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.

Association between Mid-Term Functionality and Clinical Severity in Patients Hospitalized for Pulmonary Embolism.

The aim of this study is to evaluate the relationship between clinical severity and functionality, occupational performance, and health-related quality of life in patients hospitalized with pulmonary embolism. Pulmonary embolism patients were grouped by clinical severity using the Pulmonary Embolism Severity Index. Those scoring ≥160 were in the high-severity group (HSG); those scoring < 160 in the low-moderate group (LMSG). The main variables were functionality assessed by the World Health Organization Disability Assessment Schedule (WHODAS), self-perception of occupational performance assessed by the Canadian Occupational Performance Measure (COPM), pain and fatigue assessed by a Visual Analogue Scale (VAS), and health-related quality of life assessed by the EuroQol-5Dimensions (EQ-5D). Patients were evaluated at hospital admission and at 1-month and 3-month follow-up. At admission, there were significant differences between groups in the WHODAS and health-related quality of life in favor of the LMSG. At 1-month and at 3-month follow-up, there were significant differences between the LMSG and HSG in WHODAS, COMP, NRS pain, fatigue and EQ-5D scores in favor of the LMSG. An association exists between clinical severity and mid-term functionality, self-perception of occupational performance, pain, fatigue, and health-related quality of life in PE patients.

Co-Occurring Methylenetetrahydrofolate Reductase (MTHFR) rs1801133 and rs1801131 Genotypes as Associative Genetic Modifiers of Clinical Severity in Rett Syndrome.

AIM: Remethylation disorders such as 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency reduce the remethylation of homocysteine to methionine. The resulting hyperhomocysteinemia can lead to serious neurological consequences and multisystem toxicity. The role of MTHFR genotypes has not been investigated in patients with Rett Syndrome (RTT). In this study, we sought to assess the impact of co-occurring MTHFR genotypes on symptom profiles in RTT. METHOD: Using pharmacogenomic (PGx) testing, the MTHFR genetic polymorphisms rs1801133 (c.665C>T mutation) and rs1801131 (c.1286A>C mutation) were determined in 65 patients (18.7 years ± 12.1 [mean ± standard deviation]) with RTT as part of routine clinical care within the Centre for Interventional Paediatric Psychopharmacology (CIPP) Rett Centre, a National and Specialist Child and Adolescent Mental Health Service (CAMHS) in the UK. The clinical severity of patients was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI). RESULTS: The clinical severity symptom distribution varied between the homozygous and heterozygous MTHFR rs1801133 and rs1801131 genotypes. Those with the homozygous genotype had a narrower spread of severity scores across several domains (language and communication, ambulation, hand-use and eye contact clinical domains). Patients with the homozygous genotype had statistically significantly greater CGI-Severity scores than individuals with a non-homozygous MTHFR genotype (Z = -2.44, p = 0.015). When comparing the ratings of moderately impaired (4), markedly impaired (5), severely impaired (6) and extremely impaired (7), individuals with the homozygous MTHFR genotype were more impaired than those with the non-homozygous MTHFR genotype (Z = -2.06, p = 0.039). There was no statistically significant difference in the number of prescribed anti-epileptic drugs between the genotypes. CONCLUSIONS: Our findings show that in those with a pathogenic RTT genetic variant, co-occurring homozygotic MTHFR rs1801133 and rs1801131 polymorphisms may act as associative genetic modifiers of clinical severity in a subset of patients. Profiling of rs1801133 and rs1801131 in RTT may therefore be useful, especially for high-risk patients who may be at the most risk from symptom deterioration.

Differences Between RSV A and RSV B Subgroups and Implications for Pharmaceutical Preventive Measures.

