Multicenter Registry of Common Femoral Artery Disease Treated With Endovascular Revascularization Using Interwoven Nitinol Stents: An Observational Retrospective Study.

PURPOSE: Surgical thromboendarterectomy has been the gold standard treatment for common femoral artery (CFA) disease. However, endovascular therapy (EVT) is conducted in certain patients with CFA lesions because of multiple comorbidities. The interwoven nitinol stent (IWS) has been developed to prevent stent fracture. Thus, this study aimed to evaluate the feasibility of EVT using IWS for CFA lesions in clinical practice. MATERIALS AND METHODS: This retrospective multicenter registry analyzed patients who had symptomatic lower-extremity artery disease due to CFA lesions and underwent EVT using IWS between 2019 and 2021. The primary endpoint was restenosis 2 years after EVT. RESULTS: This study enrolled a total of 177 patients with 196 CFA lesions. The 2-year estimate of freedom from restenosis was 88.0%. The 2-year freedom rates from the target-lesion revascularization, major amputation, and all-cause death were 92.9%, 99.0%, and 75.2%, respectively. The clinical features significantly associated with restenosis risk were the reference vessel diameter (RVD, per 1.0 mm, hazard ratio [HR], 0.24 [0.08-0.70]; p=0.009), external iliac artery (EIA) involvement (HR=4.03 [1.56-10.4]; p=0.004), superficial femoral artery (SFA) involvement (HR=3.05 [1.00-9.25]; p=0.049), body mass index (BMI; per 1.0, HR=0.85 [0.73-0.99]; p=0.032), occlusion of deep femoral arteries (DFAs) at baseline (HR=7.89 [2.04-30.5]; p=0.003), and chronic limb-threatening ischemia (CLTI, HR=2.63 [1.02-6.78]; p=0.045). Their significant association was also confirmed by the random survival forest analysis. During a median follow-up of 12.0 months, guiding sheaths were inserted via CFAs implanted IWSs in 73 cases (37.2%), and no patients had cannulation-related complications, such as failed hemostasis, fracture of IWS, and stent occlusion. CONCLUSIONS: Endovascular therapy using IWS in CFA lesions showed acceptable 2-year patency rates at 88.0% and might preserve the arterial access via the ipsilateral CFAs. Small RVD, involving EIA and SFA lesions, emaciation, occluded DFA, and CLTI are associated with poor 2-year patency rates following EVT, thus, IWS implantation in CFA lesions may be an option for patients unsuitable for surgical revascularization. CLINICAL IMPACT: This retrospective multicenter registry enrolled 177 patients with 199 CFA lesions treated with EVT using interwoven nitinol stents, because surgical thromboendarterectomy was difficult due to their multiple comorbidities. The 2-year estimate of freedom from restenosis was acceptable at 88.0%. The 2-year freedom rate from major amputation was also high at 99.0%. Moreover, during a median follow-up of 12.0 months, guiding sheaths were inserted via CFAs implanted IWSs in 73 cases, and no patients had cannulation-related complications such as failed hemostasis, fracture of IWS, and stent occlusion.

Guideline-Directed Medical Therapy for Elderly Patients With Acute Myocardial Infarction Who Undergo Percutaneous Coronary Intervention　- Insights From a Retrospective Observational Study.

