Ana Marin

A randomized study of mitoxantrone plus cytarabine versus daunomycin plus cytarabine in the treatment of previously untreated adult patients with acute nonlymphocytic leukemia

SummaryBetween May 1985 and November 1988, 143 adult patients with previously untreated acute nonlymphocytic leukemia were randomized to receive mitoxantrone and cytarabine (MTT+Ara-C) or daunomycin and cytarabine (DNM+Ara-C) in order to compare the efficacy and acute and chronic toxicities. Therapy consisted of 3 days of MTT 12 mg/m2/i.v. or DNM 45 mg/m2/i.v.; both groups received Ara-C 100 mg/m2 daily by continuous infusion (CI) for 7 days. Those who failed to achieve a complete remission after one induction course received a second induction course for 2 and 5 days at the same doses. All the patients who achieved complete remission received two consolidations of 2 days of MTT or DNM and 5 days of Ara-C in CI at the same dose as for induction. Of the 72 patients on MTT+Ara-C, 38 (53%) achieved complete remission, compared with 29 (43%) of 67 treated with DNM+Ara-C. Three and 5 patients had partial remission, 7 and 18 failed to respond, 24 and 15 died in the first 21 days of induction, of those treated with MTT+Ara-C or DNM+Ara-C, respectively (p=0.34). Median duration of complete remission and survival was 185 and 103 days or 165 and 160 days, respectively (p=0.85). More early deaths were observed with MTT+Ara-C due to greater myelosuppression, and a higher incidence of failure with DNM+Ara-C. No significant differences between treatment groups were observed in 21 categories of adverse events. The results demonstrate similar incidence of complete response, length of duration of complete remission, overall survival, and toxicity with MTT+Ara-C and DNM+Ara-C.

Fat Tissue Measurements by Dual-Energy X-Ray Absorptiometry: Cross-Calibration of 3 Different Fan-Beam Instruments

Analysis of total tissue composition and, particularly, body fat measurements has become progressively important in the diagnosis and follow-up of patients with different clinical conditions. Dual-energy X-ray absorptiometry (DXA) fan-beam scanners are widely used to measure body composition, but the development of translational equations to be able to compare data of different scanning systems is necessary. The aim of this study was to assess the extent of agreement for regional measurements of body composition among the following 3 fan-beam DXA scanners: (1) Hologic Discovery (Hologic, Inc., Waltham, MA), (2) Lunar iDXA (GE Healthcare, Madison, WI), and (3) Lunar Prodigy Advance (GE Healthcare, Madison, WI). The study population consisted of 91 adult healthy volunteers (40 males and 51 females; mean age 48.5±14.4yr) who underwent DXA evaluation of the lumbar spine, hip, and whole body in each machine on the same day. Agreement among the 3 scanners was evaluated according to the Bland-Altman method and Lins concordance correlation coefficient. Results showed a better agreement and concordance for the Lunar iDXA scanner than for any of them with the Hologic scanner. Differences were higher for any tissue or region than for the whole tissue mass. Translational equations were developed to ensure comparability of body composition measurements obtained with each of these 3 scanners.

Effects of an exercise programme on functional capacity, body composition and risk of falls in patients with cirrhosis: a randomized clinical trial

Patients with cirrhosis often have functional limitations, decreased muscle mass, and a high risk of falls. These variables could improve with exercise. The aim was to study the effects of moderate exercise on functional capacity, body composition and risk of falls in patients with cirrhosis. Twenty-three cirrhotic patients were randomized to an exercise programme (n = 14) or to a relaxation programme (n = 9). Both programmes consisted of a one-hour session 3 days a week for 12 weeks. At the beginning and end of the study, we measured functional capacity using the cardiopulmonary exercise test, evaluated body composition using anthropometry and dual energy X-ray absorptiometry, and estimated risk of falls using the Timed Up&Go test. In the exercise group, cardiopulmonary exercise test showed an increase in total effort time (p<0.001) and ventilatory anaerobic threshold time (p = 0.009). Upper thigh circumference increased and mid-arm and mid-thigh skinfold thickness decreased. Dual energy X-ray absorptiometry showed a decrease in fat body mass (-0.94 kg, 95%CI -0.48 to -1.41, p = 0.003) and an increase in lean body mass (1.05 kg, 95%CI 0.27 to 1.82, p = 0.01), lean appendicular mass (0.38 kg, 95%CI 0.06 to 0.69, p = 0.03) and lean leg mass (0.34 kg, 95%CI 0.10 to 0.57, p = 0.02). The Timed Up&Go test decreased at the end of the study compared to baseline (p = 0.02). No changes were observed in the relaxation group. We conclude that a moderate exercise programme in patients with cirrhosis improves functional capacity, increases muscle mass, and decreases body fat and the Timed Up&Go time. Trial Registration: ClinicalTrials.gov NCT01447537

