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ABSTRACT Purpose: To characterize the extracellular vesicle protein cargo in the aqueous humor and plasma of patients with ocular toxoplasmosis. Methods: Aqueous humor and plasma were collected from six patients with active ocular toxoplasmosis and six patients with cataract. Extracellular vesicles were isolated, and western blotting and mass spectrometry were performed for protein analysis. Results: All plasma samples from patients with ocular toxoplasmosis and cataract were positive for the tetraspanins CD63 and TSG101. However, the aqueous humor from patients with ocular toxoplasmosis was positive only for CD63. Sixty-seven new unreported proteins were identified in the aqueous humor and plasma of patients with the ocular toxoplasmosis and cataract. Of the 67 proteins, 10 and 7 were found only in the cataract and ocular toxoplasmosis groups, respectively. In general, these proteins were involved in immune system activation and retina homeostasis and were related to infections and retina-associated diseases. Conclusion: The distinct protein signatures between ocular toxoplasmosis and cataract may be helpful in the differential diagnosis of ocular toxoplasmosis. However, more studies are needed to better understand the role of these proteins in the pathogenesis of ocular toxoplasmosis.

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Introduction: Percutaneous kidney biopsy (KB) is crucial to the diagnosis and management of several renal pathologies. National data on native KB in pediatric patients are scarce. We aimed to review the demographic and clinical characteristics and histopathological patterns in children who underwent native percutaneous KB over 24 years. Methods: Retrospective observational study of patients undergoing native percutaneous KB in a pediatric nephrology unit between 1998 and 2021, comparing 3 periods: period 1 (1998-2005), period 2 (2006-2013), and period 3 (2014-2021). Results: We found that 228 KB were performed, 78 (34.2%) in period 1, 91 (39.9%) in period 2, and 59 (25.9%) in period 3. The median age at KB was 11 (7-14) years. The main indications for KB were nephrotic syndrome (NS) (42.9%), hematuria and/or non-nephrotic proteinuria (35.5%), and acute kidney injury (13.2%). Primary glomerulopathies were more frequent (67.1%), particularly minimal change disease (MCD) (25.4%), IgA nephropathy (12.7%), and mesangioproliferative glomerulonephritis (GN) (8.8%). Of the secondary glomerulopathies, lupus nephritis (LN) was the most prevalent (11.8%). In group 1, hematuria and/or non-nephrotic proteinuria were the main reasons for KB, as opposed to NS in groups 2 and 3 (p < 0.01). LN showed an increasing trend (period 1-3: 2.6%-5.3%) and focal segmental glomerular sclerosis (FSGS) showed a slight decreasing trend (period 1-3: 3.1%-1.8%), without statistical significance. Conclusions: The main indication for KB was NS, which increased over time, justifying the finding of MCD as main histological diagnosis. LN showed an increase in incidence over time, while FSGS cases did not increase.

RESUMO Introdução: A biópsia renal (BR) percutânea é fundamental para diagnóstico e manejo de diversas patologias renais. Dados nacionais sobre BR nativa em pacientes pediátricos são escassos. Nosso objetivo foi revisar características demográficas, clínicas e padrões histopatológicos em crianças submetidas a BR percutânea nativa ao longo de 24 anos. Métodos: Estudo observacional retrospectivo de pacientes submetidos a BR percutâneas nativas em unidade de nefrologia pediátrica entre 1998 e 2021, comparando três períodos: período 1 (1998-2005), período 2 (2006-2013), período 3 (2014-2021). Resultados: Constatamos que foram realizadas 228 BR, 78 (34,2%) no período 1, 91 (39,9%) no período 2, 59 (25,9%) no período 3. A idade mediana na BR foi 11 (7-14) anos. As principais indicações para BR foram síndrome nefrótica (SN) (42,9%), hematúria e/ou proteinúria não nefrótica (35,5%), lesão renal aguda (13,2%). Glomerulopatias primárias foram mais frequentes (67,1%), principalmente doença de lesão mínima (DLM) (25,4%), nefropatia por IgA (12,7%), glomerulonefrite mesangioproliferativa (GN) (8,8%). Das glomerulopatias secundárias, nefrite lúpica (NL) foi a mais prevalente (11,8%). No grupo 1, hematúria e/ou a proteinúria não nefrótica foram os principais motivos para BR, ao contrário da SN nos grupos 2 e 3 (p < 0,01). A NL apresentou tendência crescente (período 1-3: 2,6%-5,3%) e a glomeruloesclerose segmentar focal (GESF) apresentou leve tendência decrescente (período 1-3: 3,1%-1,8%), sem significância estatística. Conclusões: A principal indicação para BR foi SN, que aumentou ao longo do tempo, justificando o achado de DLM como principal diagnóstico histológico. A NL apresentou aumento na incidência ao longo do tempo, enquanto os casos de GESF não aumentaram.

