Etiological Diagnosis Research Articles

Monoclonal gammapathies: Epidemiological, immunochemical and etiological analysis of a series of 50 cases

During the period from September 2022 to January 2023, 50 cases of monoclonal gammopathy (GM) were collected at the Avicenne military hospital in Marrakech. The average age of the patients was 62 years. Thirty patients were male and 20 were female. The etiological diagnosis could be established for the 50 observations: 5 were classified as GM of undetermined significance (GMSI), 42 were classified as myeloma, two case of Waldenström's disease and one case of AL amyloidosis. The clinical symptomatology was dominated by bone pain in 78% of patients with a deterioration in general condition in 43%. The most frequently found biological abnormalities were anemia in 62% of patients, renal failure in 48% of patients and 19% had hypercalcemia. A monoclonal peak was found in the electrophoreses of 45 patients (90%), of whom 6 migrated to the beta zone and 39 migrated to the gamma zone. The IgG Kappa isotype was the most frequent with a rate of 56%, followed by IgG Lambda (27%), IgA Kappa (8%), IgA Lambda (3%), IgM Lambda (3%) and lambda free light chains (3%).

ИННОВАЦИОННЫЕ МЕТОДЫ ДИАГНОСТИКИ БРУКСИЗМА В СОВРЕМЕННОЙ СТОМАТОЛОГИИ

The article is devoted to one of the most important problems in modern dentistry – bruxism. The relevance is associated with an increase in the prevalence of bruxism in patients of different age groups. The article discusses etiological factors, clinical manifestations and various diagnostic methods for patients with bruxism. The material of the review is the long-term research of domestic and foreign scientists devoted to the etiology and modern diagnosis of patients with bruxism. Using the Elibrary search engine, 17 articles were selected for the time period from 2003 to 2023. The article uses a descriptive method that allowed us to consider the current state of the problem and outline ways to further solve it. The main content of the study is the analysis of innovative methods for the diagnosis of bruxism, which make it possible to diagnose pathology at the initial stage of the disease and start its treatment in a timely manner. The article emphasizes the need to supplement existing clinical recommendations with innovative methods and diagnostic tools for this pathology. As a result of the analysis of the literature, the authors developed a systematization of all methods of diagnosing bruxism by the subject of the study. The article discusses research aimed at studying the occlusal relationship of the jaws, the diagnosis of a psychopathological condition, the diagnosis of musculoskeletal dysfunction, the diagnosis of neurotransmitter imbalance and the detection of diseases of the musculoskeletal system. The authors concluded that with the advent and introduction of computer technologies into dental practice, innovative methods and tools for diagnosing bruxism were developed, which led to a significant improvement in the quality of dental care provided. Special attention is paid in the article to the importance of the principle of primacy and an interdisciplinary approach in conducting diagnostic studies aimed at identifying bruxism.

Visual Patterns of Diaphragmatic Motion in Acute Respiratory Failure: A Prospective Pilot Study.

Right diaphragmatic excursion is a reliable and reproducible technique used in intensive care to assess diaphragmatic function. The aim of this study was to investigate the relationship between the appearance of diaphragmatic motion and the etiological diagnosis of patients admitted to the emergency department with acute respiratory failure (ARF). A prospective, observational, and multicenter pilot study was conducted. All adult patients admitted in the emergency department with ARF were included. The different visual patterns of diaphragmatic motion were analyzed according to the three main etiologies of ARF encountered in emergency departments. A total of 39 adult patients were included. We observed a different visual pattern in patients with pneumonia. A sum of plateau times of less than 0.2 s predicted that the main diagnosis was pneumonia, with sensitivity = 89% 95%CI [52%; 100%], specificity = 87% 95%CI [69%; 96%]. Our study seems to show that the shape of diaphragmatic motion in patients with ARF secondary to pneumonia is different from that in patients with exacerbation of chronic obstructive pulmonary disease or acute heart failure. ClinicalTrials.gov: NCT04591509.

Left atrial strain differences between hypertensive and sarcomeric left ventricular hypertrophy: a sign of sarcomeric auricular myopathy?

