Interval-specific likelihood ratios and probability-based models for interpreting combined CSF biomarkers for Alzheimer's disease.

BACKGROUND: In Alzheimer's disease (AD) diagnosis, a cerebrospinal fluid (CSF) biomarker panel is commonly interpreted with binary cutoff values. However, these values are not generic and do not reflect the disease continuum. We explored the use of interval-specific likelihood ratios (LRs) and probability-based models for AD using a CSF biomarker panel. METHODS: CSF biomarker (Aß1-42, tTau and pTau181) data for both a clinical discovery cohort of 241 patients (measured with INNOTEST) and a clinical validation cohort of 129 patients (measured with EUROIMMUN), both including AD and non-AD dementia/cognitive complaints were retrospectively retrieved in a single-center study. Interval-specific LRs for AD were calculated and validated for univariate and combined (Aß1-42/tTau and pTau181) biomarkers, and a continuous bivariate probability-based model for AD, plotting Aß1-42/tTau versus pTau181 was constructed and validated. RESULTS: LR for AD increased as individual CSF biomarker values deviated from normal. Interval-specific LRs of a combined biomarker model showed that once one biomarker became abnormal, LRs increased even further when another biomarker largely deviated from normal, as replicated in the validation cohort. A bivariate probability-based model predicted AD with a validated accuracy of 88% on a continuous scale. CONCLUSIONS: Interval-specific LRs in a combined biomarker model and prediction of AD using a continuous bivariate biomarker probability-based model, offer a more meaningful interpretation of CSF AD biomarkers on a (semi-)continuous scale with respect to the post-test probability of AD across different assays and cohorts.

Visibility of esophageal squamous cell carcinoma under iodine staining on texture and color enhancement imaging.

Objective: Iodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining. Methods: Twenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow-band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging. Result: The median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow-band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01). Conclusions: The visibility of ESCC after iodine staining was greater on TXI than on WLI.

Rare case of mantle cell lymphoma of the lacrimal sac

ABSTRACT Mantle cell lymphoma of the ocular and periorbital regions is extremely rare but should be considered in the differential diagnosis of lesions affecting the periorbital tissues. In this study, we present a rare case of mantle cell lymphoma of the lacrimal sac in a 65-year-old male presenting with a mass in the lacrimal sac region and epiphora. After clinical examinations and imaging studies, the mucocele was misdiagnosed. Considering the unexpected findings during external dacryocystorhinostomy, a frozen biopsy was performed, which confirmed the diagnosis of lymphoma.

Anterior lamellar corneoscleral keratoplasty for the management of corneal thinning following treatment with mitomycin-C and interferon to treat highly suspected ocular surface squamous neoplasia: a case report

ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

Clinical, epidemiological, and care profile of hospitalized patients with retinoblastoma in Brazil

ABSTRACT Purpose: To describe the epidemiological and clinical profile of hospitalized patients with retinoblastoma in Brazil. Methods: Using data from the Hospital Cancer Registry of the Instituto Nacional de Câncer, patients with the morphological codes of retinoblastoma who were diagnosed between 2000 to 2018, aged 0-19 years, and followed up in registered hospitals (analytical cases) were selected. The relative and absolute frequencies of demographic, clinical, diagnostic, therapeutic, and outcome variables were described. Hospital performance indicators were calculated and compared between hospitals qualified and not qualified to treat pediatric oncology cases and between hospitals with different case volumes (<20, 20-75, >75 cases). Results: Of the 2,269 identified analytical cases from 86 institutions, 48% were from the Southeast, 54% were male, and 66% were aged <4 years. The proportion of missing data (NA) was too high for several variables. Approximately 84% of the patients were from the public health system, 40% had a positive family history, and 88% had unilateral involvement. The first treatment included surgery in 58.3% of the patients (NA=2), Approximately 36.6% of these patients achieved complete remission, 10.8% achieved partial remission, and 12.7% died (NA=59%). Hospital performance indicators were within the target in >90% of the patients. The median time between the first appointment and diagnosis (6 days, interquartile range [IQR] 1-14) was significantly lower and the median time to death was longer (343 days, IQR, 212-539) in high-volume hospitals (>75 cases) than in medium- and low-volume hospitals. Conclusions: Despite the high proportion of missing data, we found that the delay in diagnosis is due to prehospital factors. Additionally, there is a need for educational programs for healthcare professionals and families that emphasize early identification and referral to specialized centers. Future studies should focus on the impact of Hospital Cancer Registry data completeness on outcomes, causes of delay in diagnosis, regional inequalities, and barriers to accessing specialized services.

