Cluster analysis after TAVR

Aims The aim of this study was to identify phenotypes with potential prognostic significance in aortic stenosis (AS) patients after transcatheter aortic valve replacement (TAVR) through a clustering approach. Methods and results This multi-centre retrospective study included 1365 patients with severe AS who underwent TAVR between January 2015 and March 2019. Among demographics, laboratory, and echocardiography parameters, 20 variables were selected through dimension reduction and used for unsupervised clustering. Phenotypes and outcomes were compared between clusters. Patients were randomly divided into a derivation cohort (n = 1092: 80%) and a validation cohort (n = 273: 20%). Three clusters with markedly different features were identified. Cluster 1 was associated predominantly with elderly age, a high aortic valve gradient, and left ventricular (LV) hypertrophy; Cluster 2 consisted of preserved LV ejection fraction, larger aortic valve area, and high blood pressure; and Cluster 3 demonstrated tachycardia and low flow/low gradient AS. Adverse outcomes differed significantly among clusters during a median of 2.2 years of follow-up (P < 0.001). After adjustment for clinical and echocardiographic data in a Cox proportional hazards model, Cluster 3 (hazard ratio, 4.18; 95% confidence interval, 1.76–9.94; P = 0.001) was associated with increased risk of adverse outcomes. In sequential Cox models, a model based on clinical data and echocardiographic variables (χ2 = 18.4) was improved by Cluster 3 (χ2 = 31.5; P = 0.001) in the validation cohort. Conclusion Unsupervised cluster analysis of patients after TAVR revealed three different groups for assessment of prognosis. This provides a new perspective in the categorization of patients after TAVR that considers comorbidities and extravalvular cardiac dysfunction

Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis

Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes. Moreover, skin tissues of K14-Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9 deletion. This finding suggests that decreasing S100A9 levels may not ameliorate all cases of psoriasis and that diverse mechanisms underlie the condition. Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful to investigate psoriasis pathogenesis and for preclinical testing of new therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes enhances psoriasis susceptibility

Geriatric nutritional risk index predicts all‐cause deaths in heart failure with preserved ejection fraction

AimsThe objective of the study was to evaluate whether the geriatric nutritional risk index (GNRI) at discharge may be helpful in predicting the long‐term prognosis of patients hospitalized with heart failure (HF) with preserved ejection fraction (HFpEF, left ventricular ejection fraction ≥50%), a common HF phenotype in the elderly.Methods and resultsOverall, 110 elderly HFpEF patients (≥65 years) from the Ibaraki Cardiovascular Assessment Study‐HF (n = 838) were enrolled. The mean age was 78.5 ± 7.2 years, and male patients accounted for 53.6% (n = 59). All‐cause mortality was compared between the low GNRI (<92) with moderate or severe nutritional risk group and the high GNRI (≥92) with no or low nutritional risk group. Cox proportional hazard regression models were constructed to evaluate the influence of the GNRI on all‐cause death with the following covariates using forward stepwise selection: age, sex, nutritional status based on the GNRI as a categorical variable, history of HF hospitalization, haemoglobin level, estimated glomerular filtration rate, log brain natriuretic peptide levels (logBNP), history of hypertension, log C‐reactive protein levels, left ventricular ejection fraction, left ventricular mass index, and the New York Heart Association functional classification (I/II or III class). The prognostic value of the GNRI was compared with that of serum albumin using C‐statistics. The GNRI was added to the logBNP, serum albumin or the body mass index was added to the logBNP, and the C‐statistic was compared using DeLong\u27s test. Cox regression analysis revealed that age and a low GNRI were independent predictors of all‐cause death (P < 0.05, n = 103; hazard ratio = 1.095, 95% confidence interval = 1.031–1.163, for age, and hazard ratio = 3.075, 95% confidence interval = 1.244–7.600, for the GNRI). DeLong\u27s test for the two correlated receiver operating characteristic curves [area under the receiver operating characteristic curve (AUROC) of serum albumin, 0.71; AUROC of the GNRI, 0.75] demonstrated significant differences between the groups (P = 0.038). Adding the GNRI to the logBNP increased the AUROC for all‐cause death significantly (0.71 and 0.80, respectively; P = 0.040, n = 105). The addition of serum albumin or the body mass index to the logBNP did not significantly increase the AUROC for all‐cause death (P = 0.082 and P = 0.29, respectively).ConclusionsNutritional screening using the GNRI at discharge is helpful to predict the long‐term prognosis of elderly HFpEF patients

