5-year Results Research Articles

Radiofrequency ablation without excision for breast cancer: 5-year results of ipsilateral breast tumor recurrence-free survival in the RAFAELO study (NCCH1409).

578 Background: The RAFAELO study is designed to evaluate the safety and efficacy of breast radiofrequency ablation, enabling women between 20 and 79 years of age with small breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. Methods: The RAFAELO study is a prospective, multi-center, single-arm, confirmatory trial including women between 20 and 79 years of age with unifocal, MRI and ultrasound-visible invasive ductal carcinoma or ductal carcinoma in situ size 1.5 cm or smaller diagnosed by preoperative core-needle biopsy, and classified as any grade, any hormone receptor (HR) status, and any human epidermal growth factor receptor 2 (HER2) status. The primary endpoint was Ipsilateral breast tumor recurrence (IBTR) -free survival at 5 years. e planned sample size was set at 372 considering patients lost to follow-up to achieve the power of 80% with the one-sided alpha of 5%, the expected 5-year IBTR-free survival of 93.7%, and the threshold of 90%. The IBTR-free survival time was estimated using the Kaplan-Meier method. Results: Between August 2013 and November 2017, 372 patients were enrolled in this study. A total of 370 patients received successful radiofrequency ablation per protocol and 353 patients were included for the efficacy analysis. The median age was 55 years (range, 32-78 years). With median follow-up period of 5 years, IBTR was observed in 2 patients among 353 patients. The 5-year IBTR-free survival was 98.6% (90% CI 97.1%-99.3%) and the primary endpoint was met as its lower limit of 90% CI exceeded the threshold (90%). As device-related adverse events during radiofrequency ablation, burns were observed in 4 (1.1%) for Grade 1 and 3 (0.8%) for Grade 2 among 370 patients. No severe device-related adverse events were reported. Conclusions: Breast radiofrequency ablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Breast cancer patients in Japan can now avail themselves of this minimally invasive treatment that’s subsidized by public insurance. Further analysis within this clinical trial or registry is needed to confirm radiofrequency ablation as a viable alternative to surgical excision for breast cancer patients in the point of cosmetic results and patient’s satisfaction. Clinical trial information: jRCTs032180229 .

Implant stability and clinical outcome between implant placement using internal sinus floor elevation with alloplastic bone material grafting and without grafting: A 1-year randomized clinical trial.

To compare implant stability and clinical outcome in implant placement between osteotome sinus floor elevation (OSFE) with biphasic calcium phosphate (BCP) which consisted of 30% of hydroxyapatite (HA) and 70% of beta-tricalcium phosphate (β -TCP) grafting material and OSFE without using bone grafting material. The research questions is whether the BCP provides any benefit in OSFE or not. Thirty patients (30 implants) with a single edentulous area of upper premolar or molar were randomly separated into OSFE with BCP (n = 15) and OSFE without grafting (n = 15). The patients were reevaluated 3, 6, 9, and 12months after implant loading. The clinical assessments (implant stability quotient (ISQ), implant survival-failure rate, and surgical complication) were analyzed. Together with radiographic assessments in 2D (endo-sinus bone gain (ESBG), mean marginal bone change (MMBC)) and 3D (endo-sinus bone gain in CBCT (ESBG-CT)) were evaluated, with a mean follow-up time of at least 12months of functional loading and prosthetic complication. 20 remaining implants (OSFE with BCP, n = 10; OSFE without grafting, n = 10) were analyzed. Mean ISQ was 79.18 3.43 in 1-year follow-up (ISQ; OSFE with BCP = 78.72 3.46, OSFE without grafting = 79.65 3.52). ISQ in both groups increased steadily without significant differences in each follow-up. (p = 0.56). In radiographic evaluation, at 6-, 9-, and 12-month, OSFE without grafting group showed statistically significant lower MMBC (p < 0.05). The 1-year clinical results showed that 2 implants failed in OSFE with BCP, and 1 implant failed in OSFE without grafting. Graft material "BCP" (HA30:TCP70) coupled with OSFE presents no extraordinary benefit in implant stability, clinical and radiographic outcome in 1-year follow-up. Clinically, OSFE with grafting materials provides no additional benefit. TCTR20210517008 (date of registration: May 17, 2021).

