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Bisphosphonates have been the first drug of choice for osteoporosis in the recent years because of their known ability to suppress osteoclast activity. The adverse effect of long-term bisphosphonate administration in the fracture-healing process is controversial. The aim of our study was to observe not only morphology but also morphometry of the fracture site of atypical femoral fracture with and without long-term bisphosphonate administration, in a case study of two difficult-to-obtain human samples. The patients with insufficient healing of atypical femoral fracture were treated with valgus wedge osteotomy. WZ811 in vivo Histomorphometrical analysis was performed in bone samples of fracture sites harvested during osteotomy. The thickness of the femoral cortex was measured in the fracture site and the adjacent, non-fracture site. A comparative analysis of the content of hypertrophic osteoclasts in fracture sites, shape and size of osteons, mass, and ratio of the woven bone to the total bone mass was performed, comparing bisphosphonate-treated and untreated samples. In bisphosphonate-treated samples, we observed femoral cortex thickening at the fracture site; the appearance of hypertrophic osteoclasts; decreased bone resorption surface, decreased osteoclast numbers on the bone resorption surface, and increased ratio of multinuclear osteoclasts; osteons were misshapen and thin; and the mass and ratio of the woven bone to the total bone mass were higher. This study demonstrated that long-term bisphosphonate administration can alter the morphological features of the fracture site compared to its physiological state.

The validity of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) definitions of early (<1 year), late (1-4 years), and very late (>4 years) bleeding events is unknown.Methods and ResultsThis study was performed on patients (n=3,453) implanted with second-generation drug-eluting stents (DES) between 2010 and 2013. Data on all criteria of the ARC-HBR definition were collected retrospectively. The primary endpoint was Bleeding Academic Research Consortium Type 3 or 5 bleeding events; the ischemic endpoint was a composite of cardiac death, myocardial infarction, and ischemic stroke. The mean follow-up period was 7.5 years. Compared with non-high bleeding risk (HBR) patients, HBR patients (n=1,840; 53.3%) had an increased risk of the primary endpoint (early events, 3.6% vs. 0.5% [P<0.0001]; late events, 5.3% vs. 2.5% [P<0.0001]; very late events, 5.5% vs. 2.1% [P<0.0001]) and of ischemic events during follow-up. The discrimination ability of the ARC-HBR definition for late and very late bleeding events was comparable to that of early bleeding events (C statistics 0.679, 0.621, and 0.620, respectively) with high negative predictive value (96.6%, 95.1%, and 93.1%, respectively). Multivariate analysis revealed the different effects of individual criteria on bleeding events in each follow-up period.

The ARC-HBR definition consistently identified patients at risk of long-term bleeding and ischemic events after second-generation DES implantation.

The ARC-HBR definition consistently identified patients at risk of long-term bleeding and ischemic events after second-generation DES implantation.

Pulmonary embolism (PE) is a potentially fatal form of venous thromboembolism (VTE). This study compares the mortality, incidence of recurrent VTE, and incidence of major bleeding between non-cancer and cancer-associated PE patients treated with direct oral anticoagulants (DOACs).Methods and ResultsThis was a retrospective, observational, single-center study involving 130 consecutive patients (87 with active cancer; 43 without cancer) who received DOAC treatment for PE between January 2016 and December 2019. Kaplan-Meier analysis showed significantly higher mortality in cancer-associated PE patients than in non-cancer patients (35/87 [40%] vs. 1/43 [2%], P<0.001, log-rank test, HR 18.6 [95% CI 2.5-136.0]). In contrast, the cumulative incidences of recurrent VTE and major bleeding were comparable between the 2 groups. Among the cancer-associated PE patients, the incidence for the composite outcome of recurrent VTE or major bleeding was significantly higher in patients undergoing chemotherapy than in those not undergoing chemotherapy (9/37 [24%] vs. 2/50 [4%], P=0.004, log-rank test, HR 6.9 [95% CI 1.5-32.0]).

Although cancer-associated PE patients treated with DOACs showed higher mortality compared with non-cancer patients, presumably because of the presence of cancer, the risk of recurrent VTE or major bleeding was comparable between the 2 groups. Thus, DOAC is an important treatment option for cancer-associated PE, although underlying cancer-related risks (e.g., chemotherapy) remain.

Although cancer-associated PE patients treated with DOACs showed higher mortality compared with non-cancer patients, presumably because of the presence of cancer, the risk of recurrent VTE or major bleeding was comparable between the 2 groups. Thus, DOAC is an important treatment option for cancer-associated PE, although underlying cancer-related risks (e.g., chemotherapy) remain.

Rising blood pressure (BP) in the morning, known as the morning BP surge (MBPS), is known to pose a risk for cardiovascular events in hypertensive individuals. It was not known whether the MBPS was associated with a worse prognosis in patients with heart failure (HF) with a reduced (HFrEF) or preserved (HFpEF) ejection fraction.Methods and ResultsWe performed a prospective, observational cohort study of hospitalized HF patients who underwent ambulatory BP monitoring (ABPM). The MBPS was calculated by subtracting the mean systolic BP (SBP) during the 1 h that included the lowest sleep BP from the mean SBP during the 2 h after waking. The MBPS group was defined as the top decile of MBPS (>40 mmHg). In all, 456 hospitalized HF patients (mean [±SD] age 68±13 years, 63.9% male) were followed-up for a median of 1.67 years. There were 90 events (16.3 per 100 person-years) of the composite outcome (all-cause mortality and worsening HF) in the HFrEF group, compared with 53 events (19.6 per 100 person-years) in the HFpEF group. Multivariate Cox regression analysis showed that MBPS was a significant predictor of outcome (hazard ratio 2.84, 95% confidence interval 1.58-5.10, P<0.01) in the HFrEF but not HFpEF group.

