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BACKGROUND: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of ß-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII. METHODS: This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022. RESULTS: As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and - 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died. CONCLUSIONS: To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.

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The TTS package has been developed in R software to predict the mechanical properties of viscoelastic materials, at short and long observation times/frequencies by applying the Time Temperature Superposition (TTS) principle. TTS is a physical principle used in material science to estimate mechanical properties beyond the experimental range of observed times/frequencies by shifting data curves obtained at other temperatures relative to a reference temperature in the dataset. It is a methodology related to accelerated life-tests and reliability, whereas the TTS library is one of the first open source computational tool to apply the TTS principle. This R package provides free computational tools to obtain master curves that characterize materials from a thermal-mechanical approach. The TTS package also proposes, implements and explains our own method to obtain the shift factors and the master curve in a TTS analysis, based on horizontal shifting of the first derivative function of viscoelastic properties. This procedure provides shift factors estimates and smooth master curve estimates using B-spline fitting, in a fully automatic way, without assuming any parametric expression. Williams-Landel-Ferry (WLF) and Arrhenius TTS parametric models are also implemented in the TTS package. They can be fitted from shifts obtained by the our first derivative based method.

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Histoplasmosis occurs in 5-10% of HIV-infected patients in endemic areas and evolves to severe and disseminated infection with mortality rates over 50% in some regions. This report presents epidemiological, clinical and outcome data from HIV-infected patients with histoplasmosis confirmed by culture and/or at necropsy who were admitted to a Brazilian teaching hospital. Data from 65 patients were obtained from their respective medical and necropsy records. From 2005 to 2018, 36 HIV-infected patients were diagnosed with histoplasmosis confirmed by culture. At admission, most of these patients presented disseminated fungal infection, whereas 15 (41.7%) were simultaneously diagnosed with both HIV infection and histoplasmosis. Fever, weight loss, hepatosplenomegaly, respiratory and digestive symptoms were present in 86.2%, 50%, 44.4% and 41.7% of the patients, respectively. At admission, 24 patients had low CD4 T-cell count and high viral load values. Among the 30 patients who received antifungals, 16 (53.3%) were cured, 13 (43.3%) died, and one was lost to follow-up. Six patients died prior to therapy. From 1990 to 2018, 63 necropsies of patients with Histoplasma capsulatum infection were performed. Of these patients, 29 (46.0%) were HIV-infected individuals, including 21 (72.4%) who presented disseminated histoplasmosis and 21 (72.4%) who were diagnosed with histoplasmosis at necropsy. The epidemiological, clinical and outcome profiles presented herein are similar to those described elsewhere and reinforce the difficulties that are still present in limited-resource settings where advanced immunodeficiency, combined with severe fungal infection and late patient admissions, is related to poor outcomes.

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OBJECTIVE: To assess the percent agreement between diagnostic imaging modalities for the evaluation of lymphadenopathies in HIV-infected/AIDS patients. MATERIALS AND METHODS: This was an open, comparative, prospective study of diagnostic imaging methods for lymphadenopathy evaluation. We evaluated 30 patients (19 men and 11 women). All underwent ultrasound and computed tomography (CT). Twenty of the patients also underwent magnetic resonance imaging (MRI). We determined the percent agreement between two examiners using the various imaging methods to evaluate lymphadenopathies. RESULTS: CT had the highest percent agreement, at 93.3%, with a kappa coefficient of 0.85, corresponding to 28 of the 30 examinations. When we compared the percent agreement between the two examiners and between CT and ultrasound, examiner 1 had an observed rate of 80.0%, with a kappa of 0.49, corresponding to 24 of the 30 examinations, whereas examiner 2 had a rate of 70.0%, with a kappa of 0.31, corresponding to 21 of the 30 examinations. Between MRI and CT, the percent agreement for examiner 1 was 50.0%, with a kappa of -0.18, corresponding to 10 of the 20 examinations, whereas that for examiner 2 was 85.0%, with a kappa of 0.69, corresponding to 17 of the 20 examinations. For MRI and ultrasound, examiner 1 had a percent agreement of 70.0%, with a kappa of 0.20, corresponding to 14 of the 20 examinations, and examiner 2 had a percent agreement of 75.0%, with a kappa of 0.38, corresponding to 15 of the 20 examinations. CONCLUSION: This study indicates that intermethod agreement is highly dependent on the way in which the research is conducted, rather than on the level of experience of the examiner.

