Bleeding solitary SEGA in non-tuberous sclerosis complex adolescent: a case illustration and review of literature.

Subependymal giant cell astrocytoma (SEGA) represents a benign brain tumor occurring in 5-20% of individuals diagnosed with tuberous sclerosis complex (TSC), serving as a major diagnostic criterion. The presence of SEGA in a patient often prompts consideration of TSC as a probable diagnosis, given its unique association with this disorder. Typically, only one additional major criterion or two minor criteria are necessary to fulfill the diagnostic criteria for TSC. However, in rare instances, SEGA may manifest in patients without clinical features of TSC, termed solitary SEGA. The occurrence of solitary SEGA in patients lacking both clinical manifestations of TSC and genetic confirmation is extremely rare. Furthermore, the presentation of SEGA with intratumoral bleeding is exceedingly uncommon. Here, we presented a case of bleeding solitary SEGA in non-TSC adolescent who underwent surgery and has remained free of disease for a minimum of 3 years. Genetic analysis of peripheral blood and tumor tissue yielded negative results for TSC-related mutations. While SEGA occurrence in non-TSC patients is uncommon, it remains one of the possible diagnoses of intraventricular tumors. However, comprehensive genetic and physical evaluations are imperative to confirm the TSC status and guide further investigations and follow-up appropriately.

An early and trustable indicator suggestive of non-tuberculosis mycobacteria isolation in a high tuberculosis burden setting.

BACKGROUND: Distinguishing between nontuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma. METHODS: In this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB-burden setting retrospectively and prospectively. RESULTS: During the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75-96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ∼99·47% (943/948) in smear-positive tuberculosis cases. CONCLUSION: The clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.

Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

Utility of labial salivary gland biopsy in the histological diagnosis of neuronal intranuclear inclusion disease.

BACKGROUND AND PURPOSE: Neuronal intranuclear inclusion disease (NIID) poses a diagnostic challenge because of its diverse clinical manifestations. Detection of intranuclear inclusions remains the primary diagnostic criterion for NIID. Skin biopsies have traditionally been used, but concerns exist regarding postoperative complications and scarring. We sought to investigate the diagnostic utility of labial salivary gland biopsy, a less invasive alternative. METHODS: This study included a total of 19 patients and 11 asymptomatic carriers who underwent labial gland biopsies, while 10 patients opted for skin biopsies. All these individuals were confirmed to have pathogenic GGC repeat expansions in the NOTCH2NLC gene. The control group comprised 20 individuals matched for age and sex, all with nonpathogenic GGC repeat expansions, and their labial gland tissue was sourced from oral surgery specimens. RESULTS: Labial gland biopsies proved to be a highly effective diagnostic method in detecting eosinophilic intranuclear inclusions in NIID patients. The inclusions showed positive staining for p62 and ubiquitin, confirming their pathological significance. The presence of uN2CpolyG protein in the labial gland tissue further supported the diagnosis. Importantly, all patients who underwent lip gland biopsy experienced fast wound healing without any noticeable scarring. In contrast, skin biopsies led to varying degrees of scarring and one instance of a localized infection. CONCLUSION: Labial salivary gland biopsy emerged as a minimally invasive, efficient diagnostic method for NIID, with rapid healing and excellent sensitivity.

FAMILIAL NON-MEDULLARY THYROID CARCINOMA.

BACKGROUND: Familial non-medullary thyroid carcinoma (FNMTC) is defined as cancer developing in two or more first-degree relatives if predisposing factors, for example, radiation, are absent. The disease can be either syndromic, when it is a component of complex genetic syndromes, or non-syndromic (95% cases). The genetic basis of non-syndromic FNMTC is unknown; the clinical behavior of tumorsis unclear and, at times, contradictory. AIM: To analyze clinical manifestations of FNMTC and compare them with the data for sporadic papillary thyroid carcinomas in patients of the same age groups. MATERIALS AND METHODS: We examined 22 patients (a "parents" group and a "children" group) suffering from the non-syndromic FNMTC. For comparison, two groups of sporadic papillary carcinomas patients of the same age were drawn up("adult" and "young"). We analyzed tumor size and frequency of the distributionby the categoryof TNM system, invasiveness, multifocality, metastases to lymph nodes, type and extent of surgical and radioiodine treatment, and prognosis according to the MACIS criterion. RESULTS: Whether sporadic or familial, the tumor size, metastatic potential, and invasive potential are higher in young people, asalready known. There was no significant difference between the "parents" and "adult" groups of patients in terms of tumor parameters. One exception was the higher frequency of multifocal tumors in the FNMTC patients. Meanwhile, compared to the "young" sporadic papillary carcinomas patients, the FNMTC "children" had a higher frequency of T2 tumors, metastasizing (N1a-N1ab), and multifocal tumors, but a lower frequency of carcinomas with intrathyroidal invasions.In the FNMTC "children" compared to FNMTC "parents" was a higher frequency of T2 tumors, metastasizing carcinomas, and tumors with capsular invasion. CONCLUSION: FNMTC carcinomas are more aggressive than sporadic ones, especially in patients who are first-degree relatives in a family with parents already diagnosed with the disease.

SLE initially presenting with neuropsychiatric manifestations and seizure, case report.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder exhibiting variable disease courses and multiple clinical manifestations. SLE's aetiology remains unclear; however, different environmental (e.g., ultraviolet light, infections, drugs, etc.), genetic, and hormonal factors are potentially involved. A positive family history and history of having other autoimmune illnesses are considered high-risk factors for SLE; nevertheless, most SLE cases are scattered. The 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for SLE include at least one positive antinuclear antibody test as a mandatory entry criterion, followed by additive weighted standards grouped in seven clinical (constitutional, haematological, neuropsychiatric, serosal, musculoskeletal, renal, and mucocutaneous) and three immunological (antiphospholipid antibodies, complement proteins, and SLE-specific antibodies) domains weighted from 2 to 10, with patients accumulating ≥10 points being diagnosed with SLE. Herein, we report a case of neuropsychiatric lupus, a rare and severe form of SLE.