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle Closure Glaucoma Without Cataract: 1-Year Results of a Multicenter Study.

The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle closure glaucoma without cataract. To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle closure glaucoma (PACG) eyes without cataract. A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6 and 18mmHg with at least a 20% reduction compared with baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. A total of 61 eyes of 50 advanced PACGs were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8mmHg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P =0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P =0.036) reduced success rate. The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Clinical comparison of silver diamine fluoride (SDF) or silver-modified atraumatic restorative technique (SMART) on hypomineralised permanent molars with initial carious lesions: 3-year results of a prospective, randomised trial

ObjectivesThis study aimed to assess the clinical outcomes of utilizing silver diamine fluoride + potassium iodide (SDF + KI) treatment and Silver-Modified Atraumatic Restorative Technique (SMART/SDF + KI + Glass Ionomer Cement) over a three-year period on hypomineralised permanent molars with initial carious lesions. Methods112 hypomineralised permanent molars with ICDAS 1 or 2 lesions were selected in 48 children. The teeth were randomized into SDF + KI and SMART (SDF + KI + GIC) groups (n = 56 teeth/group) in a split-mouth design. Hypersensitivity and caries development were evaluated in both groups. Schiff Cold Air Sensitivity Scale (SCASS) was used for evaluation of hypersensitivity, and the modified USPHS criteria were utilised for clinical assessments of SMART sealants at 1,6,12,18,24 and 36 months. Fisher's Exact test, Kaplan-Meier Survival Curves, Log-rank test, Mann Whitney U test, and Friedman test was performed for the statistical analysis. ResultsThe caries preventive effect was 100 %, 67.9 % and 65.4 % for SDF + KI-treated teeth; and 100 %, 97.6 % and 94.7 % for SMART(SDF + KI + GIC)-treated teeth at 12, 24 and 36 months, respectively. The mean survival probabilities for caries-preventive effect were significantly lower in SDF + KI-treated teeth (31.01 months) than SMART-treated teeth (35.61 months), (p < 0.001). Twenty-six molars with initial hypersensitivity due to hypomineralization demonstrated a significant reduction at all evaluation periods compared to baseline SCASS scores (p < 0.001). Additionally, there was no significant difference in hypersensitivity scores between the groups during the re-call periods, and none of the teeth exhibited hypersensitivity at the 18-month and beyond evaluations. ConclusionsDuring the three-year assessment, both groups demonstrated effectiveness in reducing sensitivity in hypomineralised molars. However, SMART (SDF + KI + GIC) sealants offered better protection against tooth decay over time, despite experiencing gradual retention loss. Clinical significanceBoth SMART (SDF + KI + GIC) sealants and SDF + KI proved effective in alleviating hypersensitivity in hypomineralised molars for up to three years. SMART (SDF + KI + GIC) sealants showed greater caries-preventive effect compared to SDF + KI. However, continuous long-term monitoring is crucial due to the gradual decline in retention of SMART (SDF + KI + GIC) sealants. ClinicalTrials registration numberNCT03862014.

#2746 Long-term benefits in dRTA patients treated with Sibnayal®, a prolonged-release combination of potassium bicarbonate and citrate: 6-year results

Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare disease, either inherited or acquired, characterized by an hyperchloremic metabolic acidosis leading to negative effects on growth, bone metabolism and kidney function, and hearing impairment. Sibnayal®, an oral twice-daily fixed and prolonged-release combination of potassium bicarbonate and potassium citrate3, is registered in the indication of dRTA, whatever the genetic or acquired form, in patients aged 1 year and older. Both efficacy and good tolerability profile of Sibnayal® versus alkali Standard of Care (SoC) were demonstrated in the short-term in children and adults dRTA patients (B21CS study1). B22CS study2 is the long-term follow-up study with safety profile as main objective and evaluation of the impact on the long-term complications as secondary or exploratory objectives. Method Thirty patients with genetic dRTA, previously enrolled in B21CS study, were followed-up for six years on average in a multicenter open-label extension trial (B22CS) to evaluate long-term impact of Sibnayal® on safety and efficacy on metabolic acidosis control, renal function, bone remodeling and growth. Tubular damages and kidney function were assessed by bicarbonatemia, kalemia, eGFR (CKiDU25 formula), nephrocalcinosis (paired-t-test) and urinary pH (UpH) (symmetry test). Bone remodeling was assessed with spine bone mineral density (BMD) Z-score (paired t-test, McNemar-test) from baseline to end of follow-up (EoF) and bone alkaline phosphatase (bALP) until M48. Growth was assessed by Z-score of height, weight, and body mass index (BMI) (paired t-test). Results Thirty patients (24 children, 6 adults), median age 10.6 (2-21) years, with inherited dRTA were included in B22CS study (mean study duration of 5.8 ± 1.3 years). Only 20% of patients reported at least one treatment related adverse event, mainly of gastro-intestinal type, which resolved without study treatment discontinuation. Bicarbonatemia was maintained stable in the normal range over the study duration (22.0 ± 3.2 mmol/L at baseline and 22.6 ± 2.5 mmol/L at EoF, p = NS). Kalemia was also maintained in the normal range (3.8 ± 0.5 mmol/L at baseline and 3.7 ± 0.4 mmol/L at EoF, p = NS). UpH was maintained between 7 and 8 in 70% of patients and when UpH was superior to 8 there was no impact on ACCP crystals presence (47% of patients at baseline versus 35.3% at EoF, p = NS). Nephrocalcinosis was reported in 89% of patients at baseline and in 93% at EoF (p = NS). Glomerular filtration rate remained stable all over the follow-up, eGFR was 105.2 ± 16.9 mL/min/1.73 m2 at baseline versus 103.9 ± 19.9 mL/min/1.73 m2 at EoF (p = NS). Bone metabolism was improved as spine BMD Z-score significantly increased from baseline (−1.1 ± 1.0) to EoF (−0.8 ± 0.9), p = 0.0053. In addition, 88% of patients had a spine BMD Z-score in the normal range (&amp;gt; -2SD) at EoF versus 71% of patients at baseline (p = NS). bALP Z-score was in normal range at baseline versus M48 (0.9 ± 2.22 at baseline vs 0.7 ± 1.3 at M48, p = NS). Growth was improved as Z-score for height significantly increased from baseline to EoF (p = 0.0323) while both Z-scores for weight and BMI were stable (p = NS). Conclusion These data confirm the long-term good tolerability profile and efficacy of Sibnayal® in the management of metabolic acidosis, in patients with dRTA. Sibnayal® showed a preventive effect on metabolic acidosis long-term complications in this population.

Five-year outcomes of different techniques for minimally invasive mitral valve repair in Barlow's disease.

Barlow's disease is a specific sub-form of mitral valve (MV) disease, characterized by diffuse excessive tissue and multi segment prolapse. The anterolateral mini-thoracotomy represents the standard access for MV regurgitation in many centres. It still remains unclear which surgical technique provides the best results. Therefore, the aim of this study was to compare operative safety and mid-term outcomes after (i) isolated annuloplasty, (ii) use of additional artificial chordae or (iii) leaflet resection in patients suffering from Barlow's disease undergoing minimally invasive MV repair. A consecutive series of patients suffering from Barlow's disease undergoing minimally invasive MV surgery between 2001 and 2020 were analysed (n = 246). Patients were grouped and analysed according to the used surgical technique. The primary outcome was a modified Mitral Valve Academic Research Consortium combined end-point of mortality, reoperation due to repair failure or reoccurrence of severe mitral regurgitation within 5 years. The secondary outcome included operative success and safety up to 30 days. No significant difference was found between the 3 surgical techniques with regard to operative safety (P = 0.774). The primary outcome did not differ between groups (P = 0.244). Operative success was achieved in 93.5% and was lowest in the isolated annuloplasty group (77.1%). Conversion to MV replacement was increased in patients undergoing isolated annuloplasty (P < 0.001). Isolated annuloplasty, use of additional artificial chordae and leaflet resection represent feasible techniques in Barlow patients undergoing minimally invasive MV surgery with comparable 5-year results. In view of the increased conversion rate in the annuloplasty group, the pathology should not be oversimplified.