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PURPOSE: Stereotactic brain biopsies are highly efficient for diagnosing intracerebral pathologies, particularly when surgical resection is infeasible. Fluorescence-based agents such as 5-aminolevulinic acid (5-ALA) and fluorescein sodium (NaFl) can enhance diagnostic accuracy and safety, improving the visualization of lesional tissues. This meta-analysis aimed to evaluate their effect on diagnostic yield and complication rates of brain biopsies. METHODS: This study adhered to Cochrane and PRISMA guidelines. We assessed studies for diagnostic yield and complication rates. Data was analyzed using a random-effects model in RStudio. Diagnostic accuracy measures such as sensitivity and predictive values were calculated based on fluorescence visibility in biopsy samples. RESULTS: Thirty-two non-randomized studies were included, comprising 947 patients, with a mean age ranging from 37 to 77 years, and a mean sample number ranging from 1 to 15 specimens. Diagnostic yields were high: 93% for NaFl and 96% for 5-ALA. Major complications occurred in 3% of procedures with both agents, while minor complications were reported in 7% and 5% with NaFl and 5-ALA respectively. The Negative-predictive-value (NPV) of 5-ALA and NaFl were 8-11% and 60-80% respectively. NaFl demonstrates higher sensitivity and specificity at 84% and 100% compared to 5-ALA's 66%. and 85% respectively. CONCLUSION: 5-ALA and NaFl provide high diagnostic yields with acceptable safety profiles in stereotactic biopsies. NaFl showed higher sensitivity and specificity. NaFl outperforms 5ALA in terms of NPV making it more efficient for small lesions near eloquent regions or major blood vessels. The significance of these findings can be further ascertained through randomized trials.

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(Background). Canine mammary tumors (CMTs) have emerged as an important model for understanding pathophysiological aspects of human disease. Liquid biopsy (LB), which relies on blood-borne biomarkers and offers minimal invasiveness, holds promise for reflecting the disease status of patients. Small extracellular vesicles (SEVs) and their protein cargo have recently gained attention as potential tools for disease screening and monitoring. (Objectives). This study aimed to isolate SEVs from canine patients and analyze their proteomic profile to assess their diagnostic and prognostic potential. (Methods). Plasma samples were collected from female dogs grouped into CMT (malignant and benign), healthy controls, relapse, and remission groups. SEVs were isolated and characterized using ultracentrifugation (UC), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Proteomic analysis of circulating SEVs was conducted using liquid chromatography-mass spectrometry (LC-MS). (Results). While no significant differences were observed in the concentration and size of exosomes among the studied groups, proteomic profiling revealed important variations. Mass spectrometry identified exclusive proteins that could serve as potential biomarkers for mammary cancer. These included Inter-alpha-trypsin inhibitor heavy chain (ITIH2 and ITI4), phosphopyruvate hydratase or alpha enolase (ENO1), eukaryotic translation elongation factor 2 (eEF2), actin (ACTB), transthyretin (TTR), beta-2-glycoprotein 1 (APOH) and gelsolin (GSN) found in female dogs with malignant tumors. Additionally, vitamin D-binding protein (VDBP), also known as group-specific component (GC), was identified as a protein present during remission. (Conclusions). The results underscore the potential of proteins found in SEVs as valuable biomarkers in CMTs. Despite the lack of differences in vesicle concentration and size between the groups, the analysis of protein content revealed promising markers with potential applications in CMT diagnosis and monitoring. These findings suggest a novel approach in the development of more precise and effective diagnostic tools for this challenging clinical condition.

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OBJECTIVE: To describe the frequency and clinicopathological concordance of mucocutaneous manifestations in people living with HIV (PLWH) and its correlation with CD4+ T lymphocyte count and HIV viral load. METHODS: Cross-sectional study of patients diagnosed with HIV infection who underwent skin biopsy for histopathological study from 1992 to 2022. Skin diseases were categorized as opportunistic and sexually transmitted infections, inflammatory dermatoses, benign cutaneous neoplasms, and premalignant and malignant cutaneous neoplasms. Clinicopathological concordance was classified as complete, partial or discordant. Frequency of skin diseases are presented by category and according to lymphocyte CD4+ count and HIV viral load. RESULTS: A total of 659 patients were included of whom 88.5% (n = 583) were male. The most frequent diagnostic category was opportunistic or sexually transmitted infections in 34% (n = 224) and the most frequently found condition was Kaposi sarcoma in 17% (n = 112). Clinicopathological concordance was complete in 53.7% (n = 354) of cases, partial in 26.7% (n = 176) and discordant in 19.6% (n = 129). Among the 282 patients with available serological data, 58.9% (n = 166), 23.8% (n = 67) and 17.4% (n = 49) had CD4+ counts below 200, between 200 and 499, and above 500 cells/µl, respectively. CONCLUSIONS: Although there is a high variability in skin conditions which people with HIV may present, there was a high rate of clinicopathological concordance (80.4%). We emphasize the importance of diagnostic skin biopsies due to their diverse morphological presentation. The frequency of skin diseases in PLWH depending on different clinical settings should aid the clinician in reaching an adequate diagnosis in this population.

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PURPOSE: To establish a reliable machine learning model to predict malignancy in breast lesions identified by ultrasound (US) and optimize the negative predictive value to minimize unnecessary biopsies. METHODS: We included clinical and ultrasonographic attributes from 1526 breast lesions classified as BI-RADS 3, 4a, 4b, 4c, 5, and 6 that underwent US-guided breast biopsy in four institutions. We selected the most informative attributes to train nine machine learning models, ensemble models and models with tuned threshold to make inferences about the diagnosis of BI-RADS 4a and 4b lesions (validation dataset). We tested the performance of the final model with 403 new suspicious lesions. RESULTS: The most informative attributes were shape, margin, orientation and size of the lesions, the resistance index of the internal vessel, the age of the patient and the presence of a palpable lump. The highest mean negative predictive value (NPV) was achieved with the K-Nearest Neighbors algorithm (97.9%). Making ensembles did not improve the performance. Tuning the threshold did improve the performance of the models and we chose the algorithm XGBoost with the tuned threshold as the final one. The tested performance of the final model was: NPV 98.1%, false negative 1.9%, positive predictive value 77.1%, false positive 22.9%. Applying this final model, we would have missed 2 of the 231 malignant lesions of the test dataset (0.8%). CONCLUSION: Machine learning can help physicians predict malignancy in suspicious breast lesions identified by the US. Our final model would be able to avoid 60.4% of the biopsies in benign lesions missing less than 1% of the cancer cases.

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Osteolipoma is a rare benign variant of lipoma and constitutes less than 1% of all lipomas, presenting as a well-circumscribed painless mass. It is a tumor known to occur in several regions, usually intraosseous or adjacent to bone tissue, whose pathogenesis is still unclear. Imaging exams are useful in their evaluation and, mainly, in surgical planning, which consists of tumor excision. However, the definitive diagnosis of osteolipoma is made by histopathological examination. Although benign, osteolipomas can compress surrounding structures, leading to important symptomatology, as in this case reported in which it is in contact with the brachial plexus.

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This study investigated serum extracellular vesicles (EVs) in bitches with mammary neoplasms, in order to understand their size, shape, and concentration, as well as their association with tumor malignancy. Thirty bitches were categorized into control (n = 10), mammary tumor grades I and II (GI, n = 13), and grade III (GII, n = 7). Serum was separated from blood collected during mastectomy, and EVs were isolated using size exclusion chromatography. The analysis revealed no significant differences in EV concentrations among groups, with similar concentrations for control, GI, and GII. Ninety-one proteins were identified in EV-enriched samples, with six showing varied abundance across groups. Notably, keratin 18 was highly abundant in GI, while sushi domain-containing protein, EvC ciliary subunit 2, and the joining chain of multimeric IgM and IgA were increased in GII. Additionally, protocadherin 17 and albumin were upregulated in both GI and GII. ROC curves identified potential biomarkers for differentiating tumor grades. Enrichment pathway analysis revealed AFP gene upregulation in the GI. Mass spectrometry proteomics data were deposited in Mendeley Data. The study provides valuable insights into serum EV characterization in bitches, suggesting keratin 18 and protocadherin 17 as potential biomarkers for canine mammary neoplasia, with implications for future diagnostic and therapeutic strategies.

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HIV infection is a chameleon, mimicking several diseases. Herein, we report a previously healthy 39-year-old woman who, over 2 months, developed arthritis, weight loss, and confluent multiple mononeuropathy. Extensive laboratory investigation showed positive serology for HIV, with a CD4 count of 100 cells, and necrotizing vasculitis on a nerve biopsy not associated with CMV co-infection, allowing the diagnosis of polyarteritis nodosa-like vasculitis in an HIV-infected patient. Apart from the infection, HIV-related autoimmunity can affect any organ and contribute to the complexity of the clinical presentation of HIV infection.

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BACKGROUND: Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. METHODOLOGY: Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. RESULTS: Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. CONCLUSIONS: This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO.

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