Models of precision medicine for neurodegeneration.

The clinicopathologic model that defines neurodegenerative disorders has remained unchanged for over a century. According to it, clinical manifestations are defined and explained by a given pathology, that is, by the burden and distribution of selected proteins aggregated into insoluble amyloids. There are two logical consequences from this model: (1) a measurement of the disease-defining pathology represents a biomarker of that disease in everyone affected, and (2) the targeted elimination of that pathology should end that disease. But success in disease modification guided by this model has remained elusive. New technologies to probe living biology have been used to validate rather than question the clinicopathologic model, despite three important observations: (1) a disease-defining pathology in isolation (without other pathologies) is an exceptional autopsy finding; (2) many genetic and molecular pathways converge on the same pathology; (3) the presence of pathology without neurological disease is more common than expected by chance. We here discuss the rationale for abandoning the clinicopathologic model, review the competing biological model of neurodegeneration, and propose developmental pathways for biomarker development and disease-modifying efforts. Further, in justifying future disease-modifying trials testing putative neuroprotective molecules, a key inclusion criterion must be the deployment of a bioassay of the mechanism corrected by the therapy of interest. No improvements in trial design or execution can overcome the fundamental deficit created by testing experimental therapies in clinically defined recipients unselected for their biologically suitability. Biological subtyping is the key developmental milestone needed to launch precision medicine for patients living with neurodegenerative disorders.

Efeito da resina de âmbar e terapêuticas não farmacológicas para sintomatologia da erupção de dentes decíduos / Effect of amber resin and nonpharmacological therapeutic for syntptomatology of eruption of deciduous theeth

Esta tese é composta por 5 artigos científicos e 1 produto técnico. O primeiro artigo científico, é uma revisão sistemática sobre a eficácia de tratamentos para alívio dos sinais e sintomas da erupção de dentes decíduos. Foram incluídos estudos clínicos que avaliaram o efeito de qualquer intervenção para aliviar os sinais e sintomas associados à dentição em bebês e crianças. O risco de viés foi avaliado usando as ferramentas ROB-2 e ROBINS-I. Foram selecionados 5 artigos, classificados como alto ou grave risco de viés respectivamente. Três estudos usando homeopatia relataram melhora nos distúrbios do apetite, desconforto nas gengivas e excesso de salivação. Um estudo mostrou que um novo gel com ácido hialurônico foi mais eficaz do que um gel anestésico na melhora de sinais e sintomas como dor, vermelhidão gengival e má qualidade do sono. Outro estudo selecionado aplicou tratamentos não farmacológicos, que se mostraram mais eficazes, principalmente contra o excesso de salivação. O segundo artigo avaliou as práticas clínicas adotadas por odontopediatras (OPs) frente aos sinais e sintomas da erupção dos dentes decíduos e a influência do tempo de formado e de especialista no autorrelato (AR) de segurança na adoção de tais medidas. Aplicou-se um questionário online aos OPs. Coletaram-se dados sobre tipo de prática, relato de eficácia, fonte de conhecimento sobre o tema, segurança na prática adotada, tempo de formado e tempo de especialista. Realizaram-se análises descritivas e inferenciais (teste X2, α=0,05). Foram 451 respondentes. Mordedores gelados (96,8%); alimentos congelados (69,1%) e massagem digital (58,3%) foram os mais prescritos e considerados eficazes (78,2%, 30,3% e 28,8%, respectivamente). Livros de odontopediatria (58,9%), curso/congresso (56,3%) e experiência profissional (40,7%) foram as fontes de conhecimento mais citadas. O tempo médio de formado dos OPs foi 18,4±11,3 anos, sendo 13,1±11,0 anos de especialista. A maioria sente-se seguro (79,6%) no tratamento dos sinais e sintomas da erupção dentária, mas 93,1% sentem falta de estudos científicos sobre o tema. O tempo de formado (p=0,12) e o de especialista (p=0,90) não influenciaram no AR de segurança na prática adotada. O terceiro artigo analisou a composição molecular de uma amostra de âmbar báltico, verificou-se a presença ou ausência de compostos benéficos à saúde humana e discutiu o potencial terapêutico dessa resina fóssil. Para isso, foi realizada uma análise qualitativa por cromatografia gasosa acoplada à espectrometria de massas (sistema GC-MS), que é capaz de realizar uma separação automatizada em componentes individuais do âmbar. As amostras eram compostas por terpenos e terpenóides: monoterpenóides; sesquiterpenóides; diterpenóides; hidronaftaleno; ácido succínico e ácido isopimárico. Estes componentes têm potencial terapêutico para várias doenças; inibem várias fases do processo inflamatório e tem efeitos analgésicos. No quarto artigo analisouse e avaliou-se a qualidade, confiabilidade e visualizações dos vídeos disponibilizados no Youtube® como fonte de informação, relacionados ao uso terapêutico do colar de âmbar para bebês durante o período de erupção dentária. Uma busca no YouTube®, foi realizada no dia 23 de agosto de 2022. O termo escolhido para a busca foi "colar de âmbar para bebê" no site Google Trends®. Como critério de inclusão, os vídeos deveriam conter informações sobre o uso do colar de âmbar como terapia para diminuir os sintomas da erupção dentária em bebês. Os vídeos foram analisados quanto à confiabilidade das informações, com base em uma escala de 5 pontos, adaptada da ferramenta DISCERN, e quanto à qualidade com a ferramenta Global Quality Score (GQS), que varia de 1- má qualidade a 5- excelente qualidade. Foram encontrados 22 vídeos com o termo de busca, dos quais 15 foram selecionados. A frequência de qualidade GQS "1" foi a mais alta e observou-se que houve diferença de qualidade entre as origens dos vídeos (p<0,05). As fontes provenientes de jornais e profissionais de saúde foram iguais e melhores (p=0,002) na escala de confiabilidade, quando comparadas aos outros grupos como Opiniões e Fontes de marketing. No quinto artigo objetivou-se identificar os possíveis benefícios da resina de âmbar na sintomatologia da fase de erupção dentária dos bebês, através de um estudo clínico preliminar observacional. Foram incluídos bebês de ambos os gêneros, com idade entre 8 e 36 meses que já tivessem pelo menos um dente da dentição primária em erupção. A amostra foi composta por 3 grupos: 1. Grupo que não usou nenhum tratamento (controle); 2. Grupo que usou a pulseira placebo e 3. Grupo que usou a pulseira de âmbar. Os sintomas da dentição mais frequentes na linha de base (t1) foram coceira, inchaço e irritação; após o tratamento foram os mesmos, acrescido de vermelhidão. Houve diferenças de frequência, com diminuição dos sintomas, entre os grupos, para as manifestações clínicas irritação e coceira. A segunda etapa consistiu na criação de um vídeo, na plataforma de criação de vídeos PowToon®, informativo para os responsáveis, sobre a fase de erupção dentária. No vídeo procurou-se abordar sobre a sequência comum de erupção dentária, os principais sinais e sintomas e possíveis tratamentos não farmacológicos para alívio dessa fase que gera muitas dúvidas nos responsáveis. Pode-se concluir com os estudos que algumas terapias não farmacológicas podem ter um efeito favorável sobre os sinais e sintomas relacionados à dentição. No entanto, conclusões definitivas sobre sua eficácia não podem ser tiradas, devido à certeza muito baixa das evidências. Pesquisas primárias, intervencionais sobre o assunto são escassas, heterogêneas e tem falhas metodológicas; a prescrição de tratamentos não farmacológicos para a dentição decídua é uma prática comum entre os odontopediatras, e seu auto relato de segurança no uso de tais medidas não está associada ao tempo decorrido após a graduação e especialização; o âmbar da amostra testada no terceiro estudo, é formado por terpenos e terpenóides, substâncias com propriedades anti-inflamatórias e analgésicas. Entretanto, é necessário um estudo aprofundado sobre a liberação e absorção de substâncias na pele humana, ou seja, atentar a sua real eficácia; Vídeos assistidos através da plataforma do YouTube®, ainda que postados por profissionais e veículos de comunicação, não possuem embasamento científico suficiente sobre o assunto quando se fala sobre o âmbar e seu uso para saúde, o que implica baixa confiabilidade e segurança da informação. Nesse sentido, estudos clínicos controlados, com maior número de participantes, sobre os reais benefícios do uso da resina de âmbar para bebês no período de erupção dentária, são fundamentais e devem ser realizados, a fim de consolidar as evidências sobre o assunto e reais benefícios para a saúde. Da mesma forma que o vídeo criado serve como informação aos pais sobre a fase de erupção dentária, e que foi baseado no que foi encontrado em evidências científicas. Após a realização da presente tese, observou-se que não existem muitos estudos que abordem sobre os tratamentos mais eficazes para essa fase na vida do bebê. (AU)

