Association of polymorphism in leptin receptor gene with susceptibility of adolescent idiopathic scoliosis.

PURPOSE: Abnormal leptin bioavailability has play key roles in the etiology of adolescent idiopathic scoliosis (AIS). Both leptin and its receptor levels may be modulated by the presence of genetic polymorphisms. This study aimed to evaluate the role of polymorphisms in the leptin (LEP) and its main receptor (LEPR) genes in the AIS susceptibility in girls. METHODS: A retrospective case-control study was conducted with 189 AIS and 240 controls. LEP rs2167270 and LEPR rs2767485 polymorphisms were genotyped using a TaqMan validated assay. Associations were evaluated by odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The AIS group showed a predominance of girls under 18 years old (n = 140, 74.1%), 148 (78.3%) had low or normal BMI, 111 (58.7%) had Cobb ≥ 45º and 130 (68.7%) were skeletally mature. Minor allele frequencies of rs2167270 and rs2767485 were 35.7% and 18.3%, for AIS and 35.6% and 25.4% for controls, respectively. LEPR rs2767485 T and TC + TT were associated with higher risk of AIS (OR = 1.53; 95% CI = 1.09-2.13 and OR = 1.84; 95% CI = 1.69-2.01, respectively), since CC genotype was only present in the control group. In addition, the LEP rs2167270 GA + AA was more frequent in low weight group (BMI ≤ 24.9) of girls with AIS. There was no significant association between LEP rs2167270 and AIS susceptibility, and LEPR rs2767485 and BMI. CONCLUSION: The LEPR rs2767485 was associated with the genetic susceptibility of AIS and LEP rs2167270 with low BMI. These data can contribute to the identification of genetic biomarkers to improve the diagnosis and treatment.

Comparing the safety and efficacy of ruxolitinib in patients with Dynamic International Prognostic Scoring System low-, intermediate-1-, intermediate-2-, and high-risk myelofibrosis in JUMP, a Phase 3b, expanded-access study.

Ruxolitinib, a potent Janus kinase 1/2 inhibitor, has demonstrated durable improvements in patients with myelofibrosis. In this analysis of the Phase 3b JUMP study, which included patients aged ≥18 years with a diagnosis of primary or secondary myelofibrosis, we assessed the safety and efficacy of ruxolitinib in patients stratified by Dynamic International Prognostic Scoring System (DIPSS) risk categories. Baseline characteristic data were available to assess DIPSS status for 1844 of the 2233 enrolled patients; 60, 835, 755, and 194 in the low-, intermediate (Int)-1-, Int-2-, and high-risk groups, respectively. Ruxolitinib was generally well tolerated across all risk groups, with an adverse-event (AE) profile consistent with previous reports. The most common hematologic AEs were thrombocytopenia and anemia, with highest rates of Grade ≥3 events in high-risk patients. Approximately, 73% of patients experienced ≥50% reductions in palpable spleen length at any point in the ≤24-month treatment period, with highest rates in lower-risk categories (low, 82.1%; Int-1, 79.3%; Int-2, 67.1%; high risk, 61.6%). Median time to spleen length reduction was 5.1 weeks and was shortest in lower-risk patients. Across measures, 40%-57% of patients showed clinically meaningful symptom improvements, which were observed from 4 weeks after treatment initiation and maintained throughout the study. Overall survival (OS) was 92% at Week 72 and 75% at Week 240 (4.6 years). Median OS was longer for Int-2-risk than high-risk patients (253.6 vs. 147.3 weeks), but not evaluable in low-/Int-1-risk patients. By Week 240, progression-free survival (PFS) and leukemia-free survival (LFS) rates were higher in lower-risk patients (PFS: low, 90%; Int-1, 82%; Int-2, 46%; high risk, 15%; LFS: low, 92%; Int-1, 86%; Int-2, 58%; high risk, 19%). Clinical benefit was seen across risk groups, with more rapid improvements in lower risk patients. Overall, this analysis indicates that ruxolitinib benefits lower-risk DIPSS patients in addition to higher risk.

