Therapist-oriented home rehabilitation for adults with sickle cell anemia: effects on muscle strength, functional capacity, and quality of life.

OBJECTIVES: Considering the advances in functional rehabilitation in recent decades, therapist-oriented home rehabilitation (TOHR) has been increasingly used in the field of physical therapy because it increases patient compliance and reduces health system costs. The objective of this study was to investigate the effects of TOHR on functional capacity, muscle strength, and quality of life (QoL) in adults with sickle cell anemia (SCA). METHODS: Forty adults with SCA underwent manually guided TOHR for 12 weeks. Before and at the end of training, the following variables were assessed in the participants: distance covered in the 6-min walk test (6MWD); maximal inspiratory pressure (MIP); maximal expiratory pressure (MEP); handgrip strength (HGS); quadriceps strength (QS); and QoL using the Short Form-36 physical component summary (SF-36PCS) and the Short Form-36 mental component summary (SF-36MCS). RESULTS: After TOHR, significant increases were observed in the mean values for the 6MWD, MIP, MEP, HGS, QS, and SF-36PCS and SF-36MCS scores. The relative delta between the pre- and post-TOHR 6MWDs correlated significantly with the relative deltas of MIP (rs = 0.640, p < 0.0001), MEP (rs = 0.587, p < 0.0001), HGS (rs = 0.360, p = 0.022), and QS (rs = 0.351, p = 0.026). When the participants were separated according to their use of hydroxyurea, significant increases were observed in the relative deltas of the 6MWD, MIP and MEP values. CONCLUSIONS: This study shows that TOHR can potentially increase functional capacity, muscle strength, and QoL in adults with SCA. Furthermore, there appears to be a relationship between 6MWD gains and muscle strength gains with TOHR.Trial registration: ClinicalTrials.gov identifier: NCT04705792.

Diaphragm ultrasonography in adults with sickle cell anemia: evaluation of morphological and functional aspects.

OBJECTIVES: To assess morphological and functional aspects of the diaphragm by ultrasonography (US) in adults with sickle cell anemia (SCA) and evaluate if the diaphragmatic musculature can play a role in changes found in pulmonary function tests (PFTs) of these patients. METHODS: This is a cross-sectional observational and single-center study involving 40 adults with SCA who underwent diaphragm US and PFTs with a maximum of 1 month between the two tests. Diaphragm US was performed in B and M modes, and echogenicity, thickness and movement of the muscle was assessed in different respiratory maneuvers. RESULTS: Diaphragms had preserved echogenicity and the thickness was not significantly different between the groups. The SCA group exhibited significantly higher movement of the right hemidiaphragm during deep breathing (p = 0.004) and the sniff test (p = 0.0008) and lower movement of the left hemidiaphragm during quiet breathing (p = 0.009). There was a predominance of restrictive pattern (65%) and a global reduction in respiratory muscle strength (RMS) (70%). CONCLUSIONS: This study shows that adults with SCA had normal morphostructural aspects and absence of diaphragm dysfunction. Otherwise, they presented greater movement of the right hemidiaphragm during deep breathing and sniff test maneuvers. Despite the restrictive pattern and the reduction in RMS found in PFTs, the diaphragm of young adults with SCA did not have weakness or paralysis.

Respiratory resistance and reactance in adults with sickle cell anemia: Part 2-Fractional-order modeling and a clinical decision support system for the diagnosis of respiratory disorders.