BACKGROUND: The efficacy of guideline-directed medical therapy (GDMT) in the elderly remains unclear. This study evaluated the impact of GDMT (aspirin or a P2Y12inhibitor, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, ß-blocker, and statin) at discharge on long-term mortality in elderly patients with acute myocardial infarction (AMI) who had undergone percutaneous coronary intervention (PCI).Methods and Results: Of 2,547 consecutive patients with AMI undergoing PCI in 2009-2020, we retrospectively analyzed 573 patients aged ≥80 years. The median follow-up period was 1,140 days. GDMT was prescribed to 192 (33.5%) patients at discharge. Compared with patients without GDMT, those with GDMT were younger and had higher rates of ST-segment elevation myocardial infarction and left anterior descending artery culprit lesion, higher peak creatine phosphokinase concentration, and lower left ventricular ejection fraction (LVEF). After adjusting for confounders, GDMT was independently associated with a lower cardiovascular death rate (hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.16-0.81), but not with all-cause mortality (HR 0.77; 95% CI 0.50-1.18). In the subgroup analysis, the favorable impact of GDMT on cardiovascular death was significant in patients aged 80-89 years, with LVEF <50%, or with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2. CONCLUSIONS: GDMT in patients with AMI aged ≥80 years undergoing PCI was associated with a lower cardiovascular death rate but not all-cause mortality.

Influence of Endogenous Substances on Site-II to Site-I Displacement of Diclofenac Bound to Albumin in the Aqueous Humor of Patients with Cataract.

Diclofenac instillation is useful in preventing intraoperative miosis and macular edema caused by postoperative inflammation in cataract surgery; however, optimum efficacy is not attained when the instilled diclofenac strongly binds to albumin in patients' aqueous humor. Therefore, a method that inhibits diclofenac binding and increases the concentration of its free fraction is needed. We conducted a basic study regarding the effects of inhibitors on the binding of instilled diclofenac to albumin and endogenous substances in aqueous humor. Aqueous humor samples from 16 patients were pooled together for analysis. The free fraction of diclofenac was measured using ultrafiltration methods in various experiments with pooled and mimic aqueous humor. Free fraction of diclofenac, a site II drug, in pooled aqueous humor was 0.363 ± 0.013. The binding of diclofenac in the presence of phenylbutazone (PB), a site I inhibitor, was significantly inhibited (free fraction = 0.496 ± 0.013); however, no significant inhibition by ibuprofen, a site II inhibitor, (free fraction = 0.379 ± 0.004), was observed. The unexpected result was due to free fatty acids (FFAs; palmitic acid (PA)) and L-tryptophan (Trp). The inhibition of diclofenac binding by PB in the mimic aqueous humor containing these endogenous substances revealed significant binding inhibition in the presence of PA and Trp. Diclofenac is strongly rebound from site II to site I in the presence of FFAs and Trp in the aqueous humor because FFAs and Trp induce a conformational change in albumin. Therefore, PB significantly inhibits the binding of diclofenac to albumin.

Calcium Fracture After Intravascular Lithotripsy as Assessed With Optical Coherence Tomography.

BACKGROUND: Plaque characteristics associated with effective intravascular lithotripsy (IVL) treatment of calcification have not been investigated. This study identified calcified plaque characteristics that favor the use of IVL.Methods and Results: Optical coherence tomography (OCT) was performed in 16 calcified lesions in 16 patients treated with IVL and coronary stenting. Cross-sectional OCT images in 262 segments matched across pre-IVL, post-IVL, and post-stenting time points were analyzed. After IVL, 66 (25%) segments had calcium fracture. In multivariable analysis, calcium arc (odds ratio [OR] 1.22; 95% confidence interval [CI] 1.13-1.32; P<0.0001), superficial calcification (OR 6.98; 95% CI 0.07-55.57; P=0.0182), minimum calcium thickness (OR 0.66; 95% CI 0.51-0.86; P=0.0013), and nodular calcification (OR 0.24; 95% CI 0.08-0.70; P=0.0056) were associated with calcium fracture. After stenting, stent area was larger for segments with fracture (8.0 [6.9-10.6] vs. 7.1 [5.2-8.9] mm2; P=0.004). CONCLUSIONS: Post-IVL calcium fracture is more likely in calcified lesions with lower thickness, a larger calcium arc, superficial calcification, and non-nodular calcification, leading to a larger stent area.

Twelve-month safety and effectiveness of TCD-17187 drug-coated balloon for the treatment of atherosclerotic lesions in the superficial femoral and proximal popliteal artery.