Labiomandibular glossotomy approach for craniocervical pathologies - spine reconstruction / Acesso por glossotomia labiomandibular em patologias craniocervicais - reconstrução da coluna / Acceso por glosotomía labiomandibular en patologías craneocervicales - reconstrucción de la columna

ABSTRACT Objectives: Exposing the clivus and upper cervical spine should, ideally, provide an adequate surgical field in which the surgeon can safely decompress and stabilize the craniovertebral junction (CVJ). We present a series of four cases with a narrative review of the literature in which Median Labiomandibular Glossotomy was used to treat CVJ disorders, in order to highlight the importance and indications of this access. Methods: We performed a retrospective analysis of patients who underwent MLMG for several pathologies. The group comprised four patients (two men and two women). Five approaches were performed (one revision surgery). Results: The approach was suitable for all cases, clivus was achieved when necessary. Distally, C4 was exposed to obtain satisfactory osteosynthesis. Laterally, we had a good view of the tumor borders and control of the vertebral artery. Complications encountered were a superficial wound infection that was easily healed, a later pharyngeal wound dehiscence and pseudoarthrosis, all in the same patient. There are 3 main anterior surgical techniques for managing lesions of the clivus, foramen magnum or upper cervical vertebrae. We chose Median Labiomadibular Glossotomy (MLMG) as a primary option, which provided a direct view of the clivus, C3 - C4 caudally and a wider surgical field. The main advantages of the MLMG technique include direct access to spinal pathology, an avascular plane through the median pharyngeal raphe, and a wider surgical field in both the transverse and sagittal dimensions. Conclusion: This approach provides excellent exposure of the craniocervical junction and upper cervical spine. Level of evidence IV; Series of cases analyzed retrospectively.

RESUMO Objetivos: A exposição do clivo e da coluna cervical alta deve, de modo ideal, proporcionar um campo cirúrgico adequado, no qual o cirurgião possa descomprimir e estabilizar a junção craniovertebral (JCV) com segurança. Apresentamos uma série de quatro casos, com revisão narrativa da literatura, nos quais a glossotomia labiomandibular mediana foi utilizada para tratamento de afecções da JCV, com o objetivo de destacar a importância e as indicações desse acesso. Métodos: Foi realizada uma análise retrospectiva dos pacientes submetidos a GLMM para diversas patologias. O grupo foi composto por quatro pacientes (dois homens e duas mulheres). Cinco abordagens/procedimentos<??> foram realizados (uma cirurgia de revisão). Resultados: O método/via de acesso/técnica foi adequado para todos os casos e o clivo foi alcançado quando necessário. Distalmente, C4 foi exposta para obter a osteossíntese satisfatória. Lateralmente, obteve-se boa visão das margens tumorais e controle da artéria vertebral. As complicações encontradas foram infecção superficial da ferida, com fácil cicatrização, deiscência tardia da parede posterior da faringe e pseudoartrose, todas no mesmo paciente. Existem três técnicas cirúrgicas principais com acesso anterior para o tratamento de lesões do clivo, forame magno ou vértebras cervicais superiores. Escolhemos a glossotomia labiomadibular mediana (GLMM) como opção primária, que proporcionou uma visão direta do clivo, de C3-C4 caudalmente e campo cirúrgico mais amplo. As principais vantagens da GLMM incluem acesso direto à patologia espinhal, plano avascular através da parte mediana da rafe da faringe e um campo cirúrgico ampliado nas dimensões transversa e sagital. Conclusões: Esta abordagem proporciona excelente exposição da junção craniocervical e da coluna cervical alta. Nível de evidência IV; Série de casos analisados retrospectivamente.

RESUMEN Objetivos: La exposición del clivus y de la columna cervical alta debe, de modo ideal, proporcionar un campo quirúrgico adecuado, en que el cirujano pueda descomprimir y estabilizar de manera segura la unión craneovertebral (UCV). Presentamos una serie de cuatro casos con revisión narrativa de la literatura, en los que se utilizó la glosotomía labiomandibular mediana para el tratamiento de afecciones de la UCV, con el objetivo de destacar la importancia y las indicaciones de ese acceso. Métodos: Se realizó un análisis retrospectivo de los pacientes sometidos a GLMM para diversas patologías. El grupo fue compuesto por cuatro pacientes (dos hombres y dos mujeres). Fueron realizados cinco abordajes/procedimientos (una cirugía de revisión). Resultados: El método/vía de acceso/técnica fue adecuado para todos los casos y el clivus fue alcanzado cuando fue necesario. Distalmente, C4 fue expuesta para obtener la osteosíntesis satisfactoria. Lateralmente, se obtuvo buena visión de los márgenes tumorales y control de la arteria vertebral. Las complicaciones encontradas fueron infección superficial de la herida, con fácil cicatrización, dehiscencia tardía de la pared posterior de la faringe y pseudoartrosis, todas en el mismo paciente. Existen tres técnicas quirúrgicas principales con acceso anterior para el tratamiento de lesiones del clivus, foramen magno o vértebras cervicales superiores. Elegimos la glosotomía labiomandibular mediana (GLMM) como opción primaria, que proporcionó una visión directa del clivus, C3-C4 caudalmente y campo quirúrgico más amplio. Las principales ventajas de la GLMM incluyen acceso directo a la patología espinal, plano avascular a través de la parte mediana del rafe de la faringe y un campo quirúrgico ampliado en las dimensiones transversa y sagital. Conclusiones: Este abordaje proporciona excelente exposición de la unión craneocervical y de la columna cervical alta. Nivel de evidencia IV; Serie de casos analizados retrospectivamente.