Retrosynthetic analysis via deep learning to improve pilomatricoma diagnoses.

BACKGROUND: Pilomatricoma, a benign childhood skin tumor, presents diagnostic challenges due to its manifestation variations and requires surgical excision upon histological confirmation of its characteristic cellular features. Recent artificial intelligence (AI) advancements in pathology promise enhanced diagnostic accuracy and treatment approaches for this neoplasm. METHODS: We employed a multiscale transfer learning model, initiating the training process at high resolutions and adapting to broader scales. For evaluation purposes, we applied metrics such as accuracy, precision, recall, the F1 score, and the area under the receiver operating characteristic curve (AUROC) to measure the performance of the model, with the statistical significance of the results assessed via two-sided P tests. Our novel approach also included a retrosynthetic saliency mapping technique to achieve enhanced lesion visualization in whole-slide images (WSIs), supporting pathologists' diagnostic processes. RESULTS: Our model effectively navigated the challenges of global-scale classification, achieving a high validation accuracy of up to 0.973 despite some initial fluctuations. This method displayed excellent accuracy in terms of identifying basaloid and ghost cells, especially at lower scales, with slight variability in its ghost cell accuracy and more noticeable changes in the 'Other' category at higher scales. The consistent performance attained for basaloid cells was clear across all scales, whereas areas for improvement were identified in the 'Other' category. The model also excelled at generating detailed and interpretable saliency maps for lesion visualization purposes, thereby enhancing its value in digital pathology diagnostics. CONCLUSION: Our pilomatricoma study demonstrates the efficacy of a deep learning-based histopathological diagnosis model, as validated by its high performance across various scales, and it is enhanced by an innovative retrosynthetic approach for saliency mapping.

Fetal therapies - (Stem cell transplantation; enzyme replacement therapy; in utero genetic therapies).

Advances in ultrasound and prenatal diagnosis are leading an expansion in the options for parents whose fetus is identified with a congenital disease. Obstetric diseases such as pre-eclampsia and fetal growth restriction may also be amenable to intervention to improve maternal and neonatal outcomes. Advanced Medicinal Therapeutic Products such as stem cell, gene, enzyme and protein therapies are most commonly being investigated as the trajectory of treatment for severe genetic diseases moves toward earlier intervention. Theoretical benefits include prevention of in utero damage, smaller treatment doses compared to postnatal intervention, use of fetal circulatory shunts and induction of immune tolerance. New systematic terminology can capture adverse maternal and fetal adverse events to improve safe trial conduct. First-in-human clinical trials are now beginning to generate results with a focus on safety first and efficacy second. If successful, these trials will transform the care of fetuses with severe early-onset congenital disease.

Yield of skeletal surveys in national network of child abuse pediatricians: Age is key.