Spirometric Maneuvers and Inhaled Salbutamol Do Not Affect Exhaled Nitric Oxide Measurements among Patients with Allergic Asthma

Background: Exhaled nitric oxide (ENO) is used as a marker of airway inflammation. Factors such as spirometric maneuvers (SPM), β2-agonists, or tobacco smoking have been postulated to affect ENO measurements. Guidelines on measurement techniques have been published based on expert opinions. Nevertheless, there is no strong clinical evidence of many aspects because they have not been supported by research data. Objectives: The aim of this study was to evaluate the influence of performing a spirometry or receiving inhaled salbutamol on ENO readings. Methods: One hundred forty-five adults and 62 children with allergic asthma were included with a mean age of 36 ± 13 years for adults and 13 ± 2 years for children. A control group comprised 30 healthy adults and 30 children with a mean age of 37 ± 14 years and 13 ± 2 years, respectively. ENO measurements were performed with a NIOX-MINO® electrochemical device. In 179 patients ENO was measured before and after performing SPM and in 88 patients before and 15 min after SPM plus 2 puffs of salbutamol (100 µg/puff). Results: There were no significant differences in mean ENO levels before and after SPM or before and after SPM plus 2 puffs of inhaled salbutamol in adults or children (asthmatic or healthy). Conclusions: Levels of ENO are not significantly affected by SPM or salbutamol inhalation.

Impact of 3-monthly vitamin D supplementation plus exercise on survival after surgery for osteoporotic hip fracture in adult patients over 50 years: A pragmatic randomized, partially blinded, controlled trial

ObjectiveTo determine whether 3-monthly supplementation of an oral vitamin D widely used in Spain (calcifediol) plus daily exercise could influence survival at one and four years after surgery for osteoporotic hip fracture.DesignA pragmatic, randomized, partially single-blind placebo-controlled study.SettingPatients admitted to a tertiary university hospital for acute hip fracture.Participants675 healthy adult patients undergoing surgery for osteoporotic hip fracture were recruited from January 2004 to December 2007.InterventionPatients were randomized to receive either 3-monthly oral doses of 3 mg calcifediol (Hidroferol Choque®) or placebo in the 12 months postsurgery. Patients who received calcifediol were also given an exercise programme. The placebo group received standard health recommendations only.MeasurementsThe primary endpoint was survival at 1 year and at 4 year follow-up. We also recorded new fractures, medical complications and anti-osteoporotic treatment compliance.ResultsWe included a total of 88 patients, aged 62 to 99 years. Mean age was 82 years and 88.6% were women. At 12 months, 10 (11.3%) patients had died, 9 of them, from the non-intervention group. At 4 years after surgery, 20 (22.7%) had died, 3 (3.4%) from the intervention group and 17 (19.3%) from the non-intervention group. At this time, survival curve analysis showed 93% survival in the intervention group and 62% in the non-intervention group (p=0.001). At 12-month follow up, there were 18 new fractures, 9 in each group. The non-intervention group had more medical complications, with significant differences at visit 2 (p = 0.04) and 3 (p = 0.02) but not at visit 4 (p = 0.18). No significant differences between groups were found regarding treatment compliance.Conclusion3-monthly, oral supplements of 3 mg calcifediol plus daily exercise improved survival at one-year and four-year follow up after surgery for an osteoporotic hip fracture.

