A randomized, double-blind, placebo-controlled phase 3 study to assess efficacy and safety of ropeginterferon alfa-2b in patients with early/lower-risk primary myelofibrosis.

Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with "early/lower-risk PMF", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.

Reliability and validity of estimated angles information assessed using inertial measurement unit-based motion sensors.

BACKGROUND: Inertial measurement unit (IMU)-based motion sensors are affordable, and their use is appropriate for rehabilitation. However, regarding the accuracy of estimated angle information obtained from this sensor, it is reported that it is likely affected by velocity. OBJECTIVE: The present study investigated the reliability and validity of the angle information obtained using IMU-based sensors compared with a three-dimensional (3D) motion analyzer. METHODS: The Euler angle obtained using the 3D motion analyzer and the angle obtained using the IMU-based sensor (IMU angle) were compared. Reliability was assessed by comparing the Bland-Altman analysis, intra-class correlation coefficient (ICC) (1,1), and cross-correlation function. The root mean square (RMS) error, ICC (2,1), and cross-correlation function were used to compare data on the Euler and IMU angles to evaluate the validity. RESULTS: Regarding reliability, the Bland-Atman analysis indicated no fixed or proportional bias in the angle measurements. The measurement errors ranged from 0.2° to 3.2°. In the validity, the RMS error ranged from 0.3° to 2.2°. The ICCs (2,1) were 0.9. The cross-correlation functions were >0.9, which indicated a high degree of agreement. CONCLUSION: The IMU-based sensor had a high reliability and validity. The IMU angle may be used in rehabilitation.

Validity of the estimated angular information obtained using an inertial motion capture system during standing trunk forward and backward bending.

BACKGROUND: Bending the trunk forward and backward while standing are common daily activities and can have various patterns. However, any dysfunction in these movements can considerably affect daily living activities. Consequently, a comprehensive evaluation of spinal motion during these activities and precise identification of any movement abnormalities are important to facilitate an effective rehabilitation. In recent years, with the development of measurement technology, the evaluation of movement patterns using an inertial motion capture system (motion sensor) has become easy. However, the accuracy of estimated angular information obtained via motion sensor measurements can be affected by angular velocity. This study aimed to compare the validity of estimated angular information obtained by assessing standing trunk forward and backward bending at different movement speeds using a motion sensor with a three-dimensional motion analysis system. METHODS: The current study included 12 healthy older men. A three-dimensional motion analysis system and a motion sensor were used for measurement. The participants performed standing trunk forward and backward bending at comfortable and maximum speeds, and five sensors were attached to their spine. Statistical analysis was performed using the paired t-test, intraclass correlation coefficient, mean absolute error, and multiple correlation coefficient. RESULTS: Results showed that the estimated angular information obtained using each motion sensor was not affected by angular velocity and had a high validity. CONCLUSIONS: Therefore, the angular velocity in this study can be applied clinically for an objective evaluation in rehabilitation.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

Supporters' experiences of sensory characteristics of children with profound intellectual and multiple disabilities in after-school daycare centres: A qualitative study.

AIM: To examine how supporters working at after-school daycare centres, who are involved in the lives of children with profound intellectual and multiple disabilities in the community, pay attention to the sensory characteristics of these children and provide support. DESIGN: A qualitative descriptive design. METHODS: Data were collected through semi-structured interviews with 20 supporters in after-school daycare centres. Interview transcripts were analysed via qualitative content analysis. RESULTS: The participants' years of involvement in supporting children with profound intellectual and multiple disabilities ranged from 0.5 to 40 years, with an average of 9.8 years. Data were classified into 68 subcategories, 11 categories and three themes: understanding sensory characteristics and devising support, systematic support and challenges supporting the children. Supporters dealt with physical complications and cooperated with other caregivers to understand and respond to children's sensory characteristics. Difficulties dealing with sensory characteristics, challenges due to the supporters' own characteristics and challenges with the facility's infrastructure were identified. The findings could guide sensory characteristics considerations and support systems in after-school daycare facilities for children with profound intellectual and multiple disabilities. Both support content and challenges in supporting these children were identified.

Predictors of implantation failure in left bundle branch area pacing using a lumenless lead in patients with bradycardia.

Background: Left bundle branch area pacing (LBBAP) is a novel conduction system pacing technique. In this multicenter study, we aimed to evaluate the procedural success, safety, and preoperative predictors of procedural failure of LBBAP. Methods: LBBAP was attempted in 285 patients with pacemaker indications for bradyarrhythmia, which were mainly atrioventricular block (AVB) (68.1%) and sick sinus syndrome (26.7%). Procedural success and electrophysiological and echocardiographic parameters were evaluated. Results: LBBAP was successful in 247 (86.7%) patients. Left bundle branch (LBB) capture was confirmed in 54.7% of the population. The primary reasons for procedural failure were the inability of the pacemaker lead to penetrate deep into the septum (76.3%) and failure to achieve shortening of stimulus to left ventricular (LV) activation time in lead V6 (18.4%). Thickened interventricular septum (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.15-5.35), severe tricuspid regurgitation (OR, 8.84; 95% CI, 1.22-64.06), and intraventricular conduction delay (OR, 8.16; 95% CI, 2.32-28.75) were preoperative predictors of procedural failure. The capture threshold and ventricular amplitude remained stable, and no major complications occurred throughout the 2-year follow-up. In patients with ventricular pacing burden >40%, the LV ejection fraction remained high regardless of LBB capture. Conclusions: Successful LBBAP was affected by abnormal cardiac anatomy and intraventricular conduction. LBBAP is feasible and safe as a primary strategy for patients with AVB, depending on ventricular pacing.

Diverse QRS morphology reflecting variations in lead placement for left bundle branch area pacing.

AIMS: Left bundle branch area pacing (LBBAP) is a potential alternative to His bundle pacing. This study aimed to investigate the impact of different septal locations of pacing leads on the diversity of QRS morphology during non-selective LBBAP. METHODS AND RESULTS: Non-selective LBBAP and left ventricular septal pacing (LVSP) were achieved in 50 and 21 patients with atrioventricular block, respectively. The electrophysiological properties of LBBAP and their relationship with the lead location were investigated. QRS morphology and axis showed broad variations during LBBAP. Echocardiography demonstrated a widespread distribution of LBBAP leads in the septum. During non-selective LBBAP, the qR-wave in lead V1 indicated that the primary location for pacing lead was the inferior septum (93%). The non-selective LBBAP lead was deployed deeper than the LVSP lead in the inferior septum. The Qr-wave in lead V1 with the inferior axis in aVF suggested pacing lead placement in the anterior septum. The penetration depth of the non-selective LBBAP lead in the anterior septum was significantly shallower than that in the inferior septum (72 ± 11 and 87 ± 8%, respectively). In lead V6, the deep S-wave indicated the time lag between the R-wave peak and the latest ventricular activation in the coronary sinus trunk, with pacemaker leads deployed closer to the left ventricular apex. CONCLUSION: Different QRS morphologies and axes were linked to the location of the non-selective LBBAP lead in the septum. Various lead deployments are feasible for LBBAP, allowing diversity in the conduction system capture in patients with atrioventricular block.

A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera.

Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2-4 weeks. It is approved for polycythemia vera (PV) treatment in the United States and Europe with a starting dose of 100 µg (50 µg for patients receiving hydoxyurea) and intra-patient dose titrations up to 500 µg at 50 µg increments, which took approximately 20 or more weeks to reach a plateau dose level. This study aimed to assess ropeginterferon alfa-2b at an alternative dosing regimen with a higher starting dose and quicker intra-patient dose titrations, i.e., the 250-350-500 µg schema, in 49 Chinese patients with PV with resistance or intolerance to hydroxyurea. The primary endpoint of the complete hematologic response rate at treatment weak 24 was 61.2%, which was notably higher than 43.1% at 12 months with the approved dosing schema. The JAK2V617F allele burden decreased from baseline to week 24 (17.8% ± 18.0%), with one patient achieving a complete molecular response. Ropeginterferon alfa-2b was well-tolerated and most adverse events (AEs) were mild or moderate. Common AEs included alanine aminotransferase and aspartate aminotransferase increases mostly at grade 1 or 2 levels. Patients did not present with jaundice or significant bilirubin level increase. No grade 4 or 5 AEs occurred. Seven patients (14.3%) experienced reversible, drug-related grade 3 AEs. No AEs led to treatment discontinuation. Ropeginterferon alfa-2b at the 250-350-500 µg regimen is highly effective and well-tolerated and can help patients achieve greater and rapid complete hematologic and molecular responses.Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (Identifier: NCT05485948) and in China (China National Medical Products Administration Registration Number: CTR20211664).

