Sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer patients undergoing mastectomy with one to two metastatic sentinel lymph nodes: sub-analysis of the SINODAR-ONE multicentre randomized clinical trial and reopening of enrolment

Background: The initial results of the SINODAR-ONE randomized clinical trial reported that patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with breast-conserving surgery, sentinel lymph node biopsy only, and adjuvant therapy did not present worse 3-year survival, regional recurrence, or distant recurrence rates compared with those treated with axillary lymph node dissection. To extend the recommendation of axillary lymph node dissection omission even in patients treated with mastectomy, a sub-analysis of the SINODAR-ONE trial is presented here. Methods: Patients with T1-2 breast cancer and no more than two metastatic sentinel lymph nodes undergoing mastectomy were analysed. After sentinel lymph node biopsy, patients were randomly assigned to receive either axillary lymph node dissection followed by adjuvant treatment (standard arm) or adjuvant treatment alone (experimental arm). The primary endpoint was overall survival. The secondary endpoint was recurrence-free survival. Results: A total of 218 patients were treated with mastectomy; 111 were randomly assigned to the axillary lymph node dissection group and 107 to the sentinel lymph node biopsy-only group. At a median follow-up of 33.0 months, there were three deaths (two deaths in the axillary lymph node dissection group and one death in the sentinel lymph node biopsy-only group). There were five recurrences in each treatment arm. No axillary lymph node recurrence was observed. The 5-year overall survival rates were 97.8 and 98.7 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy-only treatment arm, respectively (P = 0.597). The 5-year recurrence-free survival rates were 95.7 and 94.1 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy treatment arm, respectively (P = 0.821). Conclusion: In patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with mastectomy, the overall survival and recurrence-free survival rates of patients treated with sentinel lymph node biopsy only were not inferior to those treated with axillary lymph node dissection. To strengthen the conclusion of the trial, the enrolment of patients treated with mastectomy was reopened as a single-arm experimental study

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

Effects of defibrillation shock in patients implanted with a subcutaneous defibrillator: a biomarker study

Aims Implantable cardioverter defibrillator (ICD) shocks are associated with a subsequent increased risk of death, and an elevation of cardiac enzymes has been measured after defibrillation testing (DFT). In an experimental swine study, subcutaneous ICD (S-ICD) shocks caused less myocardial damage than traditional ICD shocks. The aim of our study was to investigate the association between S-ICD shock and acute cardiac damage in humans, as evaluated by means of sensitive and highly specific circulating biomarkers.Methods and results We calculated the variation in the serum levels of high-sensitivity cardiac troponin I (hs-CTnI) and creatine kinase- and results MB mass concentration (CK-MB mass), measured before and after an S-ICD shock delivered during intraoperative DFT. We also measured the degree of haemodynamic stress, as the variation in the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and copeptin (CP), after the S-ICD shock. We analysed 30 consecutive patients who received an S-ICD and who underwent DFT by means of a single 65) shock. The levels of biomarkers did not change from baseline to 1h post-shock, i.e. hs-CTnI (from 0.029 +/- 0.005 ng/mL to 0.030 +/- 0.005 ng/mL, P = 0.079) and CK-MB mass (from 1.37 +/- 0.17 ng/mL to 1.41 +/- 0.18, P= 0.080) and remained stable 6 and 24h after DFT. The plasma NT-proBNP did not change, whereas CP levels were significantly higher at 1 h post-shock evaluation. However, 6 h after DFT, the levels had returned to the baseline and remained stable at 24 h.Conclusion The S-ICD shock did not seem to cause myocardial injuries. Although CP levels temporarily rose after DFT, they returned to basal levels within 6 h, which suggests that DFT does not have long-term prognostic implications. ICD shocks are associated with a subsequent increased risk of death, and an elevation of cardiac enzymes has been measured after DFT. We showed that serum levels of biomarkers of myocardial damage did not increase after high-energy DFT in patients who had undergone S-ICD device implantation. This suggests that S-ICD shock does not have long-term prognostic implications

Early evaluation of atrial high rate episodes using remote monitoring in pacemaker patients: Results from the RAPID study

Aim: Remote monitoring (RM) of implantable cardiac devices has enabled continuous surveillance of atrial high rate episodes (AHREs) with well-recognized clinical benefits. We aimed to add evidence on the role of the RM as compared to conventional follow-up by investigating the interval from AHRE onset to physician’s evaluation and reaction time in actionable episodes. Methods and Results: A total of 97 dual-chamber pacemaker recipients were followed with RM (RM-ON group; N = 64) or conventional in-office visits (RM-OFF group; N = 33) for 18 months. In-office visits were scheduled at 1, 6, 12, and 18 months in the RM-OFF group and at 1 and 18 months in the RM-ON group. The overall AHRE rate was 1.98 per patient-year (95% confidence interval [CI], 1.76–2.20) with no difference between the two groups (RM-ON vs. RM-OFF weighted-HR, 0.88; CI, 0.36–2.13; p =.78). In the RM-ON group, 100% AHREs evaluated within 11 days from onset, and within 202 days in the RM-OFF group, with a median evaluation delay 79 days shorter in the RM-ON group versus the RM-OFF group (p <.0001). Therapy adjustment in actionable AHREs occurred 77 days earlier in the RM-ON group versus the control group (p <.001). In the RM-ON group, there were 50% less in-office visits as compared to the RM-OFF group (p <.001). Conclusions: In our pacemaker population with no history of atrial fibrillation, RM allowed significant reduction of AHRE evaluation delay and prompted treatment of actionable episodes as compared to biannual in-office visit schedule

