Prodromal Research Articles

Pediatric autoimmune encephalitis: a review

Autoimmune encephalitis has been an emerging disease in the pediatric age group for the last few years. It is of utmost importance to recognize the disease for the timely initiation of immunotherapy. The antibody-mediated encephalitis should be considered in the differentials apart from vasculitic, metabolic encephalopathy after ruling out bacterial, viral, tubercular, parasitic, and rickettsial causes. It can even coexist with herpes encephalitis in a quarter of the cases. The prodromal symptoms and progression to psychiatric, memory, speech disturbance, movement disorder, altered mental status, dysautonomia, and seizures within a span of a month characterize the disease. The approach to diagnosis involves various antibody testing in serum and cerebrospinal fluid along with brain imaging and electroencephalography. Early treatment with steroids, intravenous immunoglobulin, and plasmapheresis leads to better outcomes. A literature search was made using keywords in the Google Scholar and Pubmed databases before January 2024. The collected materials were reviewed for appropriate titles and content focusing on diagnosis and management. The article aims to provide a comprehensive review regarding the differential diagnosis and management of autoimmune encephalitis in children.

Clinicopathological correlation of cerebrospinal fluid alpha-synuclein seed amplification assay in a behavioral neurology autopsy cohort.

Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood. Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N=56). Diagnostic performance and clinicopathological correlations were examined. Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%). In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts. A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.

(PM-20) INFLUENCE OF RELIGION ON FEMALE SEXUALITY: REVIEW OF NARRATIVE LITERATURE

Abstract Introduction Sexuality influences thoughts, feelings, actions and interactions and therefore also affects our physical and mental health. It is a complex part of life, shaped by many factors, including religious ones. Religiosity can guide the sexual and loving experience, directly influencing the individual's sexual understanding, such as the use or not of condoms during sexual practice. Therefore, the present study aims to identify in the literature the influence of religion on female sexuality. Methodology A narrative review of the literature was carried out in the PubMed database. Articles published in English, Spanish, Portuguese and Arabic from January 2017 to December 2022 were included, such as: clinical trials, meta-analysis and systematic review, which exclusively addressed female sexuality and religion. Studies that addressed male sexuality were excluded. Results 74 articles were found, of which 28 were selected for reading according to the summary and 10 studies met the inclusion criteria and were analyzed. Most of the studies were on the Muslim, Islamic and Christian religions. Important points related to religious beliefs were identified, such as non-use of contraceptive methods, lack of knowledge about reproductive health, religious conflicts, marital status, virginity, sexual submission and menstrual taboos that negatively influence the quality of sexual life of religious women. . Studies with greater methodological rigor are needed to address this important issue. Conclusion This review showed that religion can have an adverse impact on the sexual health and quality of life of Islamic, Christian and Muslim women. Highlighting the need to conduct research in this area to understand and address this relationship. Financing No conflict.

Heterogeneity of clinical symptomatology in pediatric patients at clinical high risk for psychosis

ObjectiveWidespread use of diagnostic tools like the Structured Interview for Prodromal Symptoms (SIPS) has highlighted that youth at Clinical High Risk for Psychosis (CHR-P) present with heterogeneous symptomatology. This pilot study aims to highlight the range of clinical characteristics of CHR-P youth, investigate the role of the non-positive (negative, disorganization, and general) symptoms in risk assessment, and determine if specific profiles are associated with severe symptomatology.Methods38 participants aged 7–18 were administered the SIPS and designated as CHR-P. Descriptive statistics and mean difference t-tests were used to describe the range in prevalence and severity of SIPS symptoms and to identify symptoms associated with greater overall symptomatology.ResultsParticipants who had a greater number of positive symptoms also had significantly more negative, disorganization, and general symptoms. A number of SIPS symptoms were associated with greater number of positive symptoms.ConclusionCHR-P youth represent a heterogeneous group, presenting with a wide range in clinical presentation as reflected in both the number of SIPS symptoms and their severity. Though the severity and duration of positive SIPS symptoms determines the CHR-P classification, high ratings on several of the other SIPS negative, disorganization, and general items may be useful indicators of elevated symptomatology.