BACKGROUND: A better understanding of sickle cell anemia (SCA) and improvements in drug therapy and health policy have contributed to the emergence of a large population of adults living with this disease. The mechanisms by which SCA produces adverse effects on the respiratory system of these patients are largely unknown. Fractional-order (FrOr) models have a high potential to improve pulmonary clinical science and could be useful for diagnostic purposes, offering accurate models with an improved ability to mimic nature. Part 2 of this two-part study examines the changes in respiratory mechanics in patients with SCA using the new perspective of the FrOr models. These results are compared with those obtained in traditional forced oscillation (FOT) parameters, investigated in Part 1 of the present study, complementing this first analysis. METHODOLOGY/PRINCIPAL FINDINGS: The data consisted of three categories of subjects: controls (n = 23), patients with a normal spirometric exam (n = 21) and those presenting restriction (n = 24). The diagnostic accuracy was evaluated by investigating the area under the receiver operating characteristic curve (AUC). Initially, it was observed that biomechanical changes in SCA included increased values of fractional inertance, as well as damping and hysteresivity (p<0.001). The correlation analysis showed that FrOr parameters are associated with functional exercise capacity (R = -0.57), pulmonary diffusion (R = -0.71), respiratory muscle performance (R = 0.50), pulmonary flows (R = -0.62) and airway obstruction (R = 0.60). Fractional-order modeling showed high diagnostic accuracy in the detection of early respiratory abnormalities (AUC = 0.93), outperforming spirometry (p<0.03) and standard FOT analysis (p<0.01) used in Part 1 of this study. A combination of machine learning methods with fractional-order modeling further improved diagnostic accuracy (AUC = 0.97). CONCLUSIONS: FrOr modeling improved our knowledge about the biomechanical abnormalities in adults with SCA. Changes in FrOr parameters are associated with functional exercise capacity decline, abnormal pulmonary mechanics and diffusion. FrOr modeling outperformed spirometric and traditional forced oscillation analyses, showing a high diagnostic accuracy in the diagnosis of early respiratory abnormalities that was further improved by an automatic clinical decision support system. This finding suggested the potential utility of this combination to help identify early respiratory changes in patients with SCA.

Complex karyotype including ring chromosome 11 in a patient with acute myeloid leukemia: case report

ABSTRACT CONTEXT: Complex karyotypes in acute myeloid leukemia (AML) are characterized by an overall low response rate with frequent relapses after clinical treatment. CASE REPORT: Here, we describe the case of a 61-year-old obese female with clinically diagnosed AML who presented a complex karyotype involving an uncommon abnormality: ring chromosome 11. Immunophenotypic analysis confirmed the diagnosis. Classical and molecular cytogenetic analyses, using GTG banding and FISH (fluorescence in situ hybridization), revealed the presence of complex structural rearrangement involving r(11), add(12)(p13), der(5) and der(13). CONCLUSIONS: Molecular cytogenetic analysis is suitable for better identification and characterization of chromosomal rearrangements in AML. Case reports like this, as well as population-based studies, are necessary for understanding the karyotypic changes that occur in humans.

Complex karyotype including ring chromosome 11 in a patient with acute myeloid leukemia: case report.

CONTEXT: Complex karyotypes in acute myeloid leukemia (AML) are characterized by an overall low response rate with frequent relapses after clinical treatment. CASE REPORT: Here, we describe the case of a 61-year-old obese female with clinically diagnosed AML who presented a complex karyotype involving an uncommon abnormality: ring chromosome 11. Immunophenotypic analysis confirmed the diagnosis. Classical and molecular cytogenetic analyses, using GTG banding and FISH (fluorescence in situ hybridization), revealed the presence of complex structural rearrangement involving r(11), add(12)(p13), der(5) and der(13). CONCLUSIONS: Molecular cytogenetic analysis is suitable for better identification and characterization of chromosomal rearrangements in AML. Case reports like this, as well as population-based studies, are necessary for understanding the karyotypic changes that occur in humans.

Respiratory resistance and reactance in adults with sickle cell anemia: Correlation with functional exercise capacity and diagnostic use.

