Categorization systems for tick-borne encephalitis virus (TBEV) infection lack consistency in classifying disease severity. To evaluate the need for a standard, consensus-based categorisation system for TBEV infection across subtypes, we gathered an expert panel of clinicians and scientists with diverse expertise in TBEV infection. Consensus was sought using the Delphi technique, which consisted of 2 web-based survey questionnaires and a final, virtual, consensus-building exercise. Ten panellists representing 8 European countries participated in the Delphi exercise, with specialities in neurology, infectious disease, paediatrics, immunology, virology, and epidemiology. Panellists reached unanimous consensus on the need for a standardised, international categorisation system to capture both clinical presentation and severity of TBEV infection. Ideally, such a system should be feasible for use at bedside, be clear and easy to understand, and capture both the acute and follow-up phases of TBEV infection. Areas requiring further discussion were (1) the timepoints at which assessments should be made and (2) whether there should be a separate system for children. This Delphi panel study found that a critical gap persists in the absence of a feasible and practical classification system for TBEV infection. Specifically, the findings of our Delphi exercise highlight the need for the development of a user-friendly classification system that captures the acute and follow-up (i.e., outcome) phases of TBEV infection and optimally reflects both clinical presentation and severity. Development of a clinical categorisation system will enhance patient care and foster comparability among studies, thereby supporting treatment development, refining vaccine strategies, and fortifying public health surveillance.
- MeSH
- Delphi Technique * MeSH
- Encephalitis, Tick-Borne * epidemiology virology diagnosis MeSH
- Consensus MeSH
- Humans MeSH
- Encephalitis Viruses, Tick-Borne * classification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Charcot-Marie-Tooth is the most common inherited neuromuscular disorder. Rarely, it can be associated with heart failure and various arrhythmic disturbances. This case illustrates the challenges of making decisions to prevent sudden cardiac death in a patient with Charcot-Marie-Tooth disease. CASE SUMMARY: A 69-year-old male with a history of Type 1A Charcot-Marie-Tooth disease was admitted due to repetitive runs of ventricular tachycardia. Twelve-lead electrocardiogram, echocardiography, selective coronary angiography, and cardiac magnetic resonance did not clarify the cause of the electrical storm. As conservative therapy was not successful, radiofrequency ablation was chosen to treat the electrical storm. After this procedure, implantable cardioverter defibrillator (ICD) was implanted. The follow-up revealed severe perforation by the ventricular lead. An extraction was performed with no complications and a new lead was immediately implanted. The patient remains asymptomatic. Three episodes of non-sustained ventricular tachycardia were recorded during the last follow-up. DISCUSSION: This case illustrates the challenges of making decisions to prevent sudden cardiac death in a patient with Charcot-Marie-Tooth disease after successful ablation for electrical storm. Due to a lack of evidence, atypical origin of arrhythmia, and clinical presentation, we did not consider this as idiopathic arrhythmia and decided to implant an ICD, which was complicated by severe perforation by the lead. Specific recommendations for preventing sudden cardiac death in rare cardiac conditions, such as Charcot-Marie-Tooth disease, still need to be refined.
- Publication type
- Journal Article MeSH
- Case Reports MeSH
BACKGROUND: Head tremor poses diagnostic problems, especially when present as an isolated or predominant symptom. OBJECTIVES: To assess how maneuvers activating upper limb postural tremor can help differentiate head tremor in essential tremor (ET) from dystonic tremor (DT) in cervical dystonia. METHODS: 48 patients with head tremor (25 ET, 23 DT), underwent clinical examination and accelerometric evaluation of head and upper limb tremor during routine tremor-inducing tasks. RESULTS: While accelerometric power and clinical scores of head tremor did not significantly differ between patient groups, task-induced variations revealed distinctions. ET patients exhibited increased head tremor power and clinical scores during forward outstretched and lateral wing-beating arm positions, unlike DT patients. Coherence between head and upper limb tremor remained consistent. Tremor stability index showed no significant differences. CONCLUSIONS: Task-induced changes in head tremor could aid in distinguishing between ET and DT. Further research is needed to refine diagnostic approaches for head tremor.