INTRODUCTION: Understanding the differences between respiratory syncytial virus (RSV) subgroups A and B provides insights for the development of prevention strategies and public health interventions. We aimed to describe the structural differences of RSV subgroups, their epidemiology, and genomic diversity. The associated immune response and differences in clinical severity were also investigated. METHODS: A literature review from PubMed and Google Scholar (1985-2023) was performed and extended using snowballing from references in captured publications. RESULTS: RSV has two major antigenic subgroups, A and B, defined by the G glycoprotein. The RSV F fusion glycoprotein in the prefusion conformation is a major target of virus neutralizing antibodies and differs in surface exposed regions between RSV A and RSV B. The subgroups co-circulate annually, but there is considerable debate as to whether clinical severity is impacted by the subgroup of the infecting RSV strain. Large variations between the studies reporting RSV subgroup impact on clinical severity were observed. A tendency for higher disease severity may be attributed to RSV A but no consensus could be reached as to whether infection by one of the subgroup caused more severe outcomes. RSV genotype diversity decreased over the last two decades, and ON and BA have become the sole lineages detected for RSV A and RSV B, since 2014. No studies with data obtained after 2014 reported a difference in disease severity between the two subgroups. RSV F is relatively well conserved and highly similar between RSV A and B, but changes in the amino acid sequence have been observed. Some of these changes led to differences in F antigenic sites compared to reference F sequences (e.g., RSV/A Long strain), which are more pronounced in antigenic sites of the prefusion conformation of RSV B. Initial results from the second season after vaccination suggest specific RSV B efficacy wanes more rapidly than RSV A for RSV PreF-based monovalent vaccines. CONCLUSIONS: RSV A and RSV B both contribute substantially to the global RSV burden. Both RSV subgroups cause severe disease and none of the available evidence to date suggests any differences in clinical severity between the subgroups. Therefore, it is important to implement measures effective at preventing disease due to both RSV A and RSV B to ensure impactful public health interventions. Monitoring overtime will be needed to assess the impact of waning antibody levels on subgroup-specific efficacy.

Detectable Viremia at Presentation Is a Predictor of Disease Severity in Chikungunya.

Background Chikungunya is a mosquito-borne re-emerging disease that has caused a significant number of outbreaks recently in diverse geographic settings across the globe. It leads to severe debilitating illness in a significant proportion of persons who are infected. Measures to limit the impact produced by recurrent outbreaks of the disease are limited and there is an urgent clinical need for early identification of those predisposed to develop severe disease. A comprehensive understanding regarding the proportion of individuals predisposed to developing severe disease is lacking as its correlation with detectable viremia is hinted at by some studies. In this context, we hypothesized that detectable viremia reflected in the diagnostic RT-PCR assay could be significantly associated with the development of severe disease in Chikungunya among those diagnosed on the basis of seroconversion. Our study aims to confirm the same in relation to disease severity among the suspected patients of Chikungunya in the setting of a tertiary care center. Methods In a prospective observational study at a tertiary care center, a total number of 1021 Chikungunya suspects presenting within seven days of illness were screened with Chikungunya Virus IgM ELISA from 2021 to 2023. Those having positive IgM results were further tested with RT-PCR in a blinded manner. According to the information entered into the predesigned form and the hospital follow-up/discharge data, the cases where symptoms like fever and joint pain persisted beyond two weeks were classified as severe versus those resolving within two weeks as mild. The patients in each group were compared for their clinical symptoms and association with the disease severity with detectable viremia (RT-PCR positivity). Results We identified a total of 178 (17.4%) lab-confirmed Chikungunya IgM-positive cases amongst the recruited patients. Here a total of 31 (18.9%) cases could be classified as severe and 133 (74.7%) as mild illness, the remaining 14 patients were excluded from analysis due to insufficient clinical data. Severe illness was significantly higher in elderly individuals belonging to more than 60 years (p = 0.01). Viremia was detected in 16 (9%), those with detectable viremia had higher odds (OR = 4.1) of manifesting as severe disease. Among the severe cases, the proportion of cases with RT-PCR positivity (8, 25.8%) at presentation was significantly higher (P = 0.01) versus those who presented with mild disease (7, 5.5%). Conclusion Our study reveals a correlation between detectable viremia in Chikungunya virus (CHIKV) patients and an increased risk of manifesting into a severe disease, where severe cases exhibited a significantly higher proportion of viremia, indicated by RT-PCR positivity. This study hints at the presence of viremia, joint symptoms, and elderly age as potentially useful clinical predictors of disease outcomes, these may serve as indicators for closer monitoring among individuals seeking medical attention due to Chikungunya infection. However, we need to validate these findings in future longitudinal studies incorporating multiple, time-bound follow-up data on clinical outcomes, viral titers, and its long-term complications.

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.