Alterations of Peripheral Lymphocyte Subsets in Isolated Rapid Eye Movement Sleep Behavior Disorder.

Adaptive immune dysfunction may play a crucial role in Parkinson's disease (PD) development. Isolated rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of synucleinopathies, including PD. Elucidating the peripheral adaptive immune system is crucial in iRBD, but current knowledge remains limited. This study aimed to characterize peripheral lymphocyte profiles in iRBD patients compared with healthy control subjects (HCs). This cross-sectional study recruited polysomnography-confirmed iRBD patients and age- and sex-matched HCs. Venous blood was collected from each participant. Flow cytometry was used to evaluate surface markers and intracellular cytokine production in peripheral blood mononuclear cells. Forty-four iRBD patients and 36 HCs were included. Compared with HCs, patients with iRBD exhibited significant decreases in absolute counts of total lymphocytes and CD3+ T cells. In terms of T cell subsets, iRBD patients showed higher frequencies and counts of proinflammatory T helper 1 cells and INF-γ+ CD8+ T cells, along with lower frequencies and counts of anti-inflammatory T helper 2 cells. A significant increase in the frequency of central memory T cells in CD8+ T cells was also observed in iRBD. Regarding B cells, iRBD patients demonstrated reduced frequencies and counts of double-negative memory B cells compared with control subjects. This study demonstrated alterations in the peripheral adaptive immune system in iRBD, specifically in CD4+ and INF-γ+ CD8+ T cell subsets. An overall shift toward a proinflammatory state of adaptive immunity was already evident in iRBD. These observations might provide insights into the optimal timing for initiating immune interventions in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Opportunities and Pitfalls of REM Sleep Behavior Disorder and Olfactory Dysfunction as Early Markers in Parkinson's Disease.

During its pre-motor stage, Parkinson's disease (PD) presents itself with a multitude of non-motor symptoms with different degrees of specificity and sensitivity. The most important among them are REM sleep behavior disorder (RBD) and olfactory dysfunction. RBD is a parasomnia characterized by the loss of REM sleep muscle atonia and dream-enacting behaviors. Olfactory dysfunction in individuals with prodromal PD is usually described as hyposmia (reduced sense of smell) or anosmia (complete loss of olfactory function). These symptoms can precede the full expression of motor symptoms by decades. A close comprehension of these symptoms and the underlying mechanisms may enable early screening as well as interventions to improve patients' quality of life. Therefore, these symptoms have unmatched potential for identifying PD patients in prodromal stages, not only allowing early diagnosis but potentially opening a window for early, possibly disease-modifying intervention. However, they come with certain challenges. This review addresses some of the key opportunities and pitfalls of both RBD and olfactory dysfunction as early markers of PD.

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.

Nocardia cyriacigeorgica Elicits Gut Disturbances in a Leaky Gut Model of Colitis, but Not the Harmful Cascade Leading to Gut-First Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with an unknown cause. Recent research has highlighted the importance of the gut in neuronal and immune maturation through the exchange of nutrients and cellular signals. This has led to the "gut-first PD" hypothesis, which aims to explain many of the sporadic cases and their prodromal intestinal symptoms, such as constipation and intestinal α-synuclein (aSyn) aggregation. The link between mitochondrial dysfunction and aSyn deposition is central to PD pathophysiology, since they can also trigger pro-inflammatory signals associated with aSyn deposition, potentially contributing to the onset of PD. As mitochondria are derived from ancestral alpha-proteobacteria, other bacteria may specifically target this organelle. We sought to use Nocardia cyriacigeorgica, a bacterium previously associated with parkinsonism, and dextran sulfate sodium (DSS) as pro-inflammatory modulators to gain further insight into the onset of PD. This study indicates that aSyn aggregation plus mitochondrial dysfunction without intestinal barrier leakage are not sufficient to trigger gut-first PD.

Altered resting-state functional connectivity and dynamic network properties in cognitive impairment: an independent component and dominant-coactivation pattern analyses study.