BACKGROUND: The improvement in sickle cell anemia (SCA) care resulted in the emergence of a large population of adults living with this disease. The mechanisms of lung injury in this new population are largely unknown. The forced oscillation technique (FOT) represents the current state-of-the-art in the assessment of lung function. The present work uses the FOT to improve our knowledge about the respiratory abnormalities in SCA, evaluates the associations of FOT with the functional exercise capacity and investigates the early detection of respiratory abnormalities. METHODOLOGY/PRINCIPAL FINDINGS: Spirometric classification of restrictive abnormalities resulted in three categories: controls (n = 23), patients with a normal exam (n = 21) and presenting pulmonary restriction (n = 24). FOT analysis showed that, besides restrictive changes (reduced compliance; p<0.001), there is also an increase in respiratory resistance (p<0.001) and ventilation heterogeneity (p<0.01). FOT parameters are associated with functional exercise capacity (R = -0.38), pulmonary diffusion (R = 0.66), respiratory muscle performance (R = 0.41), pulmonary volumes (R = 0.56) and airway obstruction (R = 0.54). The diagnostic accuracy was evaluated by investigating the area under the receiver operating characteristic curve (AUC). A combination of FOT and machine learning (ML) classifiers showed adequate diagnostic accuracy in the detection of early respiratory abnormalities (AUC = 0.82). CONCLUSIONS: In this study, the use of FOT showed that adults with SCA develop a mixed pattern of respiratory disease. Changes in FOT parameters are associated with functional exercise capacity decline, abnormal pulmonary mechanics and diffusion. FOT associated with ML methods accurately diagnosed early respiratory abnormalities. This suggested the potential utility of the FOT and ML clinical decision support systems in the identification of respiratory abnormalities in patients with SCA.

Predictive models of six-minute walking distance in adults with sickle cell anemia: Implications for rehabilitation.

BACKGROUND: Sickle cell anemia (SCA) is characterized by a broad spectrum of abnormalities that affect most body organs and systems. To date, there is few data on the influence of these patients' clinical characteristics on the functional exercise capacity. AIM: To investigate the effect of the clinical complications on the functional exercise capacity of adult SCA patients. METHOD: Cross-sectional study, where 45 SCA patients underwent clinical evaluations, echocardiography, pulmonary function testing, and determination of six-minute walking distance (6MWD). RESULTS: A significant correlation (P < 0.001) was found between 6MWD and hemoglobin (Hb) level, tricuspid regurgitation velocity, forced vital capacity, acute chest syndrome, and diffusing capacity for carbon monoxide. The prediction model for 6MWD explained 67% of the 6MWD variability (P < 0.001). CONCLUSIONS: Hemodynamics, cardiovascular function, pulmonary function, and episodes of acute lung injury seem to impact the 6MWD in adults with SCA.

Changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease.

OBJECTIVE: To describe and quantify the main changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease, as well as to evaluate the radiologist accuracy in determining the type of hemoglobinopathy. MATERIALS AND METHODS: A prospective study involving 44 adult patients with sickle cell disease who underwent inspiration and expiration computed tomography of the chest. The frequency of tomography findings and the extent of involvement are reported. We also calculated radiologist accuracy in determining the type of hemoglobinopathy by analyzing the pulmonary alterations and morphology of the spleen. RESULTS: The changes found on computed tomography scans, in descending order of frequency, were as follows: fibrotic opacities (81.8%); mosaic attenuation (56.8%); architectural distortion (31.8%); cardiomegaly (25.0%); lobar volume reduction (18.2%); and increased caliber of peripheral pulmonary arteries (9.1%). For most of the findings, the involvement was considered mild, five or fewer lung segments being affected. The accuracy in determining the type of hemoglobinopathy (HbSS group versus not HbSS group) was 72.7%. CONCLUSION: In adult patients with sickle cell disease, the main tomography findings reflect fibrotic changes. In addition, computed tomography can be helpful in differentiating among hemoglobinopathies.

