Objectives: Andrographis paniculata (A. paniculata) is a major medicinal herb, and andrographolide (Andro) is the main component of A. paniculata. Here we evaluated the anti-proliferative activity and anti-inflammatory effects of Andro on THP-1human monocytic leukemia cell line.

Methods: THP-1 cells were cultured in the presence or absence of Andro, Ara-C or vincristine. The anti-cancer activities of Andro were assessed by cell morphological changes, DNA fragmentation, MTT assay, annexin V positive rate and caspase-3/7 activities. The inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured after addition of Andro.

Results: MTT assays showed that Andro inhibited cell proliferation of THP-1 cells. Further, annexin V and caspase-3/7 positive rates were increased by Andro compared with untreated cells, indicating induction of apoptosis. IL-6, TNF-α and nuclear factor-kappa B (NF-κB) were increased by LPS, but the addition of Andro blocked the induction of cytokines by LPS.

Conclusions: These results suggest that Andro has anti-proliferative effects and anti-inflammatory activities via induction of apoptosis and the suppression of NF-κB, respectively.

Objectives: Proximal humeral fractures are common fractures in elderly patients. In some cases, operative treatment is difficult in elderly patients because of severe osteoporosis. An external rotation shoulder brace can maintain the arm in neutral rotation for conservative treatment, which has prompted its use for treatment of proximal humeral fractures in patients aged ≥65 years. We sought to confirm the efficacy of the neutral rotation position.

Methods: Eleven patients with a proximal humeral fracture were clinically and radiographically reviewed. Their mean age was 75 years, and the fracture type was classified according to the Neer group classification system. The duration of brace use prior to achieving bone union and the observation period were analyzed. The shoulder range of motion (ROM) was examined during the final follow-up.

Results: Displacement was not observed during the course of treatment. The patients stopped using the brace at 40 days, bone union was confirmed at 46 days, and the mean follow up period was 4 months. The mean active shoulder ROM for elevation, abduction, external rotation, and internal rotation was 148°, 146°, 50°, and L3, respectively.

Conclusion: We obtained good results during treatment of proximal humeral fractures by maintaining neutral rotation of the arm in elderly patients. Neutral rotation of the arm facilitated by use of an external rotation shoulder brace is an appropriate treatment for proximal humeral fractures in the elderly.

Objectives: Aspergillus sensitization is important for patients with asthma. In Japan, the methods applied to measure allergen-specific immunoglobulin E (IgE) levels in blood are the single antigen test, ImmunoCAP (IC), and multiple antigen simultaneous tests, View Allergy^® (VA) or MAST IV^® (MA). Here, we report the concordance rates (CR) for Aspergillus-specific IgE levels between IC and VA or MA.

Methods: Aspergillus-specific IgE levels in serum samples from 34 male and 23 female patients with bronchial asthma were measured by ImmunoCAP, View Allergy^® (both Thermo Fisher Scientific, Uppsala, Sweden) and MAST IV^® (Hitachi Chemical Diagnostics, Inc. Mountain View, CA, USA). Results of Class 1 or greater were regarded as positive, and the CRs between the methods were assessed.

Results: Of the 57 patients, 24 were found to be positive for Aspergillus-specific IgE by IC, and 5 had allergic bronchopulmonary aspergillosis (ABPA). Significant intraclass correlations were observed between IC and VA (r=0.964, p<0.001) and between IC and MA (r=0.620, p<0.001). Between IC and VA, the CR, positive concordance ratio, and negative concordance ratio was 98.2%, 100%, and 96.9%, respectively; between IC and MA, these values were 77.2%, 45.8%, and 100%, respectively. All five patients with ABPA were found to be positive for Aspergillus-specific IgE by VA, whereas only three of these patients (60%) were found to be positive by MA.

Conclusions: In patients with asthma, measurements obtained by IC were more concordant with those obtained by VA compared with those obtained by MA.

Objectives: Reports on the treatment outcome of non-24-hour sleep–wake rhythm disorder (N24SWD) are limited because of low prevalence. We retrospectively analyzed it using stoppage of free-run as the primary index.

Methods: We enrolled 24 consecutive patients who visited the sleep clinic of the Department of Psychiatry of Fujita Health University Hospital and were diagnosed with N24SWD according to the International Classification of Sleep Disorders, Third Edition. Data were retrospectively collected from medical records. When a stopped free-run was identified in an individual during the treatment period, the patient’s clinical state was determined as one of four defined categories based on the extent of the clinical improvement, including “normalization” (i.e., normalized sleep-phase for >3 months). Chronobiological interventions (e.g., bright light therapy, ramelteon administration, and hospitalization) that were considered to have a temporal association with free-run stoppage were also examined.

Results: “Normalization” occurred in 12.5% (3/24 patients) and free-run stoppage occurred in 45.8% (11/24), whereas free-run persisted throughout the course in 45.8% (11/24). The drop-out rate during the treatment course was 54.2% (13/24 patients). No single intervention achieved “normalization,” and patients with free-run stoppage tended to undergo multiple chronobiological interventions.

Conclusions: The very low “normalization” rate and the large number of patients with ongoing free-run who dropped out suggest that N24SWD is extremely refractory. The possibility of free-run stoppage using a combination of multiple chronobiological interventions may be plausible, although we were unable to identify a specific treatment that was effective. Further studies that include the analysis of therapeutic interventions are required.

Objectives: There are well-established risk prediction models of in-hospital mortality due to heart failure (HF). However, the predictors of mortality during acute hospitalization in individuals with HF receiving tolvaptan, a vasopressin type 2 receptor antagonist, are poorly understood.

Methods: Sixty-one hospitalized patients prescribed tolvaptan to treat worsening HF were consecutively enrolled in this study. The study endpoint was death during hospitalization.

Results: Compared with survivors, patients who died in hospital had higher Get With The Guidelines-Heart Failure (GWTG-HF) risk scores, decreased albumin levels, increased serum creatinine levels, smaller inferior vena cava (IVC) diameters on echocardiography, and were more likely to have received catecholamine infusion. A multivariate logistic regression analysis revealed that in addition to GWTG-HF risk score >47, albumin level ≤2.4 g/dL, creatinine level >1.5 mg/dL, IVC diameter ≤15 mm, and catecholamine infusion were all novel and significant predictors of in-hospital death. Moreover, combining these novel predictors to the GWTG-HF risk score significantly improved prediction of in-hospital death, as shown by the greater area under the receiver operating characteristic (ROC) curve.

Conclusions: In patients with worsening HF receiving oral tolvaptan, we identified novel predictors of in-hospital death. Our findings may be helpful in developing novel treatment strategies for patients receiving tolvaptan for HF in clinical settings.