Course Of Disease Research Articles

Analysis of morphological characteristics of laryngeal tuberculosis based on electronic laryngoscopy and image-enhanced endoscopy

Objective: To explore and summarize the morphological features of laryngeal tuberculosis under electronic laryngoscopy and image-enhanced endoscopy (i-scan). Methods: A retrospective analysis was conducted on the data of 31 patients diagnosed with laryngeal tuberculosis at the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to June 2024, encompassing the morphological features of electronic laryngoscopy and i-scan endoscopy, histopathological features, and supplementary clinical examination results. Descriptive statistical methods were employed for the analysis. Results: Thirty-one patients were diagnosed with laryngeal tuberculosis, including 25 males and 6 females, aged from 21 to 84 years old, with an average age of 57 years old, and the disease course was from 1 to 12 months with an average of 3 months. The clinical symptoms included hoarseness in 27 cases, foreign body sensation in the pharynx in 2 cases, and sore throat in 2 cases. Twenty-six cases involved a single site, including 24 cases of the vocal cords, 1 case of the ventricular bands, and 1 case of the epiglottis; 5 cases involved multiple sites, including 2 cases of the vocal cords and the interarytenoid area, 2 cases of the aryepiglottic fold and the epiglottis, and 1 case of the aryepiglottic fold, the ventricular bands and the epiglottis. Eighteen patients showed a single morphology type under electronic laryngoscopy, including 4 cases of the edematous exudative type, 5 cases of the ulcerative type, and 9 cases of the granulation hyperplasia type. Edema, ulcer, and granulation hyperplasia can coexist and transit between each other. A total of 13 cases presented with two or more morphological types, with the edematous exudative type, the ulcerative type, and the granulation hyperplasia type occurred 7, 9, and 10 times respectively. Twenty-two patients had active or chronic pulmonary tuberculosis, while 9 patients had normal lung imaging. The laryngeal tissue biopsy pathology of 21 patients was chronic granuloma, and 10 patients were chronic granuloma with caseous necrosis; among them, 19 cases completed the Ziel-Neelsen staining (7 cases were positive for acid-fast bacilli), and 3 cases completed the polymerase chain reaction (PCR) (All were positive). Twenty cases completed the T-cell assay for tuberculosis infection (19 cases were positive), 15 cases completed the sputum smear (6 cases were positive), 18 cases were tested for antinuclear antibody (6 cases were positive), and 14 cases completed the erythrocyte sedimentation rate (4 cases were positive). Six patients underwent i-scan examination. In cases of ulcerative laryngeal tuberculosis without granulation hyperplasia in the surrounding tissues, i-scan revealed an abundance of abundant slightly thickened and tortuous oblique and dendritic blood vessels around the ulcer. If the pseudomembrane in the deep ulcer was thick, the blood vessel shadow was not visible. In shallow ulcers, there were areas of deep congestion and scattered dot-shaped blood vessel shadowst with uneven distribution; in cases of laryngeal tuberculosis with coexistence of the edematous exudative type and the granuloma type, i-scan visualized laryngeal cord edema with white exudates on the surface. Beneath the laryngeal cord exudates, there were scattered dot-shaped and irregularly distorted linear blood vessel shadows with uneven distribution, and tortuous, oblique, and dendritic blood vessels were observed around the lesion. In granuloma-type laryngeal tuberculosis, i-scan demonstrated that the area of granulation hyperplasia around the ulcer focus was significantly congested, characterized by scattered thick dot-shaped blood vessel shadows and irregularly distorted linear blood vessel shadows. Conclusions: Laryngeal tuberculosis presents as the edematous exudative type, the ulcerative type, and the granulation hyperplasia type under electronic laryngoscopy, and these types can coexist and interact. i-scan endoscopy can reveal detailed microvascular morphology and other subtle morphological characteristics. The identification and summary of these morphological characteristics are beneficial for the early detection and diagnosis of laryngeal tuberculosis.

Low Surgery Rates in Early Crohn's Disease: Results from a Prospective Population-Based Inception Cohort-The Inflammatory Bowel Disease in South-Eastern Norway III Study.

