Effects of long‐term transdermal hormone replacement therapy on the renin–angiotensin– aldosterone system,plasma bradykinin levels and blood pressure in normotensive postmenopausal women

Aim: This study was designed to investigate the effects of 24‐month long‐term transdermal hormone replacement therapy (HRT) on the circulating levels of components of the renin–angiotensin–aldosterone system (RAAS) and bradykinin, blood pressure (BP) and lipid profile in normotensive postmenopausal women (PMW). Methods: Twenty‐two normotensive PMW were randomized to receive transdermal HRT (continuous 17‐β estradiol patch at 36 µg/day plus cyclic oral medroxyprogesterone acetate 2.5 mg/day for 12 days/month) (n = 12) or control (n = 10). The plasma renin activity (PRA), serum angiotensin‐converting enzyme (ACE) activity, plasma angiotensin (Ang) I, Ang II, aldosterone, bradykinin, and BP were measured before, and 12 and 24 months after, the start of the HRT. Results: In the HRT group, the diastolic BP and mean BP were significantly decreased at 12 and 24 months (both P < 0.05) after the start of therapy, however, no significant change of the systolic BP was noted during the study period. No changes in the RAAS components or lipid profile were noted in either group. The plasma bradykinin levels were significantly reduced at 12 (P < 0.05) and 24 months (P < 0.01), while no changes were observed in the control group. Conclusion: More than 12 months of long‐term transdermal HRT kept diastolic BP, mean BP and plasma bradykinin levels decreased in normotensive PMW, without influencing any of the components of the RAAS. This therapy may allow optimal blood pressure control and prevent elevation of the cardiovascular risk.     

Acute Angle-Closure Glaucoma After General Anesthesia for Bone Grafting

Acute angle-closure glaucoma (AACG) is a rare complication of general anesthesia. The coexistence of individual risk factors for postoperative AACG and factors associated with intraocular hypertension are considered to be required for postoperative AACG to develop. We present a case of AACG after general anesthesia for oral bone grafting in a patient with no preoperative eye symptoms. In this case, several factors such as postoperative care in a darkened room, psychological stress, and postoperative hypertension may have precipitated the event in this patient, who may have had preexisting undiagnosed elevated intraocular pressure. The interval between the earliest appearance of symptoms at 9 hours and the ultimate diagnosis was 36 hours. In the postoperative period following general anesthesia, any patient is at risk for AACG. It is important that a postoperative diagnosis of AACG should be considered and a timely consultation with an ophthalmologist be considered if a postoperative patient complains of red eyes, visual disorder, eye pain, headache, and nausea.Key Words: Acute angle-closure glaucoma, General anesthesia, Postoperative ophthalmological emergencyAcute angle-closure glaucoma (AACG) is a rare complication of general anesthesia that can have a grave prognosis. Predicting AACG after general anesthesia is difficult. In addition, preventive measures against AACG after general anesthesia have not been established. To prevent poor outcomes, early diagnosis and appropriate treatment are important. We encountered a case of AACG after general anesthesia for oral bone grafting.     

Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus eradication by DAAs

Background

It is crucial to identify risk factors for life prognosis after hepatitis C virus (HCV) eradication among patients with or without a high risk of liver cancer or complications.

Methods

This is a prospective, multicenter and observational study using the database of 1031 patients after HCV eradication by direct-acting antiviral agents (DAAs) to evaluate the development of hepatocellular carcinoma (HCC) and patients’ survival after a sustained virological response (SVR). The Cox proportional hazards regression model was used to estimate hazard ratios associated with HCC development and survival.

Results

AFP at SVR was significantly associated with HCC recurrence in the adjusted model. Liver fibrosis, Mac-2 binding protein glycosylation isomer (M2BPGi) at SVR and smoking status before treatment were positively associated with the development of HCC and M2BPGi was positively associated with HCC recurrence, although not reaching statistical significance. Among patients without a history of HCC, M2BPGi and estimated glomerular filtration rate (eGFR) at SVR were significantly associated with death after viral eradication [M2BPGi (HR 4.07, 95% CI 1.22, 13.57), eGFR (HR 0.97, 95% CI 0.94, 0.99)]. Strikingly, of 16 patients who died, among participants without a history of HCC, only two died of liver cancer associated with HCV, whereas 11 died of non-HCV- related cancer or cardiovascular diseases.

Conclusion

M2BPGi at SVR is a potential predictor for patients’ survival and a candidate biomarker for detecting individuals who are at greater risk of death due to cancer-related and unrelated to HCV, as well as cardiovascular diseases, after viral eradication.