This thesis is composed of 5 scientific articles and 1 technical product. The first scientific article is a systematic review on the effectiveness of treatments to relieve the signs and symptoms of eruption of deciduous teeth. Clinical trials evaluating the effect of any intervention to alleviate signs and symptoms associated with teething in infants and children were included. The risk of bias was assessed using the ROB-2 and ROBINS-I tools. Five articles were selected, classified as high or severe risk of bias. Three studies using homeopathy reported improvement in appetite disorders, gum discomfort and excess salivation. One study showed that a new gel with hyaluronic acid was more effective than an anesthetic gel in improving signs and symptoms such as pain, gum redness and poor sleep quality. Another selected study applied nonpharmacological treatments, which proved to be more effective, especially against excess salivation. The second article evaluated the clinical practices adopted by pediatric dentists (POs) in view of the signs and symptoms of eruption of deciduous teeth and the influence of time since graduation and specialist in the self-report (AR) of safety in the adoption of such measures. An online questionnaire was applied to the OPs. Data were collected on the type of practice, effectiveness report, source of knowledge on the subject, safety in the adopted practice, time since graduation and time as a specialist. Descriptive and inferential analyzes were performed (X2 test, α=0.05). There were 451 respondents. iced teethers (96.8%); frozen foods (69.1%) and digital massage (58.3%) were the most prescribed and considered effective (78.2%, 30.3% and 28.8%, respectively). Pediatric dentistry books (58.9%), course/conference (56.3%) and professional experience (40.7%) were the most cited sources of knowledge. The average time since graduation of OPs was 18.4±11.3 years, with 13.1±11.0 years as a specialist. Most feel confident (79.6%) in treating the signs and symptoms of tooth eruption, but 93.1% feel that there is a lack of scientific studies on the subject. Time since graduation (p=0.12) and specialist time (p=0.90) did not influence the AR of safety in the adopted practice. The third article analyzed the molecular composition of a sample of Baltic amber, verified the presence or absence of compounds beneficial to human health and discussed the therapeutic potential of this fossil resin. For this, a qualitative analysis was carried out by gas chromatography coupled to mass spectrometry (GC-MS system), which can perform an automated separation into individual amber components. The samples were composed of terpenes and terpenoids: monoterpenoids; sesquiterpenoids; diterpenoids; hydronaphthalene; succinic acid and isopimaric acid. These components have therapeutic potential for various diseases; inhibit various phases of the inflammatory process and have analgesic effects. The fourth article analyzed and evaluated the quality, reliability and views of the videos available on YouTube® as a source of information, related to the therapeutic use of the amber necklace for babies during the period of tooth eruption. A search on YouTube® was performed on August 23, 2022. The term chosen for the search was "baby amber necklace" on the Google Trends® website. As an inclusion criterion, the videos should contain information about the use of the amber necklace as a therapy to reduce the symptoms of tooth eruption in babies. The videos were analyzed for the reliability of the information, based on a 5-point scale, adapted from the DISCERN tool, and for quality with the Global Quality Score (GQS) tool, which ranges from 1-poor quality to 5-excellent quality. 22 videos were found with the search term, of which 15 were selected. The GQS quality frequency "1" was the highest and it was observed that there was a difference in quality between the origins of the videos (p<0.05). Sources from newspapers and health professionals were equal and better (p=0.002) on the reliability scale, when compared to other groups such as Opinions and Marketing sources. The fifth article aimed to identify the possible benefits of amber resin in the symptomatology of the tooth eruption phase of babies, through a preliminary observational study. Infants of both genders, aged between 8 and 36 months, who already had at least one erupting primary dentition tooth, were included. The sample consisted of 3 groups: 1. Group that did not use any treatment (control); 2. Group that used the placebo bracelet and 3. Group that used the amber bracelet. The most frequent dentition symptoms at baseline (t1) were itching, swelling and irritation; after treatment they were the same, plus redness. There were differences in frequency, with a decrease in symptoms, between the groups, for the clinical manifestations of irritation and itching. The second stage consisted of creating a video, on the PowToon® video creation platform, informative for those responsible, about the tooth eruption phase. In the video, an attempt was made to address the common sequence of tooth eruption, the main signs and symptoms and possible nonpharmacological treatments to alleviate this phase, which raises many doubts in those responsible. It can be concluded from the studies that some non-pharmacological therapies can have a favorable effect on signs and symptoms related to dentition. However, definitive conclusions about its effectiveness cannot be drawn, due to the very low certainty of the evidence. Primary, interventional research on the subject is scarce, heterogeneous and has methodological flaws; the prescription of nonpharmacological treatments for the primary dentition is a common practice among pediatric dentists, and their self-reported safety in the use of such measures is not associated with the time elapsed after graduation and specialization; the amber of the sample tested in the third study is formed by terpenes and terpenoids, substances with anti-inflammatory and analgesic properties. However, an in-depth study on the release and absorption of substances in human skin is necessary, that is, paying attention to their real effectiveness; Videos watched through the Youtube® platform, even if posted by professionals and communication vehicles, do not have sufficient scientific basis on the subject when talking about amber and its use for health, which implies low reliability and information security. In this sense, controlled clinical studies, with a larger number of participants, on the real benefits of using amber resin for babies in the period of tooth eruption, are fundamental and must be carried out, in order to consolidate the evidence on the subject and real benefits for health. In the same way that the video created serves as information to parents about the stage of tooth eruption, and which was based on what was found in scientific evidence. After carrying out this thesis, it was observed that there are not many studies that address the most effective treatments for this phase in the baby's life. (AU)