OBJETIVO: Avaliar a porcentagem de concordância entre métodos de diagnóstico por imagem na avaliação de linfonodomegalias em pacientes HIV(+)/AIDS. MATERIAIS E MÉTODOS: Foi realizado estudo aberto, comparativo e prospectivo dos métodos de diagnóstico por imagem na avaliação de linfonodomegalias. Foram avaliados 30 pacientes (19 homens e 11 mulheres). Todos foram submetidos a ultrassonografia e tomografia computadorizada (TC) e 20 também foram submetidos a ressonância magnética (RM). Foi determinado o grau de concordância entre dois examinadores usando-se métodos de diagnóstico por imagem. RESULTADOS: A TC obteve o maior grau de concordância, com taxa de 28/30 (93,3%) e coeficiente kappa de 0,85. Quando comparado o grau de concordância para linfonodomegalias entre dois examinadores e entre TC e ultrassonografia, o examinador 1 teve taxa de 24/30 (80,0%) e kappa de 0,49, e o examinador 2 teve taxa de 21/30 (70,0%) e kappa de 0,31. Entre RM e TC, o examinador 1 teve taxa de 10/20 (50,0%) e kappa de -0,18, e o examinador 2 teve taxa de 17/20 (85,0%) e kappa de 0,69. Entre RM e ultrassonografia, o examinador 1 teve taxa de 14/20 (70,0%) e kappa de 0,20, e o examinador 2 teve taxa de 15/20 (75,0%) e kappa de 0,38. CONCLUSÃO: Este estudo indica que a concordância entre métodos depende fortemente da forma como a pesquisa é conduzida e não da capacidade do examinador.

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Abstract Objective: To assess the percent agreement between diagnostic imaging modalities for the evaluation of lymphadenopathies in HIV-infected/AIDS patients. Materials and Methods: This was an open, comparative, prospective study of diagnostic imaging methods for lymphadenopathy evaluation. We evaluated 30 patients (19 men and 11 women). All underwent ultrasound and computed tomography (CT). Twenty of the patients also underwent magnetic resonance imaging (MRI). We determined the percent agreement between two examiners using the various imaging methods to evaluate lymphadenopathies. Results: CT had the highest percent agreement, at 93.3%, with a kappa coefficient of 0.85, corresponding to 28 of the 30 examinations. When we compared the percent agreement between the two examiners and between CT and ultrasound, examiner 1 had an observed rate of 80.0%, with a kappa of 0.49, corresponding to 24 of the 30 examinations, whereas examiner 2 had a rate of 70.0%, with a kappa of 0.31, corresponding to 21 of the 30 examinations. Between MRI and CT, the percent agreement for examiner 1 was 50.0%, with a kappa of −0.18, corresponding to 10 of the 20 examinations, whereas that for examiner 2 was 85.0%, with a kappa of 0.69, corresponding to 17 of the 20 examinations. For MRI and ultrasound, examiner 1 had a percent agreement of 70.0%, with a kappa of 0.20, corresponding to 14 of the 20 examinations, and examiner 2 had a percent agreement of 75.0%, with a kappa of 0.38, corresponding to 15 of the 20 examinations. Conclusion: This study indicates that intermethod agreement is highly dependent on the way in which the research is conducted, rather than on the level of experience of the examiner.

Resumo Objetivo: Avaliar a porcentagem de concordância entre métodos de diagnóstico por imagem na avaliação de linfonodomegalias em pacientes HIV(+)/AIDS. Materiais e Métodos: Foi realizado estudo aberto, comparativo e prospectivo dos métodos de diagnóstico por imagem na avaliação de linfonodomegalias. Foram avaliados 30 pacientes (19 homens e 11 mulheres). Todos foram submetidos a ultrassonografia e tomografia computadorizada (TC) e 20 também foram submetidos a ressonância magnética (RM). Foi determinado o grau de concordância entre dois examinadores usando-se métodos de diagnóstico por imagem. Resultados: A TC obteve o maior grau de concordância, com taxa de 28/30 (93,3%) e coeficiente kappa de 0,85. Quando comparado o grau de concordância para linfonodomegalias entre dois examinadores e entre TC e ultrassonografia, o examinador 1 teve taxa de 24/30 (80,0%) e kappa de 0,49, e o examinador 2 teve taxa de 21/30 (70,0%) e kappa de 0,31. Entre RM e TC, o examinador 1 teve taxa de 10/20 (50,0%) e kappa de -0,18, e o examinador 2 teve taxa de 17/20 (85,0%) e kappa de 0,69. Entre RM e ultrassonografia, o examinador 1 teve taxa de 14/20 (70,0%) e kappa de 0,20, e o examinador 2 teve taxa de 15/20 (75,0%) e kappa de 0,38. Conclusão: Este estudo indica que a concordância entre métodos depende fortemente da forma como a pesquisa é conduzida e não da capacidade do examinador.