Influence of genetic polymorphisms in glutathione-S-transferases gene in response to imatinib among Brazilian patients with chronic myeloid leukemia.

Polymorphism in metabolizing enzymes can influence drug response as well as the risk for adverse drug reactions. Nevertheless, there are still few studies analyzing the consequence of polymorphisms for the Glutathione-S-transferases (GST) gene to drug response in chronic myeloid leukemia (CML). This study reports, the influence of GSTP1*B and GSTT1/GSTM1null polymorphisms in response to imatinib in CML patients in a Brazilian population. One hundred thirty-nine CML patients from the Clinical Hospital of Goiânia, Goiás, Brazil, treated with imatinib were enrolled in this study. Genotyping of GSTT1 and GSTM1 genes deletions were performed by qPCR and of GSTP1 gene was performed by RFLP-PCR. The frequency of GSTP1*1B, GSTT1 and GSTM1null polymorphisms were determined for all patients. The influence of each patient's genotypes was analyzed with the patient's response to imatinib treatment. Brazilian CML patients revealed GSTT1 and GSTM1 genes deletions. GSTT1 deletion was found in 19.3% of patients and GSTM1 deletion in 48.7% of patients with CML. GSTT1/GSTM1 deletion was found in 11.7% in Brazilian CML patients. The "G allele" of GSTP1*B, is associated with later cytogenetic response in imatinib therapy. While, the gene presence combined with GG genotype (GSTM1 present/GSTPI-GG) conferred a tend to a later cytogenetic response to patients. GSTP1*B and GSTT1/GSTM1null polymorphisms influence treatment response in CML. Brazilian CML patients presenting GSTP1 AA/AG genotypes alone and in combination with GSTT1 null reach the cytogenetic response faster, while patients presenting GSTP1-GG and GSTMI positive genotypes may take longer to achieve cytogenetic response. As a result, it allows a better prognosis, with the use of an alternative therapy, other than reducing treatment cost.

New germline GATA1 variant in females with anemia and thrombocytopenia.

Familial forms of bone marrow defects are rare disorders and description of new cases are valuable opportunities to clarify the molecular machinery that triggers hematopoiesis and blood formation, as well as risk to malignant transformation. We investigated the genetic scenario and possible patterns of transmission in a rare case of familial myeloid disorder with a history of exposure to pesticides. Blood counts of two proband sisters, age 41 and 42, revealed mild anemia, neutrophilia and thrombocytopenia with bone marrow finding mimicking primary myelofibrosis in the cellular phase. We analyzed the coding regions of 78 myeloid neoplasms-related genes and 16 encoding xenobiotic metabolizing genes using Next-Generation Sequencing. The GATA1 variant c.788C > T, p.T263M, located in the C-terminal zinc finger domain of GATA1, was detected in the DNA of the two sisters. The screening of the other kindreds also revealed the p.T263M variant in the mother and two daughters with the same bone marrow disorder. This is the first report of an alteration in the GATA1 CF domain causing anemia, thrombocytopenia and megakaryocyte proliferation with mild myelofibrosis, correlating a new GATA1 germline variant with myeloid disorder.

Analysis of predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded-access JUMP study.

