Clinical Disease Research Articles

Bipolar androgen therapy for treatment of metastatic castration‐resistant prostate cancer: A case series

AbstractIntroductionAdvanced prostate cancer treatment has improved with androgen receptor signaling inhibitors (ARPI), yet many patients develop metastatic castration‐resistant prostate cancer (mCRPC), characterized by sustained androgen receptor (AR) signaling. Bipolar androgen therapy (BAT) introduces supraphysiologic testosterone levels to inhibit tumor growth, offering novel treatment for mCRPC by exploiting AR‐dependent mechanisms.Case PresentationsCase 1: A 53‐year‐old man with mCRPC, post multiple systemic therapies, initiated BAT and pembrolizumab, achieving PSA reduction and improved quality of life before progression. The patient exhibited AR amplification, which may have contributed to favorable response to BAT.Case 2: A 73‐year‐old man with recurrent prostate cancer, stable on ADT and abiraterone, experienced PSA decline with BAT to an undetectable level, maintaining stability post‐therapy discontinuation.Case 3: A 73‐year‐old man with metastatic prostate cancer, initially resistant to enzalutamide, achieved clinical benefit and disease control with BAT, although he did not meet PSA response criteria, patient had remarkable response upon enzalutamide rechallenge.Case 4: A 90‐year‐old man with localized prostate cancer, refractory to multiple treatments, experienced symptom relief and PSA reduction with BAT before progression.ConclusionBAT represents a promising treatment strategy for mCRPC. This case series underscores BAT's potential to induce significant clinical and biochemical responses, resensitize tumors to ARPIs, and improve patients' quality of life. Despite eventual progression in some cases, BAT offers a period of disease control. Further research is needed to optimize patient selection and understand the molecular determinants of BAT responsiveness.

The expanding host range of lumpy skin disease virus in wild and domestic animals.

Clinical lumpy skin disease (LSD) predominantly affects cattle and, to lesser extent domestic water buffalos. Whilst earlier work focussed on the disease in Africa, the recent emergence of LSD virus (LSDV) as a major cause of disease in Asia has led to a widening range of susceptible hosts for the virus. This article lists the wild and domestic ungulates in which LSDV infection has been confirmed and considers the significance of the disease for these species in Asia.

The Incidence of Endometriosis, 2014–2022. An Analysis of Nationwide Claims Data From Physicians in Private Practice.

The epidemiological characterization of endometriosis, particularly with regard to its incidence, has been inadequate to date both in Germany and other countries. The goal of this study was to determine trends in the incidence of diagnosed endometriosis and changes in age structure at the time of first diagnosis over the period 2014-2022. Nationwide claims data from physicians in private practice, obtained according to relevant German law (§ 295 SGB V), were used to identify the population at risk for a first assured diagnosis of endometriosis (ICD-10-GM: N80) during each year of the study period, consisting of women and girls aged 10-52 who were insured by the statutory health insurance system and for whom at least two years of prior observation were possible. Patients were defined as incident if they were documented as having received a first confirmed diagnosis of endometriosis, according to the case definition, during the study year. The case definition comprised multiple options for validating the diagnosis. The incidence of diagnosed endometriosis rose over the period of the study from 2.8 per 1000 persons at risk in 2014 to 4.1 per 1000 in 2022, corresponding to a 44% relative increase. There was also a marked shift in age-specific incidence toward higher values at younger ages: the median age at diagnosis fell from 37 years (2014) to 34 (2022). This is the first study providing nationwide population-based data on the incidence of endometriosis in Germany. The observed rise in newly diagnosed cases is presumably mainly due to an increased awareness of endometriosis and to the growing recognition of the disease.

