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Neurosyphilis presents significant diagnostic and therapeutic challenges due to its heterogeneous clinical manifestations, absence of a gold-standard diagnostic criterion, and variable treatment responses. This study aims to identify clinically homogeneous subtypes of suspected neurosyphilis patients and develop a machine learning-based subtyping model to support clinical decision-making. Data from 451 suspected neurosyphilis patients were retrospectively collected from West China Hospital of Sichuan University. Patients were divided into a model development cohort (n=369) and an external validation cohort (n=82) by time. Latent class analysis (LCA) was performed to identify subtypes, with the optimal class number determined by model fit indicators. Key predictive variables were selected using LASSO regression and Boruta algorithm. Six machine learning algorithms were employed to build LCA subtype prediction models. Feature importance was interpreted via SHAP analysis, and model generalizability was assessed using the external cohort. LCA classified patients into three homogeneous subtypes: \"typical neurosyphilis\" (43.7%; predominantly male, high serum TRUST titer, significant CSF abnormalities, and robust intrathecal immune activation), \"atypical neurosyphilis\" (17.9%; absence of elevated CSF protein, mild intrathecal IgG synthesis), \"non-neurosyphilis\" (38.5%; normal CSF parameters). Six variables (age, serum TRUST titer, CSF protein, CSF nucleated cells, IgG index, CSF TTs) were used for model construction. The XGBoost model demonstrated optimal performance, achieving an AUC of 0.966 (accuracy: 87.3%) on the internal test set and 0.970 (accuracy: 91.5%) on the external validation set. Key predictors included CSF nucleated cells, CSF TTs, and IgG index. This study defines three clinically meaningful latent subtypes of neurosyphilis. The developed XGBoost model effectively discriminates between these subtypes of neurosyphilis and non-neurosyphilis in clinical settings, facilitating timely diagnosis and treatment.

Neurosyphilis can occur at any stage of syphilis. After treatment, 30%-40% of syphilis patients remained serofast. But the prevalence of asymptomatic neurosyphilis (ANS) among serofast syphilis patients remains unclear. Untimely treatment or improper management for ANS may result in neurological complications. So we perform the meta-analysis to evaluate the prevalence of ANS cases among HIV-negative serofast syphilis patients for exploring their relationship and addressing their clinical management. We searched CNKI, Wan Fang, VIP, CBMdisc, PubMed, Embase and Medline from January 1st 1990 to September 22nd 2020 for both English and Chinese records. We strictly restrict the eligibility criteria. STROBE was used for reporting quality assessment. We examined forest plots and conducted both fix-effects and random-effects to estimate prevalence by R version 3.6.2/R studio 1.2.1335 statistical software packages META version 4.9-9. If appropriate, between-study heterogeneity was examined using the I2 statistic and subgroup analysis. Of 77 screened records, 5 were included. The pooled prevalence of ANS among HIV-negative serofast syphilis patients was 13% (95% CI 3%-23%; I2 = 93% P<0.01, 417 people). The prevalence of ANS for the verified ANS classification definition was 3% (95% CI 0%-7%; I2 = 67% P = 0.08, two studies, 189 people), and 21% (95% CI 6%-36%; I2 = 86% P<0.01, three studies, 228 people) for the likely ANS classification. The prevalence of ANS among the serofast syphilis patients who were followed up for one year was 29% (95% CI 22%-36%; I2 = 0% P = 0.5, two studies, 167 people) and 5% (95% CI 0%-13%; I2 = 79% P = 0.03, two studies, 144 people) for two years. The prevalence in the studies from different geographical subgroups was as follows: 9% (95% CI 0%-19%; I2 = 82% P<0.01, three studies, 169 people) in South-central China, 6% (95% CI 1%-10%; one study, 106 people) in East China, and 30% (95% CI 23%-38%; one study, 142 people) in North China. This meta-analysis showed a high estimated prevalence of ANS in HIV-negative serofast syphilis patients, the prevalence of ANS among patients diagnosed with the verified ANS case definition is much lower than that for the likely ANS classification. It may be necessary to carry out nontreponemal test, protein test and leukocyte count for cerebrospinal fluid (CSF) in treated serofast patients for better clinical management to avoid neurological complications. The case classification definition of ANS is a key factor to evaluate the prevalence. Geographical heterogeneity needs more studies to detect. In future we need better-design studies to explore relationship between ANS and serofast status.

ABSTRACTThe surveillance of neurosyphilis, an uncommon but severe consequence of syphilis, is complex; surveillance classification of neurosyphilis requires a lumbar puncture and cerebrospinal fluid analysis. We examined the prevalence of reported neurosyphilis among primary, secondary, and early latent syphilis cases reported in the United States from 2009 to 2015. Overall, the prevalence of reported neurosyphilis from 2009 to 2015 was low (0.84%); however, this is likely an underestimate of the true burden in the United States.

BACKGROUNDSyphilis can have many clinical manifestations, including eye involvement, or “ocular syphilis.” In 2015, an increase in reported cases of ocular syphilis and potential case clusters raised concern for an oculotropic strain of Treponema pallidum, the infectious agent of syphilis. Molecular typing was used to examine strains found in cases of ocular syphilis in the United States. METHODSIn 2015, after a clinical advisory issued by the Centers for Disease Control and Prevention, pretreatment clinical specimens from US patients with ocular syphilis were sent to a research laboratory for molecular analysis of T. pallidum DNA. Molecular typing was conducted on these specimens, and results were compared with samples collected from Seattle patients diagnosed with syphilis, but without ocular symptoms. RESULTSSamples were typed from 18 patients with ocular syphilis and from 45 patients with syphilis, but without ocular symptoms. Clinical data were available for 14 ocular syphilis patientsmost were men, human immunodeficiency virus–infected, and had early syphilis. At least 5 distinct strain types of Treponema pallidum were identified in these patients, and 9 types were identified in the Seattle nonocular patients. 14d/g was the most common type in both groups. An unusual strain type was detected in a small cluster of ocular syphilis patients in Seattle. CONCLUSIONSOcular syphilis is a serious sequela of syphilis. In this preliminary study, clear evidence of a predominant oculotropic strain causing ocular syphilis was not detected. Identification of cases and prompt treatment is critical in the management of ocular syphilis.

Background/aimsIn the era of increasing incidence of syphilis globally, ocular syphilis is re-emerging as an important cause of uveitis. The aim of this study was to determine the clinical and laboratory characteristics of ocular- and neurosyphilis among individuals with and without HIV infection.MethodsRetrospective analysis of patients diagnosed with ocular syphilis presenting to Tygerberg Hospital, South Africa, over a 5-year period ending December 2018.ResultsTwo-hundred and fifteen eyes of 146 patients were included. HIV coinfection was present in 52.1% of the patients, with 23.7% of these patients being newly diagnosed on presentation. The median age was 36.5±9.8 years. Bilateral involvement occurred in 47.3%, with 68.1% of these patients being HIV positive. The most frequent form of intraocular inflammation was posterior uveitis (40.9%), followed by panuveitis (38.1%), both of which were more predominant in HIV-positive eyes. Seventy-four per cent of all eyes had a visual acuity ≤20/50 and 40% <20/200 at presentation. A lumbar puncture was performed in 113 patients (77.4%). Sixteen patients had confirmed neurosyphilis and 27 probable neurosyphilis according to the UpToDate algorithms.ConclusionThis study included the largest number of ocular syphilis cases with the largest proportion of HIV infection to date. Forty-three of 146 patients (37.0%) had neurosyphilis. HIV status must be determined in all patients with ocular syphilis since almost ¼ of patients were newly diagnosed with HIV infection by doing so.

Background Tracking the evolution of scientific knowledge is challenging due to the scale and complexity of the biomedical literature. Neurosyphilis is a clinically complex and historically stigmatized condition that remains difficult to diagnose and manage. Its underexplored literature offers an ideal test case to evaluate digital methods for mapping research trends and identifying knowledge gaps. We aim to assess how large language models (LLMs), network analysis, and interrupted time series analysis (ITSA) can be combined to automate literature classification and examine how knowledge of neurosyphilis has evolved. Methods We systematically searched Web of Science, Embase, PubMed Central, the Cochrane Library, and Lens for records on neurosyphilis published until December 31, 2024. We included records with available titles and abstracts in which GPT-4o mini was identified as being focused primarily on syphilis or neurosyphilis. Eligible records were classified into 23 research fields via LLM-based prompts. Network analysis visualized changes in research structures over time, and the ITSA assessed associations between publication trends and major clinical or technological milestones. Results Among the 14 934 retrieved records, 4 646 met the inclusion criteria. LLM-based classification showed high repeatability (agreement = 99·67%, 95% CI 99·47–99·80; Cohen’s κ = 0·99, 95% CI 0·96–1·00). Biomedical, Clinical, and Health sciences were the most common domains. Network analysis revealed a shift from dense, discipline-specific clusters to larger interdisciplinary structures. ITSA revealed significant increases in publication activity following the introduction of penicillin G, HIV emergence, genome sequencing of Treponema pallidum , and the rise of digital dissemination platforms. Conclusions Combining LLMs with bibliometric and network methods provides a scalable framework for analyzing large-scale biomedical literature. When applied to neurosyphilis, the approach revealed links between research activity and clinical and technological advances. In addition to this case study, the method could support meta-research and inform evidence-based decision-making across other complex medical conditions.