Improved Tau PET SUVR Quantification in 4-Repeat Tau Phenotypes with [18F]PI-2620.

We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclear palsy or cortical basal syndrome. The study found that SUV ratios calculated using the identified reference regions (i.e., fusiform gyrus and crus-cerebellum) were significantly associated with symptom severity and disease duration. This establishes, for the first time to our knowledge, the suitability of [18F]PI-2620 for tracking disease progression in this 4-repeat disease population. This is an important step toward increased clinical utility, such as patient stratification and monitoring in disease-modifying treatment trials. Additionally, the applied methodology successfully optimized reference regions for automated detection of brain imaging tracers. This approach may also hold value for other brain imaging tracers.

[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.

Clinical Course, Laboratory Findings, and Prognosis of SARS-CoV-2 Infection in Infants up to 90 Days of Age: A Single-Center Experience and a Proposal for a Management Pathway.

AIM: To provide a comprehensive description of the clinical features, biochemical characteristics, and outcomes of infants up to 90 days old with COVID-19. Moreover, to assess the severity of the disease and propose an effective management pathway. METHODS: Retrospective single-center study spanning three years. Patient data includes age, sex, symptoms, comorbidities, blood and urine test results, cultures, admission, length of stay, therapies, intensive care unit admission, and mortality. RESULTS: A total of 274 patients were enrolled in the study, comprising 55% males. Among them, 60 patients (22%) were under the age of 29 days, while 214 (78%) fell within the 29 to 90 days age range. The overall incidence of SARS-CoV-2 infections was 0.28 per 10,000 Pediatric Emergency Department admissions. Blood inflammatory markers showed no significant abnormalities, and there were no recorded instances of positive blood cultures. Less than 1% of infants showed urinary tract infections with positive urine cultures, and 1.5% of patients had a concurrent RSV infection. Hospitalization rates were 83% for neonates and 67% for infants, with a median length of stay (LOS) of 48 h for both age groups. None of the patients required admission to the Pediatric or Neonatal Intensive Care Unit, and only one required High Flow Nasal Cannula (HFNC). No secondary serious bacterial infections were observed, and all hospitalized patients were discharged without short-term sequelae. No deaths were reported. DISCUSSION AND CONCLUSIONS: Infants with COVID-19 generally exhibit milder or asymptomatic forms of the disease, making home management a viable option in most cases. Blood tests, indicative of a mild inflammatory response, are recommended primarily for children showing symptoms of illness. Hospitalization precautions for infants without apparent illness or comorbidities are deemed unnecessary. Given the evolving nature of experiences with COVID-19 in infants, maintaining a high level of clinical suspicion remains imperative.

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.

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.

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.

Weight suppression at lowest weight as an indicator of eating disorder clinical severity: A retrospective cohort study.

OBJECTIVES: Weight suppression (WS) defines the difference between the highest weight in adulthood and the current weight. WS at lowest weight is the difference between the highest and the lowest ever weight. Weight rebound is the difference between the past lowest weight and current weight. The distinction in the capacities of WS, weight rebound, and WS at the lowest weight remains unclear regarding their efficacy in forecasting clinical endpoints. This study assessed the relationship between WS, WS at lowest weight and/or weight rebound and eating disorder (ED) clinical severity. METHODS: In this retrospective cohort study, adult participants were selected at the Outpatient Unit for multidisciplinary assessment of ED, Montpellier, France, between February 2012 and October 2014 and May 2017 and January 2020. ED clinical severity was evaluated using the Eating Disorder Examination Questionnaire (EDE-Q). RESULTS: The sample included 303 patients: 204 with anorexia nervosa (AN) and 99 with bulimia nervosa (BN). The EDE-Q total score was positively correlated with WS at lowest weight in patients with AN (Spearman's rho = 0.181, p = 0.015) and with BN (Spearman's rho = 0.377; p < 0.001). It was also positively correlated with weight rebound (Spearman's rho = 0.319; p = 0.003) in patients with BN. In the multivariate analysis, EDE-Q total score was associated with WS at lowest weight only in patients with BN (ß = 0.265; p = 0.03). CONCLUSION: WS at lowest weight seems to be a good measure of ED clinical severity. More research is needed for better understanding WS at lowest weight in assessment and treatment of patients with ED.