Calf immunization protocols with low-virulence isolates of Anaplasma marginale: Analysis of post-inoculation effects and protection against natural challenge

Bovine anaplasmosis is endemic and is of fundamental importance worldwide. Therefore, measures for controlling and preventing clinical diseases are warranted to ensure the reduction of associated economic losses. The objective of the present study was to assess the post-inoculation effects and protection conferred by three different protocols of inoculation of low-virulence live strains of Anaplasma marginale (UFMG1 and UFMG3) in field-challenged cattle. Sixty-eight Holstein calves with an average age of 17 days were randomly divided into four groups. The groups received two subcutaneous administrations spaced 40 days apart, at a dosage of 2 × 106 infected erythrocytes of the following A. marginale strains: G1 (UFMG1 + UFMG1); G2 (UFMG3 + UFMG3); G3 (UFMG1 + UFMG3); and G4 (control). Every two days, the animals were evaluated for rectal temperature, Packed Cell Volume (PCV), and blood smears. Blood samples were collected prior to inoculation, before the field challenge, and after the challenge period, nPCR and IFAT techniques were performed. There were no significant differences in rickettsemia levels, reduction in PCV, or antibody detection among the different inoculation strategies. Forty days after the second inoculation, 90 %, 84.6 %, and 90.9 % of the animals in G1, G2, and G3, respectively, tested positive using nPCR. After inoculation, the group G2, which received the UFMG3 inoculum, had a higher frequency of treatment (odds ratio of 6.7; 1.198-38.018 CI; p = 0.03), while groups G1 and G3 demonstrated similar treatment frequencies compared to the control. During the natural challenge phase, 13.3 % of animals in group G1 required treatment (odds ratio of 0.108; 0.018-0.635 CI; p = 0.014) compared to 58.8 % of the control group. Considering the results collectively, the protocol using the UFMG1 strain (G1) stands out for its potential to be safe and induce some degree of immunization against A. marginale, reducing the incidence of clinical disease and the need for treatment during natural challenge.

Clinical application of flexible fiberoptic bronchoscopy in neonatal respiratory diseases

BackgroundRespiratory disease is a predominantly observed problem in neonates. Moreover, the application of flexible bronchoscopy in newborns is gradually increasing. This study aimed to investigate the value of bronchoscopy in neonates respiratory abnormalities and evaluate the safety of bronchoscopy application.MethodsClinical data and outcomes of 56 neonates who underwent flexible bronchoscopy were retrospectively analyzed. Correlations among indications for bronchoscopy, findings, and clinical diseases were assessed.ResultsA total of 56 neonates had a minimum weight of 1200 g at the time of bronchoscopy, while the minimum gestational age at birth was 26 + 1 weeks. A total of 22 cases (39.3%) had two or more clinical indications; the five most common indications were respiratory distress in 24 (42.9%), stridor in 22 (39.3%), pulmonary atelectasis in 10 (17.6%), feeding difficulty in 10 (17.6%), and difficult weaning from mechanical ventilation in 6 (10.7%) cases. A total of 13 types of abnormalities were detected in the respiratory tract. The most common abnormalities were laryngomalacia in 29 (59.2%), tracheobroncomalacia in 8 (16.3%), and vocal cord paralysis in 6 (12.2%) cases. Bronchoalveolar lavage was performed in 39 cases. Eight cases were diagnosed by bronchoscopy and then treated with surgery in the Thoracic Surgery/Otolaryngology Department; all of them were cured and discharged from the hospital after surgery. No serious complications, such as pneumothorax or shock, occurred in any of the children, of whom none died.ConclusionsFlexible bronchoscopy could play an important role in diagnosing and identifying respiratory disorders in neonates and be safely used with few serious complications.

Comparative early effectiveness across 14 PsA drugs and 5 classes of PsA treatment: 3-month results from the PRO-SPIRIT study

BackgroundThe psoriatic arthritis (PsA) Observational Study of Persistence of Treatment (PRO-SPIRIT) assesses effectiveness and persistence of real-world PsA treatments. Ixekizumab (IXE) is an interleukin (IL)-17A inhibitor (i) (IL-17Ai), approved for...

Clinical characteristics, diagnosis and short-term outcomes of COVID-19-associated acute myocarditis in China.