Conduction system pacing: Current status and prospects.

Conduction system pacing (CSP), including His bundle pacing (HBP) and left bundle branch area pacing (LBBAP), is the most physiological of all pacing modalities for ventricular capture and a potential alternative to right ventricular pacing. It induces electrical and mechanical dyssynchrony, resulting in left ventricular dysfunction, heart failure hospitalization, and atrial arrhythmia. CSP activates the normal conduction system and restores ventricular synchrony. In 2000, HBP was first performed as permanent ventricular pacing, which improved left ventricular systolic dysfunction. The feasibility of permanent HBP has already been demonstrated in patients with bradycardia, although a high capture threshold and limited efficacy for infra-Hisian conduction diseases remain critical issues. The LBBAP is an alternative pacing form that overcomes the limitations of the HBP. A lower capture threshold was obtained at implantation and preserved during the follow-up period in patients with LBBAP. Cardiac resynchronization therapy with HBP or LBBAP may provide better synchronization than the traditional biventricular pacing. Hybrid therapy utilizing HBP or LBBAP in combination with left ventricular pacing has been introduced to treat patients with heart failure. In this review, we have focused on the clinical implications, limitations, and a literature review on CSP.

Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.

SURPASS-ET: phase III study of ropeginterferon alfa-2b versus anagrelide as second-line therapy in essential thrombocythemia.

Patients diagnosed with high-risk essential thrombocythemia (ET) have limited treatment options to reduce the risk of thrombosis and lessen the progression of the disease by targeting the molecular source. Hydroxyurea is the recommended treatment, but many patients experience resistance or intolerance. Anagrelide is an approved second-line option for ET, but concerns of a higher frequency of disease transformation may affect its role as a suitable long-term option. Interferons have been evaluated in myeloproliferative neoplasms for over 30 years, but early formulations had safety and tolerability issues. SURPASS-ET (NCT04285086) is a phase III, open-label, multicenter, global, randomized, active-controlled trial that will evaluate the safety, efficacy, tolerability and pharmacokinetics of ropeginterferon alfa-2b compared with anagrelide as second-line therapy in high-risk ET.

Essential thrombocythemia (ET) is a condition characterized by having more platelets than normal. The high number of platelets increases the risk of a life-threatening blood clot and/or bleeding. Patients with ET and at a high risk for these events are usually treated first with hydroxyurea (HU), but some patients do not respond properly or may develop significant side effects. Anagrelide is an approved medication used in patients who do not respond to HU. Ropeginterferon alfa-2b is a disease-specific, long-acting interferon with a good safety profile approved in polycythemia vera, another type of myeloproliferative neoplasm. The SURPASS-ET clinical trial will evaluate the safety, efficacy, tolerability and pharmacokinetics of ropeginterferon alfa-2b compared with anagrelide in patients with ET who are resistant or cannot tolerate HU. Clinical Trial Registration: NCT04285086 (ClinicalTrials.gov).

Relationship between occlusal force and endothelial function in community-dwelling elderly women: A pilot study.

OBJECTIVE: In this study, age, endothelial function as flow-mediated dilation (FMD), occlusal force, grip strength, and advanced glycation end products (AGEs) were obtained. AGEs were measured as indicators of aging, while grip strength was measured as an indicator of muscle strength. This study aimed to explain the relationship between occlusal force and endothelial function and determine whether occlusal force can be a new indicator in community preventative care projects. MATERIALS AND METHODS: In 38 community-dwelling women (age, 76.7 ± 5.7 years), the occlusal force and grip strength were measured, the endothelial function was evaluated by FMD, and AGEs were obtained. The relationship between occlusal force, measurement items, and factors were investigated independently related to endothelial function. RESULTS: There were significant correlations between occlusal force and grip strength (r = .54, p < .01). The degree of FMD was significantly associated with occlusal force (r = .60, p < .01) and grip strength (r = .35, p < .05) or increase in AGEs (r = -.37, p < .05). Multiple regression analysis revealed that occlusal force was significantly associated with the degree of FMD (p < .01). CONCLUSION: Occlusal force can be an important indicator of endothelial function in the community-dwelling elderly. This study may help understand the general health of the elderly in communities.

Temporal and spatial pacemap parameters for identification of cardiac surfaces with critical sites for ventricular tachycardia.

INTRODUCTION: Multisurface pacemapping may help identify the surface of interest in scar-related ventricular tachycardia (VT). This study aimed to investigate the performance of pacemap parameters for detecting critical sites through multisurface mapping. METHODS AND RESULTS: In 26 patients who underwent scar-related VT ablation, pacemap parameters including a matching score, the difference between the longest and shortest stimulus-QRS intervals (Δs-QRS), and the distance between the good pacemap sites were measured. The parameters were compared between surfaces with and without critical sites and ablation outcomes. A total of 941 pacemap at 56 surfaces targeting 35 VTs were analyzed. A greater Δs-QRS (40 vs. 8 ms, p < .001) and longer distance between two good pacemap sites (24 vs. 13 mm, p < .001) were observed on the surfaces with critical sites. A similar trend was seen in multisurface pacemapping for the same VTs (52 vs. 18 ms in Δs-QRS, p = .021; 37 vs. 12 mm in distance, p = .019), although the best pacemap scores were comparable (94 vs. 87, p = .295). The Δs-QRS > 20 ms and the distance >19 mm showed high positive likelihood ratios (19.8 and 6.1, respectively) for discriminating the surface harboring the critical site. Ablation of VTs fulfilling these parameters was successful on the surfaces, but without the required multisurface ablation. CONCLUSION: Temporal (Δs-QRS) and spatial (distance) parameters for good pacemap match sites were excellent markers for detecting the surface harboring critical sites in scar-related VT. A multisurface pacemapping can successfully identify the surface of interest.

Efficacy and safety of ropeginterferon alfa-2b in Japanese patients with polycythemia vera: an open-label, single-arm, phase 2 study.

Ropeginterferon alfa-2b is a novel, site-selective, monopegylated recombinant human interferon alfa-2b. Safety and efficacy of ropeginterferon alfa-2b for the treatment of polycythemia vera were demonstrated in clinical studies conducted in European countries, but clinical studies in Japanese patients are lacking. This phase 2, open-label, multicenter, single-arm study investigated the safety and efficacy of ropeginterferon alfa-2b in 29 Japanese patients with polycythemia vera including young patients and patients with low thrombosis risk who are difficult to receive guideline-based standard treatments. The primary outcome of durable complete hematologic response without phlebotomy at months 9 and 12 was achieved by 8/29 (27.6%) patients. The fastest complete hematologic response was observed at week 12. A corresponding reduction in the JAK2 V617F allele burden from baseline to 52 weeks was also observed (mean ± standard deviation = - 19.2% ± 22.6%). No new safety concerns were identified in Japanese patients when compared with previous studies of ropeginterferon alfa-2b in European populations; the most common treatment-related adverse events were alopecia (55.2%), fatigue (27.6%) and influenza-like illness (27.6%). Most treatment-related adverse events were mild or moderate, with none of grade ≥ 3. Ropeginterferon alfa-2b is a safe and efficacious treatment option in Japanese patients with polycythemia vera.

Fluoroscopic predictors of acceptable capture threshold during the implantation of the micra transcatheter pacing system.

INTRODUCTION: Few predictors of low capture threshold before the deployment of the Micra transcatheter pacing system (Micra TPS) have been determined. We aimed to identify fluoroscopic predictors of an acceptable capture threshold before Micra TPS deployment. METHODS: Sixty patients were successfully implanted with Micra TPS. Before deployment, gooseneck appearance of the catheter shaft was quantified using the angle between the tangent line of the shaft and the cup during diastole in the right anterior oblique (RAO) view. The direction of the device cup toward the ventricular septum was evaluated using the angle between the cup and the horizontal plane in the left anterior oblique (LAO) view. RESULTS: Of the 95 deployments we evaluated, 56 achieved an acceptable capture threshold of ≤2.0 V at 0.24 ms. In this acceptable threshold group, the deflection angle of the gooseneck shaft was significantly larger and the device cup was placed more horizontally with a lower elevation angle compared with those in the high threshold group. A deflection angle of ≥6° and an elevation angle of ≤30° were identified as the predictors of an acceptable capture threshold after deployment. An acceptable capture threshold was achieved in 24/31 (77.4%) patients in whom either angle criterion was satisfied at the first deployment. CONCLUSIONS: Diastolic gooseneck appearance of the delivery catheter in the RAO view or near-horizontal direction in the LAO view predicts an acceptable capture threshold after deployment. The shape of the delivery catheter before deployment should be evaluated using multiple fluoroscopic views to ensure successful implantation of Micra TPS.

Combined neuromuscular electrical stimulation and transcutaneous spinal direct current stimulation increases motor cortical plasticity in healthy humans.

Introduction: Neuromuscular electrical stimulation (NMES) induces neural plasticity of the central nervous system (CNS) and improves motor function in patients with CNS lesions. However, the extended stimulus duration of NMES reduces its clinical applicability. Transcutaneous spinal direct current stimulation (tsDCS), which increases afferent input, may enhance the effects and reduce the stimulus duration of NMES. This study investigated the excitability of the motor cortex, somatosensory cortex, and spinal motor neurons after the combined stimulation of NMES and tsDCS. Methods: Among the 55 participants in this study, 24 were allocated to experiment 1, 15 to experiment 2, and 16 to experiment 3. They received intervention for 20 min on different days: (1) NMES combined with tsDCS (NMES + tsDCS), (2) NMES combined with sham tsDCS (NMES + sham tsDCS), and (3) sham NMES combined with tsDCS (sham NMES + tsDCS). NMES was delivered to the right common peroneal nerve at 25 Hz with the intensity at 120% of the motor threshold. For tsDCS, the cathodal electrode was positioned on the thoracic 10th-12th vertebral levels, and the anodal electrode was located on the right shoulder. The stimulus intensity was 2.5 mA. In experiment 1, motor evoked potentials (MEPs) and short-latency intracortical inhibition (SICI) were measured by transcranial magnetic stimulation up to 60 min after stimulation. The spinal motor neurons' excitability was assessed by recording the posterior root muscle reflex (PRMR) induced via transcutaneous spinal cord stimulation in experiment 2, and the primary somatosensory cortex excitability was evaluated by recording the somatosensory evoked potentials (SEPs) in experiment 3 up to 15 min after stimulation. Results: Compared to before the stimulation, NMES + tsDCS significantly increased MEP for 60 min or more, and significantly decreased SICI immediately after. Conversely contrast, the PRMR significantly decreased immediately after, and SEPs were unchanged. Discussion: These results suggest that simultaneous afferent inputs from different stimulus positions critically induce primary motor cortex plasticity. The combined stimulation of NMES with tsDCS may facilitate the development of a new neurorehabilitation technique.

Accuracy of wristwatch-type photoplethysmography in detecting atrial fibrillation in daily life.