     

Sociogeographic Variation in the Effects of Heat and Cold on Daily Mortality in Japan

Background

Ambient temperature affects mortality in susceptible populations, but regional differences in this association remain unclear in Japan. We conducted a time-series study to examine the variation in the effects of ambient temperature on daily mortality across Japan.

Methods

A total of 731 558 all-age non-accidental deaths in 6 cities during 2002–2007 were analyzed. The association between daily mortality and ambient temperature was examined using distributed lag nonlinear models with Poisson distribution. City-specific estimates were combined using random-effects meta-analysis. Bivariate random-effects meta-regressions were used to examine the moderating effect of city characteristics.

Results

The effect of heat generally persisted for 1 to 2 days. In warmer communities, the effect of cold weather lasted for approximately 1 week. The combined increases in mortality risk due to heat (99th vs 90th percentile of city-specific temperature) and cold (first vs 10th percentile) were 2.21% (95% CI, 1.38%–3.04%) and 3.47% (1.75%–5.21%), respectively. City-specific effects based on absolute temperature changes were more heterogeneous than estimates based on relative changes, which suggests some degree of acclimatization. Northern populations with a cool climate appeared acclimatized to low temperature but were still vulnerable to extreme cold weather. Population density, average income, cost of property rental, and number of nurses appeared to influence variation in heat effect across cities.

Conclusions

We noted clear regional variation in temperature-related increases in mortality risk, which should be considered when planning preventive measures.Key words: heat, cold, mortality, time-series, distributed lag     

Evaluation of DNA and RNA quality from archival formalin‐fixed paraffin‐embedded tissue for next‐generation sequencing – Retrospective study in Japanese single institution

Genetic analysis on formalin‐fixed paraffin‐embedded (FFPE) tissue specimens has become a mainstream method, from conventional direct sequencing to comprehensive analysis using next‐generation sequencing (NGS). In this study, we evaluated the quality of DNA and RNA extracted from FFPE sections, derived from surgical specimens of different tumor types. Electrophoresis was performed using a 4200 TapeStation to evaluate DNA and RNA fragmentation. DNA Ct values were higher and significantly increased over a period of 4 years compared with those from cell lines or frozen tissues. The RNA integrity number equivalent (RIN) ranged from 1 to 4.1 and DV200 ranged from 7.3 to 81%. Twelve of the 108 cases were analyzed by NGS using the AmpliSeq Cancer HotSpot Panel v2 on a Miniseq system. A sufficient number of reads and coverage were obtained in all cases. Our results revealed that NGS analysis was sufficient for FFPE‐derived DNA within 4 years of preservation. Conversely, approximately 20% of the RNA derived from FFPE within 4 years from the collection could be inappropriate for gene analysis based on RIN and DV200. It was suggested that FFPE would be adequate for genetic analysis, although it is desirable to store frozen specimens for the tumor tissues to be subjected to genetic analysis.     

Assessment of coronary artery calcification in hemodialysis patients using multi-detector spiral CT scan.

Cardiovascular disease in association with coronary artery calcification (CAC) is the leading cause of death in patients with end-stage renal disease (ESRD). The evaluation of CAC has been performed by electron beam CT scan. The purpose of the present study was to assess CAC using multi-detector spiral CT (MDCT) and to evaluate contributors to CAC in these patients. Fifty-three patients on chronic hemodialysis participated in this study. Their mean age was 61.0+/-9.6 years, and the mean duration of dialysis therapy was 6.7+/-5.4 years. We used an automatic device to measure arterial pulse wave velocity (PWV) as an index of arterial wall stiffness. The aortic calcification index (ACI) was quantified morphometrically by CT scan. The CAC score correlated positively with ACI score (r =0.863, p <0.0001). Linear regression analysis indicated that the CAC scores correlated positively with age (r =0.406, p =0.0023), C-reactive protein (r =0.38, p =0.0047) and PWV (r =0.303, p =0.0271). Stepwise regression analysis indicated that ACI (beta-coefficient=0.862, p <0.0001) and arterial PWV (beta-coefficient=0.303, p <0.0001) were independently associated with CAC score. The mean CAC score of patients with cardiac events (2,568.5+/-2,575.1 mm3) was significantly higher than that (258.0+/-409.2 mm3) of patients without cardiac events. In conclusion, our results showed clearly that assessment of CAC score using MDCT may be predictive for detecting the presence of coronary artery disease. CAC is indirectly associated with increased arterial stiffness and the extent of aortic calcification in hemodialysis patients. We did not find a significant correlation between CAC score and parameters of mineral metabolism, including serum levels of calcium, phosphorus and parathyroid hormone. A longitudinal prospective study is required to assess the predictive value of this technique in determining cardiac events in large numbers of hemodialysis patients.