Abstract Introduction In clinical practice, left ventricular (LV) hypertrophy is a common finding that can be caused by physiologic or pathologic conditions. An etiologic diagnosis is extremely important because it may change the prognosis and management of the patient and his family. Left atrial (LA) dysfunction is common due to diastolic dysfunction but, in patients with sarcomeric LV hypertrophy, primary cardiomyopathy disease could also be present. Purpose To evaluate if there are differences in LA function between arterial hypertension (HT) and hypertrophic cardiomyopathy (HCM) patients. Methods 73 patients with HCM (according to ESC guidelines criteria) and 82 patients with HT (under treatment with ≥1 hypertensive drug for ≥3 months) and ≥13mm of LV hypertrophy underwent an echocardiography to assess LA function with strain analysis and LV diastolic function. Continuous normally distributed variables were compared with T-student test and categoric variables with square-chi or exact Fisher test if required, accepting as significant a p-value <0.05. Results Globally, HCM patients showed thicker LV walls and larger LA indexed volumes (18.7±4.7 vs. 13.3±0,8 mm and 44.9±20.7 vs. 30.7±8.8 ml/m2, p<0.000 for both). Also, HCM patients presented diastolic dysfunction and atrial fibrillation history in a higher frequency (31 vs. 7.6% and 16.4% vs. 0%, p<0.000 for both). LA strain was significantly lower in HCM patients as compared to the HT group (LA contractile 11.5±5.8 vs. 17.2±4.4, p<0.000; LA conduit 12.2±5.4 vs. 13.3±3.8, p=0.041; and LA reservoir 23.9±8.7 vs. 31.1±5.9, p<0.000). In the subgroup of patients with moderate-severe LV hypertrophy (<17mm) and no significant mitral regurgitation (n=103; HCM=21, HT=82), LA contractile strain remained lower in HCM as compared to HT patients (13.2±4.8% vs. 17.2±4.4%, p<0.000) (figure 1); without differences in diastolic dysfunction, LA volumes, significant mitral regurgitation or atrial fibrillation history. Conclusions Our results show that LA strain is more impaired in HCM patients as compared to HT patients. Specifically, contractile LA strain remained lower even in those patients with moderate-severe LV hypertrophy, despite having similar LV diastolic function, LA indexed volumes, significant mitral regurgitation, or atrial fibrillation history. These findings could be caused by HCM involvement of the LA myocytes. In the context of moderate-severe hypertrophy of unknown origin with non-significant mitral regurgitation, the detection of abnormally reduced LA strain could indicate the presence of an HCM.Figure 1

Development and implementation of a guideline-based decision support system for etiological diagnosis of Sustained Monomorphic Ventricular Tachycardia (SMVT)

Abstract Background Guideline (GL)-based decision support systems (DSSs) play a significant role in supporting physicians in their decision-making processes by providing structured clinical guidance. While these systems have shown significant success in enhancing practitioner performance and patient outcomes in general practice, their application in the context of ventricular arrhythmias remains limited. Moreover, the clinical etiological diagnosis of ventricular arrhythmias presents various challenges for healthcare professionals, such as adherence to updated diagnostic criteria and understanding of complex arrhythmia mechanisms. Purpose In this study, we aim to design, implement, and evaluate a guideline-based decision support systems for etiological diagnosis of sustained monomorphic ventricular tachycardia (SMVT), which could potentially address critical challenges associated with the disease diagnosis and management. Methods To comprehensively capture the semantics embedded in clinical guidelines, we first developed a dedicated knowledge graph tailored to the clinical decision-making. This involved extracting entities and relationships pertinent to key decision procedures from ESC guidelines for ventricular arrhythmias, clinical textbooks or literatures. Subsequently, we translated instances within the knowledge graph into archetypes within openEHR, amplifying the interoperability of clinical information. To enhance the interpretability of the DSS, we established executable diagnostic and treatment processes to offer visual representation of clinical steps in diagnosis and treatment. Ultimately, we constructed a decision support engine to implement the GL-DSS, and its effectiveness was evaluated with anonymous real-world data. Results The proposed GL-DSS was found to be quite feasible and could provide etiological diagnosis for SMVT. The knowledge base for the constructed GL-DDS included more than 2000 entities and relations, which played a vital role in representing disease pathogenesis. The proposed system can map the clinical entities to a set of openEHR archetypes, thus mitigate the interoperability issues of the hospital information systems and CDSS data integration. Also, this module improved system usability and ensured that guidelines could be easily translated and updated into decision support tools. Real-word medical records from 20 patient were collected for model evaluation, the results showed that the GL-DSS covered most of the entities and relations between diseases and diagnostic evidence recorded in clinical texts and achieved a diagnosis accuracy of 80%. Conclusions The results demonstrated that our proposed GL-DSS could completely and accurately capture the diagnostic information under the concrete EHR data. Thus, the implement decision support system could have the potential to improve clinical decision-making, patient care, and outcomes in this specialized medical domain.