The emergence of biologic therapy has coincided with a decline in surgery rates for Crohn's disease (CD). This study aims to describe the disease course, including intra-abdominal surgery rates, biologic therapy use, and variables associated with biologic therapy initiation in a cohort of newly diagnosed CD patients. The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study. From 2017 to 2019, newly diagnosed inflammatory bowel disease patients were included for prospective follow-up. The present study included CD patients ≥ 18 years. Clinical, endoscopic, and demographic data were collected at diagnosis and 1-year follow-up. Data were analyzed by using the Kaplan-Meier method and regression analyses. In total, 424 CD patients (median age 37.0 years (range 18-80), female 55.0%) were included. At diagnosis, 50.5% presented with ileal disease and 80.7% with inflammatory behavior. Within a 1-year follow-up, 39.6% of patients received their first biologic therapy and 5.2% required intra-abdominal surgery. Systemic steroid treatment, CRP ≥ 5.0mg dL-1, Harvey-Bradshaw Index score > 4, ileocolonic disease and penetrating disease behavior at diagnosis were independently associated with increased risk of initiation of biologic therapy, while age > 40 years was associated with decreased risk. A high proportion of patients had ileal disease and inflammatory behavior at diagnosis. Still, nearly 40% started biologic therapy within the 1-year follow-up, while only 5% required intra-abdominal surgery.

Anti-SRP myositis: a diagnostic and therapeutic challenge

Background. Anti-signal recognition protein (anti-SRP) myopathy is a rare idiopathic inflammatory myopathy in children. Herein, a 3-year-old patient with severe anti-SRP myopathy showing a rapidly progressive disease course is presented in order to increase the awareness of pediatricians about idiopathic inflammatory myopathies. Case Presentation. A previously healthy 3-year-old girl presented with progressive symmetrical proximal muscle weakness that caused difficulty in climbing stairs for two months prior to evaluation, and a marked elevation of the serum creatine kinase levels. A skeletal muscle biopsy revealed necrotic and regenerating processes, with mild inflammatory changes. Myositis-specific and associated autoantibodies tested by the immunoblot method were positive for anti-SRP. Pulse corticosteroid, intravenous immunoglobulin, and methotrexate were administered. However, muscle weakness progressed, respiratory distress and dysphagia developed. Rituximab was initiated. While on rituximab treatment, she was able to walk independently and muscle enzymes were within normal range at the 15th month of diagnosis. Conclusion. Early diagnosis of patients with anti-SRP myositis is important to control inflammation and prevent disease progression and complications. To our knowledge, our patient is the youngest case reported in the literature and was successfully treated with rituximab added to conventional therapy.

Does Epstein-Barr virus and intracellular Toll-like receptors affect the course of Hashimoto disease? Findings from studies on newly-diagnosed patients.

Epstein‑Barr virus (EBV) reactivation is increasingly recognized as a potential exacerbator of autoimmune diseases, including Hashimoto thyroiditis (HT). This study examined the association between EBV reactivation and intracellular Toll‑like receptor (TLR) expression in newly‑diagnosed, untreated HT patients. Its aim was to determine whether EBV reactivation and expression of specific TLRs (TLR3, TLR7, TLR8, and TLR9) contribute to the pathogenesis and progression of HT. The study involved a cohort was 54 newly‑diagnosed, untreated patients with HT and 20 healthy volunteers (HVs) matched for age and sex. Blood samples were collected to assess EBV viral load and intracellular expression levels of TLR3, TLR7, TLR8, and TLR9 using flow cytometry. The levels of specific anti‑EBV antibodies (eg, viral capsid A [VCA] immunoglobulin [Ig] M, VCA IgG, Epstein‑Barr nuclear antigen 1 [EBNA‑1] IgM, EBNA‑1 IgG) were measured to identify signs of EBV reactivation, while soluble TLRs (sTLR3, sTLR7, sTLR8, and sTLR9) were quantified in serum using enzyme‑linked immunosorbent assay. Notably, our HT patients were not euthyroid, as they exhibited significantly lower thyroid‑stimulating hormone levels and elevated free triiodothyronine and free thyroxine levels in comparison with the HVs. The study showed a significant increase in EBV reactivation among the HT patients, with 26 of 54 (48.1%) testing positive for EBV DNA, as compared with none of the HVs. The HT patients with reactivated EBV showed significantly higher intracellular expression of TLR3, TLR7, and TLR9, with TLR3+ cells constituting an average of 4.72% of CD4+ lymphocytes (vs 0.69% in the HVs), suggesting a potential synergistic effect. In addition, sTLR levels increased in the HT patients with reactivated EBV, suggesting a possible role of these receptors in potentiating autoimmune responses. These findings highlight the importance of considering both viral reactivation and TLR activity in the treatment of HT. Understanding the interplay between EBV and intracellular TLRs may lead to development of new therapeutic approaches to mitigate the impact of these factors on the disease progression. Further research is warranted to investigate the mechanisms underlying this interaction and its implications for treatment strategies.

