Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients

Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients.BackgroundThe predictor for the result of calcitriol therapy would be useful in the clinical practice of secondary hyperparathyroidism. Fibroblast growth factor-23 (FGF-23) is a newly found circulating phosphaturic factor. Its circulating level is elevated in uremia.MethodsDialysis patients with plasma intact parathyroid hormone (iPTH) levels greater than 300 pg/mL were included in the study. Calcitriol was intravenously injected three times a week. The patients whose plasma iPTH levels dropped below 300 pg/mL within 24 weeks were defined as those who had been successfully treated. A sandwich enzyme-linked immunosorbent assay (ELISA) system that detects human FGF-23 was applied.ResultsSixty-two patients were analyzed. The pretreatment FGF-23 levels were related to the iPTH levels, calcium × phosphate product levels, and history of active vitamin D therapy. The pretreatment FGF-23, iPTH, and calcium levels were lower in the patients who would be successfully treated with calcitriol. A logistic regression study revealed that the pretreatment iPTH and FGF-23 levels significantly affected the therapy results. Analyses using a receiver-operated curve revealed that FGF-23 was the best screening test for identifying patients with future refractory response to calcitriol therapy. The treatment would be successful in 88.2% of those with FGF-23 ≤9860 ng/L and iPTH ≤591 pg/mL, while it would be successful in only 4.2% of those with FGF-23 >9860 ng/L and iPTH >591 pg/mL.ConclusionPretreatment serum FGF-23 levels were a good indicator in predicting the response to calcitriol therapy. The measurement of serum FGF-23 levels, especially in combination with iPTH levels, is a promising laboratory examination for the clinical practice of secondary hyperparathyroidism

Self-Expandable Metal Stent Placement as a Bridge to Laparoscopic or Open Surgery for Obstructive Colorectal Cancer: Short-Term Outcomes of Nineteen Consecutive Cases

Purpose Laparoscopic colorectal resection is a feasible and less invasive procedure with short-term advantages compared with open surgery; however, the evidence for its efficacy for treating obstructive colorectal cancer (CRC) is lacking. In this study, we aimed to determine short-term outcomes of SEMS placement for obstructive CRC followed by laparoscopic colorectal resection.Methods As of August 2013, 51 patients with obstructive CRC underwent stent insertion. Thirty-two patients received palliation therapy not intended for tumor resection. After decompression of the proximal intestine, nine and 10 patients underwent laparoscopic and open surgery, respectively. Clinicopathological, intraoperative, and postoperative data were retrospectively collected.Results There were no differences in resection rates and curabilities between the two groups. All surgeries were performed with a single-stage anastomosis, and no anastomotic leakage was observed. There was one patient with abdominal morbidity in the open group (Open) and none in the Lap group. There was no mortality in either group. Time to flatus (3.4 ± 1.8 days, Lap; 2.6 ± 1.1 days, Open) and time to oral intake (7.9 ± 2.5 days, Lap; 7.7±1.9 days, Open) were similar between the groups. Postoperative hospitalization times for the Lap group were shorter, but the difference was not statistically significant (15.2 ± 3.9 days, Lap; 21 ± 11.7 days, Open, p = 0.21).Conclusion Our findings indicate that laparoscopic surgery combined with preoperative stent placement is feasible as well as safe compared with open surgery for obstructive CRC

Type I Angiotensin II Receptor Blockade Reduces Uremia-Induced Deterioration of Bone Material Properties

Chronic kidney disease (CKD) is associated with a high incidence of fractures. However, the pathophysiology of this disease is not fully understood, and limited therapeutic interventions are available. This study aimed to determine the impact of type 1 angiotensin II receptor blockade (AT-1RB) on preventing CKD-related fragility fractures and elucidate its pharmacological mechanisms. AT-1RB use was associated with a lower risk of hospitalization due to fractures in 3276 patients undergoing maintenance hemodialysis. In nephrectomized rats, administration of olmesartan suppressed osteocyte apoptosis, skeletal pentosidine accumulation, and apatite disorientation, and partially inhibited the progression of the bone elastic mechanical properties, while the bone mass was unchanged. Olmesartan suppressed angiotensin II-dependent oxidation stress and apoptosis in primary cultured osteocytes in vitro. In conclusion, angiotensin II-dependent intraskeletal oxidation stress deteriorated the bone elastic mechanical properties by promoting osteocyte apoptosis and pentosidine accumulation. Thus, AT-1RB contributes to the underlying pathogenesis of abnormal bone quality in the setting of CKD, possibly by oxidative stress. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Wakamatsu T., Iwasaki Y., Yamamoto S., et al. Type I Angiotensin II Receptor Blockade Reduces Uremia-Induced Deterioration of Bone Material Properties. Journal of Bone and Mineral Research, 36, 1, 67. https://doi.org/10.1002/jbmr.4159

Impact of lifestyle and psychosocial factors on the onset of hypertension after the Great East Japan earthquake: a 7-year follow-up of the Fukushima Health Management Survey

Natural disasters force many evacuees to change several aspects of their lifestyles. This longitudinal study aimed to investigate whether factors such as living environment and lifestyle factors were related to new-onset hypertension in survivors of the Great East Japan Earthquake over a long-term follow-up of up to 7 years after the earthquake. The present study examined data collected from 29,025 Japanese participants aged 39-89 years, sourced from general health checkups and the Fukushima Mental Health and Lifestyle Survey, which was conducted in 13 communities between 2011 and 2018. A total of 10,861 participants received follow-up examinations. During a median follow-up of 4.3 years, 3744 participants (1588 men, 41.4%; 2,156 women, 30.7%) had newly developed hypertension. Heavy drinking (adjusted hazard ratio 1.38, 95% confidence interval 1.21-1.57, p < 0.001) and obesity (adjusted hazard ratio 1.27, 95% confidence interval 1.19-1.37, p < 0.001) were significantly associated with new-onset hypertension after the disaster in multivariate-adjusted analysis. Furthermore, experiencing evacuation after the disaster was also significantly associated with the risk of new-onset hypertension in men (adjusted hazard ratio 1.14, 95% confidence interval 1.02-1.27, p = 0.016). The present study indicated that lifestyle factors, such as drinking and obesity, and evacuation experience in men had significant effects on the risk of new-onset hypertension in the long term after the earthquake

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong