Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer.

BACKGROUND: The addition of pembrolizumab to neoadjuvant chemotherapy led to a significantly higher percentage of patients with early triple-negative breast cancer having a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery in an earlier analysis of this phase 3 trial of neoadjuvant and adjuvant therapy. The primary results regarding event-free survival in this trial have not been reported. METHODS: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response (the results for which have been reported previously) and event-free survival, defined as the time from randomization to the date of disease progression that precluded definitive surgery, local or distant recurrence, occurrence of a second primary cancer, or death from any cause. Safety was also assessed. RESULTS: Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. The median follow-up at this fourth planned interim analysis (data cutoff, March 23, 2021) was 39.1 months. The estimated event-free survival at 36 months was 84.5% (95% confidence interval [CI], 81.7 to 86.9) in the pembrolizumab-chemotherapy group, as compared with 76.8% (95% CI, 72.2 to 80.7) in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% CI, 0.48 to 0.82; P<0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy. CONCLUSIONS: In patients with early triple-negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab after surgery, resulted in significantly longer event-free survival than neoadjuvant chemotherapy alone. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).

21-gene expression assay and clinical outcomes of premenopausal patients with hormone receptor-positive breast cancer.

The prognostic role of the recurrence score (RS) based on the 21-gene expression assay in premenopausal women is not well delineated, and we investigated the association of outcomes and the RS in premenopausal patients who had 21-gene expression assay at Asan Medical Center, Seoul, Korea, between June 2005 and July 2018. Invasive breast cancer-free survival (IBCFS) by STEEP version 2.0 was compared according to the RS and clinical risk factors. A total of 554 patients were included in our study and 116 patients (20.9%) had age <40 years, 238 patients (43.0%) had luminal B subtype (Ki67 ≥ 20%), and 83 patients (15.0%) had RS >25. All patients received adjuvant tamoxifen ± chemotherapy. Overall, patients with RS >25 showed trend toward worse IBCFS from multivariable analysis (adjusted HR 1.89 [95% CI: 0.95-3.73], P = .069). When comparing outcomes according to age and luminal subtypes, patients with luminal B subtype and age <40 years (n = 60) showed significantly worse outcomes compared to the others (luminal A or luminal B + age ≥40 years, n = 494; adjusted HR 2.95 [95% CI: 1.49-5.82], log-rank P < .001). Among patients with luminal B subtype and age <40 years, there was no significant association observed between IBCFS and the RS (log-rank P = .51). In conclusion, while RS >25 showed association with poor outcomes in premenopausal women, it may have less prognostic significance among those with luminal B subtype and age <40 years.

Phase 2 trial of avelumab in combination with gemcitabine in advanced leiomyosarcoma as a second-line treatment (EAGLES, Korean Cancer Study Group UN18-09).

BACKGROUND: In this single-arm, multicenter, phase 2 trial, the authors evaluated the efficacy and safety of avelumab plus gemcitabine in patients with leiomyosarcoma (LMS) who failed on first-line chemotherapy. METHODS: Patients with advanced LMS received avelumab 10 mg/kg on days 1 and 15 (for up to 24 months) plus gemcitabine 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle until they developed disease progression or intolerable toxicity. The primary end point was the objective response rate (ORR). RESULTS: In total, 38 patients were enrolled. Of these, 35 patients were evaluable, and the ORR was 20% (95% confidence interval; [CI], 8%-37%). The disease control rate was 71%, and the median duration of response was 21.8 months (range, 7.6 to ≥43.3 months). The median progression free-survival was 5.6 months (95% CI, 4.5-6.8 months), and the median overall survival was 27.5 months (95% CI, 20.4-34.6 months). Grade 3-4 adverse events occurred in 70% of patients, of which neutropenia was the most common (54%). Immune-mediated adverse events occurred in five patients (14%; hypothyroidism, n = 3; hepatitis, n = 2). Patients who had a higher density of tumor-infiltrating lymphocytes (greater than the median) exhibited better ORR (35% vs. 8%; p = .104), progression-free survival (median, 7.3 vs. 3.3 months; p = .024), and overall survival (median, not reached vs. 21.5 months; p = .027). CONCLUSIONS: The combination of avelumab and gemcitabine demonstrated promising efficacy and manageable safety in patients with advanced LMS who progressed on first-line therapy. Tumor-infiltrating lymphocyte density may be an important factor in predicting the response to combining immunotherapy with chemotherapy.