Peripheral blood immune cells distribution in biopsy-proven myocarditis: etiology and prognostic correlates

Abstract Background Myocarditis is an inflammatory disease of the myocardium with viral or immune-mediated/autoimmune etiology. Definite etiological diagnosis relays on endomyocardial biopsy (EMB). High titre anti-heart autoantibodies (AHA) define severe autoimmune forms. Virus-negative myocarditis may require immunosuppression (IS) to reduce progression to dilated cardiomyopathy, heart transplant or death. Prognostic stratification is incomplete and IS is not always efficacious. Animal and human studies suggest a pathogenetic role of immune cells, but little is known on their peripheral distribution or prognostic role. Purpose Characterize EMB-proven myocarditis patients’ peripheral blood to identify new non-invasive etiological and prognostic biomarkers. Methods Seventy-eight EMB-proven myocarditis patients and 9 healthy controls (HC) were enrolled according to the Declaration of Helsinki and written informed consent was collected for each participant. Peripheral blood mononuclear cells were purified by Ficoll stratification and immune cells distribution was evaluated by flow cytometry. Variables were analysed by Mann-Whitney or Kruskall-Wallis and Dunn post-hoc tests clustering patients according to clinical features, EMB and AHA results. Results Compared to HC (figure 1), plasmacytoid dendritic cells were reduced in myocarditis patients: with autoimmune/lymphocytic forms (p=0.0091); without extra cardiac autoimmune diseases (AD, p=0.0075); in those unresponsive to IS (p=0.0379) or never treated because of spontaneous healing (p=0.0015). Moreover, several immunophenotypical features discriminated myocarditis type/IS-response from HC. Viral forms were characterized by reduced CD94+ NK cells and CCR2 over-expression in intermediate monocytes (p=0.029, p=0.013). Autoimmune cases were defined by: higher CD62L+ NK cells when AHA negative (p=0.019); increased Th1 if not requiring IS (p=0.03); higher γδ-TCR+ Th17 and reduced Treg cells if without other AD (both p=0.04), or higher CD4+/IL17+ cells with concurrent AD (p=0.02) and AHA positivity (p=0.036). Moreover, ongoing IS treatment influenced peripheral cells distribution: whole blood cell counts were more frequently altered and total NK cells were reduced (p=0.007); treg cells were reduced in patients actively treated but unresponsive to IS (p=0.036). Conclusion Biopsy-proven myocarditis patients showed a skewed peripheral blood distribution of either innate or adaptive immune cells according to different histology, etiology (viral vs autoimmune) and response to IS in autoimmune forms, unveiling potential new non-invasive immunological biomarkers for myocarditis. Figure: Plasmacytoid dendritic cells (pDCs) percentage was assessed by flow-cytometry and data were showed by boxplots clustering myocarditis patients for etiology (A), EMB histological result (B), presence of extracardiac AD (C) or IS response (D). Data were analysed by Kruskall-Wallis (graph bottom) and Dunn post-hoc tests.

A case of severe psittacosis pneumonia complicated by splenic infarction

Clinical dataChlamydia psittaci pneumonia is a community-acquired pneumonia caused by Chlamydia psittaci. While severe cases may lead to critical conditions such as respiratory failure, splenic infarction is relatively uncommon. A severe patient with Chlamydia psittaci pneumonia admitted to our hospital experienced a splenic infarction during treatment. Fortunately, the patient’s situation was improved after careful treatment. Now, the patient has been discharged. Further exploration of the mechanism of concurrent splenic infarction is required.BackgroudPsittacosis pneumonia, a zoonotic infectious disease transmitted from birds to humans, is caused by Chlamydia psittaci and represents a type of chlamydial pneumonia [1]. Insome instances, the disease may progress to severe pneumonia and respiratory failure, necessitating intensive support measures, including mechanical ventilation. The advent of technologies such as Metagenomic Next-Generation Sequencing (mNGS) for the etiological diagnosis of infectious diseases [2] has improved the diagnostic and treatment success rates for Psittacosis. Instances of severe chlamydial pneumonia with complications such as splenic infarction are uncommon. A patient with severe Psittacosis pneumonia complicated by splenic infarction was admitted to the Emergency Intensive Care Unit (EICU) of Haining People’s Hospital and subsequently improved following effective anti-infective and anticoagulant therapy. This report is provided herein.

Exploring the Etiology and Clinical Diagnosis and Treatment of Upper Gastrointestinal Bleeding

Upper gastrointestinal bleeding refers to bleeding caused by the digestive tract above the flexor ligament, including diseases of the esophagus, stomach, duodenum, pancreas, biliary tract, and lesions after gastrojejunostomy. It is a common and critical condition in internal medicine. In recent years, with the continuous development of medical technology and the improvement of treatment methods, the diagnosis and treatment level of this disease has been greatly improved. However, this disease has the characteristics of fast onset, complex condition, and certain mortality rate. Therefore, exploring and analyzing the etiology, causes, and treatment plans of this disease is of great significance for improving the cure rate and prognosis of patients with this disease. Due to inflammation, mechanical injury, vascular disease, or adjacent organ lesions, the choice of treatment plan varies depending on the cause. Based on the above situation, this article, The etiology and diagnosis and treatment plan of upper gastrointestinal bleeding have been explored, which can provide reference for improving the treatment level of this disease

Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients.

Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common.

The impact of tau-PET in a selected memory clinic cohort: rationale and design of the TAP-TAU study

BackgroundTau-PET is a diagnostic tool with high sensitivity and specificity for discriminating Alzheimer’s disease (AD) dementia from other neurodegenerative disorders in well-controlled research environments. The role of tau-PET in real-world clinical practice, however, remains to be established. The aim of the TAP-TAU study is therefore to investigate the impact of tau-PET in clinical practice.MethodsTAP-TAU is a prospective, longitudinal multi-center study in 300 patients (≥ 50 years old) with mild cognitive impairment or mild dementia across five Dutch memory clinics. Patients are eligible if diagnostic certainty is < 85% after routine dementia screening and if the differential diagnosis includes AD. More specifically, we will include patients who (i) are suspected of having mixed pathology (e.g., AD and vascular pathology), (ii) have an atypical clinical presentation, and/or (iii) show conflicting or inconclusive outcomes on other tests (e.g., magnetic resonance imaging or cerebrospinal fluid). Participants will undergo a [18F]flortaucipir tau-PET scan, blood-based biomarker sampling, and fill out questionnaires on patient reported outcomes and experiences. The primary outcomes are change (pre- versus post- tau-PET) in diagnosis, diagnostic certainty, patient management and patient anxiety and uncertainty. Secondary outcome measures are head-to-head comparisons between tau-PET and less invasive and lower cost diagnostic tools such as novel blood-based biomarkers and artificial intelligence-based classifiers.ResultsTAP-TAU has been approved by the Medical Ethics Committee of the Amsterdam UMC. The first participant is expected to be included in October 2024.ConclusionsIn TAP-TAU, we will investigate the added clinical value of tau-PET in a real-world clinical setting, including memory clinic patients with diagnostic uncertainty after routine work-up. Findings of our study may contribute to recommendations regarding which patients would benefit most from assessment with tau-PET. This study is timely in the dawning era of disease modifying treatments as an accurate etiological diagnosis becomes increasingly important.Trial registrationThis trial is registered and authorized on December 21st, 2023 in EU Clinical Trials with registration number 2023-505430-10-00.

Interpretable Clinical Decision-Making Application for Etiological Diagnosis of Ventricular Tachycardia Based on Machine Learning.