Cognitive impairment (CI) due to Alzheimer's disease (AD) encompasses a decline in cognitive abilities and can significantly impact an individual's quality of life. Early detection and intervention are crucial in managing CI, both in the preclinical and prodromal stages of AD prior to dementia. In this preliminary study, we investigated differences in resting-state functional connectivity and dynamic network properties between 23 individual with CI due to AD based on clinical assessment and 15 healthy controls (HC) using Independent Component Analysis (ICA) and Dominant-Coactivation Pattern (d-CAP) analysis. The cognitive status of the two groups was also compared, and correlations between cognitive scores and d-CAP switching probability were examined. Results showed comparable numbers of d-CAPs in the Default Mode Network (DMN), Executive Control Network (ECN), and Frontoparietal Network (FPN) between HC and CI groups. However, the Visual Network (VN) exhibited fewer d-CAPs in the CI group, suggesting altered dynamic properties of this network for the CI group. Additionally, ICA revealed significant connectivity differences for all networks. Spatial maps and effect size analyses indicated increased coactivation and more synchronized activity within the DMN in HC compared to CI. Furthermore, reduced switching probabilities were observed for the CI group in DMN, VN, and FPN networks, indicating less dynamic and flexible functional interactions. The findings highlight altered connectivity patterns within the DMN, VN, ECN, and FPN, suggesting the involvement of multiple functional networks in CI. Understanding these brain processes may contribute to developing targeted diagnostic and therapeutic strategies for CI due to AD.

Mitochondrial DNA deletions in the cerebrospinal fluid of patients with idiopathic REM sleep behaviour disorder

Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) represents the prodromal stage of Lewy body disorders (Parkinson's disease (PD) and dementia with Lewy bodies (DLB)) which are linked to variations in circulating cell-free mitochondrial DNA (cf-mtDNA). Here, we assessed whether altered cf-mtDNA release and integrity are already present in IRBD. We used multiplex digital PCR (dPCR) to quantify cf-mtDNA copies and deletion ratio in cerebrospinal fluid (CSF) and serum in a cohort of 71 participants, including 1) 17 patients with IRBD who remained disease-free (non-converters), 2) 34 patients initially diagnosed with IRBD who later developed either PD or DLB (converters), and 3) 20 age-matched controls without IRBD or Parkinsonism. In addition, we investigated whether CD9-positive extracellular vesicles (CD9-EVs) from CSF and serum samples contained cf-mtDNA. Patients with IRBD, both converters and non-converters, exhibited more cf-mtDNA with deletions in the CSF than controls. This finding was confirmed in CD9-EVs. The high levels of deleted cf-mtDNA in CSF corresponded to a significant decrease in cf-mtDNA copies in CD9-EVs in both IRBD non-converters and converters. Conversely, a significant increase in cf-mtDNA copies was found in serum and CD9-EVs from the serum of patients with IRBD who later converted to a Lewy body disorder. Alterations in cf-mtDNA copy number and deletion ratio known to occur in Lewy body disorders are already present in IRBD and are not a consequence of Lewy body disease conversion. This suggests that mtDNA dysfunction is a primary molecular mechanism of the pathophysiological cascade that precedes the full clinical motor and cognitive manifestation of Lewy body disorders. Funded by Michael J. Fox Foundation research grant MJFF-001111. Funded by MICIU/AEI/10.13039/501100011033 "ERDF A way of making Europe", grants PID2020-115091RB-I00 (RT) and PID2022-143279OB-I00 (ACo). Funded by Instituto de Salud Carlos III and European Union NextGenerationEU/PRTR, grant PMP22/00100 (RT and ACo). Funded by AGAUR/Generalitat de Catalunya, grant SGR00490 (RT and ACo). MP has an FPI fellowship, PRE2018-083297, funded by MICIU/AEI/10.13039/501100011033 "ESF Investing in your future".