Data from the large, prospective, multinational, phase 3b JUMP study were analyzed to identify factors predictive of spleen and symptom responses in myelofibrosis patients receiving ruxolitinib. Factors associated with higher spleen response rates included International Prognostic Scoring System (IPSS) low/intermediate-1 risk vs intermediate-2/high risk (43.1% vs 30.6%; adjusted OR [aOR] 0.65 [95% CI 0.44-0.95]), ruxolitinib as first- vs second- or later-line therapy (40.2% vs 31.5%; aOR 0.53 [95% CI 0.38-0.75]), and a ruxolitinib total daily dose at Week 12 of >20 mg/day vs ≤20 mg/day (41.3% vs 30.4%; aOR 0.47 [95% CI 0.33-0.68]). No association was seen between baseline characteristics or total daily dose at Week 12 and symptom response. Ruxolitinib led to higher spleen response rates in patients with lower IPSS risk, and when used earlier in treatment. Higher doses of ruxolitinib were associated with higher spleen response rates, but not with symptom improvement.Trial registrationINC424 for patients with primary myelofibrosis, post polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis (JUMP).2010-024473-39; NCT01493414Date of registration: 16 December 2011https://www.clinicaltrialsregister.eu/ctr-search/search?query=2010-024473-39https://clinicaltrials.gov/ct2/show/NCT01493414.

Guidelines for therapy of patients with chronic myeloproliferative neoplasms during the novel coronavirus SARS-CoV2 pandemic

ABSTRACT The novel coronavirus has swept across the world in 2020 and ushered a new era. In the current scenario, it is not clear how patients with myeloproliferative neoplasms (including chronic myelogenous leukemia) should be managed, considering the risk of therapy, the need for social distancing and the risk of untimely therapy discontinuation of delay. This guideline aims to give providers a sense of direction in order to better take care of patients and prioritize care.

Guidelines for therapy of patients with chronic myeloproliferative neoplasms during the novel coronavirus SARS-CoV2 pandemic.

The novel coronavirus has swept across the world in 2020 and ushered a new era. In the current scenario, it is not clear how patients with myeloproliferative neoplasms (including chronic myelogenous leukemia) should be managed, considering the risk of therapy, the need for social distancing and the risk of untimely therapy discontinuation of delay. This guideline aims to give providers a sense of direction in order to better take care of patients and prioritize care.

A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort

Abstract Introduction Ruxolitinib has been approved for the treatment of myelofibrosis (MF). In this study, we present safety and efficacy findings from an analysis of 104 patients with intermediate- and high-risk MF in a Brazilian cohort of the JUMP study who received treatment with ruxolitinib. Methods JUMP is a single-arm, open-label, phase IIIb, expanded-access study. The primary endpoint was to evaluate the safety and tolerability (frequency, duration, and severity of adverse events [AEs]) of ruxolitinib. Results All of the 104 patients received the treatment. Median duration of exposure was 35.8 months. The most common hematologic AEs were anemia (57.7), thrombocytopenia (38.5%), neutropenia (11.5%), and leukopenia (9.6%). Second malignancies (all grades) occurred in 19.2% of patients (n = 20). Serious AEs were reported in 62.5% of patients (n = 65). The proportions of patients with ≥50% reduction from baseline in palpable spleen length at weeks 24 and 48 were 62.7% and 69.2%, respectively. The mean change from the baseline in the Functional Assessment of Cancer Therapy (FACT)-Lymphoma total score was 10.8 [15.6%] at week 4, 12.6 [14.1%] at week 24, and 12.2 [14.3%] at week 48. The mean change from the baseline for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale was 3.9 [42.8%] at week 4, 4.9 [29.9%] at week 24, and 4.7 [28%] at week 48. At week 48, the estimated progression-free survival, leukemia-free survival, and overall survival probabilities were 91%, 91% and 93%, respectively Overall, 21 deaths were observed in the present study. Conclusion Findings from this study suggest that ruxolitinib could be evaluated as a standard-of-care treatment for the MF population in need of a viable treatment option. NCT01493414

Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts.

Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF). Ruxolitinib was assessed in JUMP, a large (N = 2233), phase 3b, expanded-access study in MF in countries without access to ruxolitinib outside a clinical trial, which included patients with low platelet counts (<100 × 109 /l) and patients without splenomegaly - populations that have not been extensively studied. The most common adverse events (AEs) were anaemia and thrombocytopenia, but they rarely led to discontinuation (overall, 5·4%; low-platelet cohort, 12·3%). As expected, rates of worsening thrombocytopenia were higher in the low-platelet cohort (all grades, 73·2% vs. 53·5% overall); rates of anaemia were similar (all grades, 52·9% vs. 59·5%). Non-haematologic AEs, including infections, were mainly grade 1/2. Overall, ruxolitinib led to meaningful reductions in spleen length and symptoms, including in patients with low platelet counts, and symptom improvements in patients without splenomegaly. In this trial, the largest study of ruxolitinib in patients with MF to date, the safety profile was consistent with previous reports, with no new safety concerns identified. This study confirms findings from the COMFORT studies and supports the use of ruxolitinib in patients with platelet counts of 50-100 × 109 /l. (ClinicalTrials.gov identifier NCT01493414).

A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort.

INTRODUCTION: Ruxolitinib has been approved for the treatment of myelofibrosis (MF). In this study, we present safety and efficacy findings from an analysis of 104 patients with intermediate- and high-risk MF in a Brazilian cohort of the JUMP study who received treatment with ruxolitinib. METHODS: JUMP is a single-arm, open-label, phase IIIb, expanded-access study. The primary endpoint was to evaluate the safety and tolerability (frequency, duration, and severity of adverse events [AEs]) of ruxolitinib. RESULTS: All of the 104 patients received the treatment. Median duration of exposure was 35.8 months. The most common hematologic AEs were anemia (57.7), thrombocytopenia (38.5%), neutropenia (11.5%), and leukopenia (9.6%). Second malignancies (all grades) occurred in 19.2% of patients (n=20). Serious AEs were reported in 62.5% of patients (n=65). The proportions of patients with ≥50% reduction from baseline in palpable spleen length at weeks 24 and 48 were 62.7% and 69.2%, respectively. The mean change from the baseline in the Functional Assessment of Cancer Therapy (FACT)-Lymphoma total score was 10.8 [15.6%] at week 4, 12.6 [14.1%] at week 24, and 12.2 [14.3%] at week 48. The mean change from the baseline for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale was 3.9 [42.8%] at week 4, 4.9 [29.9%] at week 24, and 4.7 [28%] at week 48. At week 48, the estimated progression-free survival, leukemia-free survival, and overall survival probabilities were 91%, 91% and 93%, respectively Overall, 21 deaths were observed in the present study. CONCLUSION: Findings from this study suggest that ruxolitinib could be evaluated as a standard-of-care treatment for the MF population in need of a viable treatment option. NCT01493414.

Splenic marginal zone lymphoma: a literature review of diagnostic and therapeutic challenges.

Splenic marginal zone lymphoma (SMZL) is a low-grade B-cell non-Hodgkin's lymphoma characterized by massive splenomegaly, moderate lymphocytosis with or without villous lymphocytes, rare involvement of peripheral lymph nodes and indolent clinical course. As a rare disease, with no randomized prospective trials, there is no standard of care for SMZL so far. Splenectomy has been done for many years as an attempt to control disease, but nowadays it has not been encouraged as first line because of new advances in therapy as rituximab, that are as effective with minimal toxicity. Facing these controversies, this review highlights advances in the literature regarding diagnosis, prognostic factors, treatment indications and therapeutic options.

Splenic marginal zone lymphoma: a literature review of diagnostic and therapeutic challenges

ABSTRACT Splenic marginal zone lymphoma (SMZL) is a low-grade B-cell non-Hodgkin's lymphoma characterized by massive splenomegaly, moderate lymphocytosis with or without villous lymphocytes, rare involvement of peripheral lymph nodes and indolent clinical course. As a rare disease, with no randomized prospective trials, there is no standard of care for SMZL so far. Splenectomy has been done for many years as an attempt to control disease, but nowadays it has not been encouraged as first line because of new advances in therapy as rituximab, that are as effective with minimal toxicity. Facing these controversies, this review highlights advances in the literature regarding diagnosis, prognostic factors, treatment indications and therapeutic options.