Pain syndrome in panic attack clinical presentation

Introduction. In modern medicine, great attention has been paid to the study of patients with panic attacks (PAs) for a long time. One of the areas of scientifi c research is the study of the patients′ personality traits, as well as social, genetic and physiological factors causing the development of panic disorder. But peculiarities of pain syndrome in patients with PAs remain understudied. As a result, treatment and rehabilitation of patients with PAs remain insuffi ciently effective.The aim: to research the role of pain syndrome in the clinical presentation of panic attacks.Materials and methods. The studies involved 197 participants aged 38,65±10,91 including 41 men (20,8 %) and 156 women (79,2 %). They were divided into two groups based on the presence or the absence of PAs with the fi rst group representing 147 people with panic attacks and the second group — 50 people without panic attacks. In all patients, pain syndrome (headache, chest pain, neck pain, and pain in the lumbosacral region) was assessed according to a 10-point Visual Analogue Scale (VAS). To study the dependence of pain syndrome characteristics on the severity of the disease course, patients with PAs from the fi rst group were divided into 3 groups according to PA frequency in a four-week period: group of 31 people with infrequent PAs (less than four panic attacks), group of 48 people with mid-frequent PAs (at least four panic attacks), and a group of 68 people with frequent PAs (at least four panic attacks per week).Results. According to our research, pain syndrome of different localization and intensity is more common in patients with PAs than in those without PAs, and was detected in 93,2 % of patients with PAs. Patients with PAs more frequently reported multisite pain, differently from those without PAs predominantly presenting complaints of pain in one body region. The intensity of headache, chest or neck pain is signifi cantly higher in patients with PAs than in patients without PAs (р<0,05). In the majority of patients with PAs (75,9 %), pain syndrome preceded developing of PAs.Conclusion. Pain syndrome can serve as a predisposing factor for the development of panic attacks and be the reason for the aggravation of the disease course, which is why pain syndrome in patients with PAs should undoubtedly be corrected. Taking into consideration the fact that a medication burden on such patients is high, the correction should primarily be performed using non-drug treatment options, including osteopathic methods.

A biomathematical model of SARS-CoV-2 in Syrian hamsters

When infected with SARS-CoV-2, Syrian hamsters (Mesocricetus auratus) develop moderate disease severity presenting key features of human COVID-19. We here develop a biomathematical model of the disease course by translating known biological mechanisms of virus-host interactions and immune responses into ordinary differential equations. We explicitly describe the dynamics of virus population, affected alveolar epithelial cells, and involved relevant immune cells comprising for example CD4+ T cells, CD8+ T cells, macrophages, natural killer cells and B cells. We also describe the humoral response dynamics of neutralising antibodies and major regulatory cytokines including CCL8 and CXCL10. The model is developed and parametrized based on experimental data collected at days 2, 3, 5, and 14 post infection. Pulmonary cell composition and their transcriptional profiles were obtained by lung single-cell RNA (scRNA) sequencing analysis. Parametrization of the model resulted in a good agreement of model and data. The model can be used to predict, for example, the time course of the virus population, immune cell dynamics, antibody production and regeneration of alveolar cells for different therapy scenarios or after multiple-infection events. We aim to translate this model to the human situation in the future.

Important tool in our rare disease toolbox: hybrid retrospective-prospective natural history studies serve well as external comparators for rare disease studies

Natural history studies (NHS) can support regulatory decision-making at different stages of the drug product life cycle and are especially important in the context of rare diseases, which are associated with not only delayed or erroneous diagnoses but also a lack of approved treatments. Real-world evidence can fill knowledge gaps and support treatment decision-making, thereby benefiting affected patients. In this context, there are three important options for NHS design: retrospective, prospective, and cross-sectional. Each of these has been successfully used to support regulatory approval as external comparator arms (ECAs) for clinical studies, especially single-arm trials (SATs). While longitudinal data obtained from retrospective or prospective designs have been more commonly used and have been the focus of regulatory guidance documents, hybrid designs that combine retrospective and prospective data collection are particularly powerful for rare disease studies. This is due, in part, to the smaller number of patients impacted by each rare disease. In these settings, retrospective or prospective data collection alone may not be sufficient or fit-for-purpose for an external comparator. Rather, a strategic combination of all available data, regardless of timing, can deliver the right information of the desired quality and completeness to answer these important questions and support regulatory evidentiary needs. For instance, patients included in retrospective studies may differ from recently treated patients in terms of disease severity, disease variants, clinical management, or other important aspects of the disease that may impact patient outcomes. Further, retrospectively collected data may lack specific data elements required to achieve adequate comparison with the treated group in single-arm studies. In the context of prospective designs, the recruitment of sufficient new patients for prospective follow-up may not be feasible or may be prolonged due to the rarity of the disease. Further, the potential for premature truncation of patient follow-up may result in insufficient longitudinal data, or prospectively collected data alone may not provide insights into the disease course for specific groups of patients. In these situations, primary data collection in a prospective study may be supplemented with retrospectively collected data from chart reviews, registries, or electronic medical record databases, either for the same patients, in an ambispective design, or for a different set of patients. These hybrid designs allow for broader and more robust contextual information on the patient journey and the natural course of the disease to be obtained, which can improve the suitability of the data as an external comparator for SATs or studies that lack internal control in situations where a prospective design alone might not be sufficient. Because retrospective and prospective data, or any two data sources that are being combined, may differ in availability and quality, there are unique challenges alongside the strengths of these designs. In this paper, we discuss considerations for the design, analysis, and conduct of hybrid NHS intended as ECAs for single-arm studies in clinical development programs for rare diseases.