Background. Strain typing is a tool for determining the diversity and epidemiology of infections. Methods. Treponema pallidum DNA was isolated from 158 patients with syphilis from the United States, China, Ireland, and Madagascar and from 15 T. pallidum isolates. Six typing targets were assessed: (1) the number of 60- bp repeats in the acidic repeat protein gene, (2) restriction fragment length polymorphism (RFLP) analysis of T. pallidum repeat (tpr) subfamily II genes, (3) RFLP analysis of the tprC gene, (4) determination of tprD allele in the tprD gene locus, (5) the presence of a 51-bp insertion between tp0126 and tp0127, and (6) sequence analysis of an 84-bp region of tp0548. The combination of targets 1 and 2 comprises the Centers for Disease Control and Prevention (CDC) T. pallidum subtyping method. Results. Adding sequence analysis of tp0548 to the CDC method yielded the most discriminating typing system. Twenty-five strain types were identified and designated as “CDC subtype/tp0548 sequence type.” Type 14d/f was found in samples from 5 of 6 locations. In Seattle, Washington, strain types changed from 1999 through 2008 ( P < .001). Twenty-one (50%) of 42 patients infected with type 14d/f had neurosyphilis compared with 10 (24%) of 41 patients infected with any of the other types combined (P=.02). Conclusion. We describe an enhanced T. pallidum strain typing system that shows biological and clinical relevance.

In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used (\"psychotic disorder with delusions due to known physiological condition\" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p  < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with \"no reliable diagnostic classification\". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 ( p  = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.

Of 76 infants born to women with syphilis who had no in utero or postnatal exposure to antibiotics, 17 (22 percent) had spirochetes detected in the cerebrospinal fluid. Most of the infants with central nervous system infection could be identified by abnormalities on the physical examination, radiographic studies, or conventional tests, such as the cerebrospinal fluid white-cell count and the Venereal Disease Research Laboratory test. However, the results of IgM immunoblotting of serum and the polymerase-chain-reaction assay of serum or blood proved to be the best predictors of the detection of central nervous system infection by the rabbit-infectivity test. In infants with suspected congenital syphilis, the detection of central nervous system infection by Treponema pallidum remains an elusive but important diagnostic goal. The diagnosis of congenital neurosyphilis has major therapeutic implications because penicillin G benzathine does not reach treponemicidal concentrations in the cerebrospinal fluid, 1 , 2 even though this drug is one of the recommended alternative treatments for infants at risk for congenital syphilis. 3 , 4 In addition, establishing the prevalence of central nervous system infection among infants with congenital syphilis would help determine the extent to which the central nervous system constitutes a reservoir of infection. Neurosyphilis is believed to . . .

Background Rapidly progressive dementia (RPD) is a syndrome originating from various diseases. Recent advances have allowed a better understanding of its categories and spectrum; however, it remains challenging to make an accurate differential diagnosis and prognosis prediction. Methods This study was a retrospective evaluation of all participants admitted to the neurology department of a single center in China from January 2015 to December 2019. The screened patients met the RPD criteria and their characteristics were collected to explore a diagnostic pattern of RPD. In addition, outcomes of RPD were evaluated with the Glasgow Outcome Scale (GOS), activities of daily living scale (ADL), and simplified Mini-Mental State Examination (MMSE), and different prognostic analysis methods were performed to determine the prognostic factors of RPD. Results A total of 149 RPD patients among 15,731 inpatients were identified with an average MMSE value of 13.0 ± 4.6 at baseline. Etiological epidemiology revealed infectious, neurodegenerative and toxic/metabolic diseases as the three largest groups, accounting for 26.2%, 20.8% and 16.8% of all cases, respectively. In particular, prevalence rates of Creutzfeldt–Jakob disease (13.4%), Alzheimer’s disease (11.4%), carbon monoxide poisoning (8.1%), neurosyphilis (5.4%) and dementia with Lewy bodies (5.4%) were highest in this series. A recommended diagnostic framework for RPD etiology was thus established. Follow-up evaluations showed a negative correlation between age and GOS scores (r=-0.421, P < 0.001), as well as age and simplified MMSE scores (r s =- 0.393, P < 0.001), and a positive correlation between age and ADL scores (r s =0.503, P < 0.001), and significantly different GOS, ADL and simplified MMSE scores across various etiologies (P = 0.003; F = 9.463, P  < 0.001; F = 6.117, P  < 0.001). Conclusion Infectious, neurodegenerative and toxic-metabolic entities were the most common RPD categories, and establishing a practical approach to RPD etiology would allow better disease management.