BACKGROUND: Skeletal surveys (SS) are recommended for the evaluation of suspected physical abuse in children <2 years old. No guidelines exist for SS completion in children between 2 and 5 years old. OBJECTIVE: To determine rates of SS completion by age and examine variables associated with occult fracture identification in older children. PARTICIPANTS AND SETTING: Observational cross-sectional multi-center study of 10 US pediatric centers 2/2021-9/2022 including children <6 years old evaluated for physical child abuse. METHODS: The principal outcome is occult fracture identified on SS. Non-parametric tests were conducted from comparison between age groups and those with and without occult fractures. RESULTS: The rate of SS completion declined with increasing age from a high of 91 % in infants <6 months old to 7 % in children 5-5.9 years old. The proportion of SS with occult fractures also decreased with age. Of 450 children 2-5 years old with a SS, 20 [4 % (95 % CI: 3-8 %)] had an occult fracture. The rate of occult fractures among children 2-5 years old who were diagnosed with abuse and not admitted to the hospital was 0.3 % (95 % CI 0-0.6 %)]. Over 30 % of children 2-5 years old were diagnosed with child abuse by a child abuse pediatrician without completion of a SS. CONCLUSION: In children 2-5 years of age being evaluated for physical abuse, use of SS and the rate of occult fractures is low. The number of SS performed in children in this age group could potentially be decreased by up to 60 % by limiting SS to children admitted to the hospital.

Connexin 43 controls metastatic behavior in triple negative breast cancer through TGFß1-Smad3-intergin αV signaling axis Based on optical image diagnosis.

Abnormal expression of connexin 43 (Cx43) contributes to the development and progression of cancer. However, its regulation is complex and dependent on the environment. The expression of Cx43 in triple-negative cancer lesions was analyzed by immunohistochemistry and optical coherence tomography using experimental models and clinical samples. The model of TGFß1-SMad3-in-αv signal axis was established and verified by experiments. The results show that Cx43 plays a key role in the regulation of triple-negative cancer metastasis. In vivo, over-expressed Cx43 decreased tumor volume and inhibited ITGαV, TGF-ß1, Smad3 and N-cadherin expressions, but enhanced the E-cadherin. Cx43 had the lowest expression in the TNBC samples, especially in lymph node metastatic TNBC patients and had a negative correlation with ITG alpha V, TGF-ß1 and Smad3.The study demonstrated Cx43 controlled metastatic behavior through TGF-ß1 -Smad3-ITG αV signaling axis in MDA-MB-231 cells, providing evidence for Cx43's function in TNBC. The optical image diagnosis method can realize the identification and quantitative evaluation of early cancer triple negative, and provide a new strategy and means for the treatment of cancer triple negative.

Evaluation of the diagnostic ability of the Fränkel manoeuvre to detect the contributing jaw in angle class II division 1 malocclusion.

BACKGROUND: A correct diagnosis of patients with an Angle Class II malocclusion is needed to guide treatment decisions toward the contributing jaw and to achieve better treatment outcomes. The aim of the study is to evaluate the diagnostic potential of the Fränkel manoeuvre (FM) for detecting the components determining sagittal discrepancy in Angle Class II division 1. MATERIALS AND METHODS: Anonymous questionnaires containing photographs were distributed totwo groups: general practitioner (GP) dentists and orthodontists. The level of the patient's profile aesthetics before (T0) and after (T1) the manoeuvre was determined using a 100 mm visual analog scale, and the 'profile improvement' score was defined as T1 minus T0. The diagnostic ability of the FM was calculated by comparison with lateral cephalometry as a reference standard using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 102 respondents participated in the survey; 40 were orthodontists, and 62 were GP dentists. According to the post-FM images, the "profile improvement" score (T1-T0) was significantly greater in patients with mandibular retrusion than in those with maxillary protrusion (p < 0.05). The predictive power of FM, coinciding with the area under the ROC curve, was 0.62 for GPs and 0.78 for orthodontists. CONCLUSIONS: The FM method is a useful and accurate tool for diagnosing skeletal Angle Class II malocclusion etiology (mandibular retrusion or maxillary protrusion), especially when used by orthodontists.

Evaluation of DIAGNOdent pen for initial occlusal caries diagnosis in permanent teeth.