Lack of an association between spleen volume and risk of pneumococcal infection in cancer patients: a nested case-control study

BackgroundThe spleen is a key organ in preventing pneumococcal infection, especially in patients with immunocompromised condition such as those with cancer. Previous studies have shown that a small spleen volume in pneumococcal pneumonia patients is associated with severe disease course. However, it is unknown whether a small spleen increases risk of pneumococcal infection. We investigated the association between spleen volume and risk of pneumococcal infection.MethodsThis study was a retrospective cohort study using a nested case-control design and involved adult patients with malignancy who underwent chest and/or abdominal CT scans from January 1, 2008, to September 30, 2020, at a tertiary care center in Japan. Exclusion criteria comprised patients diagnosed with hepatic cirrhosis, leukemia, lymphoma, and/or post-splenectomy. From the cohort group that met all selection criteria (n = 22475), we identified all incident cases of pneumococcal infection (pneumococcal pneumonia and/or invasive pneumococcal diseases) and matched them with four controls by age, sex, and follow-up duration. Odds ratios (ORs) for the association between spleen volume and pneumococcal infection were estimated using conditional logistic regression models adjusted for body surface area, performance status, Charlson comorbidity index, and metastatic cancer.ResultsThe median spleen volume was 85.8 (interquartile range, 65.8–120.8) cm3. Over a median follow-up of 4.95 (interquartile range, 1.54–9.25) years, 60 patients were diagnosed with pneumococcal infection (20 with invasive pneumococcal disease and 40 with pneumonia without invasive pneumococcal disease) and matched with 240 controls. Spleen volume reduction (per 10 cm3) did not increase risk of pneumococcal infection in a crude analysis [OR 1.04 (95% CI 0.98–1.11)]. The outcome remained unchanged in the multivariable analysis (OR 1.01 [95% CI 0.95–1.08]).ConclusionsSmall spleen volume did not increase risk of pneumococcal infection in cancer patients.

Circulating tumor DNA dynamics and clinical outcome in metastatic colorectal cancer patients undergoing front-line chemotherapy.

we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT). 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA. 83 paired samples from 75 patients were available for analysis. 12 pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients that cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared to non-normalized patients [OS= 22.6 months (Log-rank p = 0.01) and PFS= 10.7 months (Log-rank p = 0.036) respectively]. In addition, higher response rate was observed in patients with ctDNA clearance (72.9%) compared to non-normalized cases (38.2%). Longitudinal sequencing of at least four timepoints in pts with a PFS>10 months showed emerging variants in 47.8% of cases; in all these patients the trajectory of these new "outlier" variants appeared in stark contrast with the clinical-radiological course of disease and the trend in other mutations. ctDNA clearance represents an early indicator of benefit from SACT in mCRC patients; serial tracking of multiple variants is warranted to improve specificity and to avoid misleading information due to the emergence of mutations of unknown clinical significance.

Translational Medicine in Alzheimer's Disease: The Journey of Donanemab From Discovery to Clinical Application

ABSTRACTSubstantial research has been conducted to identify an efficient treatment for Alzheimer's disease (AD). Existing treatments, including cholinesterase inhibitors and N‐methyl D‐aspartate (NMDA) receptor antagonists, do not reverse or slow the disease course but only treat its manifestations. This limitation has brought attention to the need for treatments that modify the amyloid‐beta (Aβ) and tau pathology of the disease. One recent advancement in AD treatment is donanemab, a monoclonal antibody intended to clear Aβ plaques in the brain. It targets pyroglutamyl(3)‐Aβ protein (3–42) to remove Aβ deposits and alter the disease course. This review explores the timeline of donanemab use from discovery to clinical use. The pharmacodynamics and pharmacokinetics of the drug are discussed along with typical and suboptimal preclinical and clinical trial results in terms of efficacy, safety, and tolerability. Thus, donanemab is more effective than donepezil and rivastigmine in removing plaques and improving cognition. At the same time, it is not devoid of safety concerns that are typical of the majority of amyloid‐targeted medicines. The control to end the treatment after plaque cleaning is a unique selling point for some patients, making it more attractive. The innovation and development of donanemab from research to clinical practice are a clear representation of the role of the field of translational medicine in the practical application of new knowledge in the treatment of AD.

