Effects of hemodialysis and reduced estimated glomerular filtration rate in nonhemodialysis on clinical outcomes after fractional flow reserve-guided deferral of revascularization

The effect of renal dysfunction on clinical outcomes following fractional flow reserve (FFR)-guided deferral of revascularization remains unelucidated.We retrospectively analyzed 224 patients with atherosclerotic coronary lesions who underwent deferred revascularization based on an FFR of >0.80. The median follow-up interval was 28.1 months. Patients were divided into 2 groups: the hemodialysis (HD) and the non-HD group. The non-HD group was further classified into 2 subgroups according to their estimated glomerular filtration rate (eGFR) level: eGFR <45, equivalent to chronic kidney disease stage 3b-5 and eGFR ≥45. We evaluated major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and any revascularization.MACE occurred in 36 patients (16.1%). The rate of HD was significantly higher in the MACE group (19% vs 6%, P < .01). In non-HD patients, the eGFR was significantly lower in the MACE group (51.2 vs 63.2 mL/min/1.73 m², P < .01). Overall, univariate Cox regression analysis revealed a significant relationship between HD and MACE (HR 2.91, P = .01), as did the multivariate model (HR 2.90, P = .01). Of the MACE, more deaths occurred in HD patients (15.8% vs 2.9%, P = .03). Among non-HD patients, eGFR <45 (HR 2.70, P = .02), FFR (per 0.01, HR 0.87, P < .01), and low-density lipoprotein cholesterol (per 10 mg/dL, HR 1.17, P = .02) were independent predictors of MACE. Any revascularization was more common in patients with eGFR<45 than in those with eGFR ≥45 (21.4% vs 7.3%, P = .02). Kaplan–Meier estimates revealed that the HD group showed a significantly lower MACE-free survival rate than the nonHD group (log-rank P < .01). In non-HD patients, the eGFR<45 group showed a lower MACE-free survival rate than the eGFR ≥45 group (log-rank P = .01).HD and reduced eGFR in non-HD patients were associated with adverse cardiac events after FFR-guided deferral of revascularization.     

Combining the Tumor Contact Length and Apparent Diffusion Coefficient Better Predicts Extraprostatic Extension of Prostate Cancer with Capsular Abutment: A 3 Tesla MR Imaging Study

Purpose: To assess the diagnostic performance of the tumor contact length (TCL) and apparent diffusion coefficient (ADC) for predicting extraprostatic extension (EPE) of prostate cancer with capsular abutment (CA).Methods: Ninety-three patients with biopsy-proven prostate cancer underwent 3-Tesla MRI, including diffusion-weighted imaging (b value = 0, 2000 s/mm²) and radical prostatectomy. Two experienced radiologists, blinded to the clinicopathological data, retrospectively assessed the presence of CA on T2-weighted imaging (T2WI). TCL on T2WI and ADC values were measured on detecting CA in prostate cancer. We used the receiver operating characteristic curves to assess the diagnostic performance of TCL and ADC values for predicting EPE.Results: CA was present in 58 prostate cancers among 93 patients. The cut-off value for TCL was 6.9 mm, which yielded an area under the curve (AUC) of 0.75. This corresponded to a sensitivity, specificity, and accuracy of 84.2%, 61.5%, and 69.0%, respectively. The cut-off value for ADC was 0.63 × 10^–3 mm²/s, which yielded an AUC of 0.76. This, in turn, corresponded to a sensitivity, specificity, and accuracy of 84.2%, 59.0%, and 67.2%, respectively. The combined cut-off value of TCL and ADC yielded an AUC of 0.82. The specificity (84.6%) and accuracy (81.0%) of the combined value were superior to their individual values (P < 0.05).Conclusion: A combination of TCL and ADC values provided high specificity and accuracy for detecting EPE of prostatic cancer with CA.     