Acute myocarditis (AM) has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) infection. This study was conducted to present the clinical characteristics, disease courses and short-term prognoses of Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced AM in China, which has been unavailable so far. Data from 28 patients diagnosed with definite COVID-19-associated AM from 6 hospitals in China between 1 December 2022 and 30 June 2023 were collected and analysed. The diagnosis of AM was based on increased troponin level plus typical findings of AM on cardiac magnetic resonance (CMR) imaging and/or endomyocardial biopsy. Among 28 patients with definite COVID-19-related AM, median age was 37years (Q1-Q3: 22-52) and 53.6% were men. Twenty-three patients occurred within 2weeks of the onset of COVID-19 infection, 10 patients underwent endomyocardial biopsy and CMR was performed in all patients. Seven (25.0%) patients developed fulminant myocarditis that required inotropic agents or temporary mechanical circulatory support. Of the nine patients (32.1%) with left ventricular ejection fraction (LVEF) below 50% on admission, five had fully recovered LVEF and two demonstrated improvement but to levels below normal at discharge. The comparison of CMR parameters between the baseline and first follow-up showed that ECV was decreased at the first follow-up [28.95 (25.38, 32.55)% vs. 33.65 (31.58, 37.55)%, P=0.028), while other CMR parameters had no significant changes. Eighteen patients (64.3%) were prescribed with corticosteroids, and seven patients (25.0%) underwent temporary mechanical circulatory support. Only two patients died during hospitalization. The majority of COVID-19-associated AM occurred within 2weeks of Omicron variant infection. Fulminant myocarditis complicated by hemodynamic instability requiring temporary mechanical circulatory support was not uncommon. However, short-term outcome was generally good and most AM patients fully recovered.

Giant gallbladder cyst with acute cholecystitis: a case report

BackgroundGallbladder cysts are rare diseases with very few reported cases, and no clinical or histological definition has been established. Furthermore, cases of giant cysts outside the gallbladder wall are extremely rare. We report a rare case of giant gallbladder cyst with acute cholecystitis.Case presentationAn 85-year-old woman with appetite loss and right lower abdominal pain lasting 2 days presented to our hospital. At first, the patient’s abdominal pain was mild to moderate with no fever. Blood tests revealed a white blood cell count of 10,950/mm3, and the C-reactive protein (CRP) level was 14.35 mg/dl. A contrast-enhanced computed tomography (CT) scan of the abdomen revealed a grossly distended gallbladder (14.5 × 14.5 × 8.7 cm) with an incarcerated stone in the cystic duct. The patient was treated by percutaneous transhepatic gallbladder drainage (PTGBD) with 735 ml of drainage fluid. Oral contrast magnetic resonance cholangiopancreatography (MRCP) revealed that gallbladder swelling remained (14.0 × 6.5 cm) 3 days after PTGBD. We performed laparoscopic cholecystectomy 6 days after PTGBD. Because of the severe adhesion around the junction of the cystic and common bile ducts, we performed open cholecystectomy.The resected specimen was 14 × 11 cm in size and consisted of a gallbladder (6 × 7 cm) with a stone (2.4 × 1.8 cm) in the gallbladder and a large cystic lesion (18 × 18 cm) outside the gallbladder wall. The cystic lesion had a wall thickness of 6 to 12 mm and internal septal structures and contained hemorrhagic and necrotic tissue.Histological examination revealed that the specimens showed a mildly swollen gallbladder and a cystic lesion on the outside of the gallbladder wall, adjacent to the gallbladder wall, with wall thickening and inflammation. The cystic lesion suggested gallbladder duplication, gallbladder diverticulum or extension of the Rokitansky-Aschoff sinus (RAS). There was no malignancy. The patient’s postoperative course was uneventful, and she was discharged 5 days after the operation.ConclusionWe present a very rare case of giant gallbladder cyst with acute cholecystitis revealed by cholecystectomy.