CT-Measured Angulation Between the Frontal Bone and Bony Nasolacrimal Duct: Variations in Obstructed and Healthy Lacrimal Ducts

ABSTRACT Purpose The aim of this study was to analyze the characteristics of CT-measured intersection angle (FB-BNLD) between the frontal bone and bony nasolacrimal duct and to provide suggestions for treating primary acquired nasolacrimal duct obstruction (PANDO) patients in West China. Methods Three hundred and nine participants’ CT were, respectively, evaluated with RadiAnt DICOM Viewer. We defined the FB-BNLD angle >0° as the anterior type and the FB-BNLD angle ≤0° as the posterior type. Results The mean FB-BNLD was −2.52° (95% CI, −3.16° to −1.88°) across all participants, of whom 37.2% were of the anterior type and 62.8% of the posterior type. Approximately 65.0% of the female patients had a posterior FB-BNLD type, and 54.2% of the male patients had an anterior FB-BNLD type (p = .002). Posterior FB-BNLD was the dominant type in the PANDO and control groups (p = .011), and the angle of FB-BNLD was statistically different in both groups (PANDO group, −2.54° to −0.71°; control group, −4.42° to −2.67°; p < .001). Among the male participants, the type of FB-BNLD differed between the two groups (p = .036), with differences in the angle of FB-BNLD (PANDO group, 0.59° to 5.13°; control group, −4.08° to 1.89°; p = .034). There was no difference in the type of FB-BNLD in female participants between the two groups (p = .051). Conclusion The present study revealed individual differences in the type of FB-BNLD, with anterior-type majority in males and posterior-type dominance in females. Evaluating the FB-BNLD type on CT can provide a fast method for knowing the nasolacrimal duct condition during planning for lacrimal manipulation.

Revealing the Unseen: Detecting Negative Symptoms in Students.

Background: The transnosographic nature of negative symptoms (NS) makes them fruitful for detecting psychiatric symptoms. The main objective of this study was to determine whether NS can be useful in screening for ultra-high risk of psychosis (UHR) or depressive symptoms in the no-help-seeking student population. The most prevalent NS and their relationship with cannabis use were also researched. Methods: From an online survey sent to students, 2128 filled out the Self-evaluation of Negative Symptoms (SNS), Prodromal Questionnaire 16 (PQ-16), Beck Depression Inventory (BDI), and Cannabis Abuse Screening Test (CAST). Results: 367 students (17.2%, 95% CI [15.6-18.9]) were considered to have UHR (PQ-16 distress score ≥ 9) and/or depression (BDI ≥ 16). The receiver operation characteristic curve showed that a threshold of 13 for the SNS score discriminated this subgroup of students with a sensitivity and specificity of 79.8% and 70.6%, respectively. The motivational dimension was overrepresented and linked to cannabis use. Conclusions: The early detection of NS in the no-help-seeking student population is relevant for detecting depressive and prodromal symptoms. This will enable early intervention to limit the progression to chronic mental disorders. The predominance of NS linked to the amotivational dimension was observed and related to cannabis use.

Survival throughout the annual cycle of first year Canada Jays in the context of sibling competition, expulsion, and adoption

Abstract For most birds that exhibit delayed dispersal (remaining on the natal territory rather than dispersing to seek a breeding opportunity), siblings appear free to stay or leave the natal area. However, in rare cases, delaying dispersal is determined via conflict among siblings, with the dominant individual remaining on the natal territory. We used radio-tracking to examine brood reduction, and subsequent juvenile survival, of first-year Canada Jays (Perisoreus canadensis) in Algonquin Provincial Park, Ontario, Canada. Soon after juveniles become nutritionally independent, intra-brood struggles lead to one “dominant juvenile” remaining on the natal territory after permanently expelling the subordinate siblings (“ejectees”). Males in above-average condition when nestlings were the most likely to become the dominant juveniles and females did so only when broods were all-female at the time of the expulsion. Dominant juveniles were much more likely to survive their first summer compared to ejectees (survival probabilities = 0.84 and 0.45, respectively), suggesting that ejectees are especially vulnerable to mortality risk in the critical interval between their expulsion from the natal territory and their settlement on a new territory. However, if ejectees lived to autumn, they had only a slightly lower probability of first-winter survival (0.73) than dominant juveniles (0.85). These results suggest that the survival advantage gained by dominant juveniles is greatest during the first summer after hatching, with a much smaller difference over the first winter after ejectees have settled on non-natal territories. Our work provides insight into potential evolutionary and ecological mechanisms driving social dominance hierarchies in wild birds.

