Renal denervation reverses ventricular structural and functional remodeling in failing rabbit hearts.

Renal denervation (RDN) suppresses the activity of the renin-angiotensin-aldosterone system and inflammatory cytokines, leading to the prevention of cardiac remodeling. Limited studies have reported the effects of renal denervation on ventricular electrophysiology. We aimed to use optical mapping to evaluate the effect of RDN on ventricular structural and electrical remodeling in a tachycardia-induced cardiomyopathy rabbit model. Eighteen rabbits were randomized into 4 groups: sham control group (n = 5), renal denervation group receiving RDN (n = 5), heart failure group receiving rapid ventricular pacing for 1 month (n = 4), and RDN-heart failure group (n = 4). Rabbit hearts were harvested for optical mapping. Different cycle lengths were paced (400, 300, 250, 200, and 150 ms), and the results were analyzed. In optical mapping, the heart failure group had a significantly slower epicardial ventricular conduction velocity than the other three groups. The RDN-heart failure, sham control, and RDN groups had similar velocities. We then analyzed the 80% action potential duration at different pacing cycle lengths, which showed a shorter action potential duration as cycle length decreased (P for trend < 0.01), which was consistent across all groups. The heart failure group had a significantly longer action potential duration than the sham control and RDN groups. Action potential duration was shorter in the RDN-heart failure group than the heart failure group (P < 0.05). Reduction of conduction velocity and prolongation of action potential duration are significant hallmarks of heart failure, and RDN reverses these remodeling processes.

Genes Encoding Structurally Conserved Serpins in the Wheat Genome: Identification and Expression Profiles during Plant Development and Abiotic and Biotic Stress.

Serpins constitute a family of proteins with a very wide distribution in nature. Serpins have a well-conserved tertiary structure enabling irreversible protease inhibition or other specific biochemical functions. We examined the 189 putative wheat serpin genes previously identified by Benbow et al. (2019) via analysis of gene annotations (RefSeq v1.0) and combined our previous examinations of wheat ESTs and the 454 genome assembly. We found that 81 of the 189 putative serpin genes, plus two manually annotated genes, encode full-length, structurally conserved serpins. Expression of these serpin genes during wheat development and disease/abiotic stress responses was analysed using a publicly available RNAseq database. Results showed that the wheat LR serpins, homologous to Arabidopsis AtSerpin1 and barley BSZx, are ubiquitously expressed across all tissues throughout the wheat lifecycle, whereas the expression of other wheat serpin genes is tissue-specific, including expression only in the grain, only in the root, and only in the anther and microspore. Nine serpin genes were upregulated in both biotic and abiotic responses. Two genes in particular were highly expressed during disease and abiotic challenges. Our findings provide valuable information for further functional study of the wheat serpins, which in turn may lead to their application as molecular markers in wheat breeding.

Urban-rural differences in outcomes and management of vertebral fractures: A real-world observational study.

BACKGROUND: A fracture liaison services (FLSs) and its modified services reduce refractures and mortality and can be cost-effective. Limited studies have addressed whether urban-rural differences exist in vertebral fracture outcomes and management. Therefore, the aims of the study were to investigate any urban-rural differences in refracture, mortality, prescription pattern, and associated factors of vertebral fractures after receiving assistance from an FLSs. METHODS: Baseline characteristics and osteoporosis medication prescription patterns of participants were collected. After 1-year follow-up, mortality, refracture rate, and osteoporosis medication switching and adherence were evaluated. Multivariate logistic regressions were performed to identify baseline correlates on one-year mortality. RESULTS: There was higher mortality rate in the rural group but no urban-rural difference in the 1-year refracture rate after implementation of FLSs and medication management services (MMSs). The types of osteoporosis medications prescribed for both groups were similar, but participants in the rural group were less likely to change their osteoporosis medications during the 1-year follow-up timeframe and with lower adherence rate. The likelihood of being older and having chronic kidney disease, osteoarthritis, and neurological disease was higher in the rural group. CONCLUSION: Our multicomponent services have similar effectiveness in osteoporosis treatment between urban and rural areas. The overall adherence rate was lower in the rural group with higher mortality but no difference in the refracture rate in one year.

Lack of direct association between viral hepatitis and sleep disturbances.