Impact of Seton Use on Clinical, Patient-Reported, and Healthcare Resource Utilization Outcomes in Complex Crohn’s Perianal Fistulas: A Systematic Literature Review

Abstract Background Optimal treatment strategies for seton use in patients with Crohn’s perianal fistulas (CPF) remain elusive. This systematic literature review aimed to summarize clinical, patient-reported, and healthcare resource utilization (HCRU) outcomes associated with seton use for symptomatic relief and treatment of complex CPF. Methods Electronic databases (MEDLINE, Embase, EBM Reviews, EconLit) were searched. Titles, abstracts, and relevant full texts were screened by 2 reviewers for inclusion using prespecified PICOS-T criteria. Articles published in English between January 1, 1980 and September 6, 2021 were included; animal/in vitro studies and case reports with <5 patients were excluded. Outcomes of interest included rates of complete response/remission and fistula recurrence in patients receiving seton with/without infliximab or biologics. Data were summarized using descriptive statistics. Results Overall, 56 studies were included (full texts: n = 43; congress abstracts: n = 13). CPF and clinical outcome definitions were heterogeneous. Rates (range) of complete response/remission varied widely (seton: 13%-75%; seton + infliximab: 23%-100%; seton + biologics: 23%-59%) as did rates for fistula recurrence (seton: 4%-68%; seton + infliximab: 0%-50%; seton + biologics: 0%-17%). Rates of fistula-related reintervention, new fistula or abscess formation, and abscess recurrence were also varied; more consistency was observed regarding the use of patient-reported outcomes. Few studies reported outcomes from pediatric/adolescent patients or HCRU. Conclusions Optimal use of seton in patients with CPF remains unclear. International standardization of definitions for CPF and related clinical outcomes are required to permit data comparability and identify the most effective treatment strategies involving seton use in CPF.

Musculoskeletal Injury in Australian Infantry Personnel: A Cross-sectional Study to Understand Prevention Priorities.

Musculoskeletal injury patterns are under-investigated in the Royal Australian Infantry Corps. Subsequently, more evidence is needed to support injury prevention processes in this population. One difficulty in collecting injury information to monitor injury patterns within combat populations accurately is known injury concealment behaviors in such populations. This study aims to examine musculoskeletal injury epidemiology within Australian infantry battalions using a tailored approach to mitigate reporting avoidance. A cross-sectional study using an anonymous online survey captured musculoskeletal injury information directly from personnel serving within 2 Australian infantry battalions. The survey requested information on participants' injury frequency in the previous 12 months and the context of participants' most severe injury. Injury context was restricted to the most severe during the period to limit recall bias. The applied injury case definition encompassed all injuries that affected an individual's ability to perform in their role. A descriptive analysis of all data recorded across the 2 battalions was conducted. Subgroup statistical difference was assessed by examining the 95% CI overlap between groups. The Department of Defence and Veterans' Affairs Human Research Ethics Committee granted ethical approval for this study. Overall, 166 individuals self-reported at least 1 injury in the past 12 months, representing a period prevalence of 55.5% (95% CI, 49.8-61.0%). No statistically significant prevalence differences existed between employment type, age, or sex. Approximately a quarter of injured participants were medically reclassified because of their injury, impacting their deployment fitness (n = 40, 24.4%). The following results relate to the most severe injury personnel experienced. Most injuries were service-related (n = 152, 91.6%). Field activities (n = 64, 39.3%) and physical training (n = 59, 36.2%) were the most common injury-related activities. Running was the most reported injury mechanism (n = 35, 21.7%), followed by pack marching (n = 29, 18.9%) and fall, slip, or trip (n = 18, 11.2%). Musculoskeletal injuries are common in the Australian infantry and significantly burden the workforce. Physical training and field exercises are most associated with injury and represent opportunities for injury risk-mitigation strategies to support the overall deployability of personnel and the combat effectiveness of their battalions. Future research should more formally explore the injury risk factors related to these activities using more robust study designs to collect injury and exposure information more accurately and reliably. One study strength includes using military-specific international injury surveillance guidelines to inform the survey design, to collect the recommended injury information for effective surveillance, and to enable future research comparison. A second study strength was tailoring the survey to promote participatory engagement, providing a high completion rate. A challenge in conducting this research was coordinating participant recruitment and data collection during domestic operations. Such challenges reflect the reality of conducting research in the military.