PURPOSE: The aim of this preapproval trial was to evaluate the 12-month safety and effectiveness of the TCD-17187 drug-coated balloon (DCB) for the treatment of atherosclerotic lesions in the superficial femoral artery (SFA) and/or proximal popliteal artery (PA). METHODS: This was a prospective, multicenter, core laboratory adjudicated, single-arm trial. From October 2019 to November 2020, a total of 121 symptomatic peripheral artery disease patients with SFA and/or proximal PA lesions were enrolled. The primary effectiveness endpoint was 12-month primary patency defined as freedom from restenosis as determined by duplex ultrasonography in the absence of clinically driven target lesion revascularization (CD-TLR). The safety endpoint was the major adverse event (MAE) rate defined as freedom from a composite of device- and procedure-related death within 30 days, and index limb major amputation and/or CD-TLR through follow-up. RESULTS: Average age was 74.5 ± 7.3 years and the frequency of diabetes mellitus was 67.5%. Average lesion length and vessel diameter were 106.0 ± 52.6 and 5.2 ± 0.8 mm, respectively. The frequency of chronic total occlusion and bilateral calcification was 17.5% and 50.8% of patients, respectively. The 12-month primary patency rate calculated by Kaplan-Meier analysis was 81.1%, while 12-month freedom from CD-TLR was 95.8%. The MAE rate at 30 days was 1.7% and all events comprised CD-TLR. There were no instances of device- or procedure-related deaths, major amputations, or thrombosis throughout the 12-month evaluation period. CONCLUSION: This preapproval trial confirmed the safety and effectiveness of TCD-17187 DCB in the treatment of atherosclerotic lesions in the SFA and/or proximal PA.

Severity of constipation related to palonosetron during first-line chemotherapy: a retrospective observational study.

PURPOSE: Palonosetron, a long-acting 5-HT3 receptor antagonist, is an effective antiemetic agent for chemotherapy-induced nausea and vomiting; however, it sometimes causes severe constipation. The aim of the present study was to evaluate the severity of palonosetron-related constipation. METHODS: We retrospectively analyzed the incidence and severity of constipation after intravenous administration of 0.75-mg palonosetron in 150 chemotherapy-naïve patients who received first-line chemotherapy at Saga University Hospital. Constipation was classified into grades 1-5 according to the Common Terminology Criteria for Adverse Events version 5.0. Multiple logistic regression analysis was performed to identify factors associated with palonosetron-related worsening of constipation to grade 2 or higher. RESULTS: Palonosetron significantly increased the incidence and severity of constipation (incidence: before vs. after palonosetron, 35.4% vs. 74.0%, p < 0.0001, and severity: before vs. after palonosetron, 26.7% and 8.7% in grades 1 and 2, respectively, vs. 46.7%, 23.3%, and 4.0% in grades 1, 2, and 3, respectively, p < 0.0001). Despite the use of laxatives, 4.0% of patients had grade 3 constipation requiring manual evacuation. Combination treatment with aprepitant (odds ratio (OR), 10.9; 95% confidence interval (CI), 1.3-90.0; p = 0.026) and older age (OR, 1.25; 95% CI, 1.01-1.57; p = 0.039) were factors associated with the severity of constipation. CONCLUSION: Constipation was more severe in patients receiving combination treatment with aprepitant than in those treated with palonosetron alone. Older age was also associated with increased risk of severe palonosetron-related constipation. Identification of risk factors can help target risk-based laxative therapy.

Impact of green tea intake on the pharmacokinetics of celiprolol in healthy subjects.

OBJECTIVE: To assess the effect of green tea intake on the pharmacokinetics of the ß-blocker celiprolol. MATERIALS AND METHOD: In an open-label crossover study, 3 healthy subjects were given water or a green tea beverage daily for 3 days. On day 4, each subject received a single oral dose of 200 mg celiprolol with water or green tea. Serum and urinary concentrations of celiprolol were measured for up to 24 hours. RESULTS: Green tea intake decreased the area under the serum concentration-time curve and urinary excretion of celiprolol by 98.6 and 98.0%, respectively. CONCLUSION: Green tea intake might have a negative impact on the clinical effectiveness of celiprolol.

[Selection of Operative Procedure for Breast Cancer in Carriers of BRCA VUS in Japan].

Risk classification and clinical management of the DNA variant of unknown significance(VUS)in BRCA 1/2 remains unestablished. The Japanese hereditary breast and ovarian cancer(HBOC)consortium and myriad genetics reported that the VUS rate of BRCA is 6.5% in Japanese patients, but is <2% in the USA. The types of mutation supposedly differ between Asian and European ethnicities. Breast-conserving therapy(BCT)is not recommended in HBOC breast cancer, according to the 2017 Japanese guidelines by the Ministry of Health, because of the risk of ipsilateral breast recurrence(IBR)and carcinogenesis by radiation. In our hospital, we recommend an initial mastectomy and breast reconstruction with an implant for patients with HBOC breast cancer, considering future surgery on the contralateral side and symmetry of the reconstructed breast. However, the risk of IBR after BCT is not significantly high in patients with HBOC breast cancer, and BCT is a reasonable option even for definite HBOC breast cancer under low risk conditions. Hence, BCT is feasible for treating breast cancer in carriers of VUS following decision-making and informed consent from the patients.

Development of a sandwich enzyme-linked immunosorbent assay for the quantification of ponatinib in serum.

The tyrosine kinase inhibitor ponatinib is extensively metabolized in the body, and consequently the development of specific immunoassays for pharmacokinetic studies and therapeutic drug monitoring of ponatinib is challenging. If two antibodies simultaneously recognize the entire structure of ponatinib, they could be utilized to establish an ultra-specific sandwich immunoassay for ponatinib, free of any interference from ponatinib metabolites. In this study, we created two types of anti-ponatinib polyclonal antibodies that recognize two different ponatinib epitopes, and sandwiched almost all structural components of ponatinib in these two antibodies in order to develop an enzyme-linked immunosorbent assay (ELISA) technique not affected by any ponatinib metabolites. After optimization, this sandwich ELISA showed a linear detection range of 640 pg/mL to 2000 ng/mL and a limit of quantification of 640 pg/mL. This sandwich ELISA was specific to ponatinib and showed no cross-reactivity with the major metabolite M14. Comparison between the sandwich ELISA and HPLC, using serum samples from 15 rats orally administered a single dose of 15 mg/kg ponatinib, showed a linear regression (y = 0.9662x + 3.5354, r = 0.9683). Thus, in this study, we successfully developed the first ultra-specific sandwich ELISA for ponatinib in serum.

Establishment of a new initial dose plan for vancomycin using the generalized linear mixed model.

BACKGROUND: When administering vancomycin hydrochloride (VCM), the initial dose is adjusted to ensure that the steady-state trough value (Css-trough) remains within the effective concentration range. However, the Css-trough (population mean method predicted value [PMMPV]) calculated using the population mean method (PMM) often deviate from the effective concentration range. In this study, we used the generalized linear mixed model (GLMM) for initial dose planning to create a model that accurately predicts Css-trough, and subsequently assessed its prediction accuracy. METHODS: The study included 46 subjects whose trough values were measured after receiving VCM. We calculated the Css-trough (Bayesian estimate predicted value [BEPV]) from the Bayesian estimates of trough values. Using the patients' medical data, we created models that predict the BEPV and selected the model with minimum information criterion (GLMM best model). We then calculated the Css-trough (GLMMPV) from the GLMM best model and compared the BEPV correlation with GLMMPV and with PMMPV. RESULTS: The GLMM best model was {[0.977 + (males: 0.029 or females: -0.081)] × PMMPV + 0.101 × BUN/adjusted SCr - 12.899 × SCr adjusted amount}. The coefficients of determination for BEPV/GLMMPV and BEPV/PMMPV were 0.623 and 0.513, respectively. CONCLUSION: We demonstrated that the GLMM best model was more accurate in predicting the Css-trough than the PMM.

Predictors of Recurrent In-Stent Restenosis After Paclitaxel-Coated Balloon Angioplasty.

BACKGROUND: Although paclitaxel-coated balloon (PCB) angioplasty is an effective procedure for in-stent restenosis (ISR) after coronary stenting, recurrent ISR after PCB angioplasty still occurs. The aim of this study was to evaluate the predictors of recurrent ISR after PCB angioplasty for ISR.Methods and Results:A total of 157 ISR lesions treated with PCB angioplasty from January 2014 to May 2015 were retrospectively examined. Recurrent ISR was judged on 6-month follow-up angiography. Clinical, angiographic and procedural parameters were evaluated as possible predictors of recurrent ISR. Recurrent ISR occurred in 13.9% of lesions after PCB angioplasty. On multivariate analysis the following independent predictors of recurrent ISR were identified: (1) smaller acute gain after initial ballooning (OR, 3.06; 95% CI: 1.08-8.71; P=0.04); (2) geographic mismatch between PCB position and initial ballooning (OR, 5.59; 95% CI: 1.64-19.1; P=0.006); and (3) use of percutaneous transluminal coronary rotational atherectomy (PTCRA) at primary percutaneous coronary intervention (PCI; OR, 5.53; 95% CI: 1.89-16.2; P=0.002). CONCLUSIONS: Optimal expansion at initial ballooning before PCB angioplasty and careful positioning of PCB are important technical tips to prevent recurrent ISR after PCB angioplasty. Recurrent ISR occurred more frequently in severely calcified lesions that required PTCRA at primary PCI.

Clinical Implications of Additional Pedal Artery Angioplasty in Critical Limb Ischemia Patients With Infrapopliteal and Pedal Artery Disease.

PURPOSE: To evaluate the clinical implications of additional pedal artery angioplasty (PAA) for patients with critical limb ischemia (CLI). METHODS: Twenty-nine patients (mean age 77.8±8.6 years; 21 men) with CLI (32 limbs) presenting with de novo infrapopliteal and pedal artery (Kawarada type 2/3) disease were reviewed. The need for PAA was based on the existence of sufficient wound blush (WB) around the target wounds after conventional above-the-ankle revascularization. Fourteen patients with insufficient WB in 14 limbs received additional PAA, while 15 patients with sufficient WB in 18 limbs did not. The groups were compared for overall survival, limb salvage, and amputation-free survival within 1 year after the procedure. The wound healing rate, time to wound healing, and freedom from reintervention rate were also evaluated. RESULT: The success rate of additional PAA was 93% (13/14). All limbs with successful PAA achieved sufficient WB (13/13). Despite insufficient WB before the additional PAA, overall survival (86% vs 73%, p=0.350), limb salvage (93% vs 83%, p=0.400), amputation-free survival (79% vs 53%, p=0.102), and freedom from reintervention (64% vs 73%, p=0.668) rates were similar in both groups. Furthermore, the wound healing rate (93% vs 60%, p=0.05) was higher and time to wound healing (86.0±18.7 vs 152.0±60.2 days, p=0.05) was shorter in the patients who received PAA. CONCLUSION: Additional PAA might improve the WB and clinical outcomes (especially speed and extent of wound healing) in patients with CLI attributed to infrapopliteal and pedal artery disease.

Albumin-binding of diclofenac and the effect of a site II inhibitor in the aqueous humor of cataract patients with the instillation of diclofenac.