OBJETIVO: Descrever e quantificar as principais alterações na tomografia computadorizada do tórax em pacientes adultos oligossintomáticos com doença falciforme e, secundariamente, avaliar o índice de acerto do radiologista quanto ao tipo de hemoglobinopatia. MATERIAIS E MÉTODOS: Estudo prospectivo em que 44 pacientes adultos com doença falciforme foram submetidos a tomografia computadorizada do tórax tanto em inspiração como em expiração. Foram descritos a frequência dos achados tomográficos e os graus de acometimento. Por meio da análise das alterações pulmonares e do padrão morfológico do baço, foi calculado o índice de acerto do radiologista quanto ao tipo de hemoglobinopatia. RESULTADOS: As alterações encontradas nos exames de tomografia computadorizada, em ordem decrescente de frequência, foram: opacidades reticulares (81,8%), padrão de atenuação em mosaico (56,8%), distorção arquitetural (31,8%), cardiomegalia (25%), redução volumétrica lobar (18,2%) e aumento do calibre de ramos periféricos das artérias pulmonares (9,1%). Na maioria dos achados o grau de acometimento foi considerado leve, com até cinco segmentos pulmonares acometidos. O índice de acerto quanto ao tipo de hemoglobinopatia (grupo HbSS versus grupo não HbSS) foi 72,7%. CONCLUSÃO: Em pacientes adultos com doença falciforme os principais achados tomográficos refletem alterações fibróticas. Além do mais, a tomografia computadorizada pode ser útil na diferenciação do tipo de hemoglobinopatia.

Changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease / Alterações na tomografia computadorizada do tórax em pacientes adultos oligossintomáticos com doença falciforme

Abstract Objective: To describe and quantify the main changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease, as well as to evaluate the radiologist accuracy in determining the type of hemoglobinopathy. Materials and Methods: A prospective study involving 44 adult patients with sickle cell disease who underwent inspiration and expiration computed tomography of the chest. The frequency of tomography findings and the extent of involvement are reported. We also calculated radiologist accuracy in determining the type of hemoglobinopathy by analyzing the pulmonary alterations and morphology of the spleen. Results: The changes found on computed tomography scans, in descending order of frequency, were as follows: fibrotic opacities (81.8%); mosaic attenuation (56.8%); architectural distortion (31.8%); cardiomegaly (25.0%); lobar volume reduction (18.2%); and increased caliber of peripheral pulmonary arteries (9.1%). For most of the findings, the involvement was considered mild, five or fewer lung segments being affected. The accuracy in determining the type of hemoglobinopathy (HbSS group versus not HbSS group) was 72.7%. Conclusion: In adult patients with sickle cell disease, the main tomography findings reflect fibrotic changes. In addition, computed tomography can be helpful in differentiating among hemoglobinopathies.

Resumo Objetivo: Descrever e quantificar as principais alterações na tomografia computadorizada do tórax em pacientes adultos oligossintomáticos com doença falciforme e, secundariamente, avaliar o índice de acerto do radiologista quanto ao tipo de hemoglobinopatia. Materiais e Métodos: Estudo prospectivo em que 44 pacientes adultos com doença falciforme foram submetidos a tomografia computadorizada do tórax tanto em inspiração como em expiração. Foram descritos a frequência dos achados tomográficos e os graus de acometimento. Por meio da análise das alterações pulmonares e do padrão morfológico do baço, foi calculado o índice de acerto do radiologista quanto ao tipo de hemoglobinopatia. Resultados: As alterações encontradas nos exames de tomografia computadorizada, em ordem decrescente de frequência, foram: opacidades reticulares (81,8%), padrão de atenuação em mosaico (56,8%), distorção arquitetural (31,8%), cardiomegalia (25%), redução volumétrica lobar (18,2%) e aumento do calibre de ramos periféricos das artérias pulmonares (9,1%). Na maioria dos achados o grau de acometimento foi considerado leve, com até cinco segmentos pulmonares acometidos. O índice de acerto quanto ao tipo de hemoglobinopatia (grupo HbSS versus grupo não HbSS) foi 72,7%. Conclusão: Em pacientes adultos com doença falciforme os principais achados tomográficos refletem alterações fibróticas. Além do mais, a tomografia computadorizada pode ser útil na diferenciação do tipo de hemoglobinopatia.

Relationship between pulmonary and cardiac abnormalities in sickle cell disease: implications for the management of patients.

OBJECTIVE: To evaluate the association between clinical, pulmonary, and cardiovascular findings in patients with sickle cell disease and, secondarily, to compare these findings between sickle cell anemia patients and those with other sickle cell diseases. METHODS: Fifty-nine adults were included in this cross-sectional study; 47 had sickle cell anemia, and 12 had other sickle cell diseases. All patients underwent pulmonary function tests, chest computed tomography, and echocardiography. RESULTS: Abnormalities on computed tomography, echocardiography, and pulmonary function tests were observed in 93.5%, 75.0%; and 70.2% of patients, respectively. A higher frequency of restrictive abnormalities was observed in patients with a history of acute chest syndrome (85% vs. 21.6%; p-value<0.0001) and among patients with increased left ventricle size (48.2% vs. 22.2%; p-value=0.036), and a higher frequency of reduced respiratory muscle strength was observed in patients with a ground-glass pattern (33.3% vs. 4.3%; p-value=0.016). Moreover, a higher frequency of mosaic attenuation was observed in patients with elevated tricuspid regurgitation velocity (61.1% vs. 24%; p-value=0.014). Compared to patients with other sickle cell diseases, sickle cell anemia patients had suffered increased frequencies of acute pain episodes, and acute chest syndrome, and exhibited mosaic attenuation on computed tomography, and abnormalities on echocardiography. CONCLUSION: A significant interrelation between abnormalities of the pulmonary and cardiovascular systems was observed in sickle cell disease patients. Furthermore, the severity of the cardiopulmonary parameters among patients with sickle cell anemia was greater than that of patients with other sickle cell diseases.

Relationship between pulmonary and cardiac abnormalities in sickle cell disease: implications for the management of patients

ABSTRACT Objective: To evaluate the association between clinical, pulmonary, and cardiovascular findings in patients with sickle cell disease and, secondarily, to compare these findings between sickle cell anemia patients and those with other sickle cell diseases. Methods: Fifty-nine adults were included in this cross-sectional study; 47 had sickle cell anemia, and 12 had other sickle cell diseases. All patients underwent pulmonary function tests, chest computed tomography, and echocardiography. Results: Abnormalities on computed tomography, echocardiography, and pulmonary function tests were observed in 93.5%, 75.0%; and 70.2% of patients, respectively. A higher frequency of restrictive abnormalities was observed in patients with a history of acute chest syndrome (85% vs. 21.6%; p-value < 0.0001) and among patients with increased left ventricle size (48.2% vs. 22.2%; p-value = 0.036), and a higher frequency of reduced respiratory muscle strength was observed in patients with a ground-glass pattern (33.3% vs. 4.3%; p-value = 0.016). Moreover, a higher frequency of mosaic attenuation was observed in patients with elevated tricuspid regurgitation velocity (61.1% vs. 24%; p-value = 0.014). Compared to patients with other sickle cell diseases, sickle cell anemia patients had suffered increased frequencies of acute pain episodes, and acute chest syndrome, and exhibited mosaic attenuation on computed tomography, and abnormalities on echocardiography. Conclusion: A significant interrelation between abnormalities of the pulmonary and cardiovascular systems was observed in sickle cell disease patients. Furthermore, the severity of the cardiopulmonary parameters among patients with sickle cell anemia was greater than that of patients with other sickle cell diseases.

Avaliação do método da imunofenotipagem por citometria de fluxo no diagnóstico das doenças displásicas (SMD, LMA-relacionada à mielodisplasia, LMMC e LMMJ) em adultos e crianças / Evaluation of the method of immunophenotyping by flow cytometry in the diagnosis of dysplastic disease (MDS, AML-related to myelodysplasia,CMML and JMML) in adults and children

As síndromes mielodisplásicas (SMD) se caracterizam por terem uma hematopoese displásica, citopenias e pelo risco de progressão para leucemia mielóide aguda. O diagnóstico baseia-se na clínica e nos achados citomorfológicos da medula óssea (MO) e citogenéticos. Na fase inicial ou quando a MO é hipocelular o diagnóstico é difícil e a citogenética frequentemente é normal. A imunofenotipagem (IMF) tem sido cada vez mais utilizada nos casos de SMD em adultos e pouco explorada na SMD pediátrica. Os nossos objetivos foram: estudar os casos de SMD e doenças correlatas (LMA relacioanda à SMD: LMA-rMD; leucemia mielomonocítica crônica: LMMC e leucemia mielomonocítica juvenil: LMMJ) em adultos e crianças, associando os dados clínicos e laboratoriais aos obtidos pela IMF, que utilizou um painel de anticorpos monoclonais para as várias linhagens medulares. No período compreendido entre 2000 e 2010 foram estudados 87 pacientes (64 adultos e 23 crianças) oriundos do HUPE/UERJ e IPPMG/UFRJ e 46 controles (23 adultos e 20 crianças). Todos os doentes realizaram mielograma, biópsia óssea, citogenética, citoquímica e estudo imunofenotípico. Segundo os critérios da OMS 50 adultos foram classificados como SMD, 11 como LMA-rMD e 3 LMMC. Entre as crianças 18 eram SMD, 2 LMA e 3 LMMJ. Os pacientes adultos com SMD foram divididos em alto risco (n=9; AREB-1 e AREB-2) e baixo risco (n=41; CRDU, CRDM, CRDM-SA, SMD-N e SMD-5q). As crianças com SMD em CR (n=16) e AREB (n=2). Anormalidades clonais recorrentes foram encontradas em 22 pacientes adultos e em 7 crianças. Na análise de IMF foi utilizada a metodologia da curva ROC para a determinação dos valores de ponto de corte a fim de identificar os resultados anormais dos anticorpos monoclonais nos pacientes e nos controles, permitindo determinar a sensibilidade e especificidade desses em cada linhagem. A IMF foi adequada para a análise em todos os pacientes e 3 ou mais anormalidades foram encontradas. A associação da IMF...

Myelodysplastic syndrome (MDS) is characterized by having a dysplastic hematopoiesis, cytopenias and risk of progression to acute myeloid leukemia. The diagnosis is based on clinical and cytomorphologic findings in bone marrow (BM) and cytogenetics. In the initial phase of when the BM is hypocellular, diagnosis is difficult and often with normal karyotype. The flow cytometry immunophenotyping (FCI) analysis has been broadly used in adult MDS cases but is rarely in pediatric MDS. The objectives of this work were: to study MDS cases and correlated diseases (AML with myelodysplasia-related changes; chronic myelomonocytic leukemia - CMML and juvenite myelomonocytic leukemia - JMML) and to correlate laboratorial data to FCI using a panel of monoclonal antibodies for the various marrow lineages in both adult and children. In the period between 2000 and 2010, 87 patients were studied (64 adults and 23 children) coming from HUPE/UERJ and IPPMG/UFRJ and 46 controls (26 adults and 20 children). All patients were submitted to myelogram, bone marrow biopsy, cytogenetic, cytochemistry and immunophenotypic study. According to WHO criteria 50 adults were classified MDS, 12 AML and 3 CMML. Among the children there were 18 MDS, 2 AML, and 3 JMML. MDS adult patients were subdivided into high risk (n=9; RAEB-1 and RAEB-2) and low risk (n=41; RCUD, RCMD-RS, MDS-U and MDS-5q). MDS children were classified as RCC (n=16) and RAEB (n=2). Clonal abnormalities were found in 22 (35%) adult patients and 7 (30%) children. In the analysis of FCI methodology ROC curve was used for determination of cut off abnormalities at monoclonal antibodies in patients and controls which allowed to estimate the sensitivity and specificity of each strain. The FCI was suitable for analysis in all patients and 3 or more abnormalities were found. The association of the FCI increased the sensitivity of morphological analysis in the erythroid lineage from 70 to 97% in adults and from 59 to 86% in children...