Cognitive, Emotional, and Daily Functioning Domains Involved in Decision-Making among Patients with Mild Cognitive Impairment: A Systematic Review.

Mild cognitive impairment (MCI) is a transitional or prodromal stage of dementia in which autonomies are largely preserved (autonomies are not particularly affected). However, this condition may entail a depletion of decision-making (DM) abilities likely due to a gradual deterioration of the prefrontal cortex and subcortical brain areas underlying cognitive-emotional processing. Given the clinical implications of a decline in self-determination observed in some MCI sufferers, the present systematic review was aimed at investigating the literature addressing DM processes in patients with MCI, consistent with PRISMA guidelines. The six online databases inquired yielded 1689 research articles that were screened and then assessed based on eligibility and quality criteria. As a result, 41 studies were included and classified following the PICOS framework. Overall, patients with MCI who underwent neuropsychological assessment were found to be slightly or moderately impaired in DM abilities related to financial management, medical adherence, specific cognitive performances, risky conditions, and especially uncertain life circumstances. Comparative cross-sectional studies indicated not only mid-stage cognitive functioning in MCI but also borderline or deficit DM patterns evaluated through different tasks and procedures. Further research addressing MCI profiles suggested an association between explicit memory, executive functions, and DM performance. These findings highlight the diversity of MCI manifestations, in addition to the critical importance of DM features and correlates in patients' daily functioning. Due to a lack of consensus on both MCI and DM, this review paper sought to shed light on assessment and intervention strategies accounting for the interplay between emotion, motivation, and learning to foster DM in cognitively impaired individuals.

Observed Adverse Effects of Sinopharm COVID-19 Vaccine in Healthcare Workers

Abstract: Background: Covid-19 was first identified in Wuhan China in December 2019, and rapidly spread world over. Vaccine was always thought as first line defence against viral infections, and Covid was no exception. Although developed through different technologies, Pakistan got its share of Sinopharm from China and vaccination started in February 2021, with priority for Healthcare workers. There were lot of myths and hesitancy related with the adverse effects and urgency in approving these vaccines. Addressing adverse effects in post vaccinated population hence, became an important matter. Objective: Aim of this study was to observe the adverse effects of this vaccine in Pakistani population, to assess safety and develop confidence in Healthcare Workers. Materials and Methods: A cross-sectional Observation study was carried out in vaccinated Healthcare Professional through Non-probability purposive sampling over a period of one month. A team collected data directly, as well as on the telephone call. A Google form was also generated and sent. Information was collected and analysed on IBM-SPSS 23.0 Result: Majority of the participants were less than 55 years with female dominance. Among co-morbidities, hypertension was most common, followed by diabetes. In local and systemic adverse effects, pain and fatigue were most common, followed by muscle weakness, fever and headache respectively. These effects were also more common after first injection. Conclusion: Results favor that people should be more careful after the first dose as more adverse effects were felt after that. This vaccine has a good safety profile as no major adverse effects were noticed. It was also considered safe for patients with co-morbidities.

Prodromal symptoms of rheumatoid arthritis in a primary care database: variation by ethnicity and socioeconomic status.

To assess whether prodromal symptoms of rheumatoid arthritis (RA), as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between January 1st 2004 to May 1st 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI, and smoking status. White ethnicity and the highest socioeconomic quintile were comparators. In total, 70115 cases were eligible for inclusion, of which 66.4% female. Twenty-one symptoms were coded in > 0.1% of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (OR 1.71, 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82). There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data.