Background: Ventricular tachycardia (VT) can broadly be categorised into ischemic heart disease, non-ischemic structural heart disease, and idiopathic VT. There are few studies related to the application of machine learning for the etiological diagnosis of VT, and the interpretable methods are still in the exploratory stage for clinical decision-making applications. Objectives: The aim is to propose a machine learning model for the etiological diagnosis of VT. Interpretable results based on models are compared with expert knowledge, and interpretable evaluation protocols for clinical decision-making applications are developed. Methods: A total of 1305 VT patient data from 1 January 2013 to 1 September 2023 at the Arrhythmia Centre of Fuwai Hospital were included in the study. Clinical data collected during hospitalisation included demographics, medical history, vital signs, echocardiographic results, and laboratory test outcomes. Results: The XGBoost model demonstrated the best performance in VT etiological diagnosis (precision, recall, and F1 were 88.4%, 88.5%, and 88.4%, respectively). A total of four interpretable machine learning methods applicable to clinical decision-making were evaluated in terms of visualisation, clinical usability, clinical applicability, and efficiency with expert knowledge interpretation. Conclusions: The XGBoost model demonstrated superior performance in the etiological diagnosis of VT, and SHAP and decision tree interpretable methods are more favoured by clinicians for decision-making.

Chinese expert consensus on the etiological diagnosis of adult bronchiectasis

Bronchiectasis is a highly heterogeneous chronic airway disease for which accurate etiological diagnosis is crucial for effective management. A group of experts from the China Bronchiectasis Alliance and the Infection Assembly of the Chinese Thoracic Society conducted a comprehensive review of recent research into the etiology of bronchiectasis. Using the widely accepted Delphi methodology, the experts reached a consensus on the etiological diagnosis of bronchiectasis through multiple rounds of discussion and revision. The consensus is divided into four sections: the definition and classification of the etiology of bronchiectasis, the etiological diagnostic procedures for bronchiectasis, the treatable causes of bronchiectasis, and other causes of bronchiectasis. The ultimate goal of this consensus is to improve the diagnostic accuracy and optimize the management of bronchiectasis in China. The main recommendations of Section 1 focused on chest thin-section computed tomography (CT) for the diagnosis of bronchiectasis and the etiological classification. The main recommendations of Section 2 focused on the medical history collection for bronchiectasis and the etiological diagnostic protocol for bronchiectasis. The main recommendations of Section 3 focused on the recommendations of the diagnosis of bronchiectasis secondary to COPD, the diagnosis of bronchiectasis due to asthma, diffuse pan-bronchiolitis, allergic bronchopulmonary aspergillosis, connective tissue disease (CTD)-related bronchiectasis or gastroesophageal reflux disease (GERD)-related bronchiectasis. The main recommendations of Section 4 focused on suspected primary ciliary dyskinesia (PCD)-associated bronchiectasis, cystic fibrosis and the diagnosis of congenital airway malformations.

Outcomes of severe lower respiratory tract infection in Mexican children with cancer