Preliminary evidence supporting use of UK consensus definitions for necrotising otitis externa

BackgroundInfections of the external ear canal (EAC) exist as a spectrum of disease from severe otitis externa (SOE) to necrotising otitis externa (NOE), but distinguishing between these is challenging. The UK consensus case definition (UKCCD) was established in 2022, but had not yet been assessed in clinical practice. MethodsAll consecutive adult patients undergoing CT to investigate a diagnosis of possible NOE between November 2018 and October 2019 were prospectively included in the cohort. Clinical diagnosis at baseline and the end of 12 months follow-up were compared to the diagnosis defined by UKCCD. Results55 patients were included in the analysis. 27 % (15/55) had an initial clinical diagnosis of NOE, of which 47 % (7/15) did not have changes on CT consistent with NOE. Only 9 % (5/55) patients had an MRI scan performed within 7 days of the baseline CT. At the end of 12 months, 9 % (5/55) patients had a change in diagnosis to or from NOE. All cases diagnosed as NOE by UKCCD had a clinical diagnosis of ‘NOE’ at baseline, while no cases clinically diagnosed as NOE were mislabelled by UKCCD as ‘not NOE’. All cases that had a change of diagnosis in the 12-month period or had an initial CT with no changes consistent with NOE, were captured by the UKCCD category of ‘possible NOE’. Median duration of antibiotics of clinically defined NOE cases were 14 days of intravenous (IQR: 7.3–23.8), 28 days of oral (IQR: 21.0–40.3), and 49.5 days combined (IQR: 29.8–67.3). ConclusionUKCCD has excellent clinical concordance with clinical diagnosis. Further work is warranted to assess its utility for risk stratification of patients presenting with severe infections of the EAC in a larger cohort.

Characterization of Neutrophil Functional Responses to SARS-CoV-2 Infection in a Translational Feline Model for COVID-19.

There is a complex interplay between viral infection and host innate immune response regarding disease severity and outcomes. Neutrophil hyperactivation, including excessive release of neutrophil extracellular traps (NETs), is linked to exacerbated disease in acute COVID-19, notably in hospitalized patients. Delineating protective versus detrimental neutrophil responses is essential to developing targeted COVID-19 therapies and relies on high-quality translational animal models. In this study, we utilize a previously established feline model for COVID-19 to investigate neutrophil dysfunction in which experimentally infected cats develop clinical disease that mimics acute COVID-19. Specific pathogen-free cats were inoculated with SARS-CoV-2 (B.1.617.2; Delta variant) (n = 24) or vehicle (n = 6). Plasma, bronchoalveolar lavage fluid, and lung tissues were collected at various time points over 12 days post-inoculation. Systematic and temporal evaluation of the kinetics of neutrophil activation was conducted by measuring markers of activation including myeloperoxidase (MPO), neutrophil elastase (NE), and citrullinated histone H3 (citH3) in SARS-CoV-2-infected cats at 4 and 12 days post-inoculation (dpi) and compared to vehicle-inoculated controls. Cytokine profiling supported elevated innate inflammatory responses with specific upregulation of neutrophil activation and NET formation-related markers, namely IL-8, IL-18, CXCL1, and SDF-1, in infected cats. An increase in MPO-DNA complexes and cell-free dsDNA in infected cats compared to vehicle-inoculated was noted and supported by histopathologic severity in respiratory tissues. Immunofluorescence analyses further supported correlation of NET markers with tissue damage, especially 4 dpi. Differential gene expression analyses indicated an upregulation of genes associated with innate immune and neutrophil activation pathways. Transcripts involved in activation and NETosis pathways were upregulated by 4 dpi and downregulated by 12 dpi, suggesting peak activation of neutrophils and NET-associated markers in the early acute stages of infection. Correlation analyses conducted between NET-specific markers and clinical scores as well as histopathologic scores support association between neutrophil activation and disease severity during SARS-CoV-2 infection in this model. Overall, this study emphasizes the effect of neutrophil activation and NET release in SARS-CoV-2 infection in a feline model, prompting further investigation into therapeutic strategies aimed at mitigating excessive innate inflammatory responses in COVID-19.