BACKGROUND: To verify the validity of diagnosing initial caries on occlusal surface of permanent posterior teeth by laser fluorescence instrument DIAGNOdent pen. METHODS: Patients from School of Stomatology in Wuhan University were selected and their posterior teeth were examined using DIAGNOdent pen and the International Caries Detection and Assessment System (ICDAS II) by an experienced dentist. After teeth extraction, histological criteria were used to determine the severity of the lesions. The sensitivity, specificity, accuracy, the area under the curve (AUC), and correlation of DIAGNOdent pen and ICDAS II were analyzed compared with histological criteria. Examiners' agreement was measured. RESULTS: The sensitivity range was 0.440-1 while that of specificity was 0.750-0.994. The accuracy and AUC were above 80% and 0.7 respectively. Consistency of examiners' kappa values of ICDAS II, DIAGNOdent pen, and histological criteria were ranged from 0.629 to 0.840. CONCLUSIONS: ICDAS II and DIAGNOdent pen can be effectively used in tandem or independently for the assessment of initial caries.

Differential diagnosis of autism, attachment disorders, complex post-traumatic stress disorder and emotionally unstable personality disorder: A Delphi study.

Individuals diagnosed with autism, attachment disorders, emotionally unstable personality disorder (EUPD) or complex post-traumatic stress disorder (CPTSD) can present with similar features. This renders differential and accurate diagnosis of these conditions difficult, leading to diagnostic overshadowing and misdiagnosis. The purpose of this study was to explore professionals' perspectives on the differential diagnosis of autism, attachment disorders and CPTSD in young people; and of autism, CPTSD and EUPD in adults. A co-produced three-round Delphi study gathered information through a series of questionnaires from 106 international professionals with expertise in assessing and/or diagnosing at least one of these conditions. To provide specialist guidance and data triangulation, working groups of experts by experience, clinicians and researchers were consulted. Delphi statements were considered to have reached consensus if at least 80% of participants were in agreement. Two hundred and seventy-five Delphi statements reached consensus. Overlapping and differentiating features, methods of assessment, difficulties encountered during differential diagnosis and suggestions for improvements were identified. The findings highlight current practices for differential diagnosis of autism, attachment disorders, CPTSD and EUPD in young people and adults. Areas for future research, clinical and service provision implications, were also identified.

Diagnosing Cataracts in the Digital Age: A Survey on AI, Metaverse, and Digital Twin Applications.

PURPOSE: The study explores the evolving landscape of cataract diagnosis, focusing on both traditional methods and innovative technological integrations. It aims to address challenges with subjectivity in traditional cataract grading and to evaluate how new technologies can enhance diagnostic accuracy and accessibility. METHODS: The research introduces and examines the use of Artificial Intelligence (AI), Machine Learning (ML), and Deep Learning (DL) in automating and improving cataract screening processes. It also explores the role of the Metaverse, Digital Twins, and Teleophthalmology for immersive patient education, real-time virtual replicas of eyes, and remote access to specialized care. RESULTS: Various ML and DL techniques demonstrated significant accuracy in cataract detection. The integration of these technologies, along with the Metaverse, Digital Twins, and Teleophthalmology, provides a comprehensive framework for accurate and accessible cataract diagnosis. CONCLUSION: There is a notable paradigm shift toward individualized, predictive, and transformative eye care. The advancements in technology address existing diagnostic challenges and mitigate the shortage of ophthalmologists by extending high-quality care to underserved regions. These developments pave the way for improved cataract management and broader accessibility.

Dormancy and awakening of cancer cells: the extracellular vesicle-mediated cross-talk between Dr. Jekill and Mr. Hyde.