COVID-19 outcomes in patients with sickle cell disease and sickle cell trait compared with individuals without sickle cell disease or trait: a systematic review and meta-analysis.

Background: Clinical manifestations and severity of SARS-CoV-2 infection in individuals with sickle cell disease (SCD) and sickle cell trait (SCT) are not well understood yet. Methods: We performed a systematic review and meta-analysis to assess COVID-19 outcomes in individuals with SCD or SCT compared to individuals without sickle cell disease or trait. An electronic search on PubMed, Embase, and Cochrane Library was performed on August 3, 2023. Two authors (IFM and ISP) independently screened (IFM and ISP) and extracted data (IFM and ILC) from included studies. Main exclusion criterion was the absence of the non-SCD/SCT group. Exposure effects for binary endpoints were compared using pooled odds ratio (OR) with 95% confidence intervals (CI). I2 statistics was used to assess the heterogeneity and DerSimonian and Laird random-effects models were applied for all analyses to minimize the impact of differences in methods and outcomes definitions between studies. The overall quality of evidence was assessed using the GRADE system. Review Manager 5.4 and R software (v4.2.2) were used for statistical analyses. Registered with PROSPERO, CRD42022366015. Findings: Overall, 22 studies were included, with a total of 1892 individuals with SCD, 8677 individuals with SCT, and 1,653,369 individuals without SCD/SCT. No difference in all-cause mortality was seen between SCD/SCT and non-SCD/SCT (OR 1.18; 95% CI 0.78-1.77; p = 0.429; I2 = 82%). When considering only studies adjusted for confounders (8 studies), patients with SCD/SCT were shown to be at increased risk of death (OR 1.86; 95% CI 1.30-2.66; p = 0.0007; I2 = 34%). No significant difference was seen between individuals with SCD and SCT (p = 0.863). The adjusted for confounders analysis for hospitalisation revealed higher rates for the SCD (OR 5.44; 95% CI 1.55-19.13; p = 0.008; I2 = 97%) and the SCT groups (OR 1.31; 95% CI 1.10-1.55; p = 0.002; I2 = 0) compared to the non-SCD/SCT population. Moreover, it was significantly higher for the SCD group (test for subgroup difference; p = 0.028). Interpretation: Our findings suggest that patients with SCD or SCT may present with a higher mortality and hospitalisation rates due to COVID-19 infection. Funding: None.

Manifestaciones clínicas "no criterio" del Síndrome Antifosfolipídico. Presentación de una cohorte nacional

Introducción: El síndrome antifosfolipídico (SAF) es una afección de origen autoinmune caracterizada por trombosis, pérdidas fetales recurrentes y anticuerpos antifosfolipídicos (aFL). Existen manifestaciones clínicas no contempladas en los criterios clasificatorios, que se denominan manifestaciones no criterio. Objetivo: Analizar las manifestaciones clínicas del SAF, enfatizando las manifestaciones no criterio y su relación con el perfil de autoanticuerpos en un hospital general de Montevideo, Uruguay. Métodos: Se realizó un estudio retrospectivo de las historias clínicas de pacientes con diagnóstico definitivo o sospecha de SAF en un servicio de medicina ambulatoria de enfermedades autoinmunes, en el Hospital Maciel, asistidos entre el 2010 y 2019. Resultados: Se incluyeron 78 pacientes, con edad media de 50,3 ± 14,5 años, 69 (88,5%) correspondió a sexo femenino. Cuarenta y seis (59,0%) pacientes presentaron SAF secundario, de los cuales 28 (35,9%) asociaron LES. La trombosis venosa de miembros inferiores fue la manifestación más frecuente (51,3%). Dieciocho (24,0%) pacientes presentaron trombosis arteriales en forma de accidente cerebrovascular. Cincuenta y nueve (75.6%) casos presentaron, además de las manifestaciones clasificatorias, alguna de las manifestaciones "no criterio" y éstas se manifestaron de forma aislada en 10 (12.8%) pacientes. Las manifestaciones no clasificatorias más frecuentes fueron artralgias, livedo reticularis, migraña y trombocitopenia. Se observó una asociación significativa entre la presencia de anti-ß2GPI con manifestaciones cutáneas y de trombocitopenia con al menos una manifestación trombótica. Conclusiones: Las manifestaciones "no criterio" del SAF se presentaron en casi 3 de cada 4 casos, frecuencia similar a la observada en otras series. La presencia aislada de manifestaciones "no criterio" podrían hacer sospechar un SAF y en algunos casos, conducir a la solicitud de anticuerpos.

Introduction: Antiphospholipid syndrome (APS) is an autoimmune condition characterized by thrombosis, recurrent fetal loss, and antiphospholipid antibodies. There are clinical manifestations not contemplated in the classification criteria, which are called non-criterion manifestations. Objective: To analyze the clinical manifestations of APS, emphasizing the non-criterion manifestations and their relationship with the autoantibody profile in a general hospital in Montevideo, Uruguay. Methods: A retrospective analysis of the medical records of patients with a definitive or suspected diagnosis of APS in an outpatient medicine service for autoimmune diseases, at the Maciel Hospital, assisted between 2010 and 2019, was carried out. Results: 78 patients were included, with a mean age of 50.3 +/- 14.5 years, 69 (88.5%) were female. Forty-six (59.0%) patients presented secondary APS, of which 28 (35.9%) associated SLE. Venous thrombosis of the lower limbs was the most frequent manifestation (51.3%). Eighteen (24.0%) patients presented arterial thrombosis in the form of cerebrovascular accident. Fifty-nine (75.6%) cases presented, in addition to the classification manifestations, some of the "non-criterion" manifestations and these manifested in an isolated way in 10 (12.8%) patients. The most frequent non-classifying manifestations were arthralgia, livedo reticularis, migraine and thrombocytopenia. A significant association was observed between the presence of anti-ß2GPI with cutaneous manifestations and thrombocytopenia with at least one thrombotic manifestation. Conclusions: Non-criterion manifestations of APS occurred in almost 3 out of 4 cases, a frequency similar to that observed in other series. The isolated presence of "non-criterion" manifestations could lead to suspicion of APS and, in some cases, lead to the request for antibodies.

Introdução: A síndrome antifosfolipídica (SAF) é uma doença de origem auto-imune caracterizada por trombose, perdas fetais recorrentes e anticorpos antifosfolípidos (aFL). Existem manifestações clínicas não abrangidas pelos critérios de classificação, que são designadas por manifestações não-critério. Objetivo: Analisar as manifestações clínicas da SAF, enfatizando as manifestações não-critério e sua relação com o perfil de auto-anticorpos em um hospital geral de Montevidéu, Uruguai. Métodos: Foi realizado um estudo retrospectivo dos prontuários de pacientes com diagnóstico definitivo ou suspeita de SAF em um serviço ambulatorial de doenças autoimunes do Hospital Maciel, atendidos entre 2010 e 2019. Resultados: Foram incluídos 78 pacientes, com idade média de 50,3 +/- 14,5 anos, sendo 69 (88,5%) do sexo feminino. Quarenta e seis (59,0%) pacientes apresentavam PFS secundária, dos quais 28 (35,9%) tinham LES associado. A trombose venosa dos membros inferiores foi a manifestação mais frequente (51,3%). Dezoito (24,0%) doentes apresentaram trombose arterial sob a forma de acidente vascular cerebral. Cinquenta e nove (75,6%) casos apresentaram, para além das manifestações classificatórias, algumas das manifestações "não-critério" e estas manifestações foram isoladas em 10 (12,8%) doentes. As manifestações não classificatórias mais frequentes foram artralgias, livedo reticularis, enxaqueca e trombocitopenia. Foi observada uma associação significativa entre a presença de anti-ß2GPI com manifestações cutâneas e trombocitopenia com pelo menos uma manifestação trombótica. Conclusões: As manifestações "não-critério" de SAF ocorreram em quase 3 de cada 4 casos, frequência semelhante à observada noutras séries. A presença isolada de manifestações "não-critério" pode levantar a suspeita de SAF e, nalguns casos, levar à pesquisa de anticorpos.

Performance of the clinical assessment scale for autoimmune encephalitis in a pediatric autoimmune encephalitis cohort.

Background: The Clinical Assessment Scale for Autoimmune Encephalitis (CASE), a new scale used for rating the severity of autoimmune encephalitis (AE), has demonstrated good validity and reliability in adults with AE, but there is a shortage of data on its performance in children with AE. This study aimed to assess the reliability and validity of the CASE in a cohort of children with AE. Methods: Forty-seven pediatric inpatients with AE who visited Guizhou Provincial People's Hospital between January 1, 2017, and October 31, 2021, were enrolled in the study. The CASE and mRS scores were obtained through a review of detailed medical records from the Health Information System by two pediatric neurologists. Finally, the performance of the CASE in this pediatric AE cohort was analyzed. Results: The results showed that anti-NMDA receptor encephalitis was the most common (61.70%) type of AE in children. The most common clinical manifestations were language problems (85.1%), psychiatric symptoms (80.9%), and dyskinesia/dystonia (78.7%). The CASE had good item reliability and interevaluator reliability; the Cronbach's alpha value of the total score was 0.825, and the intraclass correlation (ICC) was 0.980. The Cronbach's alpha value by item ranged from 0.16 to 0.406; items 1 and 9 had the lowest and highest Cronbach's alpha values, respectively. The criterion validity between CASE and mRS total scores, as quantified by Pearson correlation, was 0.459, indicating slight to good criterion validity. The area under the curve (AUC) was 0.992 (95% confidence interval: 0.974-1.00). A cutoff value of 14 was selected to determine whether a patient needed admission to the ICU; this cutoff had a sensitivity of 100% and a specificity of 92%. The changes in EEG, MRI, and antibody titers were not related to the severity of AE. A CASE score cutoff of 9 was selected to indicate whether second-line treatment would be needed. Conclusion: The CASE has good reliability and validity in children with AE; however, some items of the CASE may not apply to this population. Thus, an in-depth study of the CASE is needed in children with AE.