Diclofenac instillation has been used widely in cataract surgery to prevent postoperative inflammation. Since diclofenac binds strongly to albumin in the circulation, it does not have a sufficient effect on patients in whom diclofenac binds strongly to albumin in the aqueous humor. A decrease in diclofenac binding and an increase in free diclofenac levels are necessary in these patients. The binding of diclofenac to albumin was investigated in the aqueous humor. In a diclofenac binding assay with albumin in the aqueous humor of individual patients, diclofenac was extracted from aliquots of the aqueous humor, and its total levels were measured using ultra high performance liquid chromatography (UHPLC). Free diclofenac levels were measured using ultrafiltration and UHPLC. The albumin-binding fraction of diclofenac was 0.8 or higher in the aqueous humor of some patients. Ibuprofen significantly inhibited diclofenac binding to site II of albumin in mimic aqueous humor, but not in pooled aqueous humor. This difference may have been due to the weak binding of diclofenac to site II in the pooled aqueous humor. Flurbiprofen was used instead of diclofenac. Flurbiprofen has been shown to bind more strongly than diclofenac to the same site of albumin. Thus, the inhibitory effect of ibuprofen on the binding of flurbiprofen to albumin was investigated in pooled aqueous humor. The results indicated that ibuprofen significantly inhibited the flurbiprofen binding. An effective diclofenac administration method may be established for clinical application by the instillation of an appropriate inhibitor of binding to the albumin site II.

Impact of Periprocedural Myocardial Injury on Long-Term Outcomes After Percutaneous Coronary Intervention Requiring Atherectomy.

The prognostic implications of cardiac troponin elevation after percutaneous coronary intervention (PCI) with atherectomy have not been established. The aim of this study was to investigate the incidence of periprocedural myocardial injury (PMI) and its association with cardiovascular events in patients with severely calcified lesions who underwent PCI with atherectomy. The study analyzed 346 patients (377 lesions) who underwent PCI with atherectomy between January 2018 and December 2021. Peak post-PCI high-sensitivity cardiac troponin (hs-cTn) was measured. The primary outcome was target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction, and clinically driven target lesion revascularization. A lesion-based analysis was conducted to assess the association of PMI with TLF up to 5 years after PCI. Increase of hs-cTn was seen with 362 lesions (96%), and significant PMI, defined as hs-cTn increase ≥70 × upper reference limit, was seen with 83 lesions (22%). Significant PMI was associated with a significantly greater risk of TLF (adjusted hazard ratio 1.93, 95% confidence interval 1.12 to 3.30, p = 0.017), primarily driven by an increased risk of cardiovascular death (adjusted hazard ratio 5.29, 95% confidence interval 1.46 to 19.16, p = 0.011). In conclusion, hs-cTn increase was frequently observed in patients who underwent PCI with atherectomy, and significant PMI was associated with an increased risk of TLF and cardiovascular death.

Association Between Antidiabetic Drugs and Delirium: A Study Based on the Adverse Drug Event Reporting Database in Japan.

BACKGROUND AND OBJECTIVE: Several associations between diabetes mellitus and delirium have been reported; however, they have been inconsistent, and evidence on the effects of antidiabetic medications on delirium is also limited. This study aimed to investigate whether the use of antidiabetic drugs is a risk factor for delirium development. METHODS: Using the Japanese Adverse Event Reporting Database, we analyzed 662,899 reports between 2004 and 2022. Reporting odds ratios (RORs) and 95% confidence intervals (CIs) for delirium associated with diabetes and using each antidiabetic medication were calculated after adjusting for potential confounders. RESULTS: Overall, 8892 of the reports analyzed were associated with delirium. A comparison of the incidence of delirium between patients with and without diabetes showed no significant difference, with 1.34% in patients without diabetes and 1.37% in those with diabetes. In each antidiabetic medication, signals for delirium were detected for sulfonylurea (crude ROR, 1.35; 95% CI 1.21-1.51) and insulin (crude ROR, 1.28; 95% CI 1.13-1.44). These results were maintained even after adjusting for factors with potential confounders (sulfonylurea: adjusted ROR, 1.75; 95% CI 1.54-2.00, insulin: adjusted ROR, 1.35; 95% CI 1.20-1.54). CONCLUSIONS: Our results suggest no association between diabetes and delirium; however, using sulfonylurea and insulin may be associated with delirium development. Nonetheless, these findings should be validated in future studies.