Favorable clinical efficacy of cytotoxic chemotherapy in patients with progressive desmoid tumors: a retrospective real-world study.

BACKGROUND: The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. METHODS: The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. RESULTS: A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56%), followed by the trunk and abdominal wall (24%), extremities (16%), and head and neck (4%). Sixty percent of the patients had familial adenomatous polyposis and 76% received doxorubicin plus dacarbazine. The objective response rate and disease control rate was 64% (95% confidence interval [CI]: 40.7-82.8) and 96% (95% CI: 77.2-99.9), respectively. With the median follow-up time of 55 months (95% CI: 41.0-68.2), the 3-year PFS rate was 65% (95% CI: 41.1-80.5), and the 3-year OS rate was 89% (95% CI: 63.8-97.3). Grade 3 or 4 hematologic adverse events were reported in 14 patients, all of which were manageable. CONCLUSION: Our real-world evidence suggests that doxorubicin-based cytotoxic chemotherapy can be an effective treatment option for recurrent and progressive desmoid tumors with respect to favorable clinical outcomes.

Randomized phase III trial of a neoadjuvant regimen of four cycles of adriamycin plus cyclophosphamide followed by four cycles of docetaxel (AC4-D4) versus a shorter treatment of three cycles of FEC followed by three cycles of docetaxel (FEC3-D3) in node-positive breast cancer (Neo-shorter; NCT02001506).

PURPOSE: To determine whether six cycles of FEC3-D3 has a comparable efficacy to eight of AC4-D4. METHODS: The enrolled patients (pts) were clinically diagnosed with stage II or III breast cancer. The primary endpoint was a pathologic complete response (pCR), and the secondary endpoints were 3 year disease-free survival (3Y DFS), toxicities, and health-related quality of life (HRQoL). We calculated that 252 pts were needed in each treatment group to enable the detection of non-inferiority (non-inferiority margin of 10%). RESULTS: In terms of ITT analysis, 248 pts were finally enrolled. The 218 pts who completed the surgery were included in the current analysis. The baseline characteristics of these subjects were well balanced between the two arms. By ITT analysis, pCR was achieved in 15/121 (12.4%) pts in the FEC3-D3 arm and 18/126 (14.3%) in the AC4-D4 arm. With a median follow up of 64.1 months, the 3Y DFS was comparable between the two arms (75.8% in FEC3-D3 vs. 75.6% in AC4-D4). The most common adverse event (AE) was Grade 3/4 neutropenia, which arose in 27/126 (21.4%) AC4-D4 arm pts vs 23/121 (19.0%) FEC3-D3 arm cases. The primary HRQoL domains were similar between the two groups (FACT-B scores at baseline, P = 0.35; at the midpoint of NACT, P = 0.20; at the completion of NACT, P = 0.44). CONCLUSION: Six cycles of FEC3-D3 could be an alternative to eight of AC4-D4. Trial registration ClinicalTrials.gov NCT02001506. Registered December 5,2013. https://clinicaltrials.gov/ct2/show/NCT02001506.

Safety and efficacy of intracardiac echocardiography-guided zero-fluoroscopic cryoballoon ablation for atrial fibrillation: a prospective randomized controlled trial.

AIMS: The development of intracardiac echocardiography (ICE) has enabled fluoroless atrial fibrillation (AF) ablation using three-dimensional electroanatomical mapping systems. However, fluoroless cryoballoon ablation (CBA) remains challenging, mainly because of the lack of a visual mapping system. Hence, this study aimed to investigate the safety and efficacy of fluoroless CBA for AF under ICE guidance. METHODS AND RESULTS: Patients (n = 100) who underwent CBA for paroxysmal AF were randomly assigned to zero-fluoroscopic (Zero-X) and conventional groups. Intracardiac echocardiography was used to guide the transseptal puncture and catheter and balloon manipulation in all enrolled patients. The patients were prospectively followed for 12 months after CBA. The mean age was 60.4 years, and the left atrial (LA) size was 39.4 mm. Pulmonary vein isolation (PVI) was achieved in all patients. In the Zero-X group, fluoroscopy was used in only one patient because of unstable phrenic nerve capture during right-sided PVI. The procedure time and LA indwelling time in the Zero-X group were not statistically different compared with that in the conventional group. Fluoroscopic time (9.0 vs. 0.008 min) and radiation exposure (29.4 vs. 0.02 mGy) were significantly shorter in the Zero-X group than in the conventional group (P < 0.001). The complication rate did not differ between the two groups. During a mean follow-up of 663.3 ± 172.3 days, the recurrence rate was similar (16.0 vs. 18.0%; P = 0.841) between the groups. Multivariate analysis revealed that LA size was the only independent predictor of clinical recurrence. CONCLUSION: Intracardiac echocardiography-guided fluoroless CBA for AF was a feasible strategy without compromising acute and long-term success or complication rates.

Subcellular progression of mesenchymal transition identified by two discrete synchronous cell lines derived from the same glioblastoma.

Glioblastomas (GBM) exhibit intratumoral heterogeneity of various oncogenic evolutional processes. We have successfully isolated and established two distinct cancer cell lines with different morphological and biological characteristics that were derived from the same tissue sample of a GBM. When we compared their genomic and transcriptomic characteristics, each cell line harbored distinct mutation clusters while sharing core driver mutations. Transcriptomic analysis revealed that one cell line was undergoing a mesenchymal transition process, unlike the other cell line. Furthermore, we could identify four tumor samples containing our cell line-like clusters from the publicly available single-cell RNA-seq data, and in a set of paired longitudinal GBM samples, we could confirm three pairs where the recurrent sample was enriched in the genes specific to our cell line undergoing mesenchymal transition. The present study provides direct evidence and a valuable source for investigating the ongoing process of subcellular mesenchymal transition in GBM, which has prognostic and therapeutic implications.

E/e' Ratio Predicts the Atrial Pacing-Induced Left Atrial Pressure Response in Patients with Preserved Ejection Fraction.

Background and Objectives: Left atrial hypertension is one of the pathophysiologies of heart failure with preserved ejection fraction. We hypothesized that left atrial pressure response (LAPR) to incremental pacing is higher in patients with atrial fibrillation (AF) and can predict left ventricular diastolic dysfunction. Materials and Methods: Patients requiring left atrial access as a part of a therapeutic procedure for AF (n = 204, AF group) or supraventricular tachycardia (n = 34, control group) were analyzed (male n = 183, 54 ± 12 years old). LAPR was measured during incremental pacing. Results: Baseline left atrial pressure and LAPR at all pacing rates were not different between the AF and control groups. They were higher in patients with a high E/e' (≥ 8) than in those with a low E/e' (<8). LAPR at a pacing interval of 400 ms and E/e' were positively correlated (r = 0.373, p < 0.001). Body mass index and a high E/e' were independent predictors of pacing-induced left atrial hypertension. Conclusions: LAPR to incremental pacing was constant regardless of AF. The non-invasive echocardiographic marker E/e' reflected pacing-induced left atrial hypertension.

A Propensity Score-matched Analysis of Long-term Oncologic Outcomes After Nipple-sparing Versus Conventional Mastectomy for Locally Advanced Breast Cancer.