Dyadic, Partner, and Social Network Influences on Intimate Partner Violence among Male-Male Couples

Introduction: Despite a recent focus on intimate partner violence (IPV) among men who have sex with men (MSM), the male-male couple is largely absent from the IPV literature. Specifically, research on dyadic factors shaping IPV in male-male couples is lacking.Methods: We took a subsample of 403 gay/bisexual men with main partners from a 2011 survey of approximately 1,000 gay and bisexual men from Atlanta. Logistic regression models of recent (,12 month) experience and perpetration of physical and sexual IPV examined dyadic factors, including racial differences, age differences, and social network characteristics of couples as key covariates shaping the reporting of IPV.Results: Findings indicate that men were more likely to report perpetration of physical violence if they were a different race to their main partner, whereas main partner age was associated with decreased reporting of physical violence. Having social networks that contained more gay friends was associated with significant reductions in the reporting of IPV, whereas having social networks comprised of sex partners or closeted gay friends was associated with increased reporting of IPV victimization and perpetration.Conclusion: The results point to several unique factors shaping the reporting of IPV within male-male couples and highlight the need for intervention efforts and prevention programs that focus on male couples, a group largely absent from both research and prevention efforts. [West J Emerg Med. 2013;14(4):316–323.

Dyadic, Partner, and Social Network Influences on Intimate Partner Violence among Male-Male Couples

Introduction: Despite a recent focus on intimate partner violence (IPV) among men who have sex with men (MSM), the male-male couple is largely absent from the IPV literature. Specifically, research on dyadic factors shaping IPV in male-male couples is lacking.Methods: We took a subsample of 403 gay/bisexual men with main partners from a 2011 survey of approximately 1,000 gay and bisexual men from Atlanta. Logistic regression models of recent (,12 month) experience and perpetration of physical and sexual IPV examined dyadic factors, including racial differences, age differences, and social network characteristics of couples as key covariates shaping the reporting of IPV.Results: Findings indicate that men were more likely to report perpetration of physical violence if they were a different race to their main partner, whereas main partner age was associated with decreased reporting of physical violence. Having social networks that contained more gay friends was associated with significant reductions in the reporting of IPV, whereas having social networks comprised of sex partners or closeted gay friends was associated with increased reporting of IPV victimization and perpetration.Conclusion: The results point to several unique factors shaping the reporting of IPV within male-male couples and highlight the need for intervention efforts and prevention programs that focus on male couples, a group largely absent from both research and prevention efforts. [West J Emerg Med. 2013;14(4):316–323.

心臓再同期療法の効果における右室・左室間相互作用の影響の解明

科学研究費助成事業 研究成果報告書：若手研究2019-2021課題番号 : 19K1751

Simvastatin-romidepsin combination kills bladder cancer cells synergistically

The HMG-CoA reductase inhibitor simvastatin activates AMP-activated protein kinase (AMPK) and thereby induces histone acetylation. We postulated that combining simvastatin with the histone deacetylase (HDAC) inhibitor romidepsin would kill bladder cancer cells by inducing histone acetylation cooperatively. The combination of romidepsin and simvastatin induced robust apoptosis and killed bladder cancer cells synergistically. In murine subcutaneous tumor models using MBT-2 cells, a 15-day treatment with 0.5 mg/kg romidepsin and 15 mg/kg simvastatin was well tolerated and inhibited tumor growth significantly. Mechanistically, the combination induced histone acetylation by activating AMPK. The combination also decreased the expression of HDACs, thus further promoting histone acetylation. This AMPK activation was essential for the combination's action because compound C, an AMPK inhibitor, suppressed the combination-induced histone acetylation and the combination's ability to induce apoptosis. We also found that the combination increased the expression of peroxisome proliferator-activated receptor (PPAR) γ, leading to reactive oxygen species production. Furthermore, the combination induced endoplasmic reticulum (ER) stress and this ER stress was shown to be associated with increased AMPK expression and histone acetylation, thus playing an important role in the combination's action. Our study also suggests there is a positive feedback cycle between ER stress induction and PPARγ expression

Towards the Development of an Intimate Partner Violence Screening Tool for Gay and Bisexual Men