Persistent fever in acute hepatitis: think beyond acute viral hepatitis

Background Acute hepatitis due to various tropical infections can mimic the clinical picture of acute viral hepatitis(AVH), leading to increased morbidity and mortality. We aimed to identify clinical and laboratory parameters that could help to distinguish acute hepatitis due to tropical infections from AVH. Methods We retrospectively analyzed our database of 150 children (107 boys) with AVH and 50 children(34 boys)with acute hepatitis due to tropical infections between January 2013 and March 2023. Clinical features, investigations, complications and outcomes were compared. Results Hepatitis A (75%) was the commonest etiology of AVH while enteric fever (34%), dengue (26%), scrub typhus (20%) and leptospirosis (16%) constituted the majority of tropical infections. Persistent fever and skin rashes were found in 88% and 16% of patients respectively in the tropical infection group and none in the AVH group (p < 0.001). On univariate analysis, prodromal symptoms, clinically detectable jaundice, cholestatic pattern, total and direct bilirubin and liver enzymes were significantly higher in AVH while headache, myalgia, leukopoenia, thrombocytopenia, hyponatremia were significantly higher in tropical infections group (all p < 0.05). Multivariate analysis identified thrombocytopenia (Odds ratio [OR] 4.237) as an independent positive predictive factor and markedly elevated total bilirubin (OR 0.575), direct bilirubin (OR 0.498), aspartate aminotransferase (OR 0.841) and alanine aminotransferase (OR 0.863) as independent negative predictive factors for acute hepatitis due to tropical infections. Conclusion High index of suspicion for tropical infections is warranted in patients with persistent fever after the onset of jaundice, especially in the presence of skin rash and thrombocytopenia. SUMMARY Acute viral hepatitis and acute hepatitis due to tropical infections can have similar clinical and biochemical parameters. Milder degree of jaundice, lower elevation of serum transaminases and thrombocytopenia can be useful predictors for acute hepatitis due to tropical infections.

Exploring the potential of fully automated LUMIPULSE G plasma assays for detecting Alzheimer’s disease pathology

BackgroundLUMIPULSE G-automated immunoassays represent a widely used method for the quantification of Alzheimer’s disease (AD) biomarkers in the cerebrospinal fluid (CSF). Less invasive blood-based markers confer a promising tool for AD diagnosis at prodromal stages (mild cognitive impairment (MCI)). Highly sensitive assays for the quantification of amyloid-beta (Aβ) and phosphorylated Tau-181 (p-Tau181) in the blood are showing promising results. In this study, we evaluated the clinical performance of the recently available fully automated LUMIPULSE plasma marker assays for detecting brain AD pathology and for predicting progression from MCI to AD dementia stage.MethodsA retrospective exploratory cohort of 138 individuals (22 neurological controls [NC], 72 MCI, and 44 AD dementia patients) was included. Data regarding baseline CSF concentrations of Aβ42, Aβ40, t-Tau, and p-Tau181 was available and used to establish the presence of AD brain pathology. Baseline Aβ42, Aβ40, and p-Tau181 concentrations were determined in stored plasma samples using high-throughput fully automated LUMIPULSE assays. Progression from MCI to AD dementia was evaluated during follow-up (mean 6.4 ± 2.5 years). Moreover, a prospective validation cohort of 72 individuals with memory complaints underwent AD biomarker quantification, closely mirroring typical clinical practice. This cohort aimed to confirm the study’s main findings.ResultsIn the exploratory cohort, correlations between CSF and plasma were moderate for p-Tau181 (ρ = 0.61, p < 0.001) and weak for Aβ42/Aβ40 ratio (ρ = 0.39, p < 0.001). Plasma p-Tau181 and p-Tau181/Aβ42 concentrations were significantly increased while Aβ42/Aβ40 was significantly decreased (p < 0.001) in patients with AD dementia and prodromal AD, as well as in individuals with CSF abnormal amyloid concentrations (A +). Plasma p-Tau181 showed a robust performance in differentiating patients clinically diagnosed as AD (AUC = 0.89; 95% CI 0.83–0.94); A + vs. A − (AUC = 0.84, 95% CI 0.77–0.91) and also in predicting conversion to AD dementia in MCI patients (AUC = 0.89, 95% CI 0.81–0.96). When tested in the validation cohort, plasma p-Tau181 displayed 83.3% of the overall percentage of agreement according to amyloid status.ConclusionsOur results show that the measurement of p-Tau181 in plasma has great potential as a non-invasive prognostic screening tool for implementation in a clinical setting.