Specific-cytokine associations with outcomes in knee osteoarthritis subgroups: breaking down disease heterogeneity with phenotyping.

BACKGROUND: Despite existing extensive literature, a comprehensive and clinically relevant classification system for osteoarthritis (OA) has yet to be established. In this study, we aimed to further characterize four knee OA (KOA) inflammatory phenotypes (KOIP) recently proposed by our group, by identifying the inflammatory factors associated with KOA severity and progression in a phenotype-specific manner. METHODS: We performed an analysis within each of the previously defined four KOIP groups, to assess the association between KOA severity and progression and a panel of 13 cytokines evaluated in the plasma and synovial fluid of our cohort's patients. The cohort included 168 symptomatic female KOA patients with persistent joint effusion. RESULTS: Overall, our analyses showed that associations with KOA outcomes were of higher magnitude within the KOIP groups than for the overall patient series (all p-values < 1.30e-16) and that several of the cytokines showed a KOIP-specific behaviour regarding their associations with KOA outcomes. CONCLUSION: Our study adds further evidence supporting KOA as a multifaceted syndrome composed of multiple phenotypes with differing pathophysiological pathways, providing an explanation for inconsistencies between previous studies focussed on the role of cytokines in OA and the lack of translational results to date. Our findings also highlight the potential clinical benefits of accurately phenotyping KOA patients, including improved patient stratification, tailored therapies, and the discovery of novel treatments.

Long-Acting Injectable Second-Generation Antipsychotics in Seriously Ill Patients with Schizophrenia: Doses, Plasma Levels, and Treatment Outcomes.

This research studies the dose-plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone three-month (PP3M) or aripiprazole one-month (ARIM). Participants were divided into standard-dose or high-dose groups. PLs were divided into "standard PL" and "high PL" (above the therapeutic reference range, TRR) groups. The dose/PL relationship, and severity, hospitalizations, tolerability, compliance, and their relationship with doses and PLs were evaluated. There was no clear linear relationship between ARIM or PP3M doses and the PLs achieved. In half of the subjects, standard doses reached PLs above the TRR. The improvements in clinical outcomes (decrease in clinical severity and relapses) were related to high PLs, without worse treatment tolerability or adherence. All participants remained in the study, regardless of dose or PL. Clinical severity and hospitalizations decreased significantly more in those patients with high PLs. Considering the non-linear dose-PL relationship of ARIM and PP3M in people with severe schizophrenia, PLs above the TRR are linked to better treatment outcomes, without worse tolerability. The need in a notable number of cases for high doses to reach those effective PLs is highlighted.

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.

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.

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.

In Vitro Activity of Quaternary Ammonium in Prototheca Isolated from Clinical Bovine Mastitis Identified by Mass Spectrometry and PCR Sequencing of the cytb Gene Marker.

The in vitro algaecide activity of quaternary ammonium (QA) against Prototheca isolated from bovine clinical mastitis was investigated, in which the clinical severity was scored, milk samples were subjected to microbiological culture, and algal species were identified by molecular typing. A total of 4275 milk clinical samples of different cows from ten large dairy farms were used. Forty-four (1%) samples of cows from three dairy farms yielded growth of Prototheca, of which 88.6% (39/44) were identified as Prototheca bovis and 11.3% (5/44) as Prototheca sp. by MALDI-TOF MS, whereas 100% of the isolates were identified as P. bovis using PCR sequencing of the cytb gene. Among cows for which clinical severity scoring was available, 78.8% (26/33) and 21.2% (7/33) had mild and moderate infections, respectively, whereas no animal showed severe clinical signs. The algaecide activity of QA in Prototheca was observed in low concentrations among all isolates, in 20.4% (9/44) at 35 ppm, 36.4% (16/44) at 17 ppm, and 43.2% (19/44) at an 8 ppm, in addition to activity on three reference Prototheca strains. Overall, the study highlights the predominance of P. bovis as the causative agent of algal mastitis in bovines. Prototheca induced abnormalities preponderantly in the milk and mammary gland tissue of cows, and to our knowledge, our study is the first to apply clinical severity scoring in protothecal mastitis. In addition, the study underlines the activity of QA in low concentrations against Prototheca, indicating its potential use as an antiseptic/disinfectant in milking facilities and dairy environments.