Abstract Background Lower respiratory tract infections (LRTI) are a very serious complication in children with cancer, with high morbidity and mortality, due to viral infections, followed by bacterial and fungal organisms. These patients with cancer are undergoing chemotherapy that damages their mucosal barrier and respiratory epithelium, and course with profound or severe neutropenia. Thus, they are high-risk to develop severe respiratory infections acquired from the community. However, the clinical characteristics, etiological agents, finding on computed tomography (CT) and outcomes of the LRTI in immunocompromised patients are not well known, these are necessary in order to start adequate management including empirical antimicrobial therapy and supplementary oxygen therapy. Methods Children with cancer who were attended in the pediatric emergency room due to fever (&amp;gt;38°C) and presence of respiratory symptoms such as increased breath rate, cough, O2Sat &amp;lt;93%, and needed to supplementary oxygen were included. To analyze the cases of children with cancer and LRTI we documented the data regarding to clinical presentation, detection of respiratory virus and findings in the CT. Data such age, sex, oncological diagnosis, absolute neutrophil count. The detection of nucleic acid of respiratory virus was performed by qPCR, whereas the identification galactomannan in serum was done for fungal diagnosis, and clinical presentation was initial used for diagnosis of bacterial LRTI. The findings on TC were included to integrate all the LRTI etiological diagnosis. The outcomes recorded were to need supplementary oxygen therapy (nasal cannula, high-flow nasal cannula or mechanical ventilation), ICU admission, and mortality on the follow for all patient included in the study. A descriptive statistical analysis was performed to estimate frequency of the etiological agents, outcomes, and mortality rate. Results A total of 10 children with cancer and severe LRTI were followed up, 60% female sex, age 5.5 years (range, 1-16 &amp;lt;); 80% had acute leukemias and 20% lymphoma. Seven (70%) children were diagnosed with bacterial LRTI, whereas two (20%) and one (10%) were viral LRTI-diagnosed. The finding in the CT were the follow: bilateral patchy consolidation and ill-defined small nodules for viral infection, centrilobular nodules and bronchial wall thickening for bacterial infection and scattered nodules or patchy focus for fungal infection. In respect to clinical presentation 90% had fever, 100% had cough, and 100% had O2Sat &amp;lt;93%. Of these patients 60% were presented with profound and 20% with severe neutropenia (p&amp;lt;0.05); 30% had required high-flow oxygen and 10% mechanical ventilation; and three (30%) patients required care in ICU. The mortality rate for severe LRTI was 30%. Conclusion Children with cancer and profound or severe neutropenia are in high-risk to develop severe LRTI and they have high mortality. The finding on the CT can help to start on adequate management for LRTI in immunosuppressed pediatric patients.

The effect of midline shift on survival time in dogs with structural brain disease diagnosed on MRI.

The effect of midline shift identified on brain MRI on survival time in dogs with structural brain disease is relatively unknown. This retrospective single-centered cohort study reviewed medical and imaging data of 77 dogs with structural brain lesions evident on MRI. Images were reviewed for the presence of midline shift, brain edema, foramen magnum herniation, and ventriculomegaly. Kaplan-Meier method and Cox regression analysis were undertaken to compare survival between dogs with and without midline shift. Midline shift was present in 40 of 77 (52%) dogs and absent in 37 of 77 (48%). Univariate analysis revealed that dogs with midline shift had a median survival time of 34.5 days (95% CI, 4-108 days) compared with 241 days (95% CI, 133,- days) in dogs without midline shift (hazard ratio=2.67, 95% CI, 1.5-4.49). Multivariate Cox regression analysis revealed a hazard ratio of 3.6 (95% CI, 1.7-7.6; P-value<.001) for dogs with midline shift. Shorter median survival times remained significant in all groups after segregation based on etiological diagnosis. The significantly shorter survival times observed herein for dogs with midline shifts, regardless of etiologic cause, provide further evidence that midline shift holds value as a negative prognostic factor in diagnostic imaging.

Deciphering infectious uveitis etiology: Immune cell profiling in keratic precipitates using in vivo confocal microscopy

PurposeTo elucidate the etiology of infectious uveitis through the comprehensive analysis of keratic precipitates (KPs) using in vivo confocal microscopy (IVCM). DesignCross-sectional, observational case series. MethodsThis single-center, cross-sectional study was conducted at a tertiary care eye hospital from January 2021 to October 2023. It involved a detailed ophthalmologic evaluation of all subjects and included a total of 46 eyes from 36 subjects who were diagnosed with infectious uveitis. IVCM, specifically utilizing the HRT II Rostock corneal module, was employed to study the biomicroscopic morphology of KPs. The categorization of KPs was based on cell size, morphology, and reflection. ResultsCells of KPs were assessed for size, morphology, and reflection through in vivo confocal microscopy. Patients, ranging in age from 13 to 80 years (median 51 years), exhibited diverse morphologic forms of KPs. Neutrophil-dominated KPs with uniform size were predominantly observed in bacterial and fungal endophthalmitis cases (19/19, 100 %), accompanied by small numbers of mononuclear-macrophages in three eyes (3/19, 15.8 %). Viral uveitis cases displayed a broader array of immune cell types, including characteristic striated or dendritic cells in all eyes (27/27, 100 %). Lymphocytes were commonly present (24/27, 88.9 %), forming clusters in sixteen eyes and dispersed in the corneal endothelium below the midline in eight eyes. Neutrophil infiltration was notable in three cytomegalovirus-infected eyes (3/27, 11.1 %). A marked increase in sub-basal corneal epithelial Langhans cells was associated with viral uveitis. ConclusionsNeutrophil-dominated KPs strongly indicate endogenous bacterial or fungal endophthalmitis, while the presence of dendritic cells and lymphocytes in KPs is suggestive of viral uveitis. In vivo confocal microscopy emerges as a crucial tool for differentiating the etiologic diagnosis of infectious uveitis.