Loss of correction after vertebrectomy for treatment of spinal deformities / Perda de correção após vertebrectomia no tratamento de deformidades da coluna vertebral / Pérdida de corrección después de vertebrectomía en el tratamiento de deformidades de la columna vertebral

ABSTRACT Objective: To evaluate the loss of correction after treatment of spine deformities with the technique of isolated posterior vertebrectomy. Methods: Twenty-one patients were followed-up for three years after surgery with panoramic X-rays, CT scans, SF-36 and Oswestry questionnaires. We evaluated the loss of correction, CAGE subsidence and the evolution of the pelvis-T1 angle during follow-up. The correlation among the radiographic changes and functional and quality of life scores was also assessed. Results: All patients had some degree of loss of correction and subsidence of CAGE, especially in the first year of follow-up. Such losses exerted negative impact on the function, pain and self-image of the patients. Factors such as the stiffness of the fusion mass and size of implant used appear to have contributed to the occurrence of subsidence, regardless of age and bone mineral density. Conclusions: The use of spacers with larger cross-sectional diameter and more rigid rods can reduce the overloading on the anterior column of Denis, reducing the subsidence and loss of correction. Additional stabilization strategies such as the use of orthoses postoperatively can also be useful, and should be evaluated in subsequent studies.

RESUMO Objetivo: Avaliar a perda de correção após o tratamento de deformidades da coluna vertebral pela técnica de vertebrectomia posterior isolada. Métodos: Vinte e um pacientes foram acompanhados durante três anos após o tratamento cirúrgico com radiografias panorâmicas, tomografias computadorizadas e através dos questionários SF-36 e Oswestry. Foram avaliadas perda de correção, subsidência do CAGE e evolução do ângulo pelve-T1 durante o acompanhamento. Também foi avaliada a correlação entre as alterações radiológicas e os índices funcionais e de qualidade de vida. Resultados: Todos os pacientes apresentaram algum grau de perda de correção e subsidência do espaçador intersomático, especialmente no primeiro ano de acompanhamento. Tais perdas exerceram impacto negativo sobre função, dor e autoimagem dos pacientes. Fatores como a rigidez da massa de artrodese e as dimensões do implante utilizado parecem ter contribuído com a ocorrência de subsidência, a despeito de faixa etária e densidade mineral óssea. Conclusões: O uso de espaçadores com maior diâmetro seccional e hastes mais rígidas podem reduzir a sobrecarga da coluna anterior de Denis, diminuindo a ocorrência de subsidência e perda de correção. Estratégias de estabilização adicionais, como o uso de órteses no pós-operatório também podem ser úteis, e devem ser avaliadas em estudos subsequentes.

RESUMEN Objetivo: Evaluar la pérdida de corrección después del tratamiento de las deformidades de la columna vertebral mediante la técnica de vertebrectomía posterior aislada. Métodos: Veintiún pacientes fueron seguidos durante tres años después de la cirugía mediante radiografías panorámicas, tomografías computarizadas y con el uso de los cuestionarios SF-36 y Oswestry. Se evaluó la pérdida de la corrección, la subsidencia del CAGE y la evolución del ángulo pelvis-T1 durante el seguimiento. También se evaluó la corrección entre las alteraciones radiográficas y los índices funcionales y de calidad de vida. Resultados: Todos los pacientes presentaron algún grado de pérdida de corrección y subsidencia del espaciador intersomático, especialmente en el primer año de seguimiento. Estas pérdidas ejercen impacto negativo sobre la función, el dolor y la autoimagen de los pacientes. Factores como la rigidez de la masa de artrodesis y el tamaño del implante usado parecen haber contribuido a la aparición de subsidencia, independientemente de la edad y la densidad mineral ósea. Conclusiones: El uso de espaciadores con diámetro de la sección transversal mayor y barras más rígidas pueden reducir la sobrecarga de la columna anterior de Denis, reduciendo la ocurrencia de subsidencia y pérdida de la corrección. Las estrategias de estabilización adicionales, tales como el uso de ortesis en el postoperatorio también pueden ser útiles, y deben ser evaluadas en estudios posteriores.

Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial.

JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis - a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib's mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov.

Results of surgical treatment in the craniocervical junction in mucopolysaccharidosis / Resultados do tratamento cirúrgico na junção craniocervical nas mucopolissacaridoses / Resultados del tratamiento quirúrgico en la unión craneocervical en las mucopolisacaridosis

ABSTRACT Objective: Evaluate the results after decompression and stabilization of craniocervical junction in patients with mucopolysaccharidosis (MPS). Method: Retrospective study of 10 patients with MPS through the analysis of medical records and additional tests. Result: All patients with mid-term and long-term follow-up achieved consolidation of the arthrodesis and 87.5% had neurological improvement of Nurick score. Conclusion: Early diagnosis and intervention in cases of stenosis and/or craniocervical instability of patients with MPS provide patients a good recovery of neurological function, despite the great technical difficulty and risk of complications.