Deciphering Developmental Epileptic Encephalopathies (DEE): Unravelling the Key Signs

<p><strong>Background:</strong> Epilepsy, a chronic neurological disorder affecting over 50 million people worldwide, is marked by recurrent seizures and loss of consciousness. It is categorized based on EEG features, etiologies, and comorbidities. Developmental Encephalopathy (DE) involves developmental delays and early-onset seizures without causing developmental regression. In contrast, Epileptic Encephalopathy (EE) features severe epilepsy syndromes where frequent seizures result in developmental delays or regression.</p><p><strong>Methods:</strong> This review explores the clinical definitions, epidemiology, and diagnostic criteria for DE, EE, and DEEs. It covers their etiologies, clinical features, diagnostic methods, and treatment strategies, including genetic, structural, metabolic, and immune-related factors.</p><p><strong>Results:</strong> DE features developmental impairment with epilepsy, while EE involves severe epilepsy causing cognitive and behavioral dysfunction. DEEs are marked by early-onset severe epilepsy and EEG abnormalities that worsen developmental impairments. Essential diagnostic tools include EEG, neuroimaging, and genetic testing. Effective management requires personalized interventions to control seizures and address cognitive deficits.</p><p><strong>Conclusion:</strong> DEEs are a complex epilepsy subset with major developmental and cognitive challenges. Early diagnosis and targeted treatments are crucial for improving outcomes. Ongoing research into DEEs' genetic and pathophysiological mechanisms is key to enhancing understanding and management.</p>

Preventive DAN- Using Deep Learning for Early Detection

Diabetes is a global health issue often linked with diabetic neuropathy, specifically diabetic autonomic neuropathy (DAN), which affects the autonomic nerve system, potentially impacting vital organs. DAN is underdiagnosed due to financial constraints, limited access to diagnostic tools, challenges in assessments,and asymptomatic stages. This research tackles these issues by using electronic health records (EHRS) and deep learning to detect DAN, Machine learning algorithms overcome traditional diagnostic barriers, achieving 85.5% accuracy with a Random Forest (RF) model. A deep learning approach using the (LSTM) model outperforms traditional methods, reaching 95.7% accuracy. This study advances healthcare technology by demonstrating the effectiveness of AI, particularly deep learning, in detecting DAN accurately and efficiently. It highlights the potential of EHRS in improving clinical diagnosis support, complication detection, and disease monitoring in diabetic patients. Key Words: Diabetic Autonomic Neuropathy (DAN), Electronic Health Records (EHRs), Long Short-Term Memory (LSTM), Clinical Diagnosis, Early Detection, Cardiac Autonomic Neuropathy (DCAN).

Longitudinal objective assessment of speech in Multiple Sclerosis

BackgroundRemote objective tests may supplement in-clinic examination to better inform treatment decisions. Previous cross-sectional studies presented objective speech metrics as potential markers of Multiple Sclerosis (MS) disease progression. ObjectiveTo examine the short-term stability and long-term sensitivity of speech metrics to MS progression. MethodsWe prospectively recorded speech from people with MS at baseline, six, twelve weeks, and at ten months or longer after baseline (1y+). Only people with a definite diagnosis of MS and without other potential causes of dysarthria were included. Speech tasks comprehended 1) a sustained vowel /a/, 2) saying the days of the week, 3) repeating the non-word pa-ta-ka multiple times as fast as possible, 4) reading the Grandfather Passage, and 5) telling a personal story. We selected speech metrics of interest according to their association with MS presence, correlation with general disability, and short-term metric stability in the absence of disease progression. Selected speech metrics were analysed for short- versus long-term changes in the whole MS cohort and in the clinically stable versus progression subgroups at 1y+. ResultsSixty-nine people with MS participated (76.8 % female, age mean 47.5 ± 11.1 SD, EDSS median 3.5, interquartile range 3.5). Twenty-six unique speech metrics satisfied the suitability criteria. On average, reading rate improved 3.5 % for all people with MS and 6.5 % for slow readers with MS from baseline to the six-week, driven by a reduction in pauses. At 1y+, participants showed a 3.1 % average reduction in vocalization time during the reading task, which was similar in the progression (n = 29) and non-progression (n = 40) groups and thus unrelated to disease progression. Both findings are in the opposite direction of what would be generally expected for deterioration in speech performance and might be attributable to familiarity and training effects. Other speech metrics showed either negligible change or a similar variability between short-term and long-term differences. ConclusionMost individual long-term changes were small and within short-term variability intervals, irrespective of clinical disease progression. Familiarity and practice effects might have blunted the measurement of change. The present lack of longitudinal sensitivity of speech in MS contradicts previous cross-sectional findings and requires further investigation.

