to mean 24 h levels of particulate matter sized <10 µm (PM10 ) and <2.5 µm (PM2.5 ) and benzo(a)pyrene (B(a)P) during a week before their hospitalization due to SARS-CoV-2 infection and symptomatology, hyperinflammation, coagulopathy, the clinical course of disease, and outcome. The analyses were conducted during two pandemic waves: (i) dominated by highly pathogenic Delta variant (n = 1440) and (ii) clinically less-severe Omicron (n = 785), while the analyzed associations were adjusted for patient's age, BMI, gender, and comorbidities. The exposure to mean 24 h B(a)P exceeding the limits was associated with increased odds of fever and fatigue as early COVID-19 symptoms, hyperinflammation due to serum C-reactive protein >200 mg/L and interleukin-6 >100 pg/mL, coagulopathy due to  d-dimer >2 mg/L and fatal outcome. Elevated PM10 and PM2. 5 levels were associated with higher odds of respiratory symptoms, procalcitonin >0.25 ng/mL and interleukin >100 pg/mL, lower oxygen saturation, need for oxygen support, and death. The significant relationships between exposure to air pollutants and the course and outcomes of COVID-19 were observed during both pandemic waves. Short-term exposure to elevated PM and B(a)P levels can be associated with a worse clinical course of COVID-19 in patients requiring hospitalization and, ultimately, contribute to the health burden caused by SARS-CoV-2 variants of higher and lower clinical significance.

Prepandemic viral community-acquired pneumonia: Diagnostic sensitivity and specificity of nasopharyngeal swabs and performance of clinical severity scores.

The objectives of this work were to assess the diagnostic sensitivity and specificity of nasopharyngeal (NP) swabs for viral community-acquired pneumonia (CAP) and the performance of pneumonia severity index (PSI) and CURB-65 severity scores in the viral CAP in adults. A prospective observational cohort study of consecutive 341 hospitalized adults with CAP was performed between January 2018 and March 2020. Demographics, comorbidities, symptoms/signs, analytical data, severity scores, antimicrobials, and outcomes were recorded. Blood, NP swabs, sputum, and urine samples were collected at admission and assayed by multiplex real time-PCR, bacterial cultures, and Streptococcus pneumoniae and Legionella pneumophila antigens detection, to determine the etiologies and quantify the viral load. The etiology was identified in 174 (51.0%) patients, and in 85 (24.9%) it was viral, the most frequent rhinovirus and influenza virus. The sensitivity of viral detection in sputum (50.7%) was higher than in NP swabs (20.9%). Compared with sputum, the positive predictive value and specificity of NP swabs for viral diagnosis were 95.8% and 96.9%, respectively. Performance of PSI and CURB-65 scores in all CAP with etiologic diagnosis were as expected, with mortality associated with higher values, but they were not associated with mortality in patients with viral pneumonia. NP swabs have lower sensitivity but high specificity for the diagnosis of viral CAP in adults compared with sputum, reinforcing the use NP swabs for the diagnostic etiology work-up. The PSI and CURB-65 scores did not predict mortality in the viral CAP, suggesting that they need to be updated scores based on the identification of the etiological agent.

Metabolic and inflammatory profiles define phenotypes with clinical relevance in female knee osteoarthritis patients with joint effusion.

OBJECTIVES: Osteoarthritis has been the subject of abundant research in the last years with limited translation to the clinical practice, probably due to the disease's high heterogeneity. In this study, we aimed to identify different phenotypes in knee osteoarthritis (KOA) patients with joint effusion based on their metabolic and inflammatory profiles. METHODS: A non-supervised strategy based on statistical and machine learning methods was applied to 45 parameters measured on 168 female KOA patients with persistent joint effusion, consecutively recruited at our hospital after a monographic OA outpatient visit. Data comprised anthropometric and metabolic factors and a panel of systemic and local inflammatory markers. The resulting clusters were compared regarding their clinical, radiographic and ultrasound severity at baseline and their radiographic progression at two years. RESULTS: Our analyses identified four KOA inflammatory phenotypes (KOIP): a group characterized by metabolic syndrome, probably driven by body fat and obesity, and by high local and systemic inflammation (KOIP-1); a metabolically healthy phenotype with mild overall inflammation (KOIP-2); a non-metabolic phenotype with high inflammation levels (KOIP-3); and a metabolic phenotype with low inflammation and cardiovascular risk factors not associated with obesity (KOIP-4). Of interest, these groups exhibited differences regarding pain, functional disability and radiographic progression, pointing to a clinical relevance of the uncovered phenotypes. CONCLUSION: Our results support the existence of different KOA phenotypes with clinical relevance and differing pathways regarding their pathophysiology and disease evolution, which entails implications in patients' stratification, treatment tailoring and the search of novel and personalized therapies.

A systematic review on Treacher Collins syndrome: Correlation between molecular genetic findings and clinical severity.

Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between phenotypic variability and their relative variants are very limited. This systematic review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype-phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified. While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5-bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies.

Impact of Age and Clinico-Biochemical Parameters on Clinical Severity of SARS-CoV-2 Infection.

INTRODUCTION: The surge in novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease-2019 (COVID-19) has overwhelmed the health system. To help health-care workers and policy makers prioritize treatment and to decrease the burden on health systems caused by COVID-19, clinical severity along with various clinico-biochemical parameters was evaluated by designing a cross-sectional study comprising 236 SARS-CoV-2-infected individuals from Kashmir Valley, India. METHODS: Briefly, real-time polymerase chain reaction (RT-PCR) was used for the confirmation of SARS-CoV-2 infection. The principles of spectrophotometry and chemiluminescent microparticle immunoassay (CMIA) were employed to estimate the levels of glucose, TSH, and 25-hydroxy vitamin D levels in serum of infected patients. RESULTS: A total of 236 patients infected with SARS-CoV-2 were taken for this cross-sectional study. Patients with COVID-19 had a male predominance (72.9 vs. 27.1%) and a higher prevalence of 25-hydroxy vitamin D deficiency (72.0 vs. 28.0%) with a mean 25-hydroxy vitamin D levels of 24.0 ± 13.9 in ng/mL. We observed a varied clinical spectrum of SARS-CoV-2 infection with 36.4%, 23.7%, and 29.7% patients having mild, moderate, and severe disease, respectively. We observed that severity of SARS-CoV-2 infection was significantly associated with older age group, hypertension, low TSH levels, and 25-hydroxy vitamin D deficiency. CONCLUSION: We conclude that not only old age but also hypertension and low levels of TSH and 25-hydroxy vitamin D levels could significantly lead to clinical severity of SARS-CoV-2 infection.

Evidence for an association of prenatal exposure to particulate matter with clinical severity of Autism Spectrum Disorder.

Early-life exposure to air pollutants, including ozone (O3), particulate matter (PM2.5 or PM10, depending on diameter of particles), nitrogen dioxide (NO2) and sulfur dioxide (SO2) has been suggested to contribute to the etiology of Autism Spectrum Disorder (ASD). In this study, we used air quality monitoring data to examine whether mothers of children with ASD were exposed to high levels of air pollutants during critical periods of pregnancy, and if higher exposure levels may lead to a higher clinical severity in their offspring. We used public data from the Portuguese Environment Agency to estimate exposure to these pollutants during the first, second and third trimesters of pregnancy, full pregnancy and first year of life of the child, for 217 subjects with ASD born between 2003 and 2016. These subjects were stratified in two subgroups according to clinical severity, as defined by the Autism Diagnostic Observational Schedule (ADOS). For all time periods, the average levels of PM2.5, PM10 and NO2 to which the subjects were exposed were within the admissible levels defined by the European Union. However, a fraction of these subjects showed exposure to levels of PM2.5 and PM10 above the admissible threshold. A higher clinical severity was associated with higher exposure to PM2.5 (p = 0.001), NO2 (p = 0.011) and PM10 (p = 0.041) during the first trimester of pregnancy, when compared with milder clinical severity. After logistic regression, associations with higher clinical severity were identified for PM2.5 exposure during the first trimester (p = 0.002; OR = 1.14, 95%CI: 1.05-1.23) and full pregnancy (p = 0.04; OR = 1.07, 95%CI: 1.00-1.15) and for PM10 (p = 0.02; OR = 1.07, 95%CI: 1.01-1.14) exposure during the third trimester. Exposure to PM is known to elicit neuropathological mechanisms associated with ASD, including neuroinflammation, mitochondrial disruptions, oxidative stress and epigenetic changes. These results offer new insights on the impact of early-life exposure to PM in ASD clinical severity.

COVID-19 increased in Italian children in the autumn and winter 2021-2022 period when Omicron was the dominant variant.

AIM: We examined the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children during the autumn and winter season from 1 September 2021 to 30 January 2022 and compared it with the same period in 2020-2021. METHODS: This study was carried out int the paediatric emergency department (PED) of a tertiary Italian hospital. We compared the clinical and demographical features of all children who presented during the two study periods and tested positive for SARS-CoV-2. RESULTS: During the 2021-2022 autumn and winter season 5813 children presented to the PED, 19.0% were tested for SARS-CoV-2 and 133 (12.0%) of those tested positive. In 2020-2021, 2914 presented to the PED, 12.3% were tested, and 30 (8.3%) of those tested positive. There were no statistically significant differences in clinical severity during the two study periods, despite a higher percentage of neurological symptoms in 2020-2021. Of the SARS-CoV-2-positive cases, 29/133 (21.8%) were hospitalised during the 2021-2022 season and 10/30 (33.3%) during the previous one. Only 3/163 children required intensive care. CONCLUSION: The greater spread of SARS-CoV-2 was probably due to the greater transmissibility of the Omicron variant, but the symptoms were mild and only 3 children required intensive care.