Cancer cell dormancy is a reversible process whereby cancer cells enter a quiescent state characterized by cell cycle arrest, inhibition of cell migration and invasion, and increased chemoresistance. Because of its reversibility and resistance to treatment, dormancy is a key process to study, monitor, and interfere with, in order to prevent tumor recurrence and metastasis and improve the prognosis of cancer patients. However, to achieve this goal, further studies are needed to elucidate the mechanisms underlying this complex and dynamic dual process. Here, we review the contribution of extracellular vesicles (EVs) to the regulation of cancer cell dormancy/awakening, focusing on the cross-talk between tumor and non-tumor cells in both the primary tumor and the (pre-)metastatic niche. Although EVs are recognized as key players in tumor progression and metastasis, as well as in tumor diagnostics and therapeutics, their role specifically in dormancy induction/escape is still largely elusive. We report on the most recent and promising results on this topic, focusing on the EV-associated nucleic acids involved. We highlight how EV studies could greatly contribute to the identification of dormancy signaling pathways and a dormancy/early awakening signature for the development of successful diagnostic/prognostic and therapeutic approaches.

Usefulness of the Upright Posture Test in the Diagnosis of Primary Aldosteronism.

Objective: To assess the usefulness of the upright posture stimulation test (UPT) in the confirmation of primary aldosteronism (PA) in patients in whom saline tests (ST) were inconclusive. Methods: One hundred eighty-seven adult patients with possible PA were retrospectively included and compared to 25 control subjects. Blood samples were obtained after a 1-hour supine posture and during 2 hours of ambulation. An increase in plasma aldosterone concentration (PAC) ≥ 50% with a suppressed renin (≤10.1 ng/L; ≤1 ng/mL/hour) and a cortisol increase ≤50% were considered abnormal. Results: PA patients had higher basal PAC and lower basal direct renin concentration (DRC) (P < .0001) and a higher maximal PAC (P = .0025) and lower maximal DRC (DRCmax) (P < .0001) during UPT compared to controls. PA was confirmed in 145 patients (77.5%), based on either oral/IV ST or UPT. DRCmax ≤12 ng/L during UPT was a predictor of PA (receiver operating characteristic curve sensitivity 93.8%, specificity 88%), and 95.6% of PA patients increased PAC ≥50% on UPT (median 222.2%), while renin remained suppressed. All 41 PA patients with false-negative IV ST (PAC < 162 pmol/L) and 88.9% with borderline response (162-240 pmol/L) had a DRCmax ≤12, while, respectively, 97.6% and 100% increased aldosterone by ≥50%. Similar responses to UPT were found in lateralized (28/63) and bilateral PA source (35/63). PA diagnosis increased from 23.6% to 88.8% using UPT results instead of IV ST and were confirmed at pathology and clinical outcome after adrenalectomy (n = 22). Conclusion: UPT can be useful to confirm PA, particularly in patients with suspected false-negative ST.

A Devastating Diagnosis: Anencephaly With Unexpected Fetal Heartbeat.

This case report describes a severe birth defect called anencephaly in a fetus at 18 weeks of pregnancy. Anencephaly occurs when the upper part of the baby's brain and skull do not form correctly. This condition is usually detected earlier in pregnancy, often in the first three months. However, this case was discovered at 18 weeks, highlighting the need for careful monitoring throughout pregnancy. The unique aspect of this case is that most pregnancies with anencephaly do not progress this far. This later diagnosis provides important information about the different ways the condition can develop. By studying cases like this, healthcare providers can improve prenatal care and potentially detect such defects earlier, even in the later stages of pregnancy. Overall, this report emphasizes the importance of continuous monitoring during pregnancy and offers insights that could lead to better diagnosis, care, and support for families facing similar situations.

Admission Pattern of Gastrointestinal Cancer for 2020-2023 From a Single Tertiary-Care Hospital in Pune, Western Maharashtra.