Epidemiology and genetic characterization of influenza viruses circulating in Bhutan in 2022.

Influenza (Flu) causes considerable morbidity and mortality globally, and in Bhutan, Flu viruses are a leading cause of acute respiratory infection and cause outbreaks during Flu seasons. In this study, we aim to analyze the epidemiology and the genetic characterization of Flu viruses circulated in Bhutan in 2022. Respiratory specimens were collected from patients who meet the case definition for influenza-like illness (ILI) and severe acute respiratory infection (SARI) from sentinel sites. Specimens were tested for Flu and SARS-CoV-2 viruses by RT-PCR using the Multiplex Assay. Selected positive specimens were utilized for Flu viral genome sequencing by next-generation sequencing. Descriptive analysis was performed on patient demographics to see the proportion of Flu-associated ILI and SARI. All data were analyzed using Epi Info7 and QGIS 3.16 software. A weekly average of 16.2 ILI cases per 1000 outpatient visits and 18 SARI cases per 1000 admitted cases were reported in 2022. The median age among ILI was 12 years (IQR: 5-28) and SARI was 6.2 (IQR: 2.5-15) years. Flu A(H3N2) (70.2%) subtype was the most predominant circulating strain. Flu A(H1N1)pdm09 and Flu B viruses belonged to subclades that were mismatched to the vaccine strains recommended for the 2021-2022 season but matched the vaccine strain for the 2022-2023 season with vaccine efficacy 85.14% and 88.07% respectively. Flu A(H3N2) virus belonged to two subclades which differed from the vaccine strains recommended in both the 2021-2022 and 2022-2023 seasons with vaccine efficacy 68.28%. Flu virus positivity rates were substantially elevated during the Flu season in 2022 compared to 2021. Flu A(H3N2) subtype was the most predominant circulating strain in the country and globally. Genetic characterization of the Flu viruses in Bhutan showed a close relatedness of high vaccine efficacy with the vaccine strain that WHO recommended for the 2022-23 season.

Neuropsychiatric symptoms in cognitive decline and Alzheimer’s disease: biomarker discovery using plasma proteomics

Background and objectivesNeuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer’s disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of...

The Protective Effect of Astragalus Polysaccharide on Experimental Autoimmune Encephalomyelitis in Mice by Activating the AMPK/JAK/STAT3/Arginase-1 Signaling Pathway.

This study aimed to investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on autoimmune encephalomyelitis. C57BL/6 mice were randomly divided into the blank control group, EAE group, and APS intervention group (n=15/group). The Experimental Autoimmune Encephalomyelitis (EAE) mouse model was established by active immunization. The pathological changes in the spinal cord were evaluated by Hematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining. The number of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in the spleen tissues of mice in each group was determined by immunofluorescence staining. The expression of Arginase-1 in the spinal cord and spleen of each group was detected by immunofluorescence double staining. The TNF-α, IL-6, and Arginase-1 levels in the spleen were detected by ELISA assay. A western blot was used to detect the protein expression of the AMPK/JAK/STAT3/Arginase-1 signaling pathway. After the intervention of APS, the incidence of autoimmune encephalomyelitis in mice of the APS group was significantly lower than that in the EAE group, and the intervention of APS could significantly delay the onset time in the EAE mice, and the score of neurological function deficit in mice was significantly lower than that in EAE group (P < 0.05). APS intervention could reduce myelin loss and improve the inflammatory response of EAE mice. Moreover, it could induce the expression of CD11b+ GR-1 + bone MDSCs in the spleen and increase the expression of Arginase-1 in the spinal cord and spleen. This study further demonstrated that APS can protect EAE mice by activating the AMPK/JAK/STAT3/Arginase-1 signaling pathway. After the intervention of APS, myelin loss and inflammatory response of EAE mice were effectively controlled. APS promoted the secretion of Arginase-1 by activating MDSCs and inhibited CD4+T cells by activating AMPK/JAK/STAT3/Arginase-1 signaling pathway, thus improving the clinical symptoms and disease progression of EAE mice.

Prevalence of symptoms of post-COVID-19 condition (long COVID) in children hospitalized with COVID-19: A systematic review of observational studies.

This systematic review aimed to investigate the prevalence of symptoms of post-COVID-19 condition (long COVID), in children hospitalized with COVID-19. We searched PUBMED and EMBASE on 15 March, 2023, using search strategy: "long COVID" OR "post-COVID-19" OR "postacute COVID-19" OR "long-term COVID" OR "COVID-19 sequelae" OR "persistent COVID-19" OR "chronic COVID-19". We included observational studies (case-control, cross-sectional, cohort, or case series) that investigated symptoms of post-COVID-19 condition (long COVID) in children (<18 years) admitted with COVID-19. We used the WHO case definition of post-COVID-19 condition. Long COVID was defined as persistence of otherwise unexplained symptoms for at least three months after SARS-CoV-2 infection. We used the command "metaprop" to perform random-effects meta-analysis. Eleven studies involving 2279 patients were included. In the period between ≥3 months and <12 months after acute COVID-19, the most frequent symptom was exercise intolerance with a pooled prevalence of 29% (95% CI: 7%-57%, I2 = 95%), followed by nonspecific respiratory symptoms (12%, 95% CI: 0%-48%, I2 = 0%), psychological disorders (10%, 95% CI: 1%-25%, I2 = 97%), and nonspecific gastrointestinal symptoms (10%, 95% CI: 0%-37%, I2 = 99%). In the period ≥12 months after the initial infection, the pooled prevalence of post COVID symptoms was lower, with 6% (95% CI: 2%-10%, I2 = 83%) for exercise intolerance and 3% (95% CI: 0%-8%, I2 = 89%) for fatigue. In conclusion, symptoms of post-COVID condition (long COVID) in hospitalized children affect multiple organ systems, with higher prevalence in the period up to 12 months after the acute phase of COVID-19.

Real-world Effectiveness of Sarilumab in RA: Results from the Open-label, Prospective, Single-arm Observational PROFILE Study.

The 1-year PROspective sarilumab (preFILled syringe/pen) multinational, obsErvational (PROFILE) study evaluated the real-world effectiveness and safety of sarilumab in patients with moderate-to-severe rheumatoid arthritis (RA). Safety endpoints included adverse events (AEs) and lab abnormalities. Effectiveness endpoints included the ACR core set. The primary endpoint was the change from baseline in Clinical Disease Activity Index (CDAI). All statistics are descriptive and pvalues were nominal. In total, 595 patients were treated, of whom 223 (37.5%) received sarilumab monotherapy and 372 (62.5%) received combination therapy. Upon initiation of sarilumab, an improvement in the mean (SD) CDAI score was observed at week 24 [11.4 (10.3)] and was maintained through week 52 [10.0 (10.5)], resulting in a mean [SD] reduction of -14.9 (12.7) and -14.4 (12.9), respectively. There were consistent improvements in disease activity that were similar for patients on monotherapy vs. combination therapy. An increase in the proportion of patients achieving remission and low disease activity was reported. By week 52, both groups had improved physical function and quality of life. There were no new safety signals. The proportions of any patients reporting a treatment-emergent adverse event (TEAE) or serious treatment-emergent AE (SAE) was 66.2% and 5.9%, respectively, and were similar between both treatment groups. Overall, 15.6% of patients discontinued sarilumab treatment due to TEAEs. The most commonly reported TEAE of interest was neutropenia (14.1%). In this 1-year, observational real-world study, sarilumab therapy resulted in improved clinical outcomes. The safety profile was consistent with that observed in sarilumab randomized clinical trials. This study was entered on the German website (Paul Ehrlich Institute) on January 11, 2018, with NIS No.: 423.