Association of Initial Side of Brain Atrophy With Clinical Features and Disease Progression in Patients With GRN Frontotemporal Dementia.

Pathogenic variants in the GRN gene cause frontotemporal dementia (FTD-GRN) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD-GRN depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease. Retrospective examination of data from the prospective Genetic Frontotemporal Initiative (GENFI) cohort study that recruits individuals who carry or were at risk of carrying a pathogenic variant causing FTD. GENFI participants underwent a standardized clinical and neuropsychological assessment, MRI, and a blood sample test yearly. We generated an asymmetry index for brain MRI to characterize brain asymmetry in participants with or at risk of FTD-GRN. Depending on the side of the asymmetry, we classified symptomatic GRN patients as right-GRN or left-GRN and compared their clinical features and disease progression. We generated generalized additive models to study how the asymmetry index evolves in carriers and noncarriers and compare its models with others created with volumetric values and plasma neurofilament light chain. A total of 399 participants (mean age 49.7 years, 59% female) were included (63 symptomatic carriers, 177 presymptomatic carriers, and 159 noncarriers). Symptomatic carriers showed higher brain asymmetry (11.6) than noncarriers (1.0, p < 0.001) and presymptomatic carriers (1.0, p < 0.001), making it possible to classify most of them as right-GRN (n = 21) or left-GRN (n = 36). Patients with right-GRN showed more disease severity at baseline (β = 6.9, 95% CI 2.4-11.0, p = 0.003) but a lower deterioration by year (β = -1.5, 95% CI -2.7 to -0.31, p = 0.015) than patients with left-GRN. Brain asymmetry could be found in GRN carriers 10.4 years before the onset of the symptoms (standard difference 0.85, CI 0.01-1.68). FTD-GRN affects the brain hemispheres asymmetrically and causes 2 anatomical asymmetry patterns depending on the side of the disease onset. We demonstrated that these 2 anatomical asymmetry patterns present different symptoms, severity at the time of the first visit, and different disease courses. Our results also suggest brain asymmetry as a possible biomarker of conversion in GRN carriers.

Triplet therapy for metastatic castration-sensitive prostate cancer: Rationale and clinical evidence.

Prostate cancer (PC) growth is hormone-dependent and it frequently develops distant metastases as disease progresses. Patients with metastatic castration-sensitive prostate cancer (mCSPC) initially respond to androgen deprivation therapy (ADT) but eventually become refractory and develop metastatic castration-resistant prostate cancer (mCRPC). Castration-resistance is associated with high lethality and metastases confer poor prognosis, therefore unmet needs in treatment for mCSPC remain high. So far, improvements in survival in mCSPC have been achieved by doublet combination therapy such as docetaxel or an androgen-receptor signaling inhibitor (ARSI) in addition to ADT. Further, recent phase 3 trials have shown that triplet therapy-a combination of ARSI, docetaxel, and ADT improves prognosis compared with docetaxel plus ADT in mCSPC. PC tumors manifest intra- and inter-tumoral heterogeneity at both the genetic and phenotypic level. As heterogeneity increases during sequential treatment and disease progression, it is reasonable to initiate combination therapy using drugs with different mechanisms of action early in the course of disease, such as mCSPC. Previous research about tumor heterogeneity and drug resistant mechanism support this rationale, as well as preclinical studies and real-world data provide the scientific evidence of benefit by combining ARSI and docetaxel. Here, we review the rationale and clinical evidence for triplet therapy in patients with mCSPC.