Percutaneous Coronary Interventions with Sirolimus-Eluting Alex Plus Stents in Patients with or without Diabetes: 4-Year Results.

We characterized the performance, as well as the safety, of a second-generation thin-strut sirolimus-eluting stent with a biodegradable polymer, Alex Plus (Balton, Poland), implanted in patients with type 2 diabetes (DM) with a 4-year follow-up. We defined the primary endpoint as the 48-month rate of major cardiovascular adverse events (MACE), including cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR). The secondary endpoints were all-cause death, cardiac death, MI, and TLR rates at 12, 24, 36, and 48 months. We enrolled 232 patients in whom 282 stents were implanted, including 97 DM and 135 non-DM patients. The mean age of the DM patients was 69.5 ± 10.1 years and females accounted for 30% of the patients. DM patients had higher rates of arterial hypertension (97% vs. 88%, p = 0.016), dyslipidemia (86% vs. 70%, p = 0.005), prior MI (61% vs. 40%, p = 0.002), prior PCI (65% vs. 50%, p = 0.020), and prior CABG (14% vs. 5.9%, p = 0.029). We recorded statistically significant differences for MACE (HR 1.85, 95% CI 1.01-3.41, p = 0.046), cardiac death (HR 4.46, 95% CI 1.44-13.8, p = 0.010), and MI (HR 3.17, 95% CI 1.10-9.12, p = 0.033), but not for TLR, between DM and non-DM patients in terms of the analyzed endpoints at 4 years. Our study showed that Alex Plus was efficient and safe in a contemporary cohort of real-world DM patients undergoing percutaneous revascularization.

Nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma previously treated with sorafenib: 5-year results from CheckMate 040

Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort. Patients were randomized 1 : 1 : 1 to arm A [nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W (four doses)] or arm B [nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W (four doses)], each followed by nivolumab 240 mg Q2W, or arm C (nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W). The primary objectives were safety, tolerability, investigator-assessed objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1. A total of 148 patients were randomized across treatment arms. At 60-month minimum follow-up (62.6-month median follow-up), the ORR was 34% (n= 17), 27% (n= 13), and 29% (n= 14) in arms A, B, and C, respectively. The median DOR was 51.2 months [95% confidence interval (CI) 12.6 months-not estimable (NE)], 15.2 months (95% CI 7.1 months-NE), and 21.7 months (95% CI 4.2 months-NE), respectively. The median overall survival (OS) was 22.2 months (34/50; 95% CI 9.4-54.8 months) in arm A, 12.5 months (38/49; 95% CI 7.6-16.4 months) in arm B, and 12.7 months (40/49; 95% CI 7.4-30.5 months) in arm C; 60-month OS rates were 29%, 19%, and 21%, respectively. In an exploratory analysis of OS by response (6-month landmark), the median OS was meaningfully longer for responders versus nonresponders for all arms. No new safety signals were identified with longer follow-up. There were no new discontinuations due to immune-mediated adverse events since the primary analysis. Consistent with the primary analysis, the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit, with no new safety signals in patients with advanced HCC following sorafenib treatment, further supporting its use as a second-line treatment in these patients.

Intraoral wear of PICN CAD-CAM composite restorations used in severe tooth wear treatment: 5-year results of a prospective clinical study using 3D profilometry

ObjectivesTo evaluate, in a prospective clinical study over 5 years with ex vivo 3D profilometry analyses, the intraoral wear of Polymer-Infiltrated Ceramic Network (PICN) CAD-CAM composite restorations used in severe tooth wear treatment with the One-Step No-Prep technique. Methods192 PICN (Vita Enamic) restorations on molars and premolars were included in a prospective clinical study involving patients treated according to the One-step No-prep protocol (n = 7). All patients showed clinical signs of bruxism. Replicas of restorations on molars and premolars were realized at each evaluation time (baseline and then every year up to 5 years) and scanned to perform 3D profilometry. Baseline and recall scans were superimposed with Geomagic Control software. The mean material wear was calculated for the full occlusal area (FOA) and for the occlusal contact area (OCA), respectively. Clinical evaluation of restorations was performed at recall. ResultsAt 5 years, the estimated mean material wear for FOA was inferior to the accuracy threshold of the profilometry measurement chain. For OCA, the estimated mean wear of the material was – 27.97 µm. This material wear was shown to be significantly influenced by time (p < 0.0001) and patient (p = 0.026), while the type of tooth (molar or premolar) had no influence. At 5 years, the survival and the success rates of restorations were 99.48% and 90.62%, respectively. SignificanceThe PICN material exhibits a low wear process in the treatment of severe tooth wear despite the presence of clinical signs of bruxism, and it constitutes a suitable material for the One-step No-prep technique.