Low T3 syndrome is associated with peripheral neuropathy in patients with type 2 diabetes mellitus.

INTRODUCTION/AIMS: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. Diabetic patients often have thyroid dysfunction. The aim of this study was to investigate the association between low triiodothyronine (T3) syndrome and DPN in patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective review was performed of 928 patients with T2DM for whom data was available for clinical manifestations and nerve conduction studies (NCS), and of 134 non-diabetic controls. The composite Z scores of conduction velocity and amplitude were calculated. Low T3 syndrome was defined as T3 levels below the lower limit of the reference interval. RESULTS: Among the patients with T2DM, 632 (68.1%) had DPN, and a larger proportion of these patients presented with low T3 syndrome than patients without DPN. After adjusting for potential confounders, low T3 syndrome was independently associated with the occurrence of DPN (odds ratio [OR] = 2.049, 95% confidence interval [CI] 1.319-3.181, p = .001) and the severity of DPN (OR = 1.597, 95% CI 1.030-2.476, p = .036). Adding the criterion of low T3 syndrome improved the prognostic performance of the traditional model (age + gender + diabetic duration + glycated hemoglobin [HbA1c]) for predicting DPN. DISCUSSION: Low T3 syndrome is associated with a higher risk and increased severity of DPN in patients with T2DM. These findings suggest that low T3 syndrome could be a predictor for risk stratification in patients with T2DM.

Chronic Obstructive Pulmonary Disease in Elderly Patients with Acute and Advanced Heart Failure: Palliative Care Needs-Analysis of the EPICTER Study.

Introduction: There are studies that evaluate the association between chronic obstructive pulmonary disease (COPD) and heart failure (HF) but there is little evidence regarding the prognosis of this comorbidity in older patients admitted for acute HF. In addition, little attention has been given to the extracardiac and extrapulmonary symptoms presented by patients with HF and COPD in more advanced stages. The aim of this study was to evaluate the prognostic impact of COPD on mortality in elderly patients with acute and advanced HF and the clinical manifestations and management from a palliative point of view. Methods: The EPICTER study ("Epidemiological survey of advanced heart failure") is a cross-sectional, multicenter project that consecutively collected patients admitted for HF in 74 Spanish hospitals. Demographic, clinical, treatment, organ-dependent terminal criteria (NYHA III-IV, LVEF <20%, intractable angina, HF despite optimal treatment), and general terminal criteria (estimated survival <6 months, patient/family acceptance of palliative approach, and one of the following: evidence of HF progression, multiple Emergency Room visits or admissions in the last six months, 10% weight loss in the last six months, and functional impairment) were collected. Terminal HF was considered if the patient met at least one organ-dependent criterion and all the general criteria. Both groups (HF with COPD and without COPD) were compared. A Kaplan−Meier survival analysis was performed to evaluate the presence of COPD on the vital prognosis of patients with HF. Results: A total of 3100 patients were included of which 812 had COPD. In the COPD group, dyspnea and anxiety were more frequently observed (86.2% vs. 75.3%, p = 0.001 and 35.4% vs. 31.2%, p = 0.043, respectively). In patients with a history of COPD, presentation of HF was in the form of acute pulmonary edema (21% vs. 14.4% in patients without COPD, p = 0.0001). Patients with COPD more frequently suffered from advanced HF (28.9% vs. 19.4%; p < 0.001). Consultation with the hospital palliative care service during admission was more frequent when patients with HF presented with associated COPD (94% vs. 6.8%; p = 0.036). In-hospital and six-month follow-up mortality was 36.5% in patients with COPD vs. 30.7% in patients without COPD, p = 0.005. The mean number of hospital admissions during follow-up was higher in patients with HF and COPD than in those with isolated HF (0.63 ± 0.98 vs. 0.51 ± 0.84; p < 0.002). Survival analysis showed that patients with a history of COPD had fewer survival days during follow-up than those without COPD (log Rank chi-squared 4.895 and p = 0.027). Conclusions: patients with HF and COPD had more severe symptoms (dyspnea and anxiety) and also a worse prognosis than patients without COPD. However, the prognosis of patients admitted to our setting is poor and many patients with HF and COPD may not receive the assessment and palliative care support they need. Palliative care is necessary in chronic non-oncologic diseases, especially in multipathologic and symptom-intensive patients. This is a clinical care aspect to be improved and evaluated in future research studies.

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications.

The coronavirus disease 2019 (COVID-19) epidemic is currently raging around the world at a rapid speed. Among COVID-19 patients, SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) is the main contribution to the high ratio of morbidity and mortality. However, clinical manifestations between SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS are quite common, and their therapeutic treatments are limited because the intricated pathophysiology having been not fully understood. In this study, to investigate the pathogenic mechanism of SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS, first, we constructed a candidate host-pathogen interspecies genome-wide genetic and epigenetic network (HPI-GWGEN) via database mining. With the help of host-pathogen RNA sequencing (RNA-Seq) data, real HPI-GWGEN of COVID-19-associated ARDS and non-viral ARDS were obtained by system modeling, system identification, and Akaike information criterion (AIC) model order selection method to delete the false positives in candidate HPI-GWGEN. For the convenience of mitigation, the principal network projection (PNP) approach is utilized to extract core HPI-GWGEN, and then the corresponding core signaling pathways of COVID-19-associated ARDS and non-viral ARDS are annotated via their core HPI-GWGEN by KEGG pathways. In order to design multiple-molecule drugs of COVID-19-associated ARDS and non-viral ARDS, we identified essential biomarkers as drug targets of pathogenesis by comparing the core signal pathways between COVID-19-associated ARDS and non-viral ARDS. The deep neural network of the drug-target interaction (DNN-DTI) model could be trained by drug-target interaction databases in advance to predict candidate drugs for the identified biomarkers. We further narrowed down these predicted drug candidates to repurpose potential multiple-molecule drugs by the filters of drug design specifications, including regulation ability, sensitivity, excretion, toxicity, and drug-likeness. Taken together, we not only enlighten the etiologic mechanisms under COVID-19-associated ARDS and non-viral ARDS but also provide novel therapeutic options for COVID-19-associated ARDS and non-viral ARDS.