Effect of the allelic background on the phenotype of primary hyperoxaluria type I.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of hepatic glyoxylate metabolism leading to nephrolithiasis and kidney failure. PH1 is caused by mutations on the AGXT gene encoding alanine:glyoxylate aminotransferase (AGT). The AGXT gene has two haplotypes, the major (Ma) and the minor (mi) alleles. This review summarizes the role of the minor allele on the molecular pathogenesis and the clinical manifestations of PH1. PH1 shows high genetic variability and significant interindividual variability. Although the minor haplotype is not pathogenic on its own, it may be crucial for the pathogenicity of some mutations or amplify the effect of others, thus affecting both symptoms and responsiveness to Vitamin B6, the only pharmacological treatment effective in a selected group of PH1 patients. In the last years, new drugs based on RNA-interference are available for patients nonresponsive to Vitamin B6, but no specific biomarkers are available to predict disease course and severity. Therefore, a clinical assessment of PH1 taking into account molecular analysis of the mutations and the allelic background and the possible synergism among polymorphic and pathogenic variants should be encouraged to promote approaches of personalized medicine that improve the management of available resources.

Effect of vitamin D supplementation

Introduction Vitamin D is one of the most important vitamins in affecting the human body. It turns out that its influence is not limited to its health-promoting effect on the skeletal system, but may also play an important role in the immune system. In our study, we focused precisely on this aspect of vitamin D's action. Review method We used materials from PubMed for this purpose. We focused on articles and research papers published between 2019 and 2024. We reviewed the publications in terms of vitamin D supplementation and its effects on immunity, disease processes, patient recovery, COVID-19 patients, and some autoimmune diseases. Results Some studies show that vitamin D supplementation significantly improves immune function. It also improves prognosis and reduces mortality in COVID-19. The number of complications and severity of the course also decreases. Vitamin D supplementation also has a positive effect on the course of autoimmune diseases, allowing a reduction in the incidence and improving the outcome of some of them. Unfortunately, not all studies prove such beneficial effects of vitamin D. What is important, however, is that vitamin D may have a beneficial effect on the course of diseases, and the low cost of its use and high availability may prove to be the key to medical development. Conclusions Based on the accumulated studies, it can be concluded that vitamin D contributes to the improvement of immune system function. Some studies prove the beneficial effect of vitamin D supplementation on the course of some autoimmune diseases. The potential benefits of vitamin D supplementation, as well as its low cost, should be a key argument for further research and knowledge on this topic.

A Retrospective Claims Data Analysis on the Burden of COVID-19-Related Hospitalization in Adults at High Risk for Severe Disease Progression in Germany.

Individuals at increased risk of severe coronavirus disease 2019 (COVID-19) progression have a higher probability of being hospitalized. Nirmatrelvir/ritonavir (NMV/r) is an antiviral drug aiming to prevent severe disease courses. Our study aimed to assess the resource utilization and costs of adults hospitalized for COVID-19 at high risk for severe disease progression. A retrospective study was conducted using German claims data. The presence of high-risk criteria was determined through recorded diagnoses, operations, procedures, and prescriptions. Individuals at high risk for severe COVID-19 progression, primarily hospitalized for COVID-19, required a recorded diagnosis for COVID-19 and additionally a diagnosis of sepsis, pulmonary embolism, acute respiratory failure, pneumonia, or a remdesivir prescription. Patients were grouped by eligibility for NMV/r treatment (eligible, eligible with restrictions, and not eligible). The outcomes of interest were reported for the timeframe of the last dominant virus variant available in the database, i.e., Delta (June 21, 2021 to December 31, 2021). Of approximately 3.7 million individuals continuously observable in the database, about 60% were identified as being at high risk for severe COVID-19 progression. Among high-risk individuals, 2938 patients were primarily hospitalized for COVID-19 between June 21, 2021, and December 31, 2021, two-thirds of which were suitable for NMV/r treatment (half without restrictions). Advanced age (86.3%) and cardiovascular conditions (83.9%) were the most prevalent of the predefined risk factors. Identified patients stayed, on average, 11.3 days in hospital, with inpatient mortality of 18.9%. These COVID-19-related hospitalizations resulted in mean healthcare costs of €8728. This study reflects the economic burden of hospitalized adult individuals with COVID-19 at high risk for severe disease progression from payer's perspective in Germany. Our findings highlight the need to prevent severe disease courses and associated hospitalizations to relieve healthcare systems regarding costs and resource allocation.

The properties of laryngeal electromyography in the non-paralyzed sides of patients with idiopathic vocal cord paralysis.