RESUMO Objetivo: Avaliar os resultados após a descompressão e estabilização da junção craniocervical em pacientes portadores de mucopolissacaridose (MPS). Método: Estudo retrospectivo de 10 pacientes portadores de MPS, por meio da análise de prontuário e de exames complementares. Resultado: Todos os pacientes com acompanhamento a médio e longo prazo atingiram a consolidação da artrodese e 87,5% tiveram melhora neurológica no escore Nurick. Conclusão: O diagnóstico e a intervenção precoces em casos de estenose e/ou instabilidade craniocervical em pacientes com MPS proporcionam aos pacientes uma boa recuperação da função neurológica, apesar da grande dificuldade técnica e do risco de complicações.

RESUMEN Objetivo: Evaluar los resultados después de la descompresión y estabilización de la unión craneocervical en pacientes con mucopolisacaridosis (MPS). Método: Estudio retrospectivo con 10 pacientes con mucopolisacaridosis, a través del análisis de las historias clínicas y de pruebas complementarias. Resultado: Todos los pacientes con seguimiento a medio y largo plazo alcanzaron la consolidación de la artrodesis y 87,5% presentaron mejoría neurológica de la puntuación Nurick. Conclusión: El diagnóstico e intervención temprana en casos de estenosis y/o inestabilidad craneocervical en pacientes con MPS proporcionan a los pacientes una buena recuperación de la función neurológica, a pesar de la gran dificultad técnica y el riesgo de complicaciones.

Interobserver evaluation of TLICS system to treat thoracolumbar fractures / Avaliação interobservadores do sistema TLICS para o tratamento das fraturas toracolombares / Evaluación entre observadores del sistema TLICS para el tratamiento de fracturas toracolumbares

To evaluate the interobserver agreement regarding the TLICS Classification (Thoracolumbar Injury Classification and Severity Score). Furthermore, evaluate the reliability, analyzing the correlation between the treatment indicated by TLICS system (surgical or conservative) and the treatment indicated by each evaluator surgeon.

Avaliar a concordância interobservadores com relação à Classificação TLICS (Thoracolumbar Injury Classification and Severity Score). Além disso, avaliar a confiabilidade, analisando a concordância entre o tratamento indicado pelo sistema TLICS (cirúrgico ou conservador) e o tratamento que cada cirurgião avaliador indicou.

Evaluar la concordancia entre observadores con respecto a clasificación TLICS (Thoracolumbar Injury Classification and Severity Score). Además, evaluar la confiabilidad, analizando la correlación entre el tratamiento indicado por el sistema de TLICS (quirúrgico o conservador) y el tratamiento que cada cirujano evaluador eligió.: Fueron evaluados de forma retrospectiva las imágenes y los datos clínicos de 22 pacientes con fracturas toracolumbares por ocho cirujanos de columna vertebral. Se realizaron dos análisis principales: el primero comparó la concordancia del sistema TLICS y el segundo comparó la correlación entre el tratamiento indicado por esta clasificación (quirúrgico o conservador) y el tratamiento indicado por cada cirujano evaluador - en base a su experiencia personal y su clasificación de preferencia.

Avaliação dos resultados clínicos e radiográficos de pacientes submetidos à ressecção de hemivértebra nas deformidades congênitas da coluna vertebral / Evaluation of clinical and radiographic results in patients undergoing resection of hemivertebra in congenital deformities of the spine / Evaluación de los resultados clínicos y radiográficos de los pacientes sometidos a resección de hemivértebra en deformidades congénitas de la columna vertebral