Statins and myositis: the role of anti-HMGCR antibodies

Muscle toxicity is a recognized adverse effect of statin use. Recently, a new myositis syndrome was described in association with antibodies directed against the pharmacologic target of statins, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR antibody). The patient’s genetic background, characteristic histologic patterns (immune-mediated necrotizing myopathy), and presence of anti-HMGCR antibodies define the syndrome. In most patients, statin discontinuation is insufficient to reverse the myositis symptoms, and immunosuppressive therapy is needed. The mechanisms by which these antibodies may lead to disease are not fully elucidated. Several important questions remain unsolved and warrant further research.

Reduction of trabecular and cortical volumetric bone mineral density at the proximal femur in patients with acromegaly

OBJECTIVE Data on dual energy absorptiometry (DXA)-measured bone mineral density (BMD) at the level of the total hip (TH) and femoral neck (FN) in patients with acromegaly (ACRO) are conflicting. Increase in bone size associated with ACRO may limit the reliability of DXA. Our objective is to evaluate trabecular and cortical volumetric BMD (vBMD) across the proximal femur in ACRO patients. DESIGN Cross sectional study in a clinical research center. PATIENTS Thirty-five ACRO patients (19 males; mean age, 48±7 years; BMI, 27.5±4.4 kg/m(2); 17 with active disease) and 35 age, gender, and BMI-matched controls. RESULTS vBMD was assessed by quantitative computed tomography at the level of the TH, FN, trochanter (TR), and intertrochanteric (IT). Trabecular vBMD was lower in both total and active ACRO as compared with controls (P<0.01). Cortical vBMD was lower in ACRO patients (active and controlled) vs controls at both TH and TR sites (P<0.05). These findings were confirmed when only eugonadal patients were analyzed. Both total cross sectional area (CSA) and average cortical thickness (ACT) were greater in ACRO patients vs controls (P<0.05). An inverse association between disease duration and trabecular vBMD at TH (r=-0.42, P=0.023) and IT (r=-0.41, P=0.026) was also found. CONCLUSION Both cortical and trabecular vBMD are reduced at the proximal femur in ACRO patients, regardless of gender, gonadal status, and disease activity. Disease duration is negatively associated with trabecular vBMD at the TH and IT.

Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations

ABSTRACT Introduction: Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy. Areas covered: Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed. The etiology and pathogenesis of statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the responsibility of the immune-mediated necrotizing myopathy is discussed. The fact that patients who have not been exposed to statins may develop statin-associated autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature search strategy included terms identified by searches of PubMed between 1969 and December 2017. The search terms ‘myositis’, ‘statin-induced autoimmune myopathy’, ‘immune-mediate necrotizing myopathy’, ‘statins’, ‘muscular manifestations’, and ‘anti-HMGCR antibodies’ were used. Expert commentary: Full characterization of the known phenotypes of statin toxicity and the specific role of the anti-HMGCR in those exposed and not exposed (i.e. juvenile forms) to statins and in some types of neoplasms is of paramount relevance.

Mixed Connective Tissue Disease and Epitope Spreading: An Historical Cohort Study

Objectives Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading. Methods All anti-U1-RNP-positive patients (2010–2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred. Results Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred. Conclusion Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.

Epicardial fat is a negative predictor of spine volumetric bone mineral density and trabecular bone score in acromegaly

Abbreviations ACRO Acromegaly aBMD Areal bone mineral density CTx C-terminal telopeptide of type 1 collagen aBMD Areal bone mineral density DKK1 Dickkopf-related protein 1 DXA Dual-energy X-ray absorptiometry EAT Epicardial adipose tissue FFA Free fatty acids GH Growth hormone GHD Growth hormone deficiency IGF-I Insulin-like growth factor-I LS vBMD Lumbar spine volumetric bone mineral density MDCT Multidetector computed tomography rGH Recombinant growth hormone QCT Quantitative computed tomography SAT Subcutaneous adipose tissue TBS Trabecular bone score P1NP Total procollagen type 1 amino-terminal propeptide VAT Visceral adipose tissue Wnt Wingless-type