Identifying venous clinical severity score thresholds for Clinical-Etiology-Anatomy-Pathophysiology classifications of venous edema and higher.

OBJECTIVE: Venous Clinical Severity Score (VCSS) is a widely used standard for assessing and grading the severity of chronic venous disease (CVD). Prior research highlighted its high validity in detecting and quantifying venous disease. However, there is little, if any, known about the precise thresholds at which VCSS discriminates important stages of deep venous disease. This study sought to elucidate the diagnostic accuracy, thresholds, and correlation at which VCSS detects salient CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classes in deep venous disease progression. METHODS: A registry of 840 patients who presented with chronic proximal venous outflow obstruction (PVOO) secondary to non-thrombotic iliac vein lesions from August 2011 to June 2021 was retrospectively analyzed. VCSS and CEAP classifications were used to evaluate preoperative symptoms. VCSS was compared to CEAP classes to determine the precise VCSS composite values at which the instrument was able to detect CEAP C3 and higher, C4 and higher, and C5 and higher. Receiver operative characteristic (ROC) curve and area under the curve (AUC) were used to evaluate VCSS for its ability to discriminate disease at these stages of CEAP classification. Spearman's rank coefficient was used to determine the correlation between CEAP VCSS composite as well as individual VCSS components (pain, varicose vein, edema, pigmentation, inflammation, induration, ulcer number, ulcer size, ulcer duration, compression). RESULTS: VCSS composite was able to detect venous edema (C3) and higher at a sensitivity of 68.9% and a specificity of 54.8% at an optimized threshold of 8.5 (AUC = 0.648; 95% C.I. = 0.575-0.721). To detect changes in skin and subcutaneous tissue from CVD (C4) and higher, an optimal threshold of 11.5 was found with a sensitivity of 51.7% and specificity of 76.5% (AUC = 0.694; 95% C.I. = 0.656-0.731). Healed venous ulcer (C4) and higher was detectable at an optimized threshold of 13.5 at a sensitivity of 67.7% and a specificity of 88.9% (AUC = 0.819; 95% C.I. = 0.766-0.873). The correlation between VCSS composites and CEAP was weak (ρ = 0.372; p < .001). Attributes of VCSS that reflect more severe venous disease correlated more closely with CEAP classes, namely pigmentation (ρ = 0.444; p < .001), inflammation (ρ = 0.348; p < .001), induration (ρ = 0.352; p < .001), number of active ulcers (ρ = 0.497; p < .001), active ulcer size (ρ = 0.485; p < .001), and ulcer duration (ρ = 0.497; p < .001). The correlation between CEAP class and the other four components of VCSS were not statistically significant. CONCLUSION: VCSS composite thresholds of 8.5, 11.5, and 13.5 are threshold values for detecting CEAP classification C3 and higher, C4 and higher, and C5 and higher, respectively. Consistent with prior work, VCSS appears to have a better ability to discriminate CVD at more severe CEAP classifications. In this registry, the correlation between VCSS and CEAP was found to be weak while components of VCSS that suggest more advanced disease exhibited the strongest correlation with CEAP.

Global Epidemiology of Human Infections With Variant Influenza Viruses, 1959-2021: A Descriptive Study.

BACKGROUND: Although human case numbers of variant influenza viruses have increased worldwide, the epidemiology of human cases and human-to-human transmissibility of different variant viruses remain uncertain. METHODS: We used descriptive statistics to summarize the epidemiologic characteristics of variant virus infections. The hospitalization rate, case-fatality, and hospitalization-fatality risks were used to assess disease severity. Transmissibility of variant viruses between humans was determined by the effective reproductive number (Re) and probability of infection following exposure to human cases. RESULTS: We identified 707 naturally infected cases of variant viruses from 1959 to 2021, and their spatiotemporal/demographic characteristics changed across subtypes. The clinical severity of cases of variant viruses was generally mild; patients older than 18 years with underlying conditions were associated with hospitalization. Of 69 clusters of human infections with variant viruses (median cluster size: 2), the upper limit of Re was 0.09 (H1N1v, H1N2v, and H3N2v: 0.20 vs 0.18 vs 0.05), whereas it was not significantly different from the pooled estimates for avian influenza A(H7N9) and A(H5N1) viruses (0.10). Moreover, contacts of H5N1 cases (15.7%) had a significantly higher probability of infection than contacts of individuals with H7N9 (4.2%) and variant virus infections (4.2%-7.2%). CONCLUSIONS: The epidemiology of cases of variant viruses varied across time periods, geographical regions, and subtypes during 1959-2021. The transmissibility of different variant viruses between humans remains limited. However, given the continuous evolution of viruses and the rapidly evolving epidemiology of cases of variant viruses, improving the surveillance systems for human variant virus infections is needed worldwide.