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High-grade endometrial carcinomas are aggressive neoplasms of difficult histological classification. Neuroendocrine differentiation in endometrial carcinomas is rare. This is the report of an endometrial large cell neuroendocrine carcinoma with foci of melanocytic differentiation in a 75-year-old woman with abnormal post-menopausal uterine bleeding for 2 years. Two initial biopsies were inconclusive. Histopathological examination of the uterus revealed large cell neuroendocrine carcinoma associated with endometrioid carcinoma and foci of melanocytic differentiation, pT3a (FIGO IIIA). There were metastases in the rectum serosa and lungs. After 8 months of diagnosis and surgical treatment, the patient is on chemotherapy and radiotherapy. We highlight the morphological characteristics and criteria that allow the definitive anatomopathological diagnosis, including immunohistochemical markers used to identify the cell types present in this unprecedented association.

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High-grade endometrial carcinomas are aggressive neoplasms of difficult histological classification. Neuroendocrine differentiation in endometrial carcinomas is rare. This is the report of an endometrial large cell neuroendocrine carcinoma with foci of melanocytic differentiation in a 75-year-old woman with abnormal post-menopausal uterine bleeding for 2 years. Two initial biopsies were inconclusive. Histopathological examination of the uterus revealed large cell neuroendocrine carcinoma associated with endometrioid carcinoma and foci of melanocytic differentiation, pT3a (FIGO IIIA). There were metastases in the rectum serosa and lungs. After 8 months of diagnosis and surgical treatment, the patient is on chemotherapy and radiotherapy. We highlight the morphological characteristics and criteria that allow the definitive anatomopathological diagnosis, including immunohistochemical markers used to identify the cell types present in this unprecedented association.

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The solid variant of aneurismal bone cysts (ABC) is considered rare. It occurs with greater frequency in pediatric patients and in the tibia, femur, pelvis and humerus. We present a case of a metaphyseal lytic lesion on the distal extremity of the radius in a child whose radiograph was requested after low-energy trauma. The hypothesis of a pathological bone fracture secondary to an aneurysmal bone cyst was suggested. After biopsy, the child underwent intralesional excision without bone grafting and the histopathological findings were compatible with the solid variant of aneurysmal bone cyst.

A variante sólida do cisto ósseo aneurismático (COA) é considerada lesão rara, ocorre com maior frequência nos pacientes pediátricos e nos ossos da tíbia, fêmur, pelve e úmero. Apresentamos o caso de uma lesão lítica metafisária na extremidade distal do rádio de uma criança em que, ao exame radiográfico feito devido a um trauma de baixa energia, foi aventada a hipótese de fratura em um osso patológico secundária a um cisto ósseo aneurismático. Após a biópsia, a criança foi submetida a ressecção intralesional sem interposição de enxerto e o exame histopatológico foi condizente com a variante sólida do cisto ósseo aneurismático.

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A Pneumonia Intersticial Aguda (PIA) é uma rara e fulminante forma de doença pulmonar difusa descrita por Hamman e Rich em 1935. Pneumonia Intersticial Aguda é classificada como Pneumonia Intersticial Idiopática, e é a mais aguda e agressiva em seu curso. Apresenta-se clinicamente de forma similar a Síndrome da Angústia Respiratória Aguda (SARA), e representa provavelmente uma parte dos casos de síndrome da Angústia Respiratória Aguda idiopática. O caso relatado é de uma paciente de 55 anos, portadora de Obesidade e Esquizofrenia, que apresentou Insuficiência Respiratória Aguda e síndrome da Angústia Respiratória Aguda grave, com piora clínica rápida e evolução para óbito com menos de 3 dias de internação hospitalar. O diagnóstico de Pneumonia Intersticial Aguda foi feito na necropsia. O objetivo deste trabalho é fazer uma breve revisão sobre a Pneumonia Intersticial Aguda e relatar um caso clínico desta doença, que é rara e com pouca descrição na literatura, devendo ser lembrada como diagnóstico diferencial nos casos de Síndrome da Angústia Respiratória Aguda

