Iron,coronary artery calcification,and mortality in patients undergoing hemodialysis

ObjectiveA high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients.MethodsWe studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston’s CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted.ResultsThe median (interquartile range) age and duration of dialysis of the participants were 67 (60–75) years and 73 (37–138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05).ConclusionWe have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

A cost-minimization analysis of measures against metallic dental restorations for head and neck radiotherapy

The aim of this study was to compare the estimated public medical care cost of measures to address metallic dental restorations (MDRs) for head and neck radiotherapy using high-energy mega-voltage X-rays. This was considered a first step to clarify which MDR measure was more cost-effective. We estimated the medical care cost of radiotherapy for two representative MDR measures: (i) with MDR removal or (ii) without MDR removal (non-MDR removal) using magnetic resonance imaging and a spacer. A total of 5520 patients received head and neck radiation therapy in 2018. The mean number of MDRs per person was 4.1 dental crowns and 1.3 dental bridges. The mean cost per person was estimated to be 121 720 yen for MDR removal and 54 940 yen for non-MDR removal. Therefore, the difference in total public medical care cost between MDR removal and non-MDR removal was estimated to be 303 268 800 yen. Our results suggested that non-MDR removal would be more cost-effective than MDR removal for head and neck radiotherapy. In the future, a national survey and cost-effectiveness analysis via a multicenter study are necessary; these investigations should include various outcomes such as the rate of local control, status of oral mucositis, frequency of hospital visits and efforts of the medical professionals.     

Reduction in cadmium in blood and dietary intake among general populations in Japan

Blood samples and 24-h duplicates of food were collected in the years around 1980 and then in 1990's from inhabitants of nonpolluted regions in Japan. The 1990 study is still in progress with 286 blood samples and 125 food duplicates already collected from 7 regions. A preliminary analysis is made in the present study with the data obtained from the 7 study regions where the survey was conducted in 1980 and then in 1990, to examine possible changes in dietary cadmium intake (Cd-D) and consequently cadmium levels in blood (Cd-B) during this 10 year period. The food duplicate analysis showed that Cd-D in 1980 was 47.1 g/day (1.74):65 [GM (GSD):N] for men and 27.7 g/day (1.75):65 for women. The counterpart values in 1990 were 29.5 g/day (1.66):40 for men and 23.8 g/day (1.73):85 for women; the difference between the two values for the same sex is significant (P<0.05) both=" in=" men=" and=" in=" women,=" suggesting=" that=" there=" occurred=" about=" 37%=" and=" 14%=" reduction=" in=" dietary=" cadmium=" intake=" during=" this=" 10=" year=" period=" in=" men=" and=" in=" women,=" respectively.=" comparison=" in=" cd-b=" showed=" that=" cd-b=" for=" men=" and=" women=" in=" 1990=" were=" 1.79=">g/l (2.01):121 and 1.84 g/l; (1.67):165, respectively, whereas the counterpart values in 1980 were 3.84 g/l (1.64):123 and 3.57 g/l (1.42):141, respectively, indicating significant (P<0.01) reduction=" in=" cd-b=" in=" both=" sexes=" in=" parallel=" to=" the=" reduction=" in=" cd-d.=" the=" role=" of=" rice=" as=" a=" major=" source=" of=" cadmium=" among=" japanese=" population=" together=" with=" recent=" reduction=" in=" the=" importance=" is=" discussed;=" cd=" in=" rice=" accounted=" for=" 72%=" in=" late=" 1970's,=" whereas=" it=" is=" about=" 35%=" in=" the=" present=">     

Enflurane reduces the excitation and inhibition of dorsal horn WDR neuronal activity induced by BK injection in spinal cats

The effects of enflurane (0.5%, 1.5% and 2.5%) on the excitation and inhibition of dorsal horn wide dynamic range (WDR) neuronal activity induced by bradykinin (BK) injection was studied in spinal cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind paw foot pads of decerebrate, spinal cord transected (L_1–2) cats. When 10µg of BK was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus, 24 of 26 WDR neurons (92%) gave excitatory responses and 2 (8%) gave inhibitory resposes. On the other hand, when the injection of 10µg of BK into the femoral artery contralateral to the recording site was used as the noxious test stimulus, 7 of 12 WDR neurons (58%) gave inhibitory responses, 3 (25%) gave excitatory responses, and 2 (17%) showed no response. The excitatory neuronal activity in WDR neurons was not depressed by 0.5% or 1.5% enflurane but was depressed significantly by 2.5%. However, the inhibitory neuronal activity in WDR neurons was significantly depressed by 0.5%, 1.5% and 2.5% enflurane. We have found that enflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection. These results suggest that the reduction of excitatory and inhibitory responses produced by noxious stimulation is likely to be the fundamental basis of the enflurane-induced anesthetic state in terms of WDR neurons.(Nagasaka H, Nakajima T, Takano Y et al.: Enflurane reduces the excitation and inhibition of dosal horn WDR neuronal activity induced by BK injection in spinal cats. J Anesth 4: 102–109, 1990)     

Nondomain biopolymers: Flexible molecular strategies to acquire biological functions

A long-standing assumption in molecular biology posits that the conservation of protein and nucleic acid sequences emphasizes the functional significance of biomolecules. These conserved sequences fold into distinct secondary and tertiary structures, enable highly specific molecular interactions, and regulate complex yet organized molecular processes within living cells. However, recent evidence suggests that biomolecules can also function through primary sequence regions that lack conservation across species or gene families. These regions typically do not form rigid structures, and their inherent flexibility is critical for their functional roles. This review examines the emerging roles and molecular mechanisms of “nondomain biomolecules,” whose functions are not easily predicted due to the absence of conserved functional domains. We propose the hypothesis that both domain- and nondomain-type molecules work together to enable flexible and efficient molecular processes within the highly crowded intracellular environment.     

Efficacy of postoperative adjuvant therapy for stage ilia breast cancer: Futraful vs futraful+tamoxifen for er-positive patients and futraful vs futraful + adriamycin for er-negative breast cancer

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located throughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage IIIa breast cancer. Patients with estrogen receptor-positive [ER( + )] breast cancer were treated with two types of regimens, ie, cyclophosphamide + adriamycin + fluorouracil (CAF; 2 cycles) + Futraful (FT) or CAF (2 cycles) + FT + tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER( + ) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation. The 5-year survival rate was 77.2% for the CAF + FT group and 74.6% for the CAF + FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF + FT + TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF + FT + TAM group was significantly higher than that for the corresponding patients in the CAF + FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF + FT+TAM group than in the CAF + FT group). Patients with estrogen receptor-negative [ER( -)] breast cancer were treated with two types of regimens, ie, CAF + FT or CAF + FT + adriamycin (ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478 (93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF + FT group and 63.0% for the CAF + FT + ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF + FT and CAF + FT + ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF + FT+ADR group than in the CAF + FT group.