To evaluate the injuries of the recurrent laryngeal nerve (RLN), superior laryngeal nerve (SLN), and their innervated laryngeal muscles on the non-paralyzed sides in patients with idiopathic vocal cord paralysis (IVCP). Eighty-four cases of patients with IVCP were evaluated using stroboscopic laryngoscopy, voice analysis, and laryngeal electromyography(LEMG). Concurrently, twenty-eight cases involving healthy volunteers without vocal cord paralysis were enrolled and examined using LEMG during the same period. Subsequently, comparisons of LEMG results were conducted between the paralyzed and non-paralyzed sides, and among the non-paralyzed sides.Furthermore, a comparison was conducted between the LEMG results of the non-paralyzed sides in patients with IVCP and the corresponding ipsilateral sides in healthy volunteers.These comparisons were stratified based on the side of paralysis and the duration of the disease course (less than 3 months versus more than 3 months) for IVCP patients. Initially, the amplitude of the RLN, the action potential durations (APDs) and amplitude of the thyroarytenoid muscle (TM), and the amplitude of the posterior cricoarytenoid muscle (PCM) on the paralyzed side were significantly lower than those on the non-paralyzed side. Conversely, the latency of the RLN on the paralyzed side was significantly longer compared to the non-paralyzed side (P < 0.05). However, there were no significant differences in the latency and amplitude of the SLN, nor in the APD and amplitude of the CM between the paralyzed and non-paralyzed sides (P > 0.05). Furthermore, no significant differences were observed in the LEMG results of the non-paralyzed sides in IVCP patients, irrespective of the paralyzed side or the duration of the disease course (P > 0.05), and no significant differences of the LEMG results were observed when comparing the non-paralyzed sides of patients with IVCP to the ipsilateral sides of healthy volunteers (P > 0.05). However, when the disease course is less than 3 months, the amplitudes of the SLN and CM in the non-paralyzed side (right side) of left-sided IVCP patients are significantly lower than those in the non-paralyzed side (left side) of right-sided IVCP patients (SLN, 6.23 ± 4.42 mv vs. 10.21 ± 7.56 mv, t=-2.296, P = 0.028; CM, 0.49 ± 0.17 mv vs. 0.60 ± 0.19 mv, t=-2.207, P = 0.032), of which the amplitude of the CM is significantly reduced compared to the right side of healthy controls (0.49 ± 0.17 mv vs. 0.61 ± 0.21 mv, t=-2.423, P = 0.019), indicating that the SLN and CM on the non-paralyzed side are vulnerable to damage. Moreover, in patients with right-sided IVCP persisting for more than 3 months, there was a significant reduction in the amplitudes of the SLN and RLN, as well as the TM and PCM on the non-paralyzed side (left side), compared to the corresponding ipsilateral sides in healthy volunteers (P < 0.05). This observation indicates that the LEMG results for the non-paralyzed side in IVCP patients are not entirely normal, particularly in cases of right-sided IVCP with a disease duration exceeding three months. In patients with IVCP, it is imperative to conduct a simultaneous analysis of LEMG results from both the paralyzed and non-paralyzed sides after determining the affected side and the progression of the paralysis. This thorough examination is crucial for accurately evaluating the condition and prognosis of individuals with IVCP.

Efficacy of double filtration plasmapheresis in the treatment of steroid and/or IVIG unresponsive neuronal surface antibodies associated autoimmune encephalitis

IntroductionWhether double filtration plasmapheresis (DFPP) is effective in the patients who do not response to the initial immunotherapy is uncertain. This retrospective study aimed to evaluate the efficacy and safety of DFPP in the treatment of patients who had no improvement after initial immunotherapy (steroids and/or immunoglobulin (IVIG)), and moreover, to investigate the factors associated with the efficacy of DFPP.MethodsFrom January 1st, 2014, to December 30th,2018, a total of 26 patients who were diagnosed autoimmune encephalitis (AE) and were received the treatment of DFPP after unsuccessful or incomplete recovery from their early immune therapy (including intravenous high-dose cortisone, IVIG and or immunosuppressant) for at least 21 days were investigated. Their plasmapheresis volume, the course of disease, treatment sessions, and complications were recorded. The efficacy of DFPP within a week were assessed by modified Rankin scale (mRS). These patients were followed until six months after the last session of DFPP treatment.ResultsThe duration between the onset of symptoms and DFPP administration was 54.5 days (range 21—243 days). The median DFPP sessions for each patient were three (range 2–6 sessions), and the mean volume of plasma exchange was 50.5 ± 11.1 ml/kg/session. Total clinically relevant improvement was observed in 57.7% of the patients. The median mRS was decreased from 5 to 4 within one week after DFPP treatment (P < 0.001). Only one patient relapsed in the following six months after DFPP. The effectiveness of DFPP has no relationship with age, gender, the type of antibody, with or without neoplasm, clinical course and the volume of plasma exchange. Most patients tolerated well, except 2 cases. One encountered mild allergic reaction and the other had a transient hypotension during DFPP treatment, but both were corrected rapidly.ConclusionDFPP is an effective and safe treatment option for patients who have poor responsiveness to early immunotherapy).

