Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.     

Localized right ventricular structural abnormalities in patients with idiopathic ventricular fibrillation: Magnetic resonance imaging study

Summary Lethal arrhythmias, including ventricular tachycardia and ventricular fibrillation, may occur in the absence of apparent morphological abnormalities. However, a recent study using magnetic resonance imaging (MRI) has suggested that localized, minor structural abnormalities of the right ventricle are responsible for right ventricular outflow tract ventricular tachycardia in a number of patients. We demonstrated regional wall thinning and systolic dyskinesia of the right ventricle by MRI in two patients with idiopathic ventricular fibrillation in whom other cardiac imaging modalities failed to show abnormalities. This finding implies that minor structural abnormalities do exist in patients with so-called idiopathic ventricular fibrillation.     

Relationship between the door-to-TIMI-3 flow time and the infarct size in patients suffering from acute myocardial infarction: analysis based on the fibrinolysis and subsequent transluminal (FAST-3) trial.

BACKGROUND: The purpose of this study was to use the findings of a fibrinolysis and subsequent transluminal trial (FAST-3) to evaluate the association between the target time for obtaining a thrombolysis in myocardial infarction (TIMI)-3 flow after arrival at the emergency room with acute myocardial infarction (AMI) and the degree of myocardial salvage. METHODS AND RESULTS: The FAST-3 trial was administered to 100 patients suffering from AMI. Ranges in the door-to-TIMI-3 flow time (D-T3-time: TIMI-3 flow after arrival at the emergency room) according to quartile were as follows: 30-54 min (quartile 1), 55-77 min (quartile 2), 78-120 min (quartile 3) and 121-330 min (quartile 4). Peak creatine kinase (CK), peak CK-MB, and peak troponin-T values increased in a stepwise fashion across the increasing quartiles of D-T3-time. The left ventricular end diastolic volume index at 30 days after the start of treatment showed low values for quartile 1. In multiple logistic regression analyses for independent predictors of myocardial damage, the adjusted odds ratios for myocardial damage (peak CK>3,000 U/L) in quartiles 3 and 4 of the D-T3-time were 4.0 (95% CI: 1.0-16.1) and 7.0 (95% confidence interval (CI): 1.4-36.0), respectively. CONCLUSIONS: These findings suggest that physicians should monitor the D-T3-time for at least 55 min.     

Quantitative assessment of chemotherapy‐induced peripheral neurotoxicity using a point‐of‐care nerve conduction device

Chemotherapy‐induced peripheral neurotoxicity (CIPN) seriously impairs patients’ quality of life cumulatively and dose‐dependently. Because assessment of CIPN usually depends on patients’ subjective evaluation of symptoms, objective and quantitative measures are needed. We evaluated a point‐of‐care nerve conduction device (POCD), previously validated for the assessment of diabetic peripheral neuropathy. Sensory nerve action potential (SNAP) amplitude and sensory nerve conduction velocity (SNCV) of the sural nerve were measured using a portable, automated POCD (DPNCheck; NeuroMetrix Inc., Waltham, MA, USA) in patients with a clinical diagnosis of CIPN of grade 1 or higher. We compared SNAP and SNCV among patients with different grades of CIPN according to the Common Terminology Criteria for Adverse Events. A total of 50 patients (22 men, 28 women; median age, 64 years; grade 1/2/3, 21/18/11) were evaluated. Anticancer drugs responsible for CIPN were cisplatin in five patients, oxaliplatin in 15, carboplatin in 5, paclitaxel in 16, docetaxel in 14, nab‐paclitaxel in 7, vincristine in 6, and bortezomib in 3. Unadjusted SNAP was 8.45 ± 3.67 μV (mean ± SD) in patients with grade 1 CIPN, 5.42 ± 2.68 μV with grade 2, and 2.45 ± 1.52 μV with grade 3. Unadjusted SNCV was 49.71 ± 4.77 m/s in patients with grade 1 CIPN, 48.78 ± 6.33 m/s with grade 2, and 44.14 ± 7.31 m/s with grade 3. The adjusted SNAP after controlling for age significantly differed between each CTCAE grade (P < 0.001, ancova ). The adjusted SNCV after controlling for age and height also differed significantly (P = 0.027). Differences in the severity of CIPN could be detected objectively and quantitatively using this POCD.     