OBJECTIVES: To compare the long-term oncologic outcomes of nipple-sparing mastectomy (NSM) with those of conventional mastectomy (CM) in patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NACT). SUMMARY OF BACKGROUND DATA: NSM has been increasingly implemented in patients with breast cancer. However, oncologic efficacy of NSM in patients with LABC has not been sufficiently demonstrated. METHODS: The study group comprised 850 patients with clinical stage IIB to IIIC breast cancer who underwent NACT followed by either NSM and immediate breast reconstruction or CM alone. After propensity score-matching, 418 patients were included in the analysis. Local recurrence-free survival, disease-free survival (DFS), distant metastasis-free survival, and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the NSM and CM groups. RESULTS: After matching, the mean follow-up period was 70 ± 25 months for the NSM group and 74 ± 27 months for the CM group ( P = 0.181). There were no significant differences between the groups in terms of 6-year local recurrence-free survival (91.6% vs. 95.8%; P = 0.239), DFS (70.5% vs. 73.4%; P = 0.583), distant metastasis-free survival (79.8% vs. 77.4%; P = 0.320), or OS (87.6% vs. 84.8%; P = 0.465) rates. Additionally, we identified 30 patients in the NSM group who initially presented with tumor extension in the subareolar area; the nipple-areola complex was successfully preserved after NACT, and no recurrence at the nipple was observed in these patients. CONCLUSIONS: In this matched control study, we demonstrated comparable long-term oncologic outcomes between NSM with immediate reconstruction and CM alone after NACT for LABC. In patients who had tumors extending to the subareolar area before NACT, NSM can be tried if tumor involvement of the nipple-areola complex appears resolved on imaging studies after chemotherapy.

Does isolation of the left atrial posterior wall using cryoballoon ablation improve clinical outcomes in patients with persistent atrial fibrillation? A prospective randomized controlled trial.

AIMS: Posterior wall isolation (PWI) of the left atrium (LA) adjunct to pulmonary vein isolation (PVI) by radiofrequency catheter ablation has shown favourable outcomes in patients with persistent atrial fibrillation (PeAF). This study was sought to investigate the efficacy and safety of additional PWI by cryoballoon ablation (CBA) alone in patients with PeAF. METHODS AND RESULTS: Patients who underwent de novo CBA for PeAF (n = 100) were randomly assigned (1 : 1) to the PVI only group and PVI combined with PWI (PVI+PWI) group. Procedural and clinical outcomes were prospectively compared over a 12-month follow-up.Baseline characteristics, including mean AF duration (56.2 ± 43.2 months) and LA size (48.2 ± 7.7 mm), were well-balanced between the groups. Successful PVI was achieved in all patients. In the PVI+PWI group, complete PWI by CBA was achieved in 31 (62%) patients. The LA indwelling and procedure times were significantly longer in the PVI+PWI group. The complication rates were not different between groups. During a mean follow-up of 457.9 ± 61.8 days, the recurrence rate of atrial tachyarrhythmia was significantly lower in the PVI+PWI group than in the PVI only group (24% vs. 46%; P = 0.035). The recurrence-free survival rate was significantly higher in the PVI+PWI group compared with the PVI only group, irrespective of complete PWI (log-rank P = 0.013). Multivariate analysis showed that adjunctive PWI [hazard ratio (HR) 0.255; P = 0.003] and LA size (HR 1.079; P = 0.014) were independent predictors of clinical recurrence. CONCLUSION: Compared with PVI only, adjunctive PWI achieved exclusively by CBA resulted in better clinical outcomes without increasing complications in patients with PeAF.

Final results of the randomized phase 2 LEO trial and bone protective effects of everolimus for premenopausal hormone receptor-positive, HER2-negative metastatic breast cancer.