MBPS was found to be a novel predictor of worsening HF in patients with HFrEF.

MBPS was found to be a novel predictor of worsening HF in patients with HFrEF.

To evaluate the safety and efficacy of a novel vascular-friendly thoracic stent graft for patients with acute complicated type B aortic dissection (ac-TBAD).

A multicenter retrospective study was undertaken in which we prospectively collected data in consecutive ac-TBAD patients treated by thoracic endovascular aortic repair (TEVAR) with the Ankura Thoracic Stent. Complications, true lumen rate (TLR), and mortality were recorded. Follow-up computed tomography angiography (CTA) was performed at 1, 6, and 12 months postoperatively and yearly thereafter.

Altogether, 63 patients with ac-TBAD in four medical centers were included. No deaths or serious complications occurred during the perioperative period. The mean follow-up time was 30.1 ± 18.9 months. All-cause mortality rate was 3.1% (n = 2). TEVAR-related mortality rate was 1.6% (n = 1) because of retrograde type A dissection (RTAD) at 6 months. The other death was caused by acute myocardial infarction (AMI) during the third postoperative month. A distal endoleak detected at 3 months in one patient (1.6%) was treated by reintervention. The use of this novel vascular-friendly thoracic stent graft in ac-TBAD postoperative patients significantly improved their TLR.

The novel vascular-friendly thoracic stent graft showed satisfactory results, with favorable stability of the aortic diameter during follow-up.

The novel vascular-friendly thoracic stent graft showed satisfactory results, with favorable stability of the aortic diameter during follow-up.Histological classification and cytology reporting format described in General Rules for the Description of Thyroid Cancer, the 8th edition (2019) (the Japanese General Rules) were briefly introduced. Moreover, the differences between "the Japanese General Rules", and WHO Histological Classification, the 4th edition (2017) and The Bethesda System for Reporting Thyroid Cytopathology, the 2nd edition (2018) were also explained. The Japanese General Rules did not accept the borderline lesions of thyroid tumor which were newly shown in WHO Histological Classification. We believe it is not necessary to introduce these borderline lesions in daily practice in Japan. Borderline lesions were proposed for avoiding over-surgery for thyroid cancer patients. In the United States, when the patient is diagnosed as malignant on cytology, total thyroidectomy is generally recommended. However, there is no over-surgery in Japan, because surgeons have several choices of treatment for thyroid cancer patients. This article is the first that the Japanese General Rules was shown by foreign language. Therefore, this will be advantageous to us when we present our opinion concerning histology and cytology of thyroid tumor to the world.Papillomatous digital dermatitis (PDD) is a polymicrobial infection causing lameness in dairy cattle. Culture-independent analysis has shown that Treponema phagedenis is present consistently and predominantly in the lesions. However, the pathogenesis of PDD, especially the tissue penetration pathway, has not been examined. In the present study, we investigated whether T. phagedenis strains isolated from PDD produce proteolytic enzyme (s) for disruption of the epithelial cell barrier and have the ability to translocate in polarized normal human epidermal keratinocytes (NHEK) in vitro. Ten strains of T. phagedenis isolated from lesions did not show proteolytic activity on modified skim milk agar, although a human strain of T. denticola used as a control showed such activity. The integrity of tight junctions was monitored by measurement of transepithelial electrical resistance (TER). The TER values after inoculation of the T. phagedenis strains examined did not change during the experimental period; however, apical to basolateral translocation of T. phagedenis was confirmed after 24 hr by microscopy and Treponema-specific PCR. We further confirmed that translocation of T. phagedenis was accelerated by co-inoculation with live T. denticola, but not with heat-killed organisms. Furthermore, tight junction ZO-1 protein was not lost intensity after inoculation with T. phagedenis and the organism was observed in NHEK cells using a florescence microscope. These results suggest that T. phagedenis strains may translocate via a transcellular route in vitro and that the invasion is accelerated by other bacteria, such as T. denticola, producing proteolytic activity.This is a review article on luminescence in water published by JSRT and JSMP (https//www.jsmp.org/en).abe.The International System of Units (SI) is recommended for the practical system of units of measurement. The decision of redefining the seven base units of the SI (the second, the meter, the kilogram, the ampere, the kelvin, the mole and the candela) was made at the 26th meeting of the General Conference on Weights and Measures on 16 November 2018. This redefinition came into force starting 20 May 2019, and it became a big historic turning point for the metrology society. This is because the kilogram, the unit of mass, was defined only by an artifact as the international prototype of the kilogram, has been kept for 130 years since its determination in 1889, and was finally changed to the new definition by taking the fixed numerical value of the Planck constant on that day.It is easily imagined that the redefinition of the SI base units has a strong impact on our daily life or the field of science. The reason why the SI redefinition had to be adapted is introduced firstly. Then, how the new definitions are applied now after a year from the redefinition and future prospective of the new definitions are discussed.

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