- MeSH
- Accelerometry instrumentation methods MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Dystonia diagnosis physiopathology MeSH
- Essential Tremor * diagnosis physiopathology MeSH
- Head * physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Arm * physiopathology MeSH
- Posture physiology MeSH
- Aged MeSH
- Torticollis diagnosis physiopathology MeSH
- Tremor * diagnosis physiopathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted in centers worldwide, with ongoing refinements to enhance results. This study aims to assess the current state of RAMIE worldwide and to identify potential areas for improvement. METHODS: This descriptive study analyzed prospective data from esophageal cancer patients who underwent transthoracic RAMIE in Upper GI International Robotic Association (UGIRA) centers. Main endpoints included textbook outcome rate, surgical techniques, and perioperative outcomes. Analyses were performed separately for intrathoracic (Ivor-Lewis) and cervical anastomosis (McKeown), divided into three time cohorts (2016-2018, 2019-2020, 2021-2023). A sensitivity analysis was conducted with cases after the learning curve (> 70 cases). RESULTS: Across 28 UGIRA centers, 2012 Ivor-Lewis and 1180 McKeown procedures were performed. Over the time cohorts, textbook outcome rates were 39%, 48%, and 49% for Ivor-Lewis, and 49%, 63%, and 61% for McKeown procedures, respectively. Fully robotic procedures accounted for 66%, 51%, and 60% of Ivor-Lewis procedures, and 53%, 81%, and 66% of McKeown procedures. Lymph node yield showed 27, 30, and 30 nodes in Ivor-Lewis procedures, and 26, 26, and 34 nodes in McKeown procedures. Furthermore, high mediastinal lymphadenectomy was performed in 65%, 43%, and 37%, and 70%, 48%, and 64% of Ivor-Lewis and McKeown procedures, respectively. Anastomotic leakage rates were 22%, 22%, and 16% in Ivor-Lewis cases, and 14%, 12%, and 11% in McKeown cases. Hospital stay was 13, 14, and 13 days for Ivor-Lewis procedures, and 12, 9, and 11 days for McKeown procedures. In Ivor-Lewis and McKeown, respectively, the sensitivity analysis revealed textbook outcome rates of 43%, 54%, and 51%, and 47%, 64%, and 64%; anastomotic leakage rates of 28%, 18%, and 15%, and 13%, 11%, and 10%; and hospital stay of 11, 12, and 12 days, and 10, 9, and 9 days. CONCLUSIONS: This study demonstrates favorable outcomes over time in achieving textbook outcome after RAMIE. Areas for improvement include a reduction of anastomotic leakage and shortening of hospital stay.
- MeSH
- Esophagectomy * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Minimally Invasive Surgical Procedures methods MeSH
- Esophageal Neoplasms * surgery pathology MeSH
- Follow-Up Studies MeSH
- Postoperative Complications epidemiology MeSH
- Prognosis MeSH
- Prospective Studies MeSH
- Registries * MeSH
- Robotic Surgical Procedures * methods MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Despite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator using chemogenetics, it also becomes an "on-demand" treatment. Here, we evaluate a targeted and specific chemogenetic therapy, the PSAM/PSEM system, which holds promise as a potential candidate for clinical application in treating drug-resistant epilepsy. We show that the inert ligand uPSEM817, which selectively activates the chloride-permeable channel PSAM4-GlyR, effectively reduces the number of depolarization-induced action potentials in vitro. This effect is likely due to the shunting of depolarizing currents, as evidenced by decreased membrane resistance in these cells. In organotypic slices, uPSEM817 decreased the number of bursts and peak amplitude of events of spontaneous epileptiform activity. Although administration of uPSEM817 in vivo did not significantly alter electrographic seizures in a male mouse model of temporal lobe epilepsy, it did demonstrate a strong trend toward reducing the frequency of interictal epileptiform discharges. These findings indicate that PSAM4-GlyR-based chemogenetics holds potential as an anti-seizure strategy, although further refinement is necessary to enhance its efficacy.
- MeSH
- Action Potentials drug effects MeSH
- Epilepsy physiopathology genetics drug therapy therapy metabolism MeSH
- Genetic Therapy methods MeSH
- Hippocampus * metabolism MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.
- MeSH
- Bipolar Disorder * genetics MeSH
- Adult MeSH
- Phenotype * MeSH
- Attention Deficit Disorder with Hyperactivity genetics MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Multifactorial Inheritance genetics MeSH
- Neurodevelopmental Disorders genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Super-resolution (SR) microscopy is a cutting-edge method that can provide detailed structural information with high resolution. However, the thickness of the specimen has been a major limitation for SR methods, and large biological structures have posed a challenge. To overcome this, the key step is to optimise sample preparation to ensure optical homogeneity and clarity, which can enhance the capabilities of SR methods for the acquisition of thicker structures. Oocytes are the largest cells in the mammalian body and are crucial objects in reproductive biology. They are especially useful for studying membrane proteins. However, oocytes are extremely fragile and sensitive to mechanical manipulation and osmotic shocks, making sample preparation a critical and challenging step. We present an innovative, simple and sensitive approach to oocyte sample preparation for 3D STED acquisition. This involves alcohol dehydration and mounting into a high refractive index medium. This extended preparation procedure allowed us to successfully obtain a unique two-channel 3D STED SR image of an entire mouse oocyte. By optimising sample preparation, it is possible to overcome current limitations of SR methods and obtain high-resolution images of large biological structures, such as oocytes, in order to study fundamental biological processes. Lay Abstract: Super-resolution (SR) microscopy is a cutting-edge tool that allows scientists to view incredibly fine details in biological samples. However, it struggles with larger, thicker specimens, as they need to be optically clear and uniform for the best imaging results. In this study, we refined the sample preparation process to make it more suitable for SR microscopy. Our method includes carefully dehydrating biological samples with alcohol and then transferring them into a mounting medium that enhances optical clarity. This improved protocol enables high-resolution imaging of thick biological structures, which was previously challenging. By optimizing this preparation method, we hope to expand the use of SR microscopy for studying large biological samples, helping scientists better understand complex biological structures.