Aims: Detection of asymptomatic paroxysmal atrial fibrillation is challenging. Smartphone- or smartwatch-based photoplethysmography is efficient at detecting irregular rhythms using pulse waves but is too complex for older patients. We aimed to evaluate the detection accuracy of atrial fibrillation by a wristwatch-type continuous pulse wave monitor (PWM) in daily life. Methods and results: Patients at high risk of atrial fibrillation but with no history of atrial fibrillation (n = 163; mean CHADS2 score, 1.9) and patients with known atrial fibrillation (n = 123, including 34 with persistent atrial fibrillation) underwent PWM and telemetry electrocardiogram recording for 3 days. Risk of atrial fibrillation was judged using the 'Kyorin Atrial Fibrillation Risk Score', a scoring system based on previously reported atrial fibrillation risk scoring systems. The PWM assessed the presence of atrial fibrillation at 30 min intervals, and the results were compared with the telemetry electrocardiogram findings. The PWMs accurately diagnosed two patients with paroxysmal atrial fibrillation in the high-risk group. The PWMs accurately diagnosed 48 of the 55 patients with atrial fibrillation in the known-atrial fibrillation group. The PWM accuracy in detecting patients with atrial fibrillation was as follows: sensitivity, 98.0%; specificity, 90.6%; positive predictive value, 69.4%; negative predictive value, 99.5%. The respective values for intervals with atrial fibrillation were 86.9%, 98.8%, 89.6%, and 98.5%. Conclusion: The wristwatch-type PWM has shown feasibility in detecting atrial fibrillation in daily life and showed the possibility of being used as a screening tool.

Left Atrial Reverse Remodeling Following the Modified Box Isolation with Centerline in Patients with Persistent Atrial Fibrillation.

Esophageal injury is a rare but serious complication of atrial fibrillation (AF) ablation. To minimize esophageal injury, our persistent AF (PerAF) protocol involves complete left atrial posterior wall (LAPW) and pulmonary vein (PV) isolation (box isolation), with a centerline away from the esophagus. However, there has been a concern that extensive LA isolation might deteriorate LA function. There has been a paucity of data on LA remodeling after box isolation. Therefore, we compared LA size pre- and post-box isolation with an LAPW centerline in patients with PerAF.Patients who underwent catheter ablation (CA) for PerAF between November 2016 and December 2018 were retrospectively evaluated.The LAPW, including all PVs, was completely isolated in 105 consecutive patients (75 men; mean age: 68 ± 10 years) with PerAF, including 58 patients with long-standing PerAF. During a follow-up of 660 ± 332 days, 76 patients (72%) were arrhythmia-free. The LA dimension (38 ± 6 mm versus 42 ± 7 mm; P < 0.0001) and volume index (38 ± 13 mL/m2 versus 47 ± 14 mL/m2; P < 0.0001) at 6 months post-ablation were significantly decreased in patients who maintained sinus rhythm compared to pre-ablation. In patients with recurrent AF/atrial tachycardia (AT), these parameters were also significantly decreased (P < 0.001, respectively).Box isolation with a posterior centerline has no esophageal complications and a high clinical success rate in patients with PerAF. Reverse remodeling could be achieved even when using extensive isolation of the PV and LAPW in patients with PerAF.

Stellate Ganglion Phototherapy Using Low-Level Laser: A Novel Rescue Therapy for Patients With Refractory Ventricular Arrhythmias.

OBJECTIVES: This study investigates the effect of stellate ganglion (SG) phototherapy in healthy participants and assesses its efficacy in suppressing electrical storm (ES) refractory to antiarrhythmic drugs and catheter ablation. BACKGROUND: Modulation of the autonomic nervous system has been shown to be an effective adjunctive therapy for ES. METHODS: Ten-minute SG phototherapy was performed twice weekly for 4 weeks in 20 healthy volunteers. To evaluate the acute and chronic effects of SG phototherapy, heart rate variability and serum concentrations of adrenaline, noradrenaline, and dopamine were obtained before phototherapy, immediately after the first phototherapy session, after 8 sessions of phototherapy, and 3 months after the first phototherapy session. In addition, the efficacy of SG phototherapy was evaluated in 11 patients with ES refractory to medication, sedation, and catheter ablation. RESULTS: In healthy participants, serum adrenaline concentration significantly decreased after phototherapy, whereas low-frequency power/high-frequency power significantly decreased during phototherapy. Moreover, the effect on heart rate variability did not last beyond 3 months. In the clinical pilot study, 7 patients had a suppression of ES after SG phototherapy; however, without maintenance therapy, 2 patients had a recurrence of ventricular arrhythmias. Furthermore, it did not control ES in 4 patients. CONCLUSIONS: SG phototherapy reduced sympathetic activity and may be a safe and effective adjunctive therapy to control ES in some patients, but its long-term efficacy remains unknown. Chronic phototherapy might help reduce ES recurrence.