Treatment of relapsed/refractory multiple myeloma in the bortezomib and lenalidomide era: a systematic review and network meta-analysis.

Multiple myeloma (MM) is an incurable disease, and patients usually receive multiple lines of therapy. Due to the abundance of novel treatments for MM, we conducted a network meta-analysis to identify combinations that could fare better than others in relapsed/refractory MM, in the setting of novel drugs. We searched PubMed and Cochrane databases for phase III trials in previously treated MM that had lenalidomide or bortezomib in the control arm. The primary endpoint was progression-free survival (PFS), extracted as hazard-ratio. We used the P score to rank treatments. Thirteen studies were included. All but two studies compared one novel agent against two, with or without dexamethasone. Based on the P score, daratumumab and pegylated liposomal doxorubicin had a higher probability of achieving better PFS, followed by isatuximab, carfilzomib, pomalidomide, and panobinostat. Although most overall survival data were not mature enough, the addition of a second or third novel agent to either immunomodulatory (IMID) or proteasome inhibitor (PI) backbone seemed to improve survival (HR = 0.84, 95CI 0.77-0.92). Severe adverse events were more frequent with isatuximab, panobinostat, and pomalidomide. In summary, in the absence of trials directly comparing two novel agents-based therapies, we provide a tool that indirectly compares these newer therapies and that can help physicians to prioritize some regimens over others.

Cryopreserved versus non-cryopreserved stem cell autografts in multiple myeloma a restrospective cohort study.

The use of non-cryopreserved hematopoietic stem cells (HSC) can be an alternative to the traditional cryopreserved infusions of HSCs in autologous stem cell transplantation (aHSCT). After high-dose melphalan conditioning (HDM), we sought to compare time to engraftment, overall survival, and safety in multiple myeloma (MM) patients undergoing a first aHSCT after high-dose melphalan conditioning (HDM). We conducted a cohort study from March 2018 to December 2019. Of all autologous transplants performed during this period, 105 were for MM as the first consolidation. Fifty-one patients received a cryopreserved graft; the remaining 54 patients received a fresh infusion. General clinical characteristics were similar between these two groups. Cell viability was higher in non-cryopreserved grafts (95% vs. 86% p < 0.01). Four deaths occurred during hospitalization in the cryopreserved group, one in the non-cryopreserved group. The cumulative incidence of neutrophil and platelet engraftment on D + 25 was higher in the non-cryopreserved compared to the cryopreserved group (98% vs 90% p < 0.01 and 96.2% vs 72.54% p < 0.01 respectively). Additionally, the hospital length of stay was reduced by 4 days for patients for the non-cryopreserved cohort. In summary, the use of non-cryopreserved HSCs after HDM is safe and effective compared to patients who received a cryopreserved graft.

Efetividade da Terapia Medicamentosa e dos Procedimentos de Revascularização como Estratégia Inicial na Doença Arterial Coronariana Estável: Estudo de Coorte / Effectiveness of Medical and Revascularization Procedures as the Initial Strategy in Stable Coronary Artery Disease: A Cohort Study

Fundamento: A cirurgia de revascularização miocárdica (CRM) e a intervenção coronária percutânea (ICP) são estratégias amplamente utilizadas no manejo da doença arterial coronariana (DAC) estável. Objetivo: Avaliar o prognóstico de pacientes com DAC estável inicialmente tratada com terapia médica (TM), em comparação com os pacientes submetidos a procedimentos de revascularização. Métodos: Estudo prospectivo de coorte com 560 pacientes ambulatoriais de um hospital terciário com seguimento médio de 5 anos. Os pacientes foram classificados nos grupos TM (n = 288), ICP (n = 159) e CRM (n = 113) de acordo com sua estratégia inicial de tratamento. Os desfechos primários foram mortalidade global e eventos combinados de morte, síndrome coronária aguda e AVC. Resultados: Durante o seguimento, as taxas de mortalidade foram de 11,1% em TM, 11,9% em ICP e 15,9% em pacientes submetidos à CRM, sem diferença estatística (Hazard Ratio [HR] para ICP, 1,05; Intervalo de Confiança de 95% [IC95%], 0,59 a 1,84; e HR para CRM, 1,20; IC95%, 0,68 a 2,15). Os desfechos combinados ocorreram com maior frequência entre os pacientes inicialmente submetidos à ICP em relação à TM (HR 1,50, IC 95% 1,05 a 2,14) e não diferiram entre TM e CRM (HR 1,24, IC95% 0,84 a 1,83). Entre os pacientes com diabetes (n = 198), a ICP foi a única estratégia terapêutica preditiva de desfechos combinados (HR 2,14; IC 95%: 1,25 a 3,63). Conclusão: Neste estudo observacional de doença arterial coronariana estável, não houve diferença na mortalidade global entre as estratégias iniciais de terapia médico ou de cirurgia de revascularização. Os pacientes inicialmente tratados com ICP tiveram maior chance de desenvolver eventos cardiovasculares maiores combinados

Background: Coronary artery bypass grafting surgery (CABG) and percutaneous coronary intervention (PCI) are widely-used strategies in the management of stable coronary artery disease (CAD). Objective: To evaluate the prognosis of patients with stable CAD initially treated by medical therapy (MT), compared to the patients who were submitted to revascularization procedures. Methods: We conducted a prospective cohort study of 560 patients from an outpatient clinic in a tertiary hospital, with a mean follow-up of 5 years. Patients were classified into MT (n = 288), PCI (n = 159) and CABG (n=113) groups according to their initial treatment strategy. Primary endpoints were overall mortality and combined events of death, acute coronary syndrome, and stroke. Results: During follow-up, death rates were 11.1% in MT, 11.9% in PCI and 15.9% in CABG patients, with no statistical difference (hazard ratio [HR] for PCI, 1.05; 95% confidence interval [95%CI], 0.59 to 1.84; and HR for CABG, 1.20; 95% CI: 0.68 to 2.15). Combined outcomes occurred more often among patients initially submitted to PCI compared to MT (HR 1.50, 95% CI 1.05 to 2.14), and did not differ between MT and CABG patients (HR 1.24, 95% CI 0.84 to 1.83). Among patients with diabetes (n=198), PCI was the only therapeutic strategy predictive of combined outcomes (HR 2.14; 95% CI 1.25 to 3.63). Conclusion: In this observational study of stable coronary artery disease, there was no difference in overall mortality between initial medical therapy or revascularization surgery strategies. Patients initially treated with PCI had greater chance to develop combined major cardiovascular events

Resultados da terapia dupla (interferon e ribavirina) para Hepatite C em um centro de referência no sul do Brasil: um estudo da vida real / Outcomes of double therapy (interferon and ribavirin) for Hepatits C in an excellence center in southern Brazil: a real-life study

Introdução: A Hepatite C tem uma prevalência estimada de cerca de 170 milhões de pessoas mundialmente e cursa com grande morbimortalidade. O tratamento deste deste vírus tem se alterado significativamente nos últimos anos, porém, no Brasil, ainda imperam os tratamentos baseados em interferon convencional ou em interferon -peguilado associado à ribavirina. Métodos: Estudo de coorte, retrospectivo, conduzido no Hospital de Clínicas de Porto Alegre. Foram incluídos 237 pacientes com Hepatite C tratados com interferon e ribavirina ou com interferon -peguilado e ribavirina. Resultados: A taxa global de resposta virológica sustentada obtida foi de 33,33%, sendo 37,93% nos pacientes com regime baseado em interferon convencional e 32,69% nos pacientes com interferon -peguilado. A análise demonstrou uma maior taxa de resposta virológica sustentada entre os pacientes que apresentaram, à análise genética, expressão CC do polimorfismo do IL 28B.

Introduction: Hepatitis C affects approximately 170 million people worldwide and it results in great morbidity and mortality. The virus treatment has changed significantly. However, in Brazil, treatments based on conventional interferon or pegylated-interferon associated with ribavirin are still the most usual ones. Methods: Retrospective cohort study conducted at Hospital de Clínicas de Porto Alegre. That included 237 patients treated for hepatitis C with interferon and ribavirin or pegylated--interferon and ribavirin. Results: The overall rate of sustained virologic response was 33.33%, with a rate of 37.93% in patients treated with conventional interferon and 32.69% in with pegylatedinterrferon. The analysis showed a higher rate of sustained virologic response among patients who, in genetic analysis, CC expression of IL28B polymorphism.

Hypertension is the main determinant behind the association between metabolic syndrome and chronic kidney disease in subjects with different degrees of glucose tolerance / A hipertensão é o principal determinante da associação entre síndrome metabólica e doença renal crônica em indivíduos com diferentes graus de tolerância à glicose

Background: Chronic kidney disease (CKD) is a significant public health problem. It is still controversial if the metabolicsyndrome (MS) is associated with CKD.Methods: Cross-sectional study of individuals at high risk of developing diabetes at the endocrine outpatient clinic of Hospitalde Clínicas de Porto Alegre. Fasting and 2h-plasma glucose levels, A1c, insulin, cholesterol, triglycerides, creatinine, andurinary albumin excretion were measured. MS was defined as the presence of three out of five of the following factors: hypertension,low HDL-cholesterol, high triglyceride levels, elevated plasma glucose, and high waist circumference. Glomerularfiltration rate (GFR) was estimated by the Modified Diet in Renal Disease (MDRD) equation and insulin resistance wasmeasure using the Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR). Correlation analyses were performedbetween each MS components and the GFR.Results: CKD was present in 20.9% of the subjects. GFR was lower in subjects with MS compared with those without MS(P =0.019). Estimated GFR decreased with the increasing number of MS criteria (mean ± SD; zero or one criterion103.09±9.5 vs. two criteria 99.14±21.2 vs. three criteria 90.9±21.1 vs. four criteria 91.0±19.4 vs. five criteria 80.9±23.5mL/min per 1.73m2; P =0.053). Only systolic arterial blood pressure was related to eGFR (r = 0.280; P =0.003).Discussion: According to our data, the previously described association between MS and decreased renal function wasconfirmed, mostly determined by the hypertension criterion.Conclusion: These data suggest that the relationship between MS and CKD is driven mostly by abnormalities in blood pressurehomeostasis.

Introdução: A Doença Renal Crônica (DRC) é um problema de saúde pública. Ainda é controversa a existência de associa-ção entre a presença de Síndrome Metabólica (SM) e DRC.Métodos: Indivíduos com risco aumentado para o desenvolvimento de diabete melito acompanhados no ambulatório deEndocrinologia do Hospital de Clínicas de Porto Alegre foram analisados em um estudo transversal. Pacientes foram submetidosao Teste de Tolerância Oral à Glicose, e hemoglobina glicada (A1c), insulina, colesterol, triglicerídeos, creatinina eexcreção urinária de albumina foram medidos. A presença de SM era baseada na presença de três entre os cinco critérios aseguir: hipertensão, níveis séricos de colesterol HDL diminuídos, níveis aumentados de triglicerídeos, hiperglicemia e circunferênciaabdominal aumentada. A taxa de filtração glomerular (TFG) foi calculada pela equação do Modified Diet in RenalDisease (MDRD) e a resistência insulínica, pelo Homeostasis Model of Assessment – Insulin Resistance (HOMA-IR).Análises de correlação foram feitas entre cada componente da SM e a TFG.Resultados: DRC esteve presente em 20,9% dos indivíduos. Níveis diminuídos de TFG foram observados em pacientescom SM comparados com aqueles sem SM (P=0,019). TFG diminuiu com o aumento no número de critérios para SM (mé-dia±DP; 0 e 1 critério 103,09±9,5; vs. 2 critérios 99,14±21,2; vs. 3 critérios 90,9±21,1; vs. 4 critérios 91,0±19,4; vs. 5 crité-rios 80,9±23,3 ml/min; P=0,053). Apenas pressão arterial sistólica mostrou-se relacionada com a TFG (r=0,280; P=0,003).Discussão: Nosso trabalho confirmou a associação entre a presença de Síndrome Metabólica e TFG diminuída descritapreviamente por outros estudos, tendo, neste presente estudo, a hipertensão como o principal determinante desta relação.Conclusão: Nossos achados sugerem que a relação existente entre a presença de SM e o desenvolvimento de DRC é determinadaprincipalmente por anormalidades na homeostase pressórica.