The COVID-19 pandemic revolutionized our understanding and treatment of pneumonia, particularly highlighting its complex immunological aspects. In this review, we synthesized recent research on COVID-19 clinical management, shedding light on the immune-related landscape of pneumonia in the post-pandemic era. We explored key features of SARS-CoV-2, such as transmission dynamics, emerging variants, and infection mechanisms, before delving into the host immune response following viral exposure. Our discussion emphasized the critical role of immune cells, inflammatory cytokines, and cytokine storms in pneumonia development, alongside immune-mediated lung damage and thrombotic complications. Clinically, we summarized evolving diagnostic methods, treatment approaches, and intensive care protocols, all with a focus on the pivotal role of immunology in pneumonia management. Looking forward, we advocated for a comprehensive approach to addressing ongoing pneumonia challenges, including strengthening epidemic surveillance and advancing immunotherapy research to target abnormal immune responses. Additionally, refining vaccine strategies for durable immunity against evolving viral strains was deemed essential. Overall, this review underscored the central role of immunology in shaping pneumonia management post-COVID-19, aiming to enhance our understanding of disease mechanisms and immunological responses in the post-pandemic era.
- MeSH
- COVID-19 * immunology therapy virology MeSH
- Cytokines immunology MeSH
- Precision Medicine MeSH
- Humans MeSH
- Pandemics MeSH
- SARS-CoV-2 * immunology pathogenicity MeSH
- Cytokine Release Syndrome immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
As one of the most significant global health emergencies, COVID-19 has placed extraordinary demands on healthcare systems worldwide. In India, its widespread transmission has been influenced by the country's diverse climatic conditions, geo-ecological complexity, and dense population. This, vector-borne diseases (VBDs)-including malaria, dengue, kala azar, Japanese encephalitis, and chikungunya-have long posed additional challenges to public health infrastructure. Intriguingly, prior exposure to these diseases may shape immune responses, potentially conferring cross-protection against multiple pathogens. A cross-sectional study aimed at assessing the role of VBDs in COVID-19 incidence and mortality revealed a multifaceted relationship. Prior dengue exposure was linked to an increased risk of SARS-CoV-2 infection and mortality, whereas kala azar, Japanese encephalitis, and chikungunya appeared to have protective influences. Notably, malaria had statistically significant protective effects against both SARS-CoV-2 infection and mortality (p < 0.04). These findings suggest that immune mechanisms-such as cross-reactive antibodies or immune regulation-may alter susceptibility to COVID-19. Given the substantial protective effect of malaria, further investigation is warranted to clarify the underlying biological processes involved. Insights from this study could guide public health strategies, optimize resource allocation, and refine intervention measures in regions where both COVID-19 and VBDs remain major concerns.
- MeSH
- COVID-19 * mortality epidemiology transmission MeSH
- Dengue epidemiology MeSH
- Chikungunya Fever epidemiology MeSH
- Incidence MeSH
- Humans MeSH
- Malaria epidemiology MeSH
- Vector Borne Diseases * epidemiology mortality MeSH
- Cross-Sectional Studies MeSH
- SARS-CoV-2 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- India MeSH
PURPOSE: STereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia. However, clinical data are scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization. METHODS AND MATERIALS: Planning target volumes (PTVs) overlapping extracardiac organs-at-risk and/or cardiac substructures were generated for 3 STAR cases. Participating centers were asked to create single-fraction treatment plans with 25 Gy dose prescriptions based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for International Commission on Radiation Units and Measurements report 91 relevant parameters and crowd dose-volume histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process. RESULTS: Twenty centers submitted 67 treatment plans for this study. In most plans (75%) intensity modulated arc therapy with 6 MV flattening filter free beams was used. Dose prescription was mainly based on PTV D95% (49%) or D96%-100% (19%). Many participants preferred to spare close extracardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D0.035cm3 ranged from 25.5 to 34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged from 2 to 80 minutes. For the consensus statements, a strong agreement was reached for beam technique planning, dose calculation, prescription methods, and trade-offs between target and extracardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target. CONCLUSIONS: This STOPSTORM multicenter treatment planning benchmark study not only showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established; however, clinical data are urgently needed for actionable guidelines for treatment planning.
- MeSH
- Benchmarking * MeSH
- Radiotherapy Dosage MeSH
- Tachycardia, Ventricular surgery radiotherapy MeSH
- Consensus * MeSH
- Organs at Risk * radiation effects MeSH
- Humans MeSH
- Radiotherapy Planning, Computer-Assisted * standards methods MeSH
- Radiosurgery * standards methods MeSH
- Radiotherapy, Intensity-Modulated methods standards MeSH
- Heart radiation effects MeSH
- Arrhythmias, Cardiac MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