Reduced functional connectivity in the default mode network in EEGs without other abnormalities in Early Creutzfeldt-Jacob disease.

Creutzfeldt-Jakob disease is a rare, neurodegenerative disorder that is incurable, always fatal, and transmissible. EEG is an integral part of the diagnostic workup with typical periodic sharp-wave complexes indicative of CJD, but early in the disease EEG is often unaltered. Accordingly, we aimed at evaluating disruption of brain network functional connectivity (FC) in regions belonging to the default mode network (DMN) as a potential early marker in CJD when EEG is considered visually normal. EEGs considered visually normal obtained from 7 CJD patients were compared to EEGs of 7 patients with subjective cognitive impairment (SCI) using Brainstorm application for Matlab. FC was calculated using the phase locking value separately for the delta-, theta-, alpha-, and beta-frequency-band. The global efficacy of the DMN was calculated as the inverse characteristic path length with brain-regions belonging to the DMN as nodes. CJD vs. SCI had significantly lower global efficacy of the DMN in the gamma band. FC was decreased between bilateral orbitofrontal regions and the right parahippocampal gyrus and between bilateral orbitofrontal gyrus and the right anterior cingulate gyrus in CJD. Our findings provide evidence of disruption of the DMN in the gamma band and alterations of FC between specific brain regions in early CJD patients with visually normal EEGs. EEG brain network properties bear potential as a diagnostic tool for CJD early in the disease course in addition to established criteria. These findings call for further studies evaluating the diagnostic value of FC in early CJD.

Defining high-risk patients: beyond the 8the AJCC melanoma staging system.

Since melanoma incidence is steadily increasing, guidelines regarding the diagnosis, staging, and treatment of melanoma are constantly being updated. In particular, the use of adjuvant therapy in stage IIb/c melanoma has been recently approved by the international regulatory agenicies. We performed a retrospective study with 92 melanoma patients namely 42 patients with IIb/c melanoma and 42 patients with IIIa stage melanoma, describing demographics, clinical, histology and disease course during the 5-year follow-up.Several significant evidences emerged between the two groups. Stage IIb/c patients possess a higher age of disease onset (69.6 vs. 55.5 years) with respect to stage III patients and the acral localization appeared as the most frequent (24% vs. 4%). Histologically, stage IIb/c melanomas more frequently exhibit ulceration (70% vs. 2%), angiotropism (54% vs. 8%) and are characterized by a greater presence of TILS (52% vs. 15%). Although it is not statistically significant, we observed a difference in terms of presence of metastasis during the 5-year follow-up: 15% of stage IIb/c patients showed metastasis vs. 4% of stage IIIa patients. Our data support the use of adiuvant immunotherapy in stage IIb/c patients.

Clinical characteristics and quality of life of patients with Behcet’s disease with arthritis in Japan

Arthritis is one of the most common symptoms of Behcet’s Disease (BD) observed in 57% of Japanese patients with BD. The relationship between arthritis and other clinical symptoms of BD and the impact of arthritis on the quality of life (QOL) of patients with BD are still unclear. Therefore, the current study aimed to clarify the differences in clinical symptoms depending on the presence or absence of arthritis and evaluate the impact of arthritis on QOL in these patients. Fifty-three Japanese patients diagnosed with BD and being treated for more than 6 months were included in this study. Patients were divided based on the presence of arthritis symptoms into an arthritis and a non-arthritis group. Clinical symptoms, disease activity, and QOL of both groups were compared using the Patient’s global assessment (PGA), Evaluator’s global assessment (EGA), and Behcet‘s disease current activity form (BDCAF) as indices of disease activity. To evaluate disease activity related to lesions other than arthritis, BDCAF excluding arthritis items was also calculated. The Behcet’s disease quality of life (BDQOL) scale was used to assess patients’ QOL. Oral ulcers and skin lesions were significantly more frequent in the arthritis group than in the non-arthritis group (p = 0.009 and 0.048, respectively). Among skin domains, papulopustular lesions tended to be more frequent in the arthritis group. EGA and BDCAF (both including and excluding arthritis-related items) scores were significantly higher in the arthritis group (p = 0.019, < 0.0001, and 0.0004 respectively). Although PGA and BDQOL tended to be higher in the arthritis group, the difference between the two groups was not statistically significant. The disease course in Japanese BD patients with arthritis was more frequently complicated by oral ulcers and skin lesions than in those without arthritis. In addition, BD patients with arthritis tended to have generally higher disease activity and low QOL than their non-arthritis counterparts. Further research is required to confirm these results.