Background
Few studies have investigated measures to prevent small bowel injuries induced by aspirin. Our aim was to evaluate the effect of probiotic treatment on the small bowel injuries induced by ...chronic low-dose aspirin use.
Methods
Thirty-five patients who took low-dose enteric-coated aspirin 100 mg daily (for more than 3 months) plus omeprazole 20 mg daily and were diagnosed as having unexplained iron deficiency anemia participated in this prospective randomized controlled trial. We assigned the patients to receive probiotic treatment with
Lactobacillus casei
for 3 months (
L. casei
group) or not receive the probiotic (control group). Patients underwent capsule endoscopy (CE) before and after treatment.
Results
Twenty-five patients, including 13 in the
L. casei
group and 12 in the control group, underwent the full analysis. Significant decreases in the number of mucosal breaks and the CE score were observed at the 3-month evaluation in the
L. casei
group as compared with the results in the control group (
P
= 0.039). The change from the baseline in the median number of mucosal breaks in the
L. casei
group was −2, as compared with 0.5 in the control group. The change from the baseline in the median CE score in the
L. casei
group was −228 compared with −4 in the control group (
P
= 0.026).
Conclusions
Co-administration of
L. casei
is effective for the treatment of aspirin-associated small bowel injury.
KRAS, CDKN2A, TP53, and SMAD4 have been recognized as major driver genes in pancreatic carcinogenesis. We examined somatic mutations in 50 cancer-related genes, including the four above-mentioned ...driver genes, to identify genomic biomarkers for predicting the outcome of patients with pancreatic cancer.
Genomic DNA was extracted from fresh-frozen specimens obtained from 100 patients with pancreatic cancer who had undergone a pancreatectomy with curative intent. The mutation profile was obtained using a single targeted deep sequencing assay performed with a next-generation sequencer, and the associations with clinicopathological factors were analyzed.
Mutations in the KRAS, CDKN2A, TP53, and SMAD4 genes were detected in 96% (96/100), 42% (42/100), 13% (13/100), and 7% (7/100) of all patients, respectively. Among the 71 patients who underwent a radical operation followed by adjuvant chemotherapy, patients with fewer mutations among the four driver genes tended to have a better outcome. A multivariate analysis using the Cox proportional hazard model showed that the presence of 0 to 2 mutated driver genes was an independent predictor of a better overall survival (hazard ratio for death, 0.20; P = 0.0040).
The number of mutated driver genes assessed using a targeted deep sequencing assay was a promising prognostic biomarker for pancreatic cancer.
We evaluated four new molecular targeting agents using our cell line panel with 17 biliary tract carcinoma cell lines. PI3K/mTOR inhibitor showed promising activity in many cell lines including ...gemcitabine-insensitive ones.
Abstract
Biliary tract carcinoma (BTC) is an extremely malignant tumor, but available treatment options are limited. Despite of needs for novel therapies, few BTC-related resources are currently available for evaluation of candidate drugs. To address this issue, we have recently established 13 cell lines from surgical specimens from Japanese BTC patients. In the present study, we evaluated four new molecular targeting agents using our BTC cell-based assay panel with 17 BTC cell lines. PI3K/mTOR dual inhibitor LY3023414 showed activity at submicromolar concentration ranges against 13 of the 17 cell lines tested, including the ones with gemcitabine insensitivity. In conclusion, we demonstrated that in vitro study with the BTC cell line panel would be an efficient approach to screen for novel therapeutic strategies. Although this is preliminary result and further investigations are required for confirmation, PI3K/mTOR inhibitor might be a potential target for BTC drug development.
