Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1–2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial

Background: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1–2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). Conclusions: The 3-year survival and relapse rates of T1–2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND

Does the cool-down content affect cortisol and testosterone production after a whole-body workout? A pilot study

Purpose: The Tactical Fitness (TACFIT®) workout has been created merging the characteristics of both high-intensity interval training and functional training, added with compensatory cool-down exercises to speed-up recovery. Aims of our research were to study the effects of two different cool-down strategies, on cortisol and testosterone responses, together with ratings of perceived exertion (RPE), to verify if they have an important role in the modulation of the endocrine responses. Methods: Nine healthy trained men (34.22 ± 7.42 years) performed the same workout, with (TACFIT®+ Asanas protocol) and without (TACFIT®protocol) Asanas postures, in different days. Saliva was collected immediately before (T0) and after (T1) each workout, one hour later its end (T2), at 11:00 p.m. (T3), at 7:00 a.m. (T4) of the following day, and during a non-training day. Before and after each workout the RPE was recorded. Results: Workouts elicited a different cortisol and testosterone production, respect to non-training day. TACFIT®+ Asanas protocol elicited lower salivary cortisol level (p = 0.002) and cortisol to testosterone ratio (p = 0.001) and higher salivary testosterone level (p = 0.01) at T2. Cortisol to testosterone ratio has been shown lower also at T3 (p = 0.02) and T4 (p = 0.04) respect to TACFIT®protocol. TACFIT®+ Asanas protocol elicited a lower RPE at T1 (p = 0.01). Conclusions: TACFIT®workouts can significantly modify salivary cortisol, testosterone, and their ratio, for several hours. The insertion of the Asanas at the end of a TACFIT®workout seems to determine lower salivary cortisol and cortisol to testosterone ratio, and higher testosterone respect to a traditional TACFIT®workout

Time to therapy delivery and effectiveness of the subcutaneous implantable cardioverter-defibrillator

Background: At the time of subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation, successful termination of ventricular fibrillation (VF) is confirmed. A previous study reported cases of prolonged time to therapy during defibrillation testing. Objectives: We sought to evaluate the time to therapy, identify possible predictors of delay, and investigate the impact of delayed therapy on VF conversion. Methods: We analyzed consecutive patients with S-ICDs who underwent initial conversion testing at a shock energy of 65 J in 53 Italian centers. Results: We analyzed 570 patients (467 [82%] male; mean age 48 \ub1 15 years; mean body mass index 25 \ub1 6 kg/m2; mean ejection fraction 47% \ub1 17%). General anesthesia was used in 165 (29%) of patients, with sub- or intermuscular positioning of the generator in (422; 74%). Cardioversion was successful at 65 J in 557 (97.7%) of patients. In 12 patients (2.1%) the shock did not convert VF, and in 1 patient the shock was not delivered because of noise from entrapped subcutaneous air. All failures were successfully managed by reprogramming or repositioning the device. The mean time to therapy was 15 \ub1 3 seconds, and it exceeded 18 seconds in 51 patients (9%). Independent predictors of delayed therapy (18 seconds) were ejection fraction (odds ratio [OR] 0.98; 95% confidence interval [CI] 0.96\u20130.99; P =.016) and a 2 7 gain programmed (OR 3.66; 95% CI 1.44\u20139.30; P =.006). Effectiveness at 65 J was not associated with time to therapy (OR 1.13; 95% CI 0.97\u20131.32; P =.122). Conclusion: In this analysis of a large population of patients with S-ICDs, delayed therapy during defibrillation testing occurred less frequently than previously reported and had no effect on VF conversion success. Delayed therapies seemed more common when a vector with a 2 7 gain was programmed

Implantable defibrillator-detected heart failure status predicts atrial fibrillation occurrence

Background: In heart failure (HF) patients, atrial fibrillation (AF) is associated with a worse prognosis. Implantable cardioverter-defibrillator (ICD) diagnostics allow continuous monitoring of AF and are equipped with algorithms for HF monitoring. Objective: We evaluated the association between the values of the multisensor HF HeartLogic index and the incidence of AF, and assessed the performance of the index in detecting follow-up periods of significantly increased AF risk. Methods: The HeartLogic feature was activated in 568 ICD patients. Median follow-up was 25 months [25th–75th percentile (15–35)]. The HeartLogic algorithm calculates a daily HF index and identifies periods of IN-alert state on the basis of a configurable threshold. The endpoints were daily AF burden ≥5 minutes, ≥6 hours, and ≥23 hours. Results: The HeartLogic index crossed the threshold value 1200 times. AF burden ≥5 minutes/day was documented in 183 patients (32%), ≥6 hours/day in 118 patients (21%), and ≥23 hours/day in 89 patients (16%). The weekly time of IN-alert state was independently associated with AF burden ≥5 minutes/day (hazard ratio [HR] 1.95; 95% confidence interval [CI] 1.22–3.13; P = .005), ≥6 hours/day (HR 2.66; 95% CI 1.60–4.44; P <.001), and ≥23 hours/day (HR 3.32; 95% CI 1.83–6.02; P <.001), after correction for baseline confounders. Comparison of the episode rates in the IN-alert state with those in the OUT-of-alert state yielded HR ranging from 1.57 to 3.11 for AF burden from ≥5 minutes to ≥23 hours. Conclusions: The HeartLogic alert state was independently associated with AF occurrence. The intervals of time defined by the algorithm as periods of increased risk of HF allow risk stratification of AF according to various thresholds of daily burden

Predicting all-cause mortality by means of a multisensor implantable defibrillator algorithm for heart failure monitoring

Background: The HeartLogic algorithm (Boston Scientific) has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation. Objective: The purpose of this study was to determine whether remotely monitored data from this algorithm could be used to identify patients at high risk for mortality. Methods: The algorithm combines implantable cardioverter-defibrillator (ICD)–measured accelerometer-based heart sounds, intrathoracic impedance, respiration rate, ratio of respiration rate to tidal volume, night heart rate, and patient activity into a single index. An alert is issued when the index crosses a programmable threshold. The feature was activated in 568 ICD patients from 26 centers. Results: During median follow-up of 26 months [25th–75th percentile 16–37], 1200 alerts were recorded in 370 patients (65%). Overall, the time IN-alert state was 13% of the total observation period (151/1159 years) and 20% of the follow-up period of the 370 patients with alerts. During follow-up, 55 patients died (46 in the group with alerts). The rate of death was 0.25 per patient-year (95% confidence interval [CI] 0.17–0.34) IN-alert state and 0.02 per patient-year (95% CI 0.01–0.03) OUT of the alert state, with an incidence rate ratio of 13.72 (95% CI 7.62–25.60; P <.001). After multivariate correction for baseline confounders (age, ischemic cardiomyopathy, kidney disease, atrial fibrillation), the IN-alert state remained significantly associated with the occurrence of death (hazard ratio 9.18; 95% CI 5.27–15.99; P <.001). Conclusion: The HeartLogic algorithm provides an index that can be used to identify patients at higher risk for all-cause mortality. The index state identifies periods of significantly increased risk of death

Design and rationale of the Impact of MultiPoint pacing in CRT patients with reduced RV-to-LV delay (IMAGE-CRT) study

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration. A biventricular device is implanted to achieve faster activation and more synchronous contraction of the ventricles. Despite the convincing effect of CRT, 30-40% of patients do not respond. We decided to investigate the role of multipoint pacing (MPP) in a selected group of patients with right ventricle (RV)-to-left ventricle (LV) intervals less than 80 ms that do not respond to traditional CRT. METHODS: We will enrol 248 patients in this patient-blinded, observational, clinical study aiming to investigate if MPP could decrease LV end-systolic volume (ESV) in patients with RV-to-LV interval less than 80 ms. MPP will be activated ON at implant in patients with RV-to-LV delay less than 80 ms and OFF in RV-to-LV at least 80 ms. At follow-up the activation of MPP will be related to CRT response. The primary study endpoint will be the responder rate at 6 months, defined as a decrease in LV ejection fraction, LV end-diastolic volume, LV end-systolic volume (LVESV) at least 15% from baseline. Secondary outcomes include 12 months relative percentage reduction in LVESV and a combined clinical outcome measure of response to CRT defined as the patient being alive, no hospitalization due to heart failure, and experiencing an improvement in New York Heart Association functional class (Composite-Score). CONCLUSION: Reducing the nonresponder rate continues to be an important goal for CRT.If an increase in reverse remodelling can be achieved by MPP, this study supports the conduct of larger trials investigating the role of MPP on clinical outcomes in selected patients treated, right now, only with traditional CRT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02713308. Registered on 18 March 2016