OBJETIVO: A proposta do estudo foi determinar nossos resultados clínicos e radiográficos de pacientes com deformidades congênitas da coluna vertebral submetidos à ressecção de hemivértebra por via posterior isolada e correção com instrumentação posterior e fusão. MÉTODOS: Registros de 31 pacientes submetidos à ressecção de hemivértebra no período de 2003 a 2010 foram revistos para identificar idade e sexo, grau de correção, níveis da artrodese, quadro neurológico, perda sanguínea, tempo cirúrgico e complicações. RESULTADOS: Foram identificados 22 pacientes com escoliose e Cobb pré-operatório médio de 46.66°(20-88°) e 9 pacientes com cifose e média angular de 83.54°(13-137°). Vinte e quatro pacientes eram do sexo feminino e 7 do sexo masculino. Foram 13 pacientes adolescentes e 18 crianças (1-19 anos). A ressecção de hemivértebra foi realizada em 1 nível (64%), 2 níveis (32%) e 3 níveis (4%). As taxas de correção da escoliose e cifose foram 63.8 e 40.1% e as médias angulares pós-operatórias foram 16.88° e 50°, respectivamente. Complicações ocorreram em 7 pacientes: pseudartrose, cifose juncional, neurite óptica, déficit neurológico, infecção de ferida operatória e óbito. A média de perda sanguínea foi de 1132ml (300ml-3500ml) e o tempo cirúrgico foi de 7.15 horas (4-13 horas). CONCLUSÕES: A ressecção de hemivértebra é uma valiosa técnica no tratamento das deformidades congênitas angulares e uma alternativa eficiente que oferece correção satisfatória nos planos coronal e sagital sem a necessidade de uma abordagem anterior.

OBJECTIVE: The purpose of this study was to determine our clinical and radiographic results of patients with congenital deformities of the spine underwent to single-stage posterior hemivertebra resection and correction with segmental posterior instrumentation and fusion. METHODS: The records of 31 consecutive patients who had undergone to hemivertebra resection between 2003 and 2010 were reviewed to identify age and sex, correction rates, fusion levels, neurological status, blood loss, time of surgery and complications. RESULTS: We identified 22 patients with scoliosis and pre-operative Cobb averaged 46.66° (range 20-88°) and 9 patients with kyphosis and averaged 83.54° (range 13-137°). Twenty four patients were female and 7 were male. Thirteen patients were teenagers and 18 were children (range 1-19 years old). The hemivertebrae resection was done in 1 level (64%), 2 levels (32%) and 3 levels (4%). The correction rates for scoliosis and kyphosis were 63.8% and 40.1% and pos-operative Cobb averaged was 16.88° and 50°. Complications occurred in 7 patients: pseudoarthrosis, junctional kyphosis, optic neuritis, neurologic deficit, wound infection, and death. The average blood loss was 1132ml (range 300ml-3500ml) and time of the surgery was 7.15 hours (range 4-13 hours). CONCLUSIONS: Posterior hemivertebra resection is a valuable technique to assessment angular congenital spinal deformities and an efficient alternative that offers satisfactory correction in both coronal and sagittal planes without need for anterior approach.

OBJETIVO: El objetivo de nuestro estudio fue determinar los resultados clínicos y radiográficos de los pacientes con deformidades congénitas de la columna vertebral que se sometieron a la resección de hemivértebra por el acceso aislado posterior con instrumentación posterior y fusión. MÉTODOS: Registros de 31 pacientes sometidos a resección de la hemivértebra el período 2003 a 2010 fueron revisados para identificar edad y sexo, grado de corrección, niveles de la fusión, estado neurológico, pérdida de sangre, tiempo quirúrgico y complicaciones. RESULTADOS: Se identificaron 22 pacientes con escoliosis y Cobb promedio preoperatorio de 46,66° (20°-88°) y 9 pacientes con un ángulo medio de cifosis y 83,54° (13°-137°). Veinticuatro pacientes eran hombres y siete mujeres. Hubo 13 adolescentes y 18 niños (1-19 años). La resección de hemivértebra se realizó en un nivel (64%), dos niveles (32%) y tres niveles (4%). Los porcentajes de corrección de la escoliosis y la cifosis fueron 63,8% y el 40,1% y el ángulo de post-operatorio promedio fue de 16.88° y 50°, respectivamente. Se presentaron complicaciones en 7 pacientes, pseudoartrosis, cifosis de la unión, neuritis óptica, déficit neurológico, infección de la herida y muerte. La pérdida de sangre promedio fue de 1132 ml (300 ml-3500 ml) y el tiempo quirúrgico medio fue de 7,15 horas (4-13 horas). CONCLUSIONES: La resección de hemivértebra es una técnica valiosa en el tratamiento de deformidades angulares congénitas y una alternativa eficaz que proporciona corrección satisfactoria en el plano coronal y sagital sin la necesidad de una vía anterior.