Introduction: Recent research suggests that gay and bisexual men experience intimate partner violence (IPV) at rates comparable to heterosexual women. However, current screening tools used to identify persons experiencing IPV were largely created for use with heterosexual women. Given the high prevalence of IPV among gay and bisexual men in the United States, the lack of IPV screening tools that reflect the lived realities of gay and bisexual men is problematic. This paper describes the development of a short-form IPV screening tool intended to be used with gay and bisexual men.Methods: A novel definition of IPV, informed by formative Focus Group Discussions, was derived from a quantitative survey of approximately 1,100 venue-recruited gay and bisexual men. From this new definition, a draft IPV screening tool was created. After expert review (n=13) and cognitive interviews with gay and bisexual men (n=47), a screening tool of six questions was finalized. A national, online-recruited sample (n=822) was used to compare rates of IPV identified by the novel tool and current standard tools.Results: The six-item, short-form tool created through the six-stage research process captured a significantly higher prevalence of recent experience of IPV compared to a current and commonly used screening tool (30.7% versus 7.5%, p&lt;0.05). The novel short-form tool described additional domains of IPV not currently found in screening tools, including monitoring behaviors, controlling behaviors, and HIV-related IPV. The screener takes less than five minutes to complete and is 6th grade reading level.Conclusion: Gay and bisexual men experiencing IPV must first be identified before services can reach them. Given emergent literature that demonstrates the high prevalence of IPV among gay and bisexual men and the known adverse health sequela of experiencing IPV, this novel screening tool may allow for the quick identification of men experiencing IPV and the opportunity for referrals for the synergistic management of IPV. Future work should focus on implementing this tool in primary or acute care settings in order to determine its acceptability and its feasibility of use more broadly. [West J Emerg Med. 2013;14(4):391–401.

Towards the Development of an Intimate Partner Violence Screening Tool for Gay and Bisexual Men

Introduction: Recent research suggests that gay and bisexual men experience intimate partner violence (IPV) at rates comparable to heterosexual women. However, current screening tools used to identify persons experiencing IPV were largely created for use with heterosexual women. Given the high prevalence of IPV among gay and bisexual men in the United States, the lack of IPV screening tools that reflect the lived realities of gay and bisexual men is problematic. This paper describes the development of a short-form IPV screening tool intended to be used with gay and bisexual men.Methods: A novel definition of IPV, informed by formative Focus Group Discussions, was derived from a quantitative survey of approximately 1,100 venue-recruited gay and bisexual men. From this new definition, a draft IPV screening tool was created. After expert review (n=13) and cognitive interviews with gay and bisexual men (n=47), a screening tool of six questions was finalized. A national, online-recruited sample (n=822) was used to compare rates of IPV identified by the novel tool and current standard tools.Results: The six-item, short-form tool created through the six-stage research process captured a significantly higher prevalence of recent experience of IPV compared to a current and commonly used screening tool (30.7% versus 7.5%, p&lt;0.05). The novel short-form tool described additional domains of IPV not currently found in screening tools, including monitoring behaviors, controlling behaviors, and HIV-related IPV. The screener takes less than five minutes to complete and is 6th grade reading level.Conclusion: Gay and bisexual men experiencing IPV must first be identified before services can reach them. Given emergent literature that demonstrates the high prevalence of IPV among gay and bisexual men and the known adverse health sequela of experiencing IPV, this novel screening tool may allow for the quick identification of men experiencing IPV and the opportunity for referrals for the synergistic management of IPV. Future work should focus on implementing this tool in primary or acute care settings in order to determine its acceptability and its feasibility of use more broadly. [West J Emerg Med. 2013;14(4):391–401.

Relationships of isometric mid-thigh pull variables to weightlifting performance

Aim. The purpose of this study was to evaluate the relationship between weightlifting performance (snatch, clean and jerk, and total) and variables obtained from the isometric mid-thigh pull (IMTP). Methods. Twelve weightlifters, ranging from novice to advanced, performed the IMTP 10 days after a competition. Correlations were used to evaluate relationships between variables of the IMTP and absolute and scaled competition results. Results. Unsealed competition results correlated strongly with IRFD (0-200ms: r=0.567-0.645, 0-250ms: r=0.722-0.781) while results correlated weakly with Peak IRFD (5ms window, r=0.360-0.426). Absolute peak force values correlated very strongly with absolute values for the competition performance (r=0.830-0.838). Force at 100ms, 150ms, 200ms and 250ms also correlated strongly with competition results (r=0.643-0.647, r=0.605-0.636, r=0.714-0.732, r=0.801-0.804). Similar findings were noted for allometrically scaled values. Conclusion. Measures of average IRFD probably represent a more relevant variable to dynamic performance than does Peak IRFD (5ms). Maximum isometric strength also is likely to have a strong role in weightlifting performance