The challenge of etiologic diagnosis of subacute and chronic meningitis: an analysis of 183 patients.

Subacute and chronic meningitis (SCM) presents significant diagnostic challenges, with numerous infectious and non-infectious inflammatory causes. This study examined patients aged 16 and older with SCM admitted to referral centers for neuroinfections and neuroinflammations in Mashhad, Iran, between March 2015 and October 2022. Among 183 episodes, tuberculous meningitis was the most common infectious cause (46.5%), followed by Brucella meningitis (24.6%). The cause of SCM was definitively proven in 40.4%, presumptive in 35.0%, and unknown in 24.6% of cases. In-hospital mortality was 14.4%, and 30.5% of survivors experienced unfavorable outcomes (Glasgow Outcome Scale 2-4). Patients with unknown causes had a significantly higher risk of death compared to those with presumptive or proven diagnoses (risk ratio 4.18). This study emphasizes the diagnostic difficulties of SCM, with one-quarter of cases remaining undiagnosed and over one-third having only a presumptive diagnosis. Improving diagnostic methods could potentially enhance prognosis and reduce mortality.

Voltage-gated potassium channels and genetic epilepsy.

Recent advances in exome and targeted sequencing have significantly improved the aetiological diagnosis of epilepsy, revealing an increasing number of epilepsy-related pathogenic genes. As a result, the diagnosis and treatment of epilepsy have become more accessible and more traceable. Voltage-gated potassium channels (Kv) regulate electrical excitability in neuron systems. Mutate Kv channels have been implicated in epilepsy as demonstrated in case reports and researches using gene-knockout mouse models. Both gain and loss-of-function of Kv channels lead to epilepsy with similar phenotypes through different mechanisms, bringing new challenges to the diagnosis and treatment of epilepsy. Research on genetic epilepsy is progressing rapidly, with several drug candidates targeting mutated genes or channels emerging. This article provides a brief overview of the symptoms and pathogenesis of epilepsy associated with voltage-gated potassium ion channels dysfunction and highlights recent progress in treatments. Here, we reviewed case reports of gene mutations related to epilepsy in recent years and summarized the proportion of Kv genes. Our focus is on the progress in precise treatments for specific voltage-gated potassium channel genes linked to epilepsy, including KCNA1, KCNA2, KCNB1, KCNC1, KCND2, KCNQ2, KCNQ3, KCNH1, and KCNH5.

Utilization of MALDI-TOF MS in the etiological diagnosis of deep-seated anaerobic bacterial infections

PurposeDeep-seated abscesses can be caused by a wide array of bacteria in various anatomical sites, the precise identification of which is crucial for implementing organism-specific treatments which can reduce morbidity and mortality. MALDI-TOF MS is a powerful proteomic method for the swift and accurate identification of anaerobic organisms. The aim of this study was to investigate deep-seated infections by MALDI-TOF MS (in comparison to VITEK®2 ANC ID card and phenotypic biochemical tests) and to determine the susceptibility pattern of identified microorganisms. Materials and methodsA total of 104 samples from patients suspected of deep-seated infections were aseptically collected and subjected to microscopy, aerobic/anaerobic cultures and subsequent identification via MALDI-TOF MS followed by antimicrobial susceptibility testing. Anaerobic bacteria were also identified using the VITEK-2 system and phenotypic biochemical tests. ResultsOut of the 104 samples tested, 41.3 % (43/104) showed positive results, predominantly in pus specimens (88 %). Mixed infections were found in 21 % of the positive cases. Of the 52 organisms identified from positive specimens, 19.2 % (10/52) were obligate anaerobes, with Bacteroides fragilis group being the most prevalent, followed by both Clostridium perfringens and Clostridium sporogenes respectively. Escherichia coli was observed to be the most common facultative anaerobic isolate. All obligate anaerobes were successfully identified to the species level via MALDI-TOF MS. In contrast, the VITEK®2 ANC ID card identified only 40 % (4/10) anaerobic bacteria to the species level. All obligate anaerobic organisms showed 100 % susceptibility to metronidazole, vancomycin and ertapenem. 25 % of the Bacteroides spp. and 50 % of Clostridium perfringens isolates were found to be resistant to clindamycin. ConclusionMALDI-TOF MS proves as a beneficial diagnostic tool for bacterial identification, eliminating the labour-intensive and time consuming conventional microbiological methods. Its accuracy of bacterial detection further helps in combating antibiotic resistance and improving patient outcomes in deep-seated infections.

Association of the Area Deprivation Index With Dementia Basic Workup and Diagnosis in Central and Western Virginia: A Cross-Sectional Study.

The Area Deprivation Index (ADI) provides a validated and multidimensional metric of areal disadvantage. Our goals were to determine if the ADI influences the likelihood of receiving workup based on published guidelines and an etiologic diagnosis of dementia in Central and Western Virginia. We collected deidentified data from the electronic health record of individuals aged 50-105 years diagnosed with dementia at the University of Virginia (UVA) Medical Center (2016-2021) and at Carillion Clinic (2018-2021). Visit-specific ICD-10 codes were used to classify each dementia diagnosis as "disease-specific" (e.g., Alzheimer disease) or "general" (e.g., unspecified dementia). Following the American Academy of Neurology guidelines, we considered the evaluation performed as "adequate" if patients had vitamin B12, thyroid-stimulating hormone, and brain CT or magnetic resonance imaging within 6 months of the initial diagnosis. Census tract ADI was linked to study participants using the unique census tract identifier derived from the participants' home addresses at the time of diagnosis. Statistical modeling occurred under a Bayesian paradigm implemented using a standard code in R. The study included 13,431 individuals diagnosed with dementia at UVA (n = 7,152) and Carillion Clinic (n = 6,279). Of those, 32.5% and 20.4% received "disease-specific" diagnoses at UVA and Carillion Clinic and 8.2% and 20.4% underwent "adequate" workup, respectively. The adjusted relationship between census tract ADI and the likelihood of a disease-specific diagnosis was U-shaped: Residence in moderately disadvantaged areas was associated with the lowest likelihood of disease-specific diagnosis. Most patients diagnosed with dementia did not receive an adequate evaluation or an etiologic diagnosis. Those living in locations just above the national median ADI levels had the lowest likelihood of receiving an etiologic diagnosis, lower than those in the least and most deprived areas. Renewed awareness efforts among providers are needed to increase compliance with diagnostic guidelines.

Staged Retrograde Intraoperative Enteroscopy: Description of the 5-Step Surgical Technique for the Diagnosis and Treatment of Small Bowel Bleeding.

Background: Small bowel bleeding (SB) comprises 5%-10% of gastrointestinal (GI) bleeding cases. This article describes the staged retrograde intraoperative enteroscopy (SRIE) surgical technique for the etiological diagnosis and treatment of small bowel bleeding. Methods: SRIE was performed on patients with persistent SB at a quaternary university hospital in Brazil from 2020 to 2023. The technique is described in 5 steps, alongside visual aids, including images and a depicting a portion of the procedure. Patients presenting with confirmed coagulopathies, pregnancy, or unwillingness for surgery were excluded. Surgical procedures were performed after informed consent. Case Series: Four participants were submitted to SRIE, including 2 females (64 and 83 years old), and 2 males (46 and 57 years old). Three out of four (75%) of the patients received a confirmed diagnosis of GI bleeding, attributed to angioectasia, acquired von Willebrand disease, and vitamin K deficiency. SRIE was conducted via enterotomy, involving a subsequent insufflation-inspection-deflation of 10 to 10 cm segments of the small bowel (Steps 1 to 5). The procedure was successfully executed in all four patients without complications, allowing confirmation of the etiological diagnosis of SB or exclusion of anatomical causes of hemorrhage. Conclusions: SRIE is a valuable but invasive tool for assessing SB hemorrhage when conventional imaging falls short. When performed systematically and standardized, it allows accurate visualization of SB using a standard endoscope.