The phase 2 LEO study showed that everolimus (EVE) plus letrozole (LET) with ovarian suppression increased progression-free survival (PFS) in tamoxifen-exposed premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer with visceral metastases. Here we report final survival outcomes from the LEO study, and the results of exploratory analyses of bone turnover marker changes and bone-specific progressive disease. Patients who were exposed to or progressed on tamoxifen as adjuvant/palliative treatments were randomly assigned (2:1) to the EVE (leuprorelin + LET + EVE, n = 92) or LET (leuprorelin + LET, n = 45) arm. In a median 51-months of follow-up, the median PFS was 17.5 and 13.8 months in the EVE and LET arms, respectively (P = .245). Patients in the EVE arm with baseline visceral (median PFS 16.4 vs 9.5 months, P = .040) and bone (median PFS 17.1 vs 10.9, P = .003) metastases had greater PFS compared to the LET arm. No differences in overall survival (OS) were observed (median OS, 48.3 vs 50.8 months, P = .948). The 1-year cumulative incidences of bone-specific disease progression were 6.0% and 23.4% in the EVE and LET arms, respectively (hazard ratio 0.26, P < .001). Bone turnover markers at 6 and 12 weeks after treatment decreased in the EVE arm but were increased or stationary in the LET arm. Skeletal-related events occurred in 6.5% and 11.1% of patients in the EVE and LET arms, respectively. EVE + LET with ovarian suppression prolonged PFS in patients with baseline visceral or bone metastases and offered bone-protective effects in the overall study population. However, these clinical benefits did not translate into an OS benefit.

Prognostic effects of cytokine levels on patients treated with taxane and zoledronic acid for metastatic breast cancer in bone (BEAT-ZO) (KCSG BR 10-13).

Advanced breast cancer frequently metastasizes to the skeleton causing major mobility issues and hazards to quality of life. To manage osteolytic bone metastasis, bone-modifying agents and chemotherapy are recommended as the standard of care. Here, we investigated serologic biomarkers that might be associated with prognosis in breast cancer patients treated with zoledronic acid (ZA) and taxane-based chemotherapy. We collected serum samples from breast cancer patients with bone metastasis who received taxane plus ZA as palliative treatment. Fourteen biomarkers of angiogenesis, immunogenicity, and apoptosis were assessed, and the correlation between serum cytokine levels and patient's prognosis was statistically analyzed. Sixty-six patients were enrolled, and samples from 40 patients were analyzed after laboratory quality control. Patients with low baseline PDGF-AA, high IFN-γ, low MCP-2, low TGF-ß1, and low TNF-α were significantly associated with longer progression-free survival (PFS). Decreasing VEGF and TNF-α and increasing FGF-2 and PDGF-AA in the early treatment phase indicated longer PFS. In univariate and multivariate analyses, low TGF-ß1 and TNF-α and high IFN-γ at baseline were associated with a significantly low hazard ratio for disease progression. Further, we designed a risk score with TGF-ß1, TNF-α, and IFN-γ levels, which could prognosticate patients for PFS. In conclusion, serum cytokine level, such as TGF-ß1, TNF-α, and IFN-γ, could be a potential prognostic biomarker for breast cancer patients with bone metastasis treated with ZA and taxane-based chemotherapy.

Role of early short-term cardiac rehabilitation in patients undergoing pacemaker implantation.

Exercise-based cardiac rehabilitation (CR) improves the clinical outcomes in patients with cardiovascular diseases. However, few data exist regarding the role of early short-term CR in patients undergoing pacemaker (PM) implantation. We assessed whether short-term CR following PM implantation was sufficient to improve both physical function and quality of life (QOL). A total of 27 patients with a 6-minute walking distance (6MWD) of less than 85% of the predicted value on the day following PM implantation were randomly assigned to either the CR group (n = 12, 44.4%) or the non-CR group (n = 15, 55.6%). The CR group involved individualized exercise-based training with moderate intensity for 4 weeks after PM implantation. Cardiopulmonary exercise test (CPET), 6MWD, muscle strength, and Short Form (SF)-36 were assessed at baseline and at the 4-week follow-up. After a mean follow-up period of 38.3 days, both groups showed significantly improved 6MWD. Peak oxygen uptake improved in both groups on CPET, but the difference was not statistically significant. Knee extension power and handgrip strength were similar in both groups. Regarding QOL, only the CR group showed improved SF-36 scores in the items of vitality and mental health. There was no difference in any subscale in the non-CR group. Neither lead dislodgement nor significant changes in PM parameters were observed in any patient. Early short-term CR following PM implantation was associated with improved psychological subscales and can be safely performed without increasing the risk of procedure-related complications.