Twenty-Four-Month Safety and Effectiveness of TCD-17187 Drug-Coated Balloon for Treatment of Atherosclerotic Lesions in Superficial Femoral and Proximal Popliteal Artery.

PURPOSE: In the present trial, the 24-month safety and effectiveness of the TCD-17187 drug-coated balloon (DCB) for the treatment of atherosclerotic lesions in the superficial femoral artery (SFA) and proximal popliteal artery (PA) were evaluated in Japanese patients. METHODS: This was a prospective, multicenter, core laboratory-adjudicated, single-arm trial. From 2019 to 2020, 121 patients with symptomatic peripheral artery disease were enrolled. The primary effectiveness outcome measure was primary patency. The safety outcome measure was the major adverse event (MAE) rate. RESULTS: Age was 74.5 ± 7.3 years, and diabetes mellitus was present in 67.5%. Lesion length and reference vessel diameter (RVD) were 106.0 ± 52.6 mm and 5.2 ± 0.8 mm, respectively. Chronic total occlusion (CTO) and bilateral calcification rate (Grade 3 and 4 by peripheral arterial calcium scoring system (PACSS)) were 17.5% and 50.8%, respectively. The 24-month primary patency rate by duplex ultrasound was 71.3%, while freedom from clinically driven target lesion revascularization (CD-TLR) was 87.0%. The MAE rate was 13.2% and all events consisted of CD-TLR. There were no instances of device- or procedure-related deaths major amputations throughout the 24 months. Multivariate Cox proportional hazards regression analysis revealed significant differences associated with loss of primary patency in the following characteristics: CTO, restenotic lesion and RVD. CONCLUSION: This trial confirmed the safety and effectiveness of TCD-17187 DCB for atherosclerotic lesions of the SFA and/or proximal PA for up to 24 months. LEVEL OF EVIDENCE: Level 3, Cohort study. CLINICAL TRIAL REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000038612&type=summary&language=J:Registration ID: UMIN000034122. Registration Date: September 13, 2018.

A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis.

Diclofenac suppository, a non-steroidal anti-inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6-methoxy-2-naphthylacetic acid (6-MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6-MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository-nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain.

Two-year results of endovascular therapy for femoropopliteal artery disease in Japan during the introduction of drug-eluting devices.

Although various devices and strategies were introduced into endovascular therapy, factors associated with chronic outcomes remain unclear. Therefore, this study aimed to build preliminary data of Japanese femoropopliteal lesions in a period of transition from non-drug to drug technology. This research was a multicenter, prospective, and observational study. A total of 1003 consecutive patients with a mean age of 73.6 ± 8.3 years from 67 institutes were registered from February 2017 to June 2018 in Japan. In addition to the baseline data, angiographic findings affecting primary patency were studied. Lesion length was 16.4 ± 9.6 cm, and chronic total occlusion was found in 42%. Calcified lesions were found in 75% of patients. The 1-year and 2-year freedom from target lesion revascularization were 81% and 75%, respectively, and maximum walking distance showed improvement over the two years (pre; 234 m ± 211 m, 1-year; 402 m ± 241 m, 2-year; 428 m ± 231 m). The independent predictors for primary patency were pre-procedure ankle-brachial index, history of minor amputation, ostium lesion, and drug-coated balloon use. Angiographic analysis revealed that only lesion length and full cover stent were related to primary patency. Two-year freedom from target vessel revascularization was 75% in the Japanese transitional period of drug-eluting devices. Maximum walking distance was improved and well maintained for up to 2-year.