Acute prevention of aheart attack : Early identification of prodromal symptoms as the Rosetta Stone in decoding the heart attack problem.

Chest discomfort before severe chest pain represents amarker of clinical ischemia and indicates live myocardium in jeopardy and often precedes cardiac arrest or acute myocardial infarction (MI). The intermittent or "stuttering" symptoms that precede MI are referred to as "prodromal symptoms." These symptoms have been shown to correlate with cyclic ST changes and repeated episodes of spontaneous reperfusion and occlusion, occurring during aperiod of hours or days before the acute ischemia proceeds to death or heart damage. These symptoms of premonitory angina have been associated with improved outcomes due to ischemic pre-conditioning or opening of collateral vascular channels around the area of ischemia. Acute prevention of an MI through recognition of prodromal symptoms represents an opportunity to significantly reduce heart attack deaths. The Early Heart Attack Care (EHAC) program puts emphasis on prodromal symptom recognition and allows for ashift in time backward to prevent the ischemic process from proceeding to MI. This strategy has been shown to detect the 15% of patients with ischemia in the low-probability group and to reduce inappropriate admissions to hospital as well as to reduce the number of patients with missed MI being sent home from the emergency department.

Immune Checkpoint Inhibition in Pediatric Oncology Patients: A Single-Institution Experience

Immunotherapy has emerged as a promising treatment approach in oncology, as it is specifically designed to boost the strength and accuracy of the immune system, allowing it to target tumor cells but spare non-tumor tissue. This treatment not only demonstrates potential for improved clinical outcomes but may also be associated with fewer adverse effects compared to traditional therapies. Despite its early success, the application of immunotherapy has largely been limited to adult cancer patients, with slow adoption noted in the treatment of pediatric cancer patients. Our objective is to demonstrate a single institution’s experience with immunotherapy in pediatric cancer patients and to discuss the use of these treatment modalities in this unique patient population. We performed a retrospective chart review and identified patients who received immune checkpoint inhibitors (ICIs) and/or underwent immunohistochemistry (IHC) testing for programmed death ligand 1 (PD-L1), quantification of tumor mutational burden (TMB), and classification of microsatellite instability (MSI) status. In total, we identified seven pediatric cancer patients who received therapy with ICIs. Four of these patients demonstrated positive PD-L1 expression, high TMB, and/or MSI-high status. These patients were treated with nivolumab alone or in combination with ipilimumab or brentuximab. The diagnoses included: multifocal epithelioid and spindle cell hemangioma (n = 1); metastatic melanoma (n = 2); histiocytic sarcoma (n = 1); rectal adenocarcinoma in the setting of constitutional mismatch repair deficiency syndrome (CMMRD) (n = 1); and Hodgkin lymphoma (n = 2). The patients received between four and nineteen cycles of immunotherapy. Immunotherapy-related adverse events included: mild allergic reaction; prodromal symptoms; anemia; neutropenia; transaminitis; endocrinopathies; and self-limiting neuritis. Of the seven patients, three are still being treated with immunotherapy (the patients with rectal adenocarcinoma, metastatic melanoma, and multifocal epithelioid and spindle cell hemangioma) with positive treatment responses observed on imaging, one is being treated with other modalities (the patient with Hodgkin lymphoma), two have achieved remission (the patients with metastatic melanoma and Hodgkin lymphoma), and one has relapsed (the patient with histiocytic sarcoma). The three patients who completed their immunotherapy regimens have been followed for 1 month, 4 months, and 10 months, respectively. This report of a single-institution experience with immunotherapy in pediatric cancer patients highlights the positive impact immunotherapy can have, especially when utilized to treat relapsed/refractory malignancies, as tumor regression or stabilization of disease burden was achieved in six of the patients described (CR = 2; PR = 4). Further research is needed to accurately identify pediatric oncology patients who could benefit from immunotherapy.