The prevalence of gastrointestinal (GI) cancer is increasing across diverse regions of India, demanding further investigation at the state level. In response, a new department of surgical gastroenterology was started at a tertiary-care hospital in Pune, Western Maharashtra, in 2019. The objective of this study was to explore the pattern of admissions in terms of demographics and types of GI cancers over the last four years (i.e., 2020-2023). Retrospective admissions data were collected from hospital records for 2020-2023. A total of 2294 patients were treated at the outpatient department (OPD), and 135 patients were admitted to the inpatient department (IPD). The data comprised OPD/IPD admissions, age, gender, diagnosis, and length of stay (LoS). In addition to basic statistical reporting, t-tests were used to explore differences among the study variables. Out of 135 GI cancer patients, 57% were male. The mean age of inpatients per year ranged from 53 to 60 years, with an average age of 56.35 ± 10.14 years. The average LoS was 12.31 ± 9.39 days. From 2020 to 2023, the number of admissions increased from 5 to 57. The increase was more pronounced in men than women (57% vs. 43%, respectively). Furthermore, increased admission of younger patients was observed, and the average LoS decreased from 17 to 11 days from 2020 to 2023, respectively. A statistically significant difference in LoS (p = 0.023) was observed based on gender, where LoS was longer for women than for men on average (13.5 ± 10.8 vs. 9.46 ± 8.28, respectively). As GI cancer incidence is predicted to continue to increase in India, these new estimates will help to plan cancer prevention and control through intervention via early detection and management.

Report of Giardia duodenalis in a non-captive chital Axis axis (Erxleben 1777) in Santa Catarina, South of Brazil.

Giardiasis is an infection of the small intestine by protozoa of the genus Giardia, which has a wide range of susceptible hosts, including domestic and wild animals and humans. Giardia is a zoonotic agent and represents one of the main human parasites, with high prevalence and great importance in public health. This report aims to describe the parasitism of a non-captive Chital deer (Axis axis) by Giardia duodenalis. The animal, after being rescued by soldiers from the 2nd Platoon of the 2nd Company of the 2nd Battalion of the Environmental Military Police of the State of Santa Catarina, was sent to the Wildlife Studies Center (NEVS) of the University of Western Santa Catarina (UNOESC). During clinical care, an exposed fracture in the left pelvic limb and signs of acute respiratory failure were found. Fecal samples were collected for later parasitological diagnosis. Two techniques were applied: centrifugal flotation with zinc sulfate, to diagnose parasites of the gastrointestinal system, and Baermann, to search for parasitism in the respiratory tract. The investigation revealed the presence of Giardia duodenalis. The animal died on the same day of its arrival due to a cardiorespiratory arrest. The presence of this parasite in an invasive exotic deer species highlights its epidemiological importance, as it can act as a source of infection and spread the disease to humans and other animals.

Giardíase é uma infecção do intestino delgado por protozoários do gênero Giardia, o qual apresenta uma ampla variedade de hospedeiros suscetíveis, incluindo animais domésticos, selvagens e também humanos. Giardia é um agente zoonótico, e representa um dos principais parasitas de humanos, com alta prevalência e grande importância em saúde pública. Este relato tem como objetivo descrever o parasitismo de um indivíduo de cervo Chital (Axis axis) de vida livre por Giardia duodenalis. O animal, após ser resgatado por soldados do 2º Pelotão da 2ª Companhia do 2º Batalhão da Polícia Militar Ambiental do Estado de Santa Catarina, foi encaminhado ao Núcleo de Estudos em Vida Selvagem (NEVS) da Universidade do Oeste de Santa Catarina (UNOESC). Durante o atendimento clínico foi constatada fratura exposta no membro pélvico esquerdo e sinais de insuficiência respiratória aguda. Amostras de fezes foram coletadas para posterior diagnóstico parasitológico. Para isso, foram usadas duas técnicas: centrífugo-flutuação em sulfato de zinco, com o objetivo de diagnosticar parasitas do sistema gastrointestinal, e Baermann, com o objetivo de pesquisar parasitas do trato respiratório. Os achados revelaram presença de cistos de Giardia duodenalis. O animal morreu no mesmo dia de sua chegada, devido a uma parada cardiorrespiratória. A presença desse parasito em uma espécie de cervídeo exótico invasor destaca sua importância epidemiológica, pois o mesmo pode atuar como fonte de infecção e de disseminação da doença para o ser humano e/ou outros animais.