Preoperative Oral Carbohydrate Loading in Laparoscopic Gynecologic Surgery: A Randomized Controlled Trial.

STUDY OBJECTIVE: To determine whether carbohydrate loading improves the postoperative quality of recovery (QoR) better than the midnight fasting policy in laparoscopic gynecologic surgeries. DESIGN: Randomized, parallel-group trial. SETTING: Tertiary university hospital. PATIENTS: Female patients scheduled for laparoscopic gynecologic surgery for nonmalignant gynecologic diseases. INTERVENTIONS: Eighty-eight women were randomly assigned to the midnight fasting group (nil per os, NPO group) or the carbohydrate loading group (carbohydrate group). Patients in both groups adhered to the enhanced recovery after surgery protocol except for carbohydrate intake in the carbohydrate group. MEASUREMENTS AND MAIN RESULTS: The postoperative QoR was evaluated using the QoR 15-item questionnaire on postoperative day 2. The times to readiness for discharge of the groups were compared. The QoR 15-item questionnaire scores were 97.7 ± 23.0 in the NPO group and 99.6 ± 22.4 in the carbohydrate group; they were not statistically different (p = .702). The times to readiness for discharge of both groups were also not different: 36.8 ± 12.2 hours in the NPO group and 37.6 ± 11.8 hours in the carbohydrate group (p = .684). CONCLUSION: The benefit of carbohydrate beverage intake was not significant in laparoscopic gynecologic surgeries when following the enhanced recovery after surgery protocol.

Feasibility of an Advance Care Planning Program (ACP) for Korean Community-Dwelling Older Adults and ACP Training of Advance Practice Nurses.

This study aimed to develop a locally suitable advance care planning (ACP) program for older community-dwelling adults and a training program for nurse facilitators in Korea, and to evaluate their feasibility from the facilitators' experiences. This was a mixed methods pilot study that assessed the feasibility of an ACP program by analyzing survey, checklist, and focus group interview data. The ACP program was named CLOSE (Communicating and Listening to Our Seniors' voices about End-of-life care). Home health care nurses (N = 9) participated in this study. The participants reported that CLOSE was applicable to older community-dwelling adults and the training program was useful for increasing facilitator competency. We suggest some lessons from this pilot study that can be used to improve the ACP program and encourage community health nurses to participate in ACP as facilitators.

The Impact of Personal Thoracic Impedance on Electrical Cardioversion in Patients with Atrial Arrhythmias.

Background and Objectives: Direct current cardioversion (DCCV) is a safe and useful treatment for atrial tachyarrhythmias. In the past, the energy delivered in DCCV was decided upon empirically, based only on the type of tachyarrhythmia. This conventional method does not consider individual factors and may lead to unnecessary electrical damage. Materials and Methods: We performed DCCV in patients with atrial tachyarrhythmias. The impedance and electrical current at the moment of shock were measured. The human thoracic impedance between both defibrillator patches and the electric current that was used were measured. Results: A total of 683 DCCVs were performed on 466 atrial tachyarrhythmia patients. The average impedance was 64 ± 11 Ω and the average successful current was 23 ± 6 mA. The magnitude of the electrical current that was successful depended upon the human impedance (linear regression, B = -0.266, p < 0.001) and the left atrial diameter (B = 0.092, p < 0.001). Impedance was directly proportional to body mass index (BMI) (B = 1.598, p < 0.001) and was higher in females than in males (77 ± 15 Ω vs. 63 ± 11 Ω, p < 0.001). Notably, the high-impedance (>70 Ω) group had a higher BMI (27 ± 4 kg/m2 vs. 25 ± 3 kg/m2, p < 0.001) and a higher proportion of females (37% vs. 9%, p < 0.001) than the low-impedance group (<70 Ω). However, thoracic impedance was not an independent predictor for successful DCCV. Conclusions: Human thoracic impedance was one of the factors that impacted the level of electrical current required for successful DCCV in patients with atrial arrhythmias. In the future, it will be helpful to consider individual predictors, such as BMI and gender, to minimize electrical damage during DCCV.

A pilot study on intermittent every other days of 5-dose Filgrastim compared with single Pegfilgrastim in breast Cancer patients receiving adjuvant Docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy.

Aim To compare the efficacy and safety of intermittent every other days 5-dose filgrastim with single pegfilgrastim in patients with breast cancer receiving adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy. Methods In this pilot study, Korean patients who had undergone complete resection for breast cancer and scheduled for adjuvant TAC chemotherapy were enrolled. Patients were randomized to receive either intermittent 5 doses of filgrastim (5 mcg/kg/day) or once-a-cycle pegfilgrastim (6 mg) as primary prophylaxis during the first three cycles of the TAC chemotherapy. Absolute neutrophil count (ANC) was analyzed as well. Results A total of 22 patients were randomly and equally divided into filgrastim or pegfilgrastim arms. Febrile neutropenia (FN) occurred in 1 patient in the pegfilgrastim arm (1 of 33 cycles) and none in the filgrastim arm. G3 neutropenia occurred in 1 patient (1 of 33 cycles) in the filgrastim arm and 2 patients (4 of 33 cycles) in the pegfilgrastim arm (P = 0.476). G4 neutropenia occurred in 11 patients (28 of 33 cycles) in the filgrastim arm and 9 patients (18 of 33 cycles) in the pegfilgrastim arm (P = 0.476). Except for on day 9 in cycle 3, there was no significant difference between the two groups in terms of ANC. Conclusion We observed no significant differences between the two methods of prophylaxis in terms of FN and G3/4 neutropenia incidence in patients receiving adjuvant TAC chemotherapy. Intermittent every other days 5-dose filgrastim may be available alternative to pegfilgrastim.

Efficacy of high-power and short-duration ablation in patients with atrial fibrillation: a prospective randomized controlled trial.

AIMS: The formation of radiofrequency lesions depends on the power and duration of ablation, and the contact force (CF). Although high power (HP) creates continuous and transmural lesions, most centres still use 25-30 W for 30-40 s for safety reasons. We evaluated the clinical efficacy and safety of a HP and short-duration (HPSD) strategy for atrial fibrillation (AF) ablation. METHODS AND RESULTS: One hundred and fifty patients [58.2 ± 10.0 years, 48% with paroxysmal AF (PAF)] scheduled for index AF ablation using a CF-sensing catheter were randomly assigned to three groups [30 W, 40 W, and 50 W at ablation sites of anterior, roof, and inferior segments of pulmonary vein (PV) antra and roof line between each upper PV]. In 25-30 W for ≤20 s was applied at posterior wall ablation site in all subjects. Compared with the 30 W and 40 W groups, procedure (P < 0.001) and ablation times (P < 0.001) were shorter and ablation number for PV isolation (P < 0.001) was smaller in the 50 W group. There were no significant differences in the CF and ablation index (AI) among the three groups. There were no significant differences in the procedure-related complication rates. During the 12-month follow-up, AF recurred in 24 (16%) patients with no significant difference among the groups (P = 0.769). In the multivariate analysis, non-PAF [hazard ratio (HR) 2.836, P = 0.045] and AI (HR 0.983, P = 0.001) were independent risk factors for AF recurrence. CONCLUSION: Radiofrequency ablation with HPSD is a safe and effective strategy with reduced ablation number and shortened procedure time compared to conventional ablation.

Synthesis and characterization of 64Cu- and Cy5.5-labeled tetraiodothyroacetic acid derivatives for tumor angiogenesis imaging.

It was previously reported that tetraiodothyroacetic acid (tetrac) inhibits angiogenesis by binding to the cell surface receptor for thyroid hormone on integrin αVß3. Therefore, we synthesized and evaluated two 64Cu-labeled tetrac derivatives and a Cy5.5-labeled tetrac derivative for tumor angiogenesis imaging. Tetrac was structurally modified to conjugate with 1,4,7,10-tetraazacyclododecane-N,N',N″,N″'-tetraacetic acid (DOTA) via its hydroxy or carboxylic acid end, and the resulting DOTA-conjugated tetrac derivatives were then labeled with 64Cu. Tetrac was also conjugated with Cy5.5 via its carboxylic acid end. All three tetrac derivatives (1-3) exhibited greater inhibitory activity than tetrac against endothelial cell tube formation. The U87MG cell binding of [64Cu]2 showed a time-dependent increase over 24 h and it was inhibited by 38% at 4 h in the presence of tetrac, indicating specificity of [64Cu]2 to the thyroid hormone receptor site on integrin αVß3. Positron emission tomography (PET) images of U87MG tumor-bearing mice injected with [64Cu]1 and [64Cu]2 revealed that high radioactivity accumulated in the tumors, and that the tumor uptake and tumor-to-nontarget uptake ratio were higher in small tumors than in large tumors. In addition, the Cy5.5-labeled tetrac derivative (3) displayed a strong near-infrared (NIR) signal in the tumors. Taken together, these results suggest that these ligands hold promise as imaging agents for visualization of tumor angiogenesis.

Comparison of vasodilatory properties between desflurane and sevoflurane using perfusion index: a randomised controlled trial.

BACKGROUND: The perfusion index (PI), calculated from the photoplethysmographic waveform, reflects peripheral vasomotor tone. As such, the PI serves as a surrogate for quantitative measures of drug-induced vasoconstriction or vasodilation. This study aimed to compare the effect on the PI of desflurane and sevoflurane at equi-anaesthetic concentrations in patients undergoing single-agent inhalation anaesthesia, where equi-anaesthetic dose was based on the known minimum alveolar concentration of these agents. METHODS: We randomly allocated patients scheduled for arthroscopic knee surgery to receive either desflurane or sevoflurane general anaesthesia after target-controlled induction of anaesthesia with propofol. Anaesthesia was maintained at age-corrected minimum alveolar concentration 1.0, under neuromuscular block (rocuronium). The PI and haemodynamic data were recorded every minute for 35 min after induction of anaesthesia and after standardised nociceptive stimulation. The primary outcome was PI, compared between the groups over time (repeated-measures analysis of variance). Secondary outcomes included MAP and HR. RESULTS: Sixty-nine participants (mean [range] age: 42 yr [19-65 yr]; 49% females) were assigned to either desflurane (n=34) or sevoflurane (n=35). The PI remained higher under desflurane compared with sevoflurane, both before (mean difference [MD]: 3.3; 95% confidence intervals [CIs]: 2.0-4.7; P<0.001) and after tetanic stimulation (MD: 2.8; 95% CI: 2.0-3.7; P<0.001). Higher PI paralleled lower MAP in participants assigned to desflurane anaesthesia (P<0.001), both before (MD: 8 mm Hg; 95% CI: 4-12) and after nociceptive stimulation (MD: 14 mm Hg; 95% CI: 7-22). HR was similar throughout. CONCLUSIONS: These findings suggest that at equipotent doses, desflurane exerts more potent vasodilatory properties and lowers blood pressure by a magnitude potentially associated with harm. CLINICAL TRIAL REGISTRATION: NCT03570164.