Application of first-generation high- and low-dose drug-coated balloons to the femoropopliteal artery disease: a sub-analysis of the POPCORN registry.

BACKGROUND: Drug-coated balloons (DCBs) have significantly changed endovascular therapy (EVT) for femoropopliteal artery (FPA) disease, in terms of the expansion of indications for EVT for symptomatic lower extremity arterial disease (LEAD). However, whether there is a difference in the performance among individual DCBs has not yet been fully discussed. The present sub-analysis of real-world data from a prospective trial of first-generation DCBs compared the clinical outcomes between high- and low-dose DCBs using propensity score matching methods. The primary endpoint was the restenosis-free and revascularization-free rates at 1 year. RESULTS: We compared 592 pairs matched for patient and lesion characteristics using propensity score matching among a total of 2,507 cases with first-generation DCBs (592 and 1,808 cases in the Lutonix low-dose and In.PACT Admiral high-dose DCB groups, respectively). There were no differences in patient/lesion characteristics, procedural success rates, or complications between the two groups. First-generation low-dose DCB had significantly lower patency (73.3% [95% confidence interval, 69.6%-77.3%] in the low-dose DCB group versus 86.2% [84.1%-88.3%] in the high-dose DCB group; P < 0.001) and revascularization-free (84.9% [81.9%-88.1%] versus 92.5% [90.8%-94.1%]; P < 0.001) rates. Chronic kidney disease on dialysis, cilostazol use, anticoagulant use, and severe calcification had a significant interaction effect in the association (all P < 0.05). CONCLUSIONS: EVT to FPA with first-generation DCBs had inferior low-dose patency outcomes as compared with high-dose outcomes in the present cohort. LEVEL OF EVIDENCE: Sub analysis of a prospective multicenter study.

Twelve-Month Clinical Outcomes of Percutaneous Deep Venous Arterialization with Alternative Techniques and Ordinary Endovascular Therapy Devices for Patients with Chronic Limb-Threatening Ischemia: Results of the DEPARTURE Japan Study.

PURPOSE: A dedicated treatment strategy is not yet established for patients with no-option chronic limb-threatening ischemia. This study aimed to evaluate the clinical outcomes of percutaneous deep venous arterialization in Japanese patients with no-option chronic limb-threatening ischemia. MATERIALS AND METHODS: Data of 18 consecutive patients with chronic limb-threatening ischemia (18 limbs; mean age: 75.5 ± 8.5 years; 14 men) who underwent percutaneous deep venous arterialization between January 2016 and November 2020 were retrospectively reviewed. The limb salvage, amputation-free survival, and wound healing rates were evaluated using the Kaplan-Meier method. RESULTS: Among 18 patients, 14 (77.8%) had diabetes, 6 (33.3%) had a non-ambulatory status, 16 (88.9%) received hemodialysis, and 15 (83.3%) had wound, ischemia, and foot infection of clinical stage 4. Rutherford 5 was observed in 33.7% of the patients and Rutherford 6 in 66.7%. The technical success rate of percutaneous deep venous arterialization was 88.9%. Four patients required major amputation within 30 days; percutaneous deep venous arterialization failed in two of these patients. At 6 and 12 months, the limb salvage rates, amputation-free survival rates, and complete wound healing rates were 72.2 and 72.2%, 55.6 and 49.4%, and 23.0 and 53.2%, respectively. The median time to complete wound healing was 234 (interquartile range, 127-306) days. CONCLUSION: This study presented the clinical outcomes of patients with chronic limb-threatening ischemia who underwent percutaneous deep venous arterialization in Japan. Acceptable, safe, and efficacious results were reported. Before major amputation, percutaneous deep venous arterialization can be considered for patients with no-option chronic limb-threatening ischemia. LEVEL OF EVIDENCE: Level 3. Non-randomized, follow-up study.