Review of the Development of Meniscus Centralization.

With an aging population, extending healthy life expectancy is a global challenge. Maintaining healthy knee joint function is one of the essential factors to preserve the ability to walk and extend healthy life expectancy. Meniscus centralization was introduced in 2012 as a procedure for meniscus extrusion, one of the causes of knee osteoarthritis (OA). Initially, it was performed only for lateral meniscus (LM) extrusion, and favorable 2-year results were reported in 2016. Gradually, basic studies supporting the effectiveness of meniscus centralization have been reported, and it has also been performed for medial meniscus (MM) extrusion, with some positive results reported. Although the surgical procedures vary among the institutions, the basic concept is to reattach the loosened meniscotibial ligament to the edge of the tibial plateau to re-tension it. This review will discuss the history of development and the current status of meniscus centralization. Current research shows that meniscus centralization is not performed in isolation but is often used as an augmentation along with the conventional repair of meniscus injuries, particularly posterior root tears. Biomechanical studies demonstrated that MM centralization with a posteromedial anchor can better restore meniscus function. Despite its relatively short publication history of just over ten years, meniscus centralization has shown potential as a treatment to curb the progression of knee OA and extend a healthy life. While more evidence is needed, this conclusion underscores the promising role for meniscus centralization, making it a topic of significant interest for knee surgeons and researchers.

Effect of bimekizumab on patient-reported disease impact in patients with psoriatic arthritis: 1-year results from two phase 3 studies.

To evaluate 1-year bimekizumab efficacy in PsA from the patient perspective using the 12-item PsA Impact of Disease (PsAID-12) questionnaire. BE OPTIMAL (NCT03895203; biologic DMARD [bDMARD]-naïve), BE COMPLETE (NCT03896581; inadequate response/intolerance to TNF inhibitors [TNFi-IR]) and BE VITAL (NCT04009499; open-label extension) assessed bimekizumab 160 mg every 4 weeks in patients with PsA. Post hoc analyses of patient-reported disease impact, assessed by the PsAID-12 questionnaire, are reported to 1 year (collected to Week 40 in BE COMPLETE). Overall, 1,112 total patients were included (698 bimekizumab, 414 placebo). Rapid improvements observed with bimekizumab treatment at Week 4 continued to Week 16 and were sustained to 1 year. At 1 year, mean (SE) change from baseline in PsAID-12 total score was comparable between bimekizumab-randomized patients and patients who switched to bimekizumab at Week 16 (bDMARD-naïve bimekizumab -2.3 [0.1], placebo/bimekizumab -2.2 [0.1]; TNFi-IR bimekizumab -2.5 [0.1], placebo/bimekizumab -2.2 [0.2]). Proportions of bimekizumab-randomized patients achieving clinically meaningful within-patient improvement (≥3-point decrease from baseline) at Week 16 were sustained to 1 year (bDMARD-naïve 49.0%; TNFi-IR 48.5%) and were similar for placebo/bimekizumab patients (bDMARD-naïve 44.4%; TNFi-IR 40.6%). Across studies and arms, 35.3% to 47.8% of patients had minimal or no symptom impact at 1 year. Improvements were observed to 1 year across all single-item domains, including pain, fatigue and skin problems. Bimekizumab treatment resulted in rapid and sustained clinically meaningful improvements in disease impact up to 1 year in bDMARD-naïve and TNFi-IR patients with PsA. BE OPTIMAL: NCT03895203; BE COMPLETE: NCT03896581; BE VITAL: NCT04009499 (ClinicalTrials.gov).

Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after ≥1 prior tyrosine kinase inhibitor: 2-year follow-up results

Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1T315I, which is resistant to most approved adenosine triphosphate–competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic activity of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years’ median exposure, 56.3% of patients continued receiving asciminib. Overall, 62.2% of evaluable patients achieved BCR::ABL1 ≤1% on the International Scale (IS); 47.6% and 81.3% of ponatinib-pretreated and -naive patients, respectively, achieved BCR::ABL1IS ≤1%. Of 45 evaluable patients, 48.9% achieved a major molecular response (MMR, BCR::ABL1IS ≤0.1%), including 34.6% and 68.4% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade ≥3 adverse events (AEs) included increased lipase level (18.8%) and thrombocytopenia (14.6%). Five (10.4%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib’s effectiveness, including in almost 50% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.

Real-World 1-Year Results of Tricuspid Edge-to-Edge Repair From the bRIGHT Study

BackgroundSevere tricuspid regurgitation (TR) is known to be associated with poor quality of life and increased risk of death when left untreated. ObjectivesWe sought to report the 1-year clinical outcomes of subjects treated by tricuspid transcatheter edge-to-edge repair (TEER) with the TriClip system (Abbott Cardiovascular) in a contemporary real-world setting. MethodsThe bRIGHT (An Observational Real-World Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip Device) postapproval study is a prospective, single-arm, open-label, multicenter postmarket registry conducted at 26 sites in Europe, with central event adjudication and echocardiographic core-laboratory assessment. ResultsEnrolled subjects (n = 511) were elderly (79 ± 7 years) with significant comorbidities. A total of 88% had baseline massive or torrential TR, and 80% of subjects were in NYHA functional class III/IV. TR was reduced to moderate or less in 81% at 1 year. Significant improvements in NYHA functional class (21% to 75% I/II, P < 0.0001) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (19 ± 26-point improvement, P <0.0001) were observed at 1 year. One-year mortality was significantly lower in subjects who achieved moderate or lower TR at 30 days; however, there was no difference in mortality among subjects who achieved moderate, mild, or trace TR at 30 days. In addition to TR reduction at 30 days, baseline serum creatinine and baseline right ventricular tricuspid annular plane systolic excursion (RV TAPSE) were independently associated with mortality at 1 year (OR: 2.169; 95% CI: 1.494-3.147; P < 0.0001; OR: 0.636; 95% CI: 0.415-0.974; P = 0.0375). Mortality was not associated with baseline TR grade or with center volume. ConclusionsTricuspid TEER using the TriClip system was safe and effective through 1 year for subjects with significant TR and advanced disease in a diverse real-world population. (An Observational Real-world Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip Device [bRIGHT]; NCT04483089)

Percutaneous intramyocardial septal radiofrequency ablation after 5-year follow-up

ObjectiveThe objective is to evaluate the 5-year follow-up results of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for hypertrophic obstructive cardiomyopathy (HOCM), including clinical status, electrocardiographic and echocardiographic characteristics.Methods27 patients (age:...

Beyond VEGF: Angiopoietin-Tie Signaling Pathway in Diabetic Retinopathy.

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

Conformal thyroidectomy is a feasible option in papillary thyroid microcarcinoma: a retrospective cohort study with 10-year follow-up results

BackgroundIn recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor.MethodsThe patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint.ResultsA total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups.ConclusionsConformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.

Sustained improvement in renal function with palopegteriparatide in adults with chronic hypoparathyroidism: 2-year results from the phase 3 PaTHway trial

Sustained improvement in renal function with palopegteriparatide in adults with chronic hypoparathyroidism: 2-year results from the phase 3 PaTHway trial

Is There a Learning Curve for the 5-Year Implant Survival Rate of Total Hip Arthroplasty Using the Direct Anterior Approach With a Traction Table? A Prospective Cohort Study