Phase IIb study of pembrolizumab combined with S‐1 + oxaliplatin or S‐1 + cisplatin as first‐line chemotherapy for gastric cancer

The KEYNOTE‐659 study evaluated the efficacy and safety of first‐line pembrolizumab plus S‐1 and oxaliplatin (SOX) (cohort 1) or S‐1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open‐label phase IIb study enrolled patients with advanced programmed death‐ligand 1 (PD‐L1)‐positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)‐negative G/GEJ adenocarcinoma. The primary end‐point was the objective response rate (ORR). Other end‐points were duration of response (DOR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow‐up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment‐related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD‐L1‐positive, HER2‐negative G/GEJ adenocarcinoma.     

Anti-tumor effects of water-soluble propolis on a mouse sarcoma cell line in vivo and in vitro

The honeybee product propolis and its extracts are known to have biological effects such as antibiotic, anti-viral, anti-inflammatory and anti-tumor activities. This study was designed to investigate whether water-soluble propolis (WSP) inhibits tumor growth. The tumor cell line used was mouse sarcoma 180 (S-180), and its growth was determined in vitro and in vivo with exposure to different concentrations of WSP. The effects of WSP on tumor cells in vitro were evaluated by measuring the intracellular uptake of 3H-thymidine. 3H-thymidine uptake was inhibited in accordance with the concentration of WSP. The minimum concentration of WSP necessary for 3H-thymidine uptake inhibition was 1.0 microg/ml and uptake was suppressed to 88% of the level in non-treated cells at this concentration. In an experiment using tumor-bearing mice, oral administration of WSP was begun 24 hours after transplantation of S-180 cells. WSP was administered to the mice 5 times, every other day for 10 days. The doses were 320 mg/kg (10 mg/mouse) or 960 mg/kg (30 mg/mouse) of body weight. All mice were sacrificed 10 days after transplantation, and tumor growth was evaluated. The orally administered WSP significantly inhibited the growth of transplanted tumors (p < 0.05). Furthermore, histological findings revealed a significant reduction in mitotic cells and tumor invasion of the muscular tissue at both dose-levels of WSP.     

Utility of SARC-F for Assessing Physical Function in Elderly Patients With Cardiovascular Disease

Objectives

A simple and inexpensive tool for screening of sarcopenia would be helpful for clinicians. The present study was performed to determine whether the SARC-F questionnaire is useful in screening of patients with cardiovascular disease (CVD) for impaired physical function.

TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

ObjectivePrecursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.MethodsWe analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.Results TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.ConclusionThe sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.     

Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type 2 diabetes by baseline age and body mass index

Aims/IntroductionMany East Asians with type 2 diabetes are elderly and have a low body mass index (BMI), especially in ''super‐aged'' populations, such as Japan. This post‐hoc analysis assessed once‐weekly semaglutide efficacy and safety in Japanese individuals with type 2 diabetes across baseline age and BMI subgroups.Materials and MethodsData were derived from the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) Japan monotherapy and SUSTAIN Japan oral antidiabetes drug (OAD) combination trials comparing once‐weekly semaglutide with sitagliptin or OADs, respectively. Participants were grouped by baseline age (<65 and ≥65 years) and/or BMI (<25 and ≥25 kg/m²). Reductions from baseline in glycosylated hemoglobin and bodyweight (efficacy), and adverse events (safety) were assessed.ResultsIn this analysis, participants from the SUSTAIN Japan monotherapy trial (n = 308; n per subgroup; range, 8–73) and SUSTAIN Japan OAD combination trial (n = 601; n per subgroup; range, 20–168) were included. Reductions in glycosylated hemoglobin and bodyweight were numerically greater with semaglutide versus comparators across all age and BMI subgroups. Reductions from baseline in glycosylated hemoglobin ranged from –1.7 to –2.1 with semaglutide 0.5 mg, –1.8 to –2.4 with semaglutide 1.0 mg and –0.6 to –1.0 with comparators. Corresponding ranges for bodyweight (kg) were –1.0 to –2.5, –2.4 to –4.3 and 1.0 to –1.0 kg, respectively. The safety profile of semaglutide was broadly similar across BMI and age subgroups.ConclusionsIn this post‐hoc analysis with modest subgroup numbers, once‐weekly semaglutide appeared consistently more efficacious versus comparators across age and BMI subgroups in Japanese patients, with a similar safety profile.