Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study

We compared the efficacy of intensified chemotherapy followed by myeloablative therapy and autologous stem cell rescue with intensified chemotherapy alone in patients newly diagnosed with multiple myeloma. There were 261 eligible patients younger than 66 years with stage II/III multiple myeloma who were randomized after remission induction therapy with vincristine, adriamycin, dexamethasone (VAD) to receive intensified chemotherapy, that is, melphalan 140 mg/m(2) administered intravenously in 2 doses of 70 mg/m(2) (intermediate-dose melphalan [IDM]) without stem cell rescue (n = 129) or the same regimen followed by myeloablative therapy consisting of cyclophosphamide, total body irradiation, and autologous stem cell reinfusion (n = 132). Interferon-alpha-2a was given as maintenance. Of the eligible patients, 79% received both cycles of IDM and 79% of allocated patients actually received myeloablative treatment. The response rate (complete remission [CR] plus partial remission [PR]) was 88% in the intensified chemotherapy group versus 95% in the myeloablative treatment group. CR was significantly higher after myeloablative therapy (13% versus 29%; P =.002). With a median follow-up of 33 months (range, 8-65 months), the event-free survival (EFS) was not different between the treatments (median 21 months versus 22 months; P =.28). Time to progression (TTP) was significantly longer after myeloablative treatment (25 months versus 31 months; P =.04). The overall survival (OS) was not different (50 months versus 47 months; P =.41). Intensified chemotherapy followed by myeloablative therapy as first-line treatment for multiple myeloma resulted in a higher CR and a longer TTP when compared with intensified chemotherapy alone. However, it did not result in a better EFS and OS.     

Postmethionine-load homocysteine determination for the diagnosis hyperhomocysteinaemia and efficacy of homocysteine lowering treatment regimens

Substantial epidemiological evidence supports the vision that moderate hyperhomocysteinaemia is a graded and independent cardiovascular risk factor. The additional value of the methionine loading test for the assessment of hyperhomocysteinaemia continues to be disputed. This overview presents the historical background for the rationale of the methionine loading test and describes determinants and variability of the postmethionine-load homocysteine concentration. The association of postmethionine-load homocysteine concentrations and the risk of cardiovascular events is discussed. Furthermore, the results of homocysteine lowering treatment on postmethionine-load homocysteine are given. Up to 50% of subjects with hyperhomocysteinaemia can only be detected after performing a methionine loading test; these subjects have a normal fasting homocysteine. Both fasting and postmethionine-load homocysteine concentrations are influenced by serum folate and creatinine concentrations and by the methylenetetrahydrofolate reductase genotype, and may be subject to a wide intra-individual variability (approximately 20%). Cross-sectional studies suggest that cardiovascular risk may increase gradually from postmethionine-load homocysteine concentrations above 38 micromol/l. Supplementation with folic acid 0.5 mg daily adequately reduces postmethionine-load homocysteine; addition of pyridoxine appears to have no further homocysteine lowering effect. Prospective studies supporting the clinical significance of the methionine loading test for individual patient counselling are lacking; it seems, therefore, prudent to restrict this test for research purposes.     

Therapy in pneumonia: what is beyond antibiotics?

Community-acquired pneumonia (CAP) is a common and serious disease with significant mortality, morbidity and associated healthcare costs. Severity of pneumonia is related to the extent of the inflammatory response. Primary goal in the treatment of pneumonia is starting adequate antibiotic therapy as soon as possible. However, antimicrobial resistance among the most common bacteria causing pneumonia is increasing. For those two reasons, extended inflammatory response and increasing antibiotic resistance, it is interesting to look at adjunctive non-antibiotic therapeutic strategies aimed at modulation of the inflammatory response or at the micro-organism itself. In this review, we discuss the current knowledge regarding these therapies and their possible role in the future.     

Group‐based trajectory modelling for BMI trajectories in childhood: A systematic review

Childhood obesity is an important public health issue. We aimed to systematically review studies that used group‐based trajectory modelling approaches to investigate body mass index (BMI) trajectories in early childhood, explore associated determinants, and the association with body composition outcomes. Five databases were searched systematically for studies using group‐based trajectory modelling approaches to track BMI trajectories from birth. Fourteen studies using latent class growth analysis or growth mixture modelling to track BMI trajectories were identified. Three or four trajectories were identified in most studies. High maternal pre‐pregnancy BMI was the most frequently identified risk factor for membership of a rapid gain trajectory. Significant associations between rapid weight gain and stable high trajectories and body measures at follow‐up were identified by several studies. Relatively similar trajectories were identified across studies. Trajectories characterized by rapid weight gain were associated with several predictors, as well as body measures at follow‐up, however not with great consistency. Similar associations with body measure outcomes were found for stable high and rapid gain trajectories, suggesting that long‐term outcomes do not differ greatly between children with consistently high BMI and children with rapid increases in BMI. As the shape and timing of the trajectories differed between studies, it is difficult to draw conclusions.     

Beneficial effect of successful HCV treatment in patients with inherited bleeding disorders, assessed by liver stiffness measurements

Hepatitis C infection is a major comorbidity in patients with inherited bleeding disorders. Successful antiviral treatment leads to a reduction in liver fibrosis, as shown by liver biopsies. Liver stiffness measurement (LSM) is a non-invasive method of assessing liver fibrosis. The aim of this cohort study was to evaluate the long-term effect of successful antiviral treatment, using LSM, in HCV-infected patients with inherited bleeding disorders. The LSM were performed in 2005 (LSM 1) and 2009 (LSM 2) in 39 patients who were successfully treated for HCV. The change in liver fibrosis between LSM 1 and 2 was assessed. The median duration of HCV infection was 28.8 years. A total of 22 patients (56%) underwent successful antiviral treatment before LSM 1 (group 1), and 17 patients between LSM 1 and LSM 2 (group 2). The median time since antiviral treatment was 8.8 years in group 1 and 2.5 years in group 2. In group 1, the median results of LSM 1 and 2 were similar (6.0 vs. 5.6 kPa, P-value 0.36), so overall, patients remained stable. In three patients in this group, all treated more than 15 years ago, an increase of liver stiffness was shown. Group 2 showed a significant improvement in median LSM results (10.3 vs. 6.1 kPa, P-value <0.01), with decrease of liver stiffness in 82%. Even after a long HCV infection duration, successful antiviral treatment led to a significant improvement of fibrosis, measured by LSM, mainly in the first few years after completing treatment.     

The adrenocortical carcinoma, a tumour of wide clinical diversity

Over the course of a few years, an obese 52-year-old woman with a 23-year history of hypertension developed a number of abdominal complaints including gall stones. Her blood pressure became increasingly difficult to control and she developed diabetes mellitus and suffered palpitations and headaches. It became noticeable that she had a moon face. Laboratory tests revealed hypercortisolism. CT-scan showed a large inhomogeneous mass of nine centimetres in her left adrenal gland, which was subsequently removed surgically. The histopathological diagnosis was consistent with an adenoma. After a number of months the patient developed bone and liver metastases and the diagnosis was amended to carcinoma of the adrenal cortex. She then underwent radiotherapy and chemotherapy treatment. One year after surgery she developed a pancytopenia and died. Adrenocortical carcinomas are rare tumours with an incidence of about 1-2 cases per million of the population. Symptoms are heterogeneous since both functional (hormonal overproduction) and non-functional (mass effect) tumours exist. Surgical resection is the only curative therapy. It may be difficult to distinguish between benign and malignant cortical tumours.