BackgroundThe direct anterior approach (DAA) for total hip arthroplasty (THA) is attracting attention as a minimally invasive surgery, but the learning curve to master this approach is a concern, and its effect on long-term results is unknown. The purpose of this prospective cohort study was to clarify how the learning curve affects the 5-year results of DAA THA with a traction table. MethodsOf 402 THA cases using DAA with a mobile traction table and fluoroscopy, 249 cases composed of the first 50 cases for each surgeon were assessed during a learning curve, and 153 cases were evaluated after more than 50 cases of experience. ResultsThe 5-year-implant survival rate was 99.2% both during and after the learning curve. The 2-year complication rate in the learning curve group was 8.9 versus 5.9%, which was not statistically significant. The 2-to-5-year complication rates also did not differ between the cohorts (0 versus 0.7%). Both groups demonstrated decreased complication rates when comparing 2-year complications to 2-to-5-year complications. Clinical scores significantly improved by 2 years and were maintained at 5 years in both groups. The cup safe-zone success rates were 96.4% during the learning curve and 98.7% after the learning curve. The stem safe-zone success rates were 97.2% during the learning curve and 96.1% after the learning curve. Surgical time was approximately 20 minutes shorter after the first 50 cases than during the learning curve (70.8 versus 90.6 minutes, P = .001). Intraoperative blood loss was significantly less after the learning curve than during the learning curve. ConclusionsThis study implies that the learning curve affects perioperative results such as surgical time and intraoperative blood loss, but has little effect on short-term results up to 2 years after surgery and no effect on mid-term results from 2 to 5 years after surgery.

Medication use before and after bariatric surgery: 5-year results from a randomised controlled trial of banded Roux-en-Y gastric bypass versus sleeve gastrectomy in patients with obesity and type 2 diabetes.

Bariatric surgery is an effective tool for weight loss and for improving weight related co-morbidities. Changes in medication usage after a silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) are unknown. This was a single-centre, double-blind, randomised controlled trial. Patients were randomised to either SR-LRYGB or LSG. A medication history was obtained at regular follow-up intervals, and mean numbers of prescribed medications were analysed over 5 years. Poisson regression and generalised estimating equations were used to test for statistically significant changes in usage. After eight patients were lost to follow-up, data from 52 patients in each group were available for analysis. There was no difference between the SR-LRYGB or LSG groups in the number of medications prescribed, with the exception of oral glucose-lowering medications, where there was a greater decrease after SR-LRYGB compared to LSG (79% vs 55% respectively) from baseline to 5 years. At 5 years, total medication prescribed was down 10% from pre-operative levels. Prescribed insulin decreased by 72%, and cardiovascular medication decreased by 56% compared to baseline. Prescriptions for analgesia increased by 50%, psychiatric medications by 133% and proton-pump inhibitors by 81%. Both SR-LRYGB and LSG reduced requirement for diabetic and cardiovascular medications, but increased requirement for nutritional supplementation, analgesia and psychiatric medications. There was a greater reduction in oral anti-diabetic medication prescriptions following SR-LRYGB compared to LSG, but no other difference in medication usage between surgical groups was found.

Treatment of chronic-phase chronic myeloid leukemia in patients randomized to dasatinib or imatinib after suboptimal responses to 3 months of imatinib therapy: final 5-year results from DASCERN.

Early molecular response at 3 months is predictive of improved overall survival and progression-free survival in patients with chronic myeloid leukemia in the chronic phase. Although about one-third of patients treated with first-line imatinib do not achieve an early molecular response, long-term overall survival and progression-free survival are still observed in most patients. DASCERN (NCT01593254) is a prospective, phase IIb, randomized trial evaluating a switch to dasatinib in patients who have not achieved an early molecular response after 3 months of treatment with first-line imatinib. Early analysis demonstrated an improved major molecular response (MMR) rate at 12 months with dasatinib versus imatinib (29% vs. 13%, P=0.005). Here, we report results from the final 5-year follow-up. In total, 174 patients were randomized to dasatinib and 86 to remain on imatinib. Forty-six (53%) patients who remained on imatinib but subsequently experienced failure were allowed to cross over to dasatinib per protocol. At a minimum follow-up of 60 months, the cumulative MMR rate was significantly higher in patients randomized to dasatinib than those randomized to imatinib (77% vs. 44%, P<0.001). The median time to MMR was 13.9 months with dasatinib versus 19.7 months with imatinib. The safety profile was consistent with previous reports. These results demonstrate that switching to dasatinib after a suboptimal response to imatinib at 3 months leads to faster MMR, provides earlier deep molecular responses, and improves some outcomes in patients with chronic myeloid leukemia in the chronic phase.