Performance of a multisensor implantable defibrillator algorithm for HF monitoring in presence of comorbidities

Background: Cardiovascular and non-cardiovascular comorbidities are common in heart failure (HF) patients and impact disease severity and prognosis. Select modern implantable defibrillators (ICDs) are equipped with multisensor algorithms for HF monitoring. The HeartLogic index com bines multiple ICD-based sensor data (heart rate, heart sounds, thoracic impedance, respiration, activity), and the associated alert has proved to be a sensitive and timely predictor of impending HF decompensation in cardiac resynchronization therapy (CRT-D) patients The algorithm was de veloped using data from CRT-D patients; the performance in non-CRT ICD patients and the impact of selected comorbidities on performance requires further study. Methods: The HeartLogic feature was activated in 568 ICD patients (410 with CRT) from 26 centers. The median follow-up was 25 months [25th 75th percentile: 15–35]. Results: During follow-up, 97 hospitalizations were reported (53 cardio vascular) and 55 patients died. We recorded 1200 HeartLogic alerts (0.71 alerts/patient-year) in 370 patients. Overall, the time IN the alert state was 13%of the total observation period. The rate of cardiovascular hospitaliza tions or death was 0.48/patient-year (95% CI: 0.37–0.60) with the Heart Logic IN alert state and 0.04/patient-year (95% CI: 0.03–0.05) OUT of alert state, with an incidence rate ratio of 13.35 (95% CI: 8.83–20.51, p<0.001). Among patient characteristics, atrial fibrillation (AF) at implantation (HR: 1.62, 95% CI: 1.27–2.07, p<0.001) and chronic kidney disease (CKD) (HR: 1.53, 95% CI: 1.21–1.93, p<0.001) independently predicted alerts. Heart Logic alerts were not associated with CRT vs. non-CRT device implan tation (HR: 1.03, 95% CI: 0.82–1.30, p=0.775). The comparisons of the clinical event rates in the IN alert state with those in the OUT of alert state yielded incidence rate ratios ranging from 9.72 to 14.54 (all p<0.001) in all groups of patients stratified by: CRT/non-CRT, AF/non-AF, CKD/non-CKD. Indeed, after multivariate correction for CKD and AF at implantation, the time IN the HeartLogic alert state >13% was associated with the occur rence of the combined endpoint of cardiovascular hospitalization or death (HR: 2.54, 95% CI: 1.61–4.01, p<0.001). Conclusions: The burden of HeartLogic alerts appears similar between CRT and non-CRT patients, while patients with AF and CKD seem more exposed to alerts. Nonetheless, the ability of the HeartLogic algorithm to identify patients during periods of significantly increased risk of clinical events is confirmed regardless of the type of device, the presence of AF, or CKD

Performance of a multisensor implantable defibrillator algorithm for HF monitoring in presence of comorbidities

Background: Cardiovascular and non-cardiovascular comorbidities are common in heart failure (HF) patients and impact disease severity and prognosis. Select modern implantable defibrillators (ICDs) are equipped with multisensor algorithms for HF monitoring. The HeartLogic index com bines multiple ICD-based sensor data (heart rate, heart sounds, thoracic impedance, respiration, activity), and the associated alert has proved to be a sensitive and timely predictor of impending HF decompensation in cardiac resynchronization therapy (CRT-D) patients The algorithm was de veloped using data from CRT-D patients; the performance in non-CRT ICD patients and the impact of selected comorbidities on performance requires further study. Methods: The HeartLogic feature was activated in 568 ICD patients (410 with CRT) from 26 centers. The median follow-up was 25 months [25th 75th percentile: 15–35]. Results: During follow-up, 97 hospitalizations were reported (53 cardio vascular) and 55 patients died. We recorded 1200 HeartLogic alerts (0.71 alerts/patient-year) in 370 patients. Overall, the time IN the alert state was 13%of the total observation period. The rate of cardiovascular hospitaliza tions or death was 0.48/patient-year (95% CI: 0.37–0.60) with the Heart Logic IN alert state and 0.04/patient-year (95% CI: 0.03–0.05) OUT of alert state, with an incidence rate ratio of 13.35 (95% CI: 8.83–20.51, p<0.001). Among patient characteristics, atrial fibrillation (AF) at implantation (HR: 1.62, 95% CI: 1.27–2.07, p<0.001) and chronic kidney disease (CKD) (HR: 1.53, 95% CI: 1.21–1.93, p<0.001) independently predicted alerts. Heart Logic alerts were not associated with CRT vs. non-CRT device implan tation (HR: 1.03, 95% CI: 0.82–1.30, p=0.775). The comparisons of the clinical event rates in the IN alert state with those in the OUT of alert state yielded incidence rate ratios ranging from 9.72 to 14.54 (all p<0.001) in all groups of patients stratified by: CRT/non-CRT, AF/non-AF, CKD/non-CKD. Indeed, after multivariate correction for CKD and AF at implantation, the time IN the HeartLogic alert state >13% was associated with the occur rence of the combined endpoint of cardiovascular hospitalization or death (HR: 2.54, 95% CI: 1.61–4.01, p<0.001). Conclusions: The burden of HeartLogic alerts appears similar between CRT and non-CRT patients, while patients with AF and CKD seem more exposed to alerts. Nonetheless, the ability of the HeartLogic algorithm to identify patients during periods of significantly increased risk of clinical events is confirmed regardless of the type of device, the presence of AF, or CK

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