Acute Interstitial Pneumonia (AIP) is a rare and fulminant diffuse lung disease described by Hamman and Rich in 1935. Acute Interstitial Pneumonia is classified as idiopathic interstitial pneumonia, and is the most aggressive and acute in its course. It is presented as Adult Respiratory Distress Syndrome (ARDS), and it is one of the cases of idiopathic as Adult Respiratory Distress Syndrome. This is a case of a 55 years-old patient, with obesity and schizophrenia who presented with acute respiratory insufficiency and severe as Adult Respiratory Distress Syndrome, with rapid clinical deterioration and progression to death in less than three days of hospitalization. The diagnosis of Acute Interstitial Pneumonia was made at necropsy. The objective of this paper is to briefly review the Acute Interstitial Pneumonia and to report a case of this disease, which is rare with limited description in the literature. It should be included as a differential diagnosis in cases of Adult Respiratory Distress Syndrome

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The solid variant of aneurismal bone cysts (ABC) is considered rare. It occurs with greater frequency in pediatric patients and in the tibia, femur, pelvis and humerus. We present a case of a metaphyseal lytic lesion on the distal extremity of the radius in a child whose radiograph was requested after low-energy trauma. The hypothesis of a pathological bone fracture secondary to an aneurysmal bone cyst was suggested. After biopsy, the child underwent intralesional excision without bone grafting and the histopathological findings were compatible with the solid variant of aneurysmal bone cyst.

A variante sólida do cisto ósseo aneurismático (COA) é considerada lesão rara, ocorre com maior frequência nos pacientes pediátricos e nos ossos da tíbia, fêmur, pelve e úmero. Apresentamos o caso de uma lesão lítica metafisária na extremidade distal do rádio de uma criança em que, ao exame radiográfico feito devido a um trauma de baixa energia, foi aventada a hipótese de fratura em um osso patológico secundária a um cisto ósseo aneurismático. Após a biópsia, a criança foi submetida a ressecção intralesional sem interposição de enxerto e o exame histopatológico foi condizente com a variante sólida do cisto ósseo aneurismático.

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Aplastic anemia is a bone marrow failure syndrome characterized by peripheral cytopenias and hypocellular bone marrow. Although aplastic anemia is idiopathic in most cases, rheumatic diseases such as systemic lupus erythematosus are recognized as causes of aplastic anemia, with their possible etiological mechanisms being T and B lymphocyte dysfunction and pro-inflammatory cytokines and autoantibody production directed against bone marrow components. In the course of the human immunodeficiency virus infection/acquired immunodeficiency syndrome, the identification of autoantibodies and the occurrence of rheumatic events, in addition to the natural course of systemic lupus erythematosus which is modified by immune changes that are characteristic of human immunodeficiency virus infection/acquired immunodeficiency syndrome, make the diagnosis of systemic lupus erythematosus challenging. This study reports the case of a woman with acquired immunodeficiency syndrome treated with a highly active antiretroviral therapy, who had prolonged cytopenias and hypocellular bone marrow consistent with aplastic anemia. The clinical picture, high autoantibodies titers, and sustained remission of the patient's hematological status through immunosuppression supported the diagnosis of systemic lupus erythematosus-associated aplastic anemia. This is the first report of aplastic anemia concurrent with systemic lupus erythematosus and acquired immunodeficiency syndrome, providing additional evidence that immune dysfunction is a key part of the pathophysiological mechanism of aplastic anemia.

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Aplastic anemia is a bone marrow failure syndrome characterized by peripheral cytopenias and hypocellular bone marrow. Although aplastic anemia is idiopathic in most cases, rheumatic diseases such as systemic lupus erythematosus are recognized as causes of aplastic anemia, with their possible etiological mechanisms being T and B lymphocyte dysfunction and pro-inflammatory cytokines and autoantibody production directed against bone marrow components. In the course of the human immunodeficiency virus infection/acquired immunodeficiency syndrome, the identification of autoantibodies and the occurrence of rheumatic events, in addition to the natural course of systemic lupus erythematosus which is modified by immune changes that are characteristic of human immunodeficiency virus infection/acquired immunodeficiency syndrome, make the diagnosis of systemic lupus erythematosus challenging. This study reports the case of a woman with acquired immunodeficiency syndrome treated with a highly active antiretroviral therapy, who had prolonged cytopenias and hypocellular bone marrow consistent with aplastic anemia. The clinical picture, high autoantibodies titers, and sustained remission of the patient's hematological status through immunosuppression supported the diagnosis of systemic lupus erythematosus-associated aplastic anemia. This is the first report of aplastic anemia concurrent with systemic lupus erythematosus and acquired immunodeficiency syndrome, providing additional evidence that immune dysfunction is a key part of the pathophysiological mechanism of aplastic anemia.

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A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989-2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies.