A New Coding System for the Identification of Left Ventricular Rotation Patterns and Their Relevance to Myocardial Function.

Rotational mechanics is a fundamental determinant of left ventricular ejection fraction (LVEF). The coding system currently employed in clinical practice does not distinguish between rotational patterns. We propose an alternative coding system that makes possible to identify the rotational pattern of the LV and relate it to myocardial function. Echocardiographic images were used to generate speckle tracking-derived transmural global longitudinal strain (tGLS) and rotational parameters. The existence of twist (basal and apical rotations in opposite directions) is expressed as a rotational gradient with a positive value that is the sum of the basal and apical rotation angles. Conversely, when there is rigid rotation (basal and apical rotations in the same direction) the resulting gradient is assigned a negative value that is the subtraction between the two rotation angles. The rotational patterns were evaluated in 87 healthy subjects and 248 patients with LV hypertrophy (LVH) and contrasted with their myocardial function. Our approach allowed us to distinguish between the different rotational patterns. Twist pattern was present in healthy controls and 104 patients with LVH and normal myocardial function (tGLS ≥ 17%, both). Among 144 patients with LVH and myocardial dysfunction (tGLS < 17%), twist was detected in 83.3% and rigid rotation in 16.7%. LVEF was < 50% in 34.7%, and all patients with rigid rotation had a LVEF < 50%. The gradient rotational values showed a close relationship with LVEF (r = 0.73; p < 0.001). The proposed coding system allows us to identify the rotational patterns of the LV and to relate their values with LVEF.

Performance patterns of primary health care in the face of COVID-19 in Brazil: characteristics and contrasts. / Padrões de desempenho da atenção primária à saúde diante da COVID-19 no Brasil: características e contrastes.

The adequate fight against pandemics requires effective coordination between primary health care (PHC) and health surveillance, guaranteed attention to acute and chronic demands, and a bond with the community dimension in the scope of basic health units (UBS, acronym in Portuguese). This study aims to contrast two extreme standards of PHC performance in the fight against COVID-19 in Brazil, comparing them with the profiles of the corresponding municipalities and characteristics of the organization of services. Based on the results of a cross-sectional national survey with a representative sample of UBSs, we created a synthetic index to evaluate how PHC performs against COVID-19 called CPI, composed of axes of health surveillance and social support (collective dimension) and of COVID-19 care and continuity of care (individual dimension). Of the 907 surveyed UBSs, 120 were selected, half of which had the highest indexes (complete standard) and the other half, the lowest ones (restricted standard). The municipalities of the UBSs with a complete standard are predominantly rural, have low Municipal Health Development Index (MHDI), high Family Health Strategy (FHS) coverage, and stand out in the collective dimension, whereas the UBSs in urban municipalities with this same standard have high MHDI, low FHS coverage, and an emphasis on the individual dimension. In the restricted standard, we highlight community health workers' reduced work in the territory. In the Brazilian Northeast, UBSs with complete standard predominate, whereas, in its Southeast, UBSs with restricted standard predominate. The study poses questions that refer to the role and organization of PHC in the health care network under situations that require prompt response to health issues and indicates the greater potential capacity of the FHS program in such situations.

O enfrentamento adequado de pandemias requer forte articulação entre atenção primária à saúde (APS) e vigilância em saúde, atenção garantida às demandas agudas e crônicas e vinculação com a dimensão comunitária no âmbito das unidades básicas de saúde (UBS). O objetivo deste artigo é contrastar dois padrões extremos de desempenho da APS no enfrentamento da COVID-19 no Brasil, cotejando-os com os perfis dos respectivos municípios e características da organização dos serviços. A partir dos resultados de inquérito nacional transversal com amostra representativa das UBS, foi criado um índice sintético de desempenho da APS em relação à COVID-19, denominado CPI, composto pelos eixos de vigilância e apoio social (dimensão coletiva) e de atendimento ao paciente com COVID-19 e continuidade do cuidado (dimensão individual). Das 907 UBS pesquisadas, foram selecionadas 120, sendo a metade com os maiores índices encontrados (padrão completo) e a outra com os menores (padrão restrito). Os municípios das UBS com padrão completo são preponderantemente rurais, com baixo Índice de Desenvolvimento Humano Municipal (IDHM), alta cobertura da Estratégia Saúde da Família (ESF) e destacam-se na dimensão coletiva, enquanto as UBS nesse mesmo padrão situadas em municípios urbanos apresentam alto IDHM, baixa cobertura de ESF, com ênfase na dimensão individual. No padrão restrito, destaca-se a reduzida atuação de agentes comunitários de saúde no território. Na Região Nordeste, predominam UBS com padrão completo, enquanto na Sudeste preponderam UBS com padrão restrito. O estudo apresenta questões que remetem ao papel e à organização da APS na rede de cuidados em situações que requerem pronta resposta aos agravos de saúde e indica maior capacidade potencial da ESF em tais situações.

El enfrentamiento adecuado de las pandemias requiere una fuerte articulación entre atención primaria de salud (APS) y la vigilancia en salud, una atención garantizada a las demandas agudas y crónicas y la vinculación con la dimensión comunitaria en el ámbito de las unidades básicas de salud (UBS). El objetivo de este artículo es contrastar dos patrones extremos de desempeño de la APS en el enfrentamiento del COVID-19 en Brasil, comparándolos con los perfiles de los respectivos municipios y características de la organización de los servicios. A partir de los resultados de una encuesta nacional transversal con una muestra representativa de las UBS fue creado un índice sintético de desempeño de la APS frente al COVID-19, denominado CPI, compuesto por los ejes de vigilancia y apoyo social (dimensión colectiva) y de atención al COVID-19 y continuidad de la atención (dimensión individual). De las 907 UBS investigadas, se seleccionaron 120, siendo la mitad con los índices más grandes encontrados (estándar completo) y la otra con los más bajos (estándar estricto). Los municipios de las UBS con estándar completo son preponderantemente rurales, con bajo índice de desarrollo humano municipal (IDHM), alta cobertura de la Estrategia Salud de la Familia (ESF) y se destacan en la dimensión colectiva, mientras que las UBS en este mismo estándar situadas en municipios urbanos presentan alto IDHM, baja cobertura de ESF, con énfasis en la dimensión individual. En el estándar estricto, se destaca la reducida actuación de los agentes comunitarios de salud en el territorio. En la región Nordeste predominan las UBS con estándar completo, mientras que en el Sureste predominan las UBS con un estándar estricto. El estudio aporta cuestiones que remiten al papel y organización de la APS en la red de atención en situaciones que requieren respuesta rápida a los problemas de salud e indica una mayor capacidad potencial de la ESF en tales situaciones.

Penile and digital calciphylaxis: A case report and literature review.

Calcific uremic arteriolopathy (CUA) represents a rare but severe disease with high morbimortality. The authors present the case of a 58-year-old male patient with chronic kidney disease due to obstructive uropathy, on hemodialysis (HD). He started HD due to uremic syndrome with a severe renal dysfunction, dysregulation of calcium and phosphate metabolism, and he presented with distal penile ischemia, which was treated with surgical debridement and hyperbaric oxygen therapy. Four months later, painful distal digital necrosis of both hands was observed. Extensive arterial calcification was observed on X-ray. A skin biopsy confirmed the presence of CUA. Sodium thiosulfate was administered for 3 months, HD was intensified, and hyperphosphatemia control was achieved, with progressive improvement of the lesions. This case illustrates an uncommon presentation of CUA in a patient on HD for a few months, non-diabetic and not anticoagulated, but with a severe dysregulation of calcium and phosphate metabolism.

Myocardial Wringing and Rigid Rotation in Cardiac Amyloidosis.

Background: The motion of the heart is a result of the helicoidal arrangement of the myofibers in the organ's wall. We aimed to study the relationship between the wringing motion state and the degree of ventricular function in patients with cardiac amyloidosis (CA). Methods: Fifty patients with CA and decreased global longitudinal strain (LS) were evaluated using 2-dimensional speckle-tracking echocardiography. We have expressed LS as positive values to facilitate understanding. Normal twist, which occurs when basal and apical rotations occur in opposite directions, was coded as positive. When the apex and base rotate in the same direction (rigid rotation), twist was coded as negative. Left ventricular (LV) wringing (calculated as twist/LS, which takes into account actions that occur simultaneously during LV systole [ie, longitudinal shortening and twist]) was evaluated according to LV ejection fraction (LVEF). Results: Most of the patients (66%) who participated in the study were diagnosed with transthyretin amyloidosis. A positive relationship was observed between wringing and LVEF (r = 0.75, P < 0.0001). In advanced stages of ventricular dysfunction, rigid rotation appeared in 66.6% of patients with LVEF ≤ 40%, in whom negative values of twist and wringing were observed. LV wringing proved to be a good discriminator of LVEF (area under the curve 0.90, P < 0.001, 95% confidence interval 0.79-0.97); for example, wringing < 1.30°/% detected LVEF < 50% with 85.7% sensibility and 89.7% specificity. Conclusions: Wringing, which integrates twist and simultaneous LV longitudinal shortening, is a conditioning rotational parameter of the degree of ventricular function in patients with CA.

Contexte: Les mouvements du cœur sont le résultat de l'orientation hélicoïdale des fibres des parois du cœur. L'objectif de notre étude était d'étudier le lien entre le mouvement « d'essorage ¼ et la fonction ventriculaire chez les patients atteints d'amylose cardiaque (AC). Méthodologie: Cinquante patients atteints d'AC et présentant une déformation longitudinale (DL) globale réduite ont fait l'objet d'une évaluation à l'aide de l'échocardiographie bidimensionnelle de suivi des marqueurs acoustiques. Nous avons choisi d'exprimer la DL en valeurs positives pour faciliter la compréhension des données. Une torsion normale, caractérisée par les mouvements de rotation opposés entre la base et l'apex du cœur, a été codée comme positive. Lorsque l'apex et la base opéraient une rotation dans la même direction (rotation rigide), la torsion était codée comme négative. Le mouvement « d'essorage ¼ du ventricule gauche (VG) (calculé comme le rapport torsion/DL, qui tient compte des actions survenant simultanément durant la systole du VG [c.-à-d., raccourcissement longitudinal et torsion]) a été évalué en fonction de la fraction d'éjection du VG (FEVG). Résultats: La plupart des patients (66 %) ayant participé à l'étude avaient reçu un diagnostic d'amylose à transthyrétine. Un lien positif a été établi entre le mouvement d'essorage et la FEVG (coefficient de corrélation [r] = 0,75, p < 0,0001). Aux stades avancés de la dysfonction ventriculaire, une rotation rigide a été observée chez 66,6 % des patients ayant une FEVG ≤ 40 % et chez qui les valeurs de torsion et d'essorage étaient négatives. L'essorage du VG s'est révélé être un facteur fiable de détermination de la FEVG (aire sous la courbe : 0,90; p < 0,001, intervalle de confiance [IC] à 95 % : 0,79-0,97); par exemple, un mouvement d'essorage < 1,30 °/% a permis de détecter une FEVG < 50 % avec une sensibilité de 85,7 % et une spécificité de 89,7 %. Conclusions: Le mouvement d'essorage, qui intègre simultanément la torsion et le raccourcissement longitudinal du VG, est un paramètre rotationnel qui influence le degré de fonction ventriculaire chez les patients atteints d'AC.

Recovering from a renal vascular catastrophe: Case report.

Renal artery thrombosis is a rare vascular event that precipitates renal infarction. Although in up to one third of cases the etiology is not identified, renal artery lesions, cardioembolism and acquired thrombophilias are the main causes. A bilateral simultaneous idiopathic renal artery thrombosis is an unlikely coincidence. We present two cases of patients with acute bilateral renal artery thrombosis of unknown etiology. Cardiac embolism, acquired thrombophilia and occult neoplasm workups were negative. Both cases were temporarily hemodialysis-dependent and partially recovered renal function under conservative approach with systemic anticoagulation. Recommendations on optimal treatment for renal artery thrombosis are still lacking. We discuss the available options.

Long-term cholecalciferol supplementation in hemodialysis patients: Effects on mineral metabolism, inflammation, and cardiac parameters.

BACKGROUND: Low levels of 25-hydroxyvitamin D [25(OH)D] are frequent in chronic kidney disease and are associated with adverse outcomes. The aim of this 5-year prospective study was to evaluate the effects of cholecalciferol supplementation on mineral metabolism, inflammation and cardiac parameters in hemodialysis (HD) patients. METHODS: The study included 97 patients. Cholecalciferol was given after HD according to 25(OH)D baseline levels measured twice (end of winter and of summer). The 25(OH)D levels, circulating bone metabolism, inflammation parameters, brain natriuretic peptide (BNP), pulse pressure (PP), and left ventricular mass index (LVMI) were evaluated before and after supplementation. RESULTS: There was a significant increase in 25(OH)D levels after supplementation (p < 0.001); however, serum calcium (p = 0.02), phosphorus (p = 0.018), and iPTH (p = 0.03) were decreased. Magnesium levels increased during the study (p = 0.03). A reduction in the number of patients under active vitamin D (p < 0.001) and in the dose and number of patients treated with darbepoetin (p = 0.02) was observed. Serum albumin increased (p < 0.001), and C-reactive protein decreased (p = 0.01). BNP (p < 0.001), PP (p = 0.007), and LVMI (p = 0.02) were significantly reduced after supplementation. CONCLUSIONS: Long-term cholecalciferol supplementation allowed correction of 25(OH)D deficiency, improved mineral metabolism with less use of active vitamin D, attenuated inflammation, reduced the dose of the erythropoiesis-stimulating agent, and improved cardiac dysfunction.

Genomics improves risk stratification of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials.

Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinicalbiological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5- year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.

Padrões de desempenho da atenção primária à saúde diante da COVID-19 no Brasil: características e contrastes / Estándares de desempeño de la atención primaria de salud frente al COVID-19 en Brasil: características y contrastes / Performance patterns of primary health care in the face of COVID-19 in Brazil: characteristics and contrasts

O enfrentamento adequado de pandemias requer forte articulação entre atenção primária à saúde (APS) e vigilância em saúde, atenção garantida às demandas agudas e crônicas e vinculação com a dimensão comunitária no âmbito das unidades básicas de saúde (UBS). O objetivo deste artigo é contrastar dois padrões extremos de desempenho da APS no enfrentamento da COVID-19 no Brasil, cotejando-os com os perfis dos respectivos municípios e características da organização dos serviços. A partir dos resultados de inquérito nacional transversal com amostra representativa das UBS, foi criado um índice sintético de desempenho da APS em relação à COVID-19, denominado CPI, composto pelos eixos de vigilância e apoio social (dimensão coletiva) e de atendimento ao paciente com COVID-19 e continuidade do cuidado (dimensão individual). Das 907 UBS pesquisadas, foram selecionadas 120, sendo a metade com os maiores índices encontrados (padrão completo) e a outra com os menores (padrão restrito). Os municípios das UBS com padrão completo são preponderantemente rurais, com baixo Índice de Desenvolvimento Humano Municipal (IDHM), alta cobertura da Estratégia Saúde da Família (ESF) e destacam-se na dimensão coletiva, enquanto as UBS nesse mesmo padrão situadas em municípios urbanos apresentam alto IDHM, baixa cobertura de ESF, com ênfase na dimensão individual. No padrão restrito, destaca-se a reduzida atuação de agentes comunitários de saúde no território. Na Região Nordeste, predominam UBS com padrão completo, enquanto na Sudeste preponderam UBS com padrão restrito. O estudo apresenta questões que remetem ao papel e à organização da APS na rede de cuidados em situações que requerem pronta resposta aos agravos de saúde e indica maior capacidade potencial da ESF em tais situações.

El enfrentamiento adecuado de las pandemias requiere una fuerte articulación entre atención primaria de salud (APS) y la vigilancia en salud, una atención garantizada a las demandas agudas y crónicas y la vinculación con la dimensión comunitaria en el ámbito de las unidades básicas de salud (UBS). El objetivo de este artículo es contrastar dos patrones extremos de desempeño de la APS en el enfrentamiento del COVID-19 en Brasil, comparándolos con los perfiles de los respectivos municipios y características de la organización de los servicios. A partir de los resultados de una encuesta nacional transversal con una muestra representativa de las UBS fue creado un índice sintético de desempeño de la APS frente al COVID-19, denominado CPI, compuesto por los ejes de vigilancia y apoyo social (dimensión colectiva) y de atención al COVID-19 y continuidad de la atención (dimensión individual). De las 907 UBS investigadas, se seleccionaron 120, siendo la mitad con los índices más grandes encontrados (estándar completo) y la otra con los más bajos (estándar estricto). Los municipios de las UBS con estándar completo son preponderantemente rurales, con bajo índice de desarrollo humano municipal (IDHM), alta cobertura de la Estrategia Salud de la Familia (ESF) y se destacan en la dimensión colectiva, mientras que las UBS en este mismo estándar situadas en municipios urbanos presentan alto IDHM, baja cobertura de ESF, con énfasis en la dimensión individual. En el estándar estricto, se destaca la reducida actuación de los agentes comunitarios de salud en el territorio. En la región Nordeste predominan las UBS con estándar completo, mientras que en el Sureste predominan las UBS con un estándar estricto. El estudio aporta cuestiones que remiten al papel y organización de la APS en la red de atención en situaciones que requieren respuesta rápida a los problemas de salud e indica una mayor capacidad potencial de la ESF en tales situaciones.

The adequate fight against pandemics requires effective coordination between primary health care (PHC) and health surveillance, guaranteed attention to acute and chronic demands, and a bond with the community dimension in the scope of basic health units (UBS, acronym in Portuguese). This study aims to contrast two extreme standards of PHC performance in the fight against COVID-19 in Brazil, comparing them with the profiles of the corresponding municipalities and characteristics of the organization of services. Based on the results of a cross-sectional national survey with a representative sample of UBSs, we created a synthetic index to evaluate how PHC performs against COVID-19 called CPI, composed of axes of health surveillance and social support (collective dimension) and of COVID-19 care and continuity of care (individual dimension). Of the 907 surveyed UBSs, 120 were selected, half of which had the highest indexes (complete standard) and the other half, the lowest ones (restricted standard). The municipalities of the UBSs with a complete standard are predominantly rural, have low Municipal Health Development Index (MHDI), high Family Health Strategy (FHS) coverage, and stand out in the collective dimension, whereas the UBSs in urban municipalities with this same standard have high MHDI, low FHS coverage, and an emphasis on the individual dimension. In the restricted standard, we highlight community health workers' reduced work in the territory. In the Brazilian Northeast, UBSs with complete standard predominate, whereas, in its Southeast, UBSs with restricted standard predominate. The study poses questions that refer to the role and organization of PHC in the health care network under situations that require prompt response to health issues and indicates the greater potential capacity of the FHS program in such situations.

Mal-positioning of a dialysis catheter: One lumen with arterial blood and the other with venous blood?

Partial anomalous pulmonary vein drainage is a rare congenital defect, where the pulmonary vein drains into a systemic vein instead of draining into the left atrium. We present a case of a 63-year-old woman on hemodialysis who was found to have a right pulmonary vein with anomalous drainage to the superior vena cava after mal-positioning of a dialysis catheter, which demonstrated unexpected blood results from the different lumina of the catheter. Multiple imaging techniques were used to deal with this rare clinical situation. This is the first case reporting a mal-positioning of a left-side internal jugular vein tunneled catheter into a right-side pulmonary vein.

Latest Contributions of Genomics to T-Cell Acute Lymphoblastic Leukemia (T-ALL).

As for many neoplasms, initial genetic data about T-cell acute lymphoblastic leukemia (T-ALL) came from the application of cytogenetics. This information helped identify some recurrent chromosomal alterations in T-ALL at the time of diagnosis, although it was difficult to determine their prognostic impact because of their low incidence in the specific T-ALL cohort analyzed. Genetic knowledge accumulated rapidly following the application of genomic techniques, drawing attention to the importance of using high-resolution genetic techniques to detect cryptic aberrations present in T-ALL, which are not usually detected by cytogenetics. We now have a clearer appreciation of the genetic landscape of the different T-ALL subtypes at diagnosis, explaining the particular oncogenetic processes taking place in each T-ALL, and we have begun to understand relapse-specific mechanisms. This review aims to summarize the latest advances in our knowledge of the genome in T-ALL. We highlight areas where the research in this subtype of ALL is progressing with the aim of identifying key questions that need to be answered in the medium-long term if this knowledge is to be applied in clinics.

Glycosuria in primary glomerulopathies: prevalence and prognostic significance / Glicosúria nas doenças glomerulares primárias: prevalência e significância prognóstica

Abstract Introduction: Tubular damage is common in glomerular diseases (GD). Glycosuria is a marker of tubular dysfunction and may be used to detect tubular lesion and CKD progression. The aim of this study was to evaluate the prevalence and prognostic value of glycosuria at the time of diagnosis in primary glomerulopathies (PG). Methods: We conducted a 24-month retrospective study in patients diagnosed with PG in our center between 2009 and 2020. We excluded diabetic patients, use of SGLT2 inhibitors, transplant patients, and secondary GD. Patients were divided in two groups according to their glycosuria status at diagnosis. Results: We studied 115 patients. Global prevalence of glycosuria was 10% (n=11) and membranous nephropathy (MN) had the highest prevalence (n=5, 17.9%). We found that patients with glycosuria had higher serum creatinine (2.4 vs. 1.2 mg/dL, p=0.030), higher albuminuria (4.8 vs. 1.9 g/g, p=0.004), and lower serum albumin (2.3 vs. 3.2 g/dL, p=0.021). We did not find association with histological prognostic factors. At the end of follow-up, patients with glycosuria had higher prevalence of the composite outcome of stage 5D CKD or 50% increase in basal SCr (45.5% vs. 17.3%, p=0.037). In patients with MN, results were similar but we were able to find an association of glycosuria with more severe interstitial fibrosis and tubular atrophy (25.0 vs. 0.0 %, p=0.032). Conclusion: Ten percent of our patients with PG have glycosuria. Glycosuria at the time of diagnosis was associated with more severe clinical presentation and worst renal outcome. The association with higher albuminuria suggests that tubular function has an impact on the severity and outcomes of PG.

Resumo Introdução: Danos tubulares são comuns em doenças glomerulares (DG). Glicosúria é um marcador de disfunção tubular e pode detectar lesão tubular e progressão da DRC. O objetivo deste estudo foi avaliar a prevalência e o valor prognóstico da glicosúria no diagnóstico em glomerulopatias primárias (GP). Métodos: Realizamos estudo retrospectivo de 24 meses em pacientes diagnosticados com GP em nosso centro entre 2009-2020. Excluímos pacientes diabéticos, uso de inibidores de SGLT2, pacientes transplantados e DG secundárias. Os pacientes dividiram-se em dois grupos de acordo com seu estado de glicosúria no diagnóstico. Resultados: Estudamos 115 pacientes. A prevalência global de glicosúria foi de 10% (n=11) e a nefropatia membranosa (NM) teve maior prevalência (n=5, 17,9%). Constatamos que pacientes com glicosúria apresentavam creatinina sérica mais elevada (2,4 vs. 1,2 mg/dL, p=0,030), albuminúria mais alta (4,8 vs. 1,9 g/g, p=0,004), e albumina sérica mais baixa (2,3 vs. 3,2 g/dL, p=0,021). Não encontramos associação com fatores prognósticos histológicos. Ao final do acompanhamento, pacientes com glicosúria tiveram maior prevalência do desfecho composto de DRC estágio 5D ou aumento de 50% na CrS basal (45,5% vs. 17,3%, p=0,037). Em pacientes com NM, os resultados foram semelhantes, mas encontramos uma associação de glicosúria com fibrose intersticial mais grave e atrofia tubular (25,0 vs. 0,0 %, p=0,032). Conclusão: 10% de nossos pacientes com GP têm glicosúria. A glicosúria no diagnóstico foi associada a uma apresentação clínica mais grave e pior desfecho renal. A associação com albuminúria mais elevada sugere que a função tubular tem um impacto na gravidade e nos desfechos da GP.

Glycosuria in primary glomerulopathies: prevalence and prognostic significance.

INTRODUCTION: Tubular damage is common in glomerular diseases (GD). Glycosuria is a marker of tubular dysfunction and may be used to detect tubular lesion and CKD progression. The aim of this study was to evaluate the prevalence and prognostic value of glycosuria at the time of diagnosis in primary glomerulopathies (PG). METHODS: We conducted a 24-month retrospective study in patients diagnosed with PG in our center between 2009 and 2020. We excluded diabetic patients, use of SGLT2 inhibitors, transplant patients, and secondary GD. Patients were divided in two groups according to their glycosuria status at diagnosis. RESULTS: We studied 115 patients. Global prevalence of glycosuria was 10% (n=11) and membranous nephropathy (MN) had the highest prevalence (n=5, 17.9%). We found that patients with glycosuria had higher serum creatinine (2.4 vs. 1.2 mg/dL, p=0.030), higher albuminuria (4.8 vs. 1.9 g/g, p=0.004), and lower serum albumin (2.3 vs. 3.2 g/dL, p=0.021). We did not find association with histological prognostic factors. At the end of follow-up, patients with glycosuria had higher prevalence of the composite outcome of stage 5D CKD or 50% increase in basal SCr (45.5% vs. 17.3%, p=0.037). In patients with MN, results were similar but we were able to find an association of glycosuria with more severe interstitial fibrosis and tubular atrophy (25.0 vs. 0.0 %, p=0.032). CONCLUSION: Ten percent of our patients with PG have glycosuria. Glycosuria at the time of diagnosis was associated with more severe clinical presentation and worst renal outcome. The association with higher albuminuria suggests that tubular function has an impact on the severity and outcomes of PG.

Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL).

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.

The Yin and Yang-Like Clinical Implications of the CDKN2A/ARF/CDKN2B Gene Cluster in Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a malignant clonal expansion of lymphoid hematopoietic precursors that exhibit developmental arrest at varying stages of differentiation. Similar to what occurs in solid cancers, transformation of normal hematopoietic precursors is governed by a multistep oncogenic process that drives initiation, clonal expansion and metastasis. In this process, alterations in genes encoding proteins that govern processes such as cell proliferation, differentiation, and growth provide us with some of the clearest mechanistic insights into how and why cancer arises. In such a scenario, deletions in the 9p21.3 cluster involving CDKN2A/ARF/CDKN2B genes arise as one of the oncogenic hallmarks of ALL. Deletions in this region are the most frequent structural alteration in T-cell acute lymphoblastic leukemia (T-ALL) and account for roughly 30% of copy number alterations found in B-cell-precursor acute lymphoblastic leukemia (BCP-ALL). Here, we review the literature concerning the involvement of the CDKN2A/B genes as a prognosis marker of good or bad response in the two ALL subtypes (BCP-ALL and T-ALL). We compare frequencies observed in studies performed on several ALL cohorts (adult and child), which mainly consider genetic data produced by genomic techniques. We also summarize what we have learned from mouse models designed to evaluate the functional involvement of the gene cluster in ALL development and in relapse/resistance to treatment. Finally, we examine the range of possibilities for targeting the abnormal function of the protein-coding genes of this cluster and their potential to act as anti-leukemic agents in patients.

Variable immunodeficiency study: Evaluation of two European cohorts within a variety of clinical phenotypes.

INTRODUCTION: Given the wide heterogeneity of common variable immunodeficiency (CVID), several groups have proposed clinical and immunological classifications to better define follow-up and prognostic algorithms. The present study aims to validate recent clinical and laboratory algorithms, based on different combinations of CVID biomarkers, to provide more personalized treatment and follow-up strategies. METHODS: We analysed clinical and immunological features of 80 patients with suspected or diagnosed CVID, in two reference centres of Portugal and Spain. Clinical manifestations were categorized into clinical phenotyping proposed by Chapel et al. [1] that included cytopenia; polyclonal lymphocytic infiltration; unexplained enteropathy; and no disease-related complications. RESULTS: 76% of patients in our cohort entered one of the four categories of clinical phenotyping, without overlap (cytopenia; polyclonal lymphocytic infiltration; unexplained enteropathy; and no disease-related complications). The most prominent phenotype was "cytopenia" (40%) followed by "polyclonal lymphocytic infiltration" (19%). The remaining 24% patients of our cohort had overlap of 2 clinical phenotypes (cytopenia and unexplained enteropathy mainly). A delay of CVID diagnosis in more than 6 years presented 3.7-fold higher risk of developing lymphoproliferation and/or malignancy (p < 0.05), and was associated with increased CD8+CD45RO + T-lymphocytes (p < 0.05). An association between decreased switched-memory B cells with lymphoproliferation and malignancy was observed (p < 0.03 and p < 0.05, respectively). CD4 + T-lymphocytopenia correlated with autoimmune phenotype, with 30% prevalence (p < 0.05). HLA-DR7 expression was related to CVID onset in early life in our patients (13 vs 25 years), and DQ2.5 or DQ2.2 with unexplained enteropathy (p < 0.05). CONCLUSIONS: The phenotypic and genetic study is crucial for an adequate clinical orientation of CVID patients. In these two independent cohorts of patients, classification based in clinical and laboratory algorithms, provides more personalized treatment and follow-up strategies.

Bone fracture risk factors in prevalent hemodialysis patients.

Bone fractures are an important cause of morbidity and mortality in hemodialysis (HD) patients. The aim of this study was to quantify the incidence of fractures in a cohort of prevalent HD patients and evaluate its relationship with possible risk factors. We performed a retrospective analysis of 341 patients, since they started HD (median of 51 months). Demographic, clinical, and biochemical parameters as well as vascular calcifications (VC) were evaluated. Fifty-seven episodes of fracture were identified with a median HD vintage of 47 months (incidence rate of 31 per 1000 person-years). Age (p < 0.001), female gender (p < 0.001), lower albumin (p = 0.02), and higher VC score (p < 0.001) were independently associated with increased risk of fracture, while active vitamin D therapy (p = 0.03) was associated with decreased risk. A significantly higher risk of incident fracture was also associated with higher values of bone-specific alkaline phosphatase (bALP) (p = 0.01) and intact parathyroid hormone (iPTH) levels either < 300 pg/mL (p = 0.02) or > 800 pg/mL (p < 0.001) compared with 300-800 pg/mL. In conclusion, bone fracture incidence in HD patients is high and its risk increases with age, female gender, lower serum albumin, and with the presence of more VC. Prevalent HD patients with low or high iPTH levels or increased bALP also had a higher fracture risk. Therapy with active vitamin D seems to have a protective role. Assessment of fracture risk and management in dialysis patients at greatest risk requires further study.

Measurement of Typhim Vi IgG as a Diagnostic Tool to Determine Anti-polysaccharide Antibody Production Deficiency in Children.

Background: The assessment of specific polysaccharide antibody production plays a pivotal role in the diagnosis of humoral primary immunodeficiencies (PID). The response to 23-valent pneumococcal vaccine (PPV) remains the gold standard for the diagnosis of polysaccharide antibodies. However, in Spain, the interpretation of pure polysaccharide 23-valent immunization is hampered by the high endemicity of pneumococcal disease and the generalization of the 13-valent adjuvant pneumococcal vaccination. Specific Typhim Vi vaccination (TV) immunoglobulin G IgG response to immunization is useful in adult PID, but there is no data regarding children. Objectives: To evaluate the clinical utility of TV IgG production as a diagnostic tool to determine anti-polysaccharide antibody production deficiency in children, when the response to PPV is unclear and isolated determination of serotypes is unfeasible. Methods: We conducted a single-institution prospective observational study on 61 children with recurrent infections. Baseline specific antibodies against PPV and TV were evaluated. In 28 children (46%), the response to the production of antibodies confirmed a clinical suspicion of humoral PID, and they were therefore immunized with 23-valent pneumococcal vaccine and Typhim Vi. Both specific antibody responses were measured by ELISA (The Binding Site Group Ltd, Birmingham, UK) using previously published cut-offs. Results: Seventy percent of the 61 children displayed baseline PPV IgG > 27 mg/L, whereas only 8% showed TV IgG > 28 U/mL (p < 0.0001). Twenty-one of 28 children (75%) achieved a 3-fold increase in post-vaccination TV IgG levels, whereas only 3% achieved a 4-fold increase in PPV IgG post vaccination, mainly due to high baseline PPV IgG titers. When we classified children according to their response to TV as responders or non-responders and compared this with the well-known clinical warning signs of the Jeffrey Modell Foundation. The proportions of children with history of pneumonia and the need for intravenous antibiotics were significantly higher in TV IgG non-responders than in TV IgG responders (p = 0.02 and p = 0.01, respectively). Conclusion: Response to TV can be considered an ancillary diagnostic tool to determine polysaccharide antibodies in children, particularly when isolated determination of pneumococcal serotypes is not feasible. TV provides a useful asset for clinicians in the era of conjugate PPV vaccination, with clinical relevance. Further research is warranted for validation.

Are high flow arteriovenous accesses associated with worse haemodialysis?

INTRODUCTION: An arteriovenous (AV) access flow (Qa) of 400 mL/min is usually sufficient for an effective hemodialysis (HD), but some accesses continue developing and become high flow accesses (HFA). Some authors postulated that an HFA might shift a significant portion of dialyzed blood from the cardiac output, which could decrease HD efficiency and lead to volume overload. OBJECTIVE: The aim of our study was to evaluate if HFA is associated with reduced HD efficiency and/or volume overload in prevalent HD patients. METHODS: We performed a 1-year retrospective study and assessed HD efficiency by the percentage of sessions in which the Kt/V > 1.4 and volume overload by bioimpedance spectroscopy. RESULTS: The study included 304 prevalent HD patients with a mean age of 67.5 years; 62.5% were males, 36.2% were diabetics, with a median HD vintage of 48 months. Sixteen percent of the patients had a HFA (defined as Qa > 2 L/min). In multivariate analysis, patients with HFA presented higher risk of volume overload (OR = 2.67, 95%CI = 1.06-6.71) and severe volume overload (OR = 4.06, 95%CI = 1.01-16.39) and attained dry weight less frequently (OR = 0.37, 95%CI = 0.14-0.94). However, HFA was not associated with lower Kt/V. CONCLUSION: Our results suggest that patients with HFA have higher risk of volume overload. However, contrarily to what has been postulated, HFA was not associated with less efficient dialysis, measured by Kt/V. Randomized controlled trials are needed to clarify these questions.

Are high flow arteriovenous accesses associated with worse haemodialysis? / Acessos arteriovenosos de alto débito estão associados a pior hemodiálise?

ABSTRACT Introduction: An arteriovenous (AV) access flow (Qa) of 400 mL/min is usually sufficient for an effective hemodialysis (HD), but some accesses continue developing and become high flow accesses (HFA). Some authors postulated that an HFA might shift a significant portion of dialyzed blood from the cardiac output, which could decrease HD efficiency and lead to volume overload. Objective: The aim of our study was to evaluate if HFA is associated with reduced HD efficiency and/or volume overload in prevalent HD patients. Methods: We performed a 1-year retrospective study and assessed HD efficiency by the percentage of sessions in which the Kt/V > 1.4 and volume overload by bioimpedance spectroscopy. Results: The study included 304 prevalent HD patients with a mean age of 67.5 years; 62.5% were males, 36.2% were diabetics, with a median HD vintage of 48 months. Sixteen percent of the patients had a HFA (defined as Qa > 2 L/min). In multivariate analysis, patients with HFA presented higher risk of volume overload (OR = 2.67, 95%CI = 1.06-6.71) and severe volume overload (OR = 4.06, 95%CI = 1.01-16.39) and attained dry weight less frequently (OR = 0.37, 95%CI = 0.14-0.94). However, HFA was not associated with lower Kt/V. Conclusion: Our results suggest that patients with HFA have higher risk of volume overload. However, contrarily to what has been postulated, HFA was not associated with less efficient dialysis, measured by Kt/V. Randomized controlled trials are needed to clarify these questions.

RESUMO Introdução: Um débito de sangue de acesso arteriovenoso (AV) (Qa) de 400 mL/min é geralmente suficiente para uma hemodiálise (HD) eficaz, mas alguns acessos continuam se desenvolvendo e se tornam acessos de alto débito (AAD). Alguns autores postularam que um AAD poderia desviar uma porção significativa do sangue dialisado do débito cardíaco, o que poderia diminuir a eficiência da HD e levar à sobrecarga de volume. Objetivo: O objetivo do nosso estudo foi avaliar se o AAD está associado à redução da eficiência da HD e/ou à sobrecarga de volume em pacientes prevalentes em HD. Métodos: Foi realizado um estudo retrospectivo de 1 ano, e avaliada a eficiência da HD pela porcentagem de sessões em que o Kt/V > 1,4 e a sobrecarga de volume avaliada pela bioimpedância. Resultados: O estudo incluiu 304 pacientes prevalentes em HD, com média de idade de 67,5 anos; 62,5% eram do sexo masculino; 36,2% eram diabéticos, com uma mediana de tempo em HD de 48 meses. Dezesseis por cento dos pacientes apresentavam AAD (definida como Qa > 2 L/min). Na análise multivariada, os pacientes com AAD apresentaram maior risco de sobrecarga de volume (OR = 2,67; IC95% = 1,06-6,71) e sobrecarga severa de volume (OR = 4,06; IC95% = 1,01-16,39) e atingiram o peso seco com menor frequência (OR = 0,37, IC 95% = 0,14-0,94). No entanto, o AAD não foi associado uma menor razão Kt/V. Conclusão: Nossos resultados sugerem que pacientes com AAD apresentam maior risco de sobrecarga de volume. No entanto, ao contrário do que foi postulado, o AAD não foi associado à diálise menos eficiente, medida pelo Kt/V. Ensaios clínicos randomizados são necessários para esclarecer essas questões.