Baseline serum PINP level is associated with the increase in hip bone mineral density seen with Romosozumab treatment in previously untreated women with osteoporosis

Summary: Baseline serum PINP value was significantly and independently associated with the increased bone mineral density (≥ 3%) in both total hip and femoral necks by 12 months of romosozumab treatment in patients with treatment-naive postmenopausal osteoporosis. Purpose: Some patients fail to obtain a sufficiently increased hip bone mineral density (BMD) by romosozumab (ROMO) treatment. This study aimed to investigate the prognostic factor for increased hip BMD with ROMO in patients with treatment-naive postmenopausal osteoporosis. Methods: This prospective, observational, and multicenter study included patients (n = 63: mean age, 72.6 years; T-scores of the lumbar spine [LS], − 3.3; total hip [TH], − 2.6; femoral neck [FN], − 3.3; serum type I procollagen N-terminal propeptide [PINP], 68.5 µg/L) treated by ROMO for 12 months. BMD and serum bone turnover markers were evaluated at each time point. A responder analysis was performed to assess the patient percentage, and both univariate and multivariate analyses were performed to investigate the factors associated with clinically significant increased BMD (≥ 3%) in both TH and FN. Results: Percentage changes of BMD from baseline in the LS, TH, and FN areas were 17.5%, 4.9%, and 4.3%, respectively. In LS, 96.8% of patients achieved ≥ 6% increased LS-BMD, although 57.1% could not achieve ≥ 3% increased BMD in either TH or FN. Multiple regression analysis revealed that only the baseline PINP value was significantly and independently associated with ≥ 3% increased BMD in both TH and FN (p = 0.019, 95% confidence interval = 1.006–1.054). The optimal cut-off PINP value was 53.7 µg/L with 54.3% sensitivity and 92.3% specificity (area under the curve = 0.752). Conclusions: In a real-world setting, baseline PINP value was associated with the increased BMD of TH and FN by ROMO treatment in treatment-naive patients.This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00198-022-06642-1Kashii M., Kamatani T., Nagayama Y., et al. Baseline serum PINP level is associated with the increase in hip bone mineral density seen with Romosozumab treatment in previously untreated women with osteoporosis. Osteoporosis International 34, 563 (2023

Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis

Purpose: To investigate the effects of prior treatment and the predictors of early treatment response to romosozumab (ROMO) in patients with postmenopausal osteoporosis. Methods: In this prospective, observational, multicenter study, 130 treatment-naïve patients (Naïve; n = 37) or patients previously treated with bisphosphonates (BP; n = 33), denosumab (DMAb; n = 45), or teriparatide (TPTD; n = 15) (age, 75.0 years; T-scores of the lumbar spine [LS] −3.2 and femoral neck [FN] −2.9) were switched to ROMO based on their physician's decision. Bone mineral density (BMD) and serum bone turnover markers were evaluated for six months. Results: At six months, LS BMD changes were 13.6%, 7.5%, 3.6%, and 8.7% (P <.001 between groups) and FN BMD changes were 4.2%, 0.4%, 1.6%, and 1.5% (P =.16 between groups) for Naïve, BP, DMAb, and TPTD groups, respectively. Changes in N-terminal type I procollagen propeptide (PINP; μg/L) levels from baseline → one month were 72.7 → 139.0, 33.5 → 85.4, 30.4 → 54.3, and 98.4 → 107.4, and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) (mU/dL) were 474.7 → 270.2, 277.3 → 203.7, 220.3 → 242.0, and 454.1 → 313.0 for Naïve, BP, DMAb, and TPTD groups, respectively. Multivariate regression analysis revealed that significant predictors of LS BMD change at six months were prior treatment difference (r = −3.1, P =.0027) and TRACP-5b percentage change (r = −2.8, P =.0071) and PINP value at one month (r = 3.2, P =.0021). Conclusion: Early effects of ROMO on the increase in LS BMD are significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers. Mini abstract: Early effects of ROMO on the increase in LS BMD at six months is significantly affected by the difference of prior treatment and also predicted by the early change of bone turnover markers in patients with postmenopausal osteoporosis.Ebina K., Hirao M., Tsuboi H., et al. Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis. Bone 140, 115574 (2020); https://doi.org/10.1016/j.bone.2020.115574

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis

Objectives: To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis. Methods: In this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n = 50) or patients previously treated with bisphosphonates (BP; n = 37) or denosumab (DMAb; n = 45) or teriparatide (TPTD; n = 16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] −3.2 and total hip [TH] −2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months. Results: At 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P < 0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P < 0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; μg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r = −2.8, P < 0.001) and value of PINP at 1 month (r = 0.04, P < 0.01) for LS, and difference of prior treatment (r = −1.3, P < 0.05) and percentage change of TRACP-5b at 1 month (r = −0.06, P < 0.05) for TH. Conclusions: The early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.Ebina K., Tsuboi H., Nagayama Y., et al. Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis. Joint Bone Spine 88, 105219 (2021); https://doi.org/10.1016/j.jbspin.2021.105219

Surgical benefits of liver hanging maneuver for hepatectomy of huge liver tumor

In hepatic surgery, it is very important to control bleeding during liver resection. However, in hepatectomy for a huge liver tumor it is often difficult to reduce bleeding volume and maintain an excellent surgical view. The anterior pproach, which is hepatectomy done using the liver hanging maneuver, has beneficial effects reducing bleeding volume and preventing scattering of cancer cells from huge liver tumors. W e investigated the surgical benefits of the liver anging maneuver during hepatectomy for huge liver tumors in our department.

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Trehalose solution viscosity at low temperatures measured by dynamic light scattering method : Trehalose depresses molecular transportation for ice crystal growth

The inhibitory effects of trehalose on ice crystal growth were discussed on the basis of the viscosity measurements of aqueous solutions via the dynamic light-scattering method. The temperature and concentration conditions of the solution were ranged between 268 and 343K and up to 50wt%, respectively, which were feasible for applying this novel technique and were useful in the indirect measurement of the macroscopic dynamic properties of the trehalose solutions. A comparison of the viscosity data with those reported in the literatures indicated the validity of this method for measuring the viscosity. The nonlinearity of the temperature and concentration dependences of the trehalose solutions suggested that two different hydrogen-bonding networks exist in the solutions within the investigated range. Dilute solutions of less than 10wt% of trehalose exhibited properties very similar to those of pure water. Higher concentration solutions had large viscosities with large temperature and concentration dependences. This was caused by the decrease in the free water in the solution and the development of hydrogen-bonding networks with hydrated trehalose clusters. Sucrose and maltose solutions had the same properties, so this would be the dominant inhibitory process of disaccharides on ice crystal growth

Drastic change of local stiffness distribution correlating to cell migration in living fibroblasts.

Sequential images of the local stiffness distribution of living fibroblasts (NIH3T3) were captured under a culture condition using scanning probe microscopy in a force modulation mode. We found a clear relation between cell migration and local stiffness distribution on the cell: When cells were stationary at one position, the stiffness distribution of their cellular surface was quite stable. On the other hand, once the cells started to move, the stiffness in their nuclear regions drastically decreased. Possible explanations for the correlation between the cell migration and the cell stiffness are proposed. Cell Motil. Cytoskeleton 50:173-179, 2001. © 2001 Wiley-Liss, Inc