Role of the suprachiasmatic nuclei of the hypothalamus on diurnal rhythm in cardiac arrhythmias

Summary Ambulatory EGG and EEG recordings were recorded under a 14/10-h light-dark illumination schedule using rats. The rats consisted of two groups: a suprachiasmatic (Sch) lesioned group (n=5) and a normal control group (n=5). Bilateral Sch nuclei were lesioned electrically (DC, 2.5 mA, 30 s for each) using a pair of platinum electrodes 0.3 mm in diameter. After recovery from surgery, recordings of ECGs (leads I, II, and III) and EEGs from the cortex and the left dorsal hippocampus were continued for 6 days. Diurnal periodicity in bradyarrhythmia (sinoatrial block, atrioventricular block) and heart rate was analyzed by the least square fit of 24-h cosines. Significant diurnal rhythm was observed in control rats, whereas Sch-lesioned rats showed no significant diurnal rhythm. The integrity of the Sch nuclei, therefore, is necessary for the generation and/or the expression of diurnal periodicity in bradyarrhythmia in rats.     

Graves' disease associated with anticardiolipin antibody positivity and acquired protein S deficiency

A 33-year-old woman had experienced recurrent pregnancy loss. She had positive anticardiolipin antibody and protein S deficiency. Her pregnancy was managed with anticoagulant therapy and she delivered a healthy infant. Three years after delivery, she reported progressive sweating, tremor, tachycardia, and a 4-kg weight loss. She was diagnosed with Graves' disease. This is a rare case of combined anticardiolipin antibody positivity, acquired protein S deficiency, and Graves' disease.     

A naturally occurring Tyr143His alpha IIb mutation abolishes alpha IIb beta 3 function for soluble ligands but retains its ability for mediating cell adhesion and clot retraction: comparison with other mutations causing ligand-binding defects

The molecular basis for the interaction between a prototypic non-I-domain integrin, alpha(IIb)beta(3), and its ligands remains to be determined. In this study, we have characterized a novel missense mutation (Tyr143His) in alpha(IIb) associated with a variant of Glanzmann thrombasthenia. Osaka-12 platelets expressed a substantial amount of alpha(IIb)beta(3) (36%-41% of control) but failed to bind soluble ligands, including a high-affinity alpha(IIb)beta(3)-specific peptidomimetic antagonist. Sequence analysis revealed that Osaka-12 is a compound heterozygote for a single (521)T>C substitution leading to a Tyr143His substitution in alpha(IIb) and for the null expression of alpha(IIb) mRNA from the maternal allele. Given that Tyr143 is located in the W3 4-1 loop of the beta-propeller domain of alpha(IIb), we examined the effects of Tyr143His or Tyr143Ala substitution on the expression and function of alpha(IIb)beta(3) and compared them with KO (Arg-Thr insertion between 160 and 161 residues of alpha(IIb)) and with the Asp163Ala mutation located in the same loop by using 293 cells. Each of them abolished the binding function of alpha(IIb)beta(3) for soluble ligands without disturbing alpha(IIb)beta(3) expression. Because immobilized fibrinogen and fibrin are higher affinity/avidity ligands for alpha(IIb)beta(3), we performed cell adhesion and clot retraction assays. In sharp contrast to KO mutation and Asp163Ala alpha(IIb)beta(3), Tyr143His alpha(IIb)beta(3)-expressing cells still had some ability for cell adhesion and clot retraction. Thus, the functional defect induced by Tyr143His alpha(IIb) is likely caused by its allosteric effect rather than by a defect in the ligand-binding site itself. These detailed structure-function analyses provide better understanding of the ligand-binding sites in integrins.     

Ambulatory blood pressure monitoring in Uygur centenarians.

Cross-sectional surveillance was carried out in long-lived Uygur in China to investigate blood pressure (BP) and pulse rate (PR) variation in centenarians. The study group comprised 33 centenarians (age > or = 100 years), 103 longevous subjects (age 90-99 years) and 100 elderly (age 65-70 years) subjects. Office BP was measured, and 24-h noninvasive ambulatory blood pressure monitoring (ABPM) was performed. The office BP was higher and hypertension occurred more frequently in the centenarians than in either the longevous or elderly subjects. Mean 24-h systolic and diastolic BP was higher in the centenarians than in the other 2 groups. However, mean 24-h PR did not differ between them. Day-night differences in systolic BP decreased, and the non-dipper-type BP pattern was common in the centenarians (79.1% vs 68% and 63.6% in longevous and elderly subjects, respectively). Circadian BP was characterized by 3 peaks in longevous subjects and multiple peaks in centenarians. Morning rising and nocturnal dipping of BP were observed in both longevous and elderly subjects. In conclusion, BP in longevous and elderly Uygur was characterized by circadian rhythmicity, but the nocturnal fall in BP was not seen in centenarians. Differences in day-night BP and circadian rhythmicity may decrease with advancing age, especially in centenarians.