T2*-weighted placental magnetic resonance imaging: a biomarker of placental dysfunction in small-for-gestational-age pregnancies.

BACKGROUND: The antenatal identification of placental dysfunction in small-for-gestational-age fetuses with normal fetal Doppler flows remains an obstetrical challenge. In a significant fraction of such pregnancies, placental dysfunction is revealed by clinical manifestations such as preeclampsia, preterm delivery, or severe small-for-gestational-age at birth or by abnormal findings in the postnatal placental histologic examination. Therefore, new methods to identify placental function directly in pregnancy at the time of small-for-gestational-age diagnosis is highly needed. T2*-weighted placental magnetic resonance imaging is sensitive to changes in placental morphology and oxygenation and is thereby related to placental function. Previous studies have demonstrated that pregnancies complicated by low birthweight and preeclampsia are characterized by low placental T2* values. However, the specific performance of placental T2* in the prediction of placenta-related outcomes in small-for-gestational-age pregnancies with normal fetal Doppler flows remains to be explored. OBJECTIVE: In small-for-gestational-age pregnancies with normal fetal Doppler flows, we aimed to evaluate T2*-weighted placental magnetic resonance imaging as an antenatal biomarker of placental dysfunction. In addition, we aimed to investigate the correlation between placental T2* and Doppler flow measurements of fetal and uterine arteries at the time of magnetic resonance imaging. STUDY DESIGN: In this prospective cohort study, the inclusion criterion was suspected small-for-gestational-age (ultrasound estimated fetal weight Z-score ≤-2.0 [2.3rd centile]) with normal fetal Doppler flows (middle cerebral artery pulsatility index Z-score > -2.0 and umbilical artery pulsatility index Z-score <2.0). The T2*-weighted placental magnetic resonance imaging scan was performed at inclusion in a 1.5 T system. The outcomes was placental dysfunction at birth defined by low birthweight (Z-score ≤-2.0), preeclampsia, preterm delivery (gestational age<37 weeks), or abnormal placental histologic examination such as placental vascular malperfusion according to the Amsterdam Consensus Statement. RESULTS: We included 92 pregnancies at 26+5 to 39+6 weeks gestation. The median time interval between the magnetic resonance imaging scan and birth was 4.6 weeks (interquartile range, 2.7-7.8 weeks). At birth, 55% (51/92) of pregnancies revealed at least 1 sign of placental dysfunction; 49% (40/81) had abnormal placental histologic examination, 29% (27/92) were born with low birthweight, 13% (12/92) were delivered preterm, and 7% (6/92) had preeclampsia. When adjusted for gestational age at magnetic resonance imaging, the placental T2* Z-score was a significant predictor of abnormal placental histologic examination (area under the curve, 0.73; P=.001), small-for-gestational-age at birth (area under the curve, 0.63; P=.030), preeclampsia (area under the curve, 0.88; P=.005), and preterm delivery (area under the curve, 0.81; P=.001). The placental T2* was reduced in pregnancies with a combination of clinical manifestations and abnormal placental histologic examination (T2* Z-score=-1.52±1.35 [mean±standard deviation]; P=.0001) and in clinically uneventful pregnancies with abnormal placental histologic examination (T2* Z-score=-0.79±0.97; P=.045). At the time of magnetic resonance imaging, the placental T2* Z-score showed a significant linear correlation with the uterine artery pulsatility index Z-scores (r=-0.24; P=.016) and the middle cerebral artery pulsatility index Z-scores (r=0.29; P=.017) but not with the umbilical artery pulsatility index Z-scores (r=0.18; P=.17) and the cerebroplacental ratio (r=0.03; P=.77). CONCLUSION: This study indicates that placental dysfunction is frequent in small-for-gestational-age fetuses with normal fetal Doppler flows. In this cohort, T2*-weighted placental magnetic resonance imaging is a sensitive biomarker of placental dysfunction regardless of the clinical manifestations. This finding supports a paradigm shift in the conception of placental dysfunction that may cover a wide spectrum of clinical and subclinical manifestations.

NONINVASIVE DIAGNOSTIC STRATEGY OF OCULAR TOXOCARIASIS BASED ON CLINICAL FEATURES.

PURPOSE: To develop a noninvasive diagnostic strategy based on the clinical manifestations of ocular toxocariasis (OT) and evaluate its sensitivity and specificity. METHODS: Patients with unilateral OT-like lesions were enrolled retrospectively and classified into OT and non-OT groups according to the immunologic diagnosis criterion of anti-OT immunoglobulin G. Nine clinical manifestations were recorded and compared between the groups. Among them, the retrolental membrane, branch-like vitreous strands, and retinal granulomas were the most common, which were further classified into three categories, including at least 1 of three signs, at least two of three signs, and all three signs positive. Diagnostic sensitivity and specificity were calculated for each strategy. RESULTS: There were 105 immunologically confirmed patients with OT and 70 patients with non-OT uveitis/vitreoretinopathy. Retinal granulomas, retrolental membrane, and branch-like vitreous strands were significantly more frequent in OT patients than in non-OT patients. At least 1 of 3 signs positive strategy showed the highest sensitivity (100.0%) but the lowest specificity (62.0%). At least 2 of 3 signs positive strategies showed 80.0% sensitivity and 94.3% specificity. All 3 signs positive strategies had the lowest sensitivity (46.7%) and the highest specificity (100.0%). The cutoff point of this revealed an area under the curve of 0.85 and a 95% confidence interval of 0.79 to 0.91. CONCLUSION: A comprehensive strategy based on at least two out of three positive signs showed excellent sensitivity and specificity and could serve as a noninvasive and fast screening strategy for the clinical diagnosis of OT.

Postural tachycardia syndrome (POTS) and antiphospholipid syndrome (APS): What do we know so far?

As part of the non-criteria clinical manifestations, postural orthostatic tachycardia syndrome (POTS), a multisystem autonomic dysfunction, can co-exist with antiphospholipid syndrome (APS). Several pieces of evidence hint on the autoimmune basis of POTS, and its possible association with several autoimmune diseases, including APS. Indeed, the evidence exists in the etiologies, symptomatology, and treatment options. Although infections, viral ones in particular, stress, and pregnancy are etiologies to both POTS and APS, the exact pathophysiological connection is still to be studied taking into consideration the activity of cytokines in both diseases. Nevertheless, certain immunomodulatory treatments used for the catastrophic or obstetrical forms of APS, such as intravenous immunoglobulins (IVIG) and steroids, have been also used for the treatment of POTS resistant to classical treatments. Therefore, our review aims to highlight the association between POTS and APS, shedding light on the common etiologies explaining the pathophysiology of the two disorders, the diagnostic approach to POTS as a possible clinical criterion of APS, and the treatment of APS in the context of treating POTS.

Safety, clinical and laboratory characteristics of donors with thalassemia minor in living donor kidney transplant: a case series.

BACKGROUND: Due to the increasing demand for kidney transplants, sometimes donors with underlying medical conditions can be considered for living kidney donor transplant. Thalassemia is amongst the most common inherited disorders of hemoglobin globally, which is not restricted as an exclusion criterion. However, there is currently no study examine the safety and characteristics of kidney donors with thalassemia minor. METHODS: All eligible live kidney donors between 2016 and 2019 with thalassemia minor at a tertiary hospital were recruited. Baseline characteristics, clinical and laboratory outcomes were investigated. RESULTS: Fifteen donors (11 women, 55.5 ± 15.0 year-old) were included with a follow-up duration of 2 (1-4) years since operation. The most prevalent gene mutation among participants was DEL-SEA. No clinical manifestations of anemia were seen but 10 participants had mild anemia diagnosed from blood tests. Cardiovascular, liver and renal function were normal before nephrectomy. Until now, all donors are alive and maintain overall good health. Anemia condition is not affected, and the post-donation eGFR = 71.04 ± 11.54 mL/min/1.73m2 is comparable to outcomes of healthy donors reported in previous studies. Two donors are at risk of proteinuria at 1-year post-transplant with A/C ratio > 30 mg/g. CONCLUSIONS: Thalassemia minor individuals who are non-transfusion-dependent, without anemia clinical manifestations and have no contraindications to kidney donation are safe to be donors in short-term. An eGFR of at least 80 mL/min/1.73m2 should be considered to avoid low post-donation eGFR, and awareness should be raised on thalassemia donors with even mild albuminuria. Nephrectomy does not worsen thalassemia.

Obstructive sleep apnea in children and adolescents with cystic fibrosis and preserved lung function or mild impairment: a systematic review and meta-analysis of prevalence.

OBJECTIVE/BACKGROUND: Sleep disorders in cystic fibrosis may be present before daytime clinical manifestations, regardless of lung function impairment, affecting quality of life and disease progression. This study investigated the prevalence of obstructive sleep apnea in children and adolescents with cystic fibrosis and preserved lung function or mild impairment, and evaluated its association with clinical variables. METHODS: A systematic review with meta-analysis of prevalence was conducted, including observational studies with polysomnographies in patients with cystic fibrosis who presented mean lung function values > 60% predicted. The methodological quality of the studies was analyzed, and a meta-analysis was performed to assess the prevalence of obstructive sleep apnea. RESULTS: Of the 2318 studies identified, 7 were included in the systematic review and 6 in the meta-analysis of prevalence. The confounding factors and strategies identified were the items with greatest weakness in the methodological quality assessment. Most studies were cross-sectional, and sample size ranged from 9 to 67 individuals. The most frequent criterion for defining obstructive sleep apnea was apnea-hypopnea index (AHI) > 1 per hour. The prevalence found ranged from 32.3 to 100% and the pooled prevalence was 65% (I2 = 53.4%), considering AHI>1, and 52% (I2 = 89.4%) for AHI>2 per hour. It was not possible to verify the association between obstructive sleep apnea and clinical variables. CONCLUSIONS: A high prevalence of obstructive sleep apnea in children and adolescents with cystic fibrosis was found, regardless of age and lung function impairment, reinforcing the importance of investigating sleep-disordered breathing during clinical visits even when lung function is not yet compromised.

Junctional Tachycardia as a Diagnostic Criterion in Acute Rheumatic Fever.

Acute rheumatic fever (ARF) is an acute inflammatory process resulting in rheumatic carditis, one of the most common acquired heart diseases in youth. Among the clinical manifestations of carditis, pathologic valve regurgitation and atrioventricular block are included in the criteria for the diagnosis of ARF. Besides atrioventricular block, ARF may often present with other arrhythmias, such as junctional tachycardia (JT). However, JT is currently not recognized as a criterion for the diagnosis of ARF. Three adolescents presented in our hospital with JT, polyarthralgia, and laboratory signs of inflammation with evidence of preceding group A Streptococcus infection. None of the patients fulfilled the diagnostic criteria of ARF. On the basis of the presumed diagnosis of ARF, all 3 patients were treated with intravenous steroids. Steroid therapy was given, and JT converted to sinus rhythm within an average of 62 hours. Subsequent electrocardiograms revealed variable degree of atrioventricular block in all 3 patients, providing clinical evidence and fulfilling the diagnostic criteria of ARF. Patients were monitored for a total 2 to 8 days before discharge on standard antiinflammatory treatment. Follow-up electrocardiograms and Holter monitoring revealed resolution of the atrioventricular block and lack of JT recurrence in all patients. On the basis of these sentinel cases, we propose that JT should be included as a diagnostic criterion for the diagnosis of ARF.