The biguanide metformin is widely used for treating diabetes mellitus. We previously showed the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis. However, besides ...epidemiologic studies, little is known about the effects of metformin on human colorectal carcinogenesis. The objective of this pilot study was to evaluate the chemopreventive effect of metformin on rectal aberrant crypt foci (ACF), which are an endoscopic surrogate marker of colorectal cancer. We prospectively randomized 26 nondiabetic patients with ACF to treatment with metformin (250 mg/d, n = 12) or no treatment (control, n = 14); 23 patients were evaluable for end point analyses (9 metformin and 14 control); the two groups were similar in ACF number and other baseline clinical characteristics. Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion (as were all laboratory end point analyses). We also examined proliferative activity in colonic epithelium (via proliferating cell nuclear antigen labeling index) and apoptotic activity (via terminal deoxynucleotidyl transferase dUTP nick-end labeling). At 1 month, the metformin group had a significant decrease in the mean number of ACF per patient (8.78 +/- 6.45 before treatment versus 5.11 +/- 4.99 at 1 month, P = 0.007), whereas the mean ACF number did not change significantly in the control group (7.23 +/- 6.65 versus 7.56 +/- 6.75, P = 0.609). The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients. This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer.
The Wound, Ischemia, foot Infection (WIfI) classification system is used to predict the amputation risk in patients with critical limb ischemia (CLI). The validity of the WIfI classification system ...for hemodialysis (HD) patients with CLI is still unknown. This single-center study evaluated the prognostic value of WIfI stages in HD patients with CLI who had been treated with endovascular therapy (EVT).
A retrospective analysis was performed of collected data on CLI patients treated with EVT between April 2007 and December 2015. All patients were classified according to their wound status, ischemia index, and extent of foot infection into the following four groups: very low risk, low risk, moderate risk, and high risk. Comorbidities and vascular lesions in each group were analyzed. The prognostic value of the WIfI classification was analyzed on the basis of the wound healing rate and amputation-free survival at 1 year.
This study included 163 consecutive CLI patients who underwent HD and successful endovascular intervention. The rate of the high-risk group (36%) was the highest among the four groups, and the proportions of very-low-risk, low-risk, and moderate-risk patients were 10%, 18%, and 34%, respectively. The mean follow-up duration was 784 ± 650 days. The wound healing rates at 1 year were 92%, 70%, 75%, and 42% in the very-low-risk, low-risk, moderate-risk, and high-risk groups, respectively (P <.01). A similar trend was observed for the 1-year amputation-free survival among the groups (76%, 58%, 61%, and 46%, respectively; P = .02).
The WIfI classification system predicted the wound healing and amputation risks in a highly selected group of HD patients with CLI treated with EVT, with a statistically significant difference between high-risk patients and other patients.
The Impella device can effectively unload the left ventricle in patients undergoing high-risk percutaneous coronary intervention (PCI) and in cases of cardiogenic shock. Herein, we report a rare case ...of a 59-year-old man who was treated using PCI and the Impella CP for acute coronary syndrome. The patient suffered from severe acute aortic regurgitation and complete atrioventricular block (CAVB) with hemodynamic instability soon after the Impella removal. The non-coronary cusp (NCC) tear occurred from the NCC and right coronary cusp commissure to the middle of the NCC. The patient successfully underwent aortic valve replacement with no CAVB postoperatively.
To investigate the usefulness of ultrasound-guided (USG) intraluminal approach for femoropopliteal (FP) lesion. 64 patients (73 limbs) with de novo long occlusive (> 15 cm) FP lesions underwent USG ...intralumial approach from April 2012 to October 2016. Periprocedural intravascular ultrasound findings were collected. Clinical outcome and predictors of restenosis after USG intraluminal approach for de novo long occlusive FP lesion were investigated. Among the study participants, 34% were female, 50% had diabetes mellitus, and 10% received hemodialysis. Lesion and chronic total occlusion (CTO) lengths were 222 ± 55 mm and 201 ± 55 mm, respectively. Procedural success was achieved in 72 lesions (99%). Distal puncture was performed in 7 limbs (10%). The proportion of within-CTO intraplaque, subintimal, and medial routes were 87 ± 21%, 9 ± 15%, and 4 ± 11%, respectively. Primary patency was 71% and 69% at 1 and 2 years. Multivariate analysis revealed that within-CTO intraplaque route proportion hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.67–0.98,
p
= 0.0339 and lesion length (HR 1.11; CI 1.00–1.22;
p
= 0.0447) were independent predictors of restenosis.USG intraluminal approach facilitated acquisition of within-CTO intraplaque route in long occlusive FP lesions and could improve clinical outcome.
•Malnutrition predicts poor outcome after transcatheter aortic valve replacement.•Malnutrition provided complementary prognostic value to the Clinical Frailty Scale.•Intervention to nutritional ...status may be potentially beneficial for prognosis.
This study aimed to elucidate the prognostic value of objective nutritional status after transcatheter aortic valve replacement (TAVR).
This study enrolled 150 consecutive patients who underwent TAVR between February 2014 and March 2017. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score before TAVR. Patients were divided into a high CONUT score (malnutrition status >4 points, n=30) or low CONUT score (normal nutritional status 1–4 points, n=120) group. The primary endpoint was mortality within 1-year post-TAVR.
Patients in the high CONUT group were characterized by low body mass index (kg/m2) (20.3±2.4 vs. 22.8±3.5, p<0.001), a higher prevalence of atrial fibrillation (43% vs. 23%, p=0.03), and more common frailty median (interquartile range) Clinical Frailty Scale (CFS) score, 4.5 (3.75–6) vs. 4 (3–5), p<0.001. Mortality rate within 1-year post-TAVR was significantly higher in the high CONUT group (43.6% vs. 6.7%, p<0.001). High CONUT score was independently associated with poor prognosis post-TAVR adjusted hazard ratio, 8.20; 95% confidence interval (CI), 3.10–22.6; p<0.001. On integrated discrimination improvement (IDI) analysis, malnutrition status improved CFS for predicting mortality post-TAVR (IDI, 0.15; 95% CI, 0.07–0.23; p<0.001).
Objective malnutrition status was predictive of mortality post-TAVR and provided complementary prognostic information to the CFS. Thus, objective nutritional status may refine the clinical risk stratification of patients who undergo TAVR.
Introduction: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular ...carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. Methods: Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. Results: Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (n = 11 50.0%), palmar-plantar erythrodysesthesia syndrome (n = 5 22.7%), and decreased appetite (n = 3 13.6%). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9–34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9–54.9%) per mRECIST for HCC. Conclusion: Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.
Objectives. To compare feasibility and safety between ultrasound-guided and conventional distal transradial access (dTRA). Background. Distal transradial access, a new technique for coronary ...angiography (CAG) and percutaneous coronary interventions (PCI), is safe and feasible and will become popular worldwide. Ultrasound-guided dTRA has been advocated to reduce failure rate and access-site complications. However, to date, the comparison of feasibility and safety between ultrasound-guided and conventional dTRA has not been reported. Method. Overall, 137 patients (144 procedures) who underwent CAG or PCI using dTRA between September 2018 and February 2019 were investigated. These patients were classified into two groups: C (dTRA with conventional punctures; 76 patients, 79 procedures) and U (dTRA with ultrasound-guided punctures; 61 patients, 65 procedures) groups. Successful procedural rate, procedural outcomes, and complication rate during hospital stays were compared between the two groups. Results. The procedural success rate was significantly higher in the U group than in the C group (97% vs. 87%, P=0.0384). However, the rate of PCI, puncture time, total fluoroscopy time, the volume of contrast medium, the rate of access-site ecchymosis, and incidence of nerve disorder were similar between the two groups. Additionally, radial artery occlusion after the procedure did not occur in this study. Conclusion. The ultrasound-guided dTRA for CAG or PCI was associated with a lower failure rate than conventional dTRA. However, there were no significant differences in puncture time and complication rate between the two procedures.
PDF