Background: Individuals with chronic viral hepatitis are at increased risk of experiencing poor sleep quality and sleep disturbances. However, it remains unclear whether the sleep disorders associated with viral hepatitis are secondary to the comorbidities related to viral hepatitis or the direct effect of hepatitis viruses on sleep. This study investigated the direct impact of viral hepatitis B and C on sleep quality. Methods: Individuals with viral hepatitis B or C and their healthy counterparts were recruited for the present study, and they were evaluated with the Parkinson's Disease Sleep Scale-2, the Epworth Sleepiness Scale, and the Pittsburgh Sleep Quality Index in the absence of common comorbidities associated with viral hepatitis. Results: Neither hepatitis B nor hepatitis C was found to cause significant differences in insomnia symptoms or excessive daytime sleepiness. However, individuals with hepatitis C, but not hepatitis B, tended to be less likely to experience restlessness of the legs or arms at night. Conclusions: This study suggests that hepatitis viruses B and C may not cause a significant impact on sleep quality and related disorders directly. Sleep disturbances in individuals with chronic viral hepatitis may instead be attributable to hepatic decompensation or the comorbid factors associated with viral hepatitis.

Risk Factors for QT Prolongation in Patients with Chronic Hydroxychloroquine Use.

Background: Hydroxychloroquine is used as an antimalarial and immunomodulator, however it can induce QT prolongation that could potentially lead to fatal arrhythmia. We investigated changes in QT interval in long-term hydroxychloroquine users, and identified possible risk factors associated with significant QTc prolongation. Methods: We retrospectively enrolled 3603 patients who received long-term hydroxychloroquine treatment from 2009 to 2019, of whom 167 had electrocardiography (ECG) results before and during hydroxychloroquine therapy. Baseline characteristics, laboratory data, comorbidities, concurrent medications, and related clinical outcomes were reviewed. Results: Overall, 225 patients (6.2%) died within the study period, with 50 patients (1.4%) continuously receiving hydroxychloroquine treatment until death. Three patients had fatal ventricular arrhythmia. No significant change in corrected QT interval (QTc) was noted before and during hydroxychloroquine treatment (451.1 ± 39.9 ms vs. 456.0 ± 37.3 ms, P = 0.140) in the ECG cohort. Multivariable logistic regression showed that diabetes mellitus [odds ratio (OR): 9.55, 95% confidence interval (CI): 2.02-45.22; P = 0.005] and use of additional QT-prolonging drugs (OR: 2.89, 95% CI: 1.40-5.94; P = 0.004) were independent risk factors for significant QTc prolongation. Multiple linear regression, with the number of QT-prolonging drugs and comorbidities including diabetes mellitus, hypertension, and atrial fibrillation as explanatory variables, predicted QTc response (adjusted R2 = 0.385) in the long-term hydroxychloroquine users. Conclusions: In the long-term users of hydroxychloroquine, those with diabetes mellitus and concurrent use of additional QT-prolonging drugs were at a higher risk of significant QTc prolongation. Baseline QTc interval, concurrent medications, and comorbidities predicted QTc response.

10-Year Outcomes of Patients With Non-Paroxysmal Atrial Fibrillation Undergoing Catheter Ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is commonly performed in patients with non-paroxysmal atrial fibrillation (AF), but because very long-term follow-up results of RFCA are limited, we investigated the 10-year RFCA outcomes of non-paroxysmal AF.Methods and Results: We retrospectively enrolled 100 patients (89 men, mean age 53.5±8.4years) with drug-refractory symptomatic non-paroxysmal AF who underwent 3D electroanatomic-guided RFCA. Procedural characteristics at index procedures and clinical outcomes were investigated. In the index procedures, all patients had pulmonary vein isolation, 56 (56.0%), 48 (48.0%), and 32 (32.0%) underwent additional linear, complex fractionated atrial electrogram (CFAE) and non-pulmonary vein (NPV) foci ablations, respectively. After 124.1±31.7 months, 16 (16%) patients remained in sinus rhythm after just 1 procedure (3 with antiarrhythmic drugs [AAD]) and after multiple (2.1±1.3) procedures in 53 (53.0%) patients (22 with AAD). Left atrial (LA) diameter (hazard ratio HR 1.061; 95% confidence interval (CI) 1.020 to 1.103; P=0.003), presence of NPV triggers (HR 1.634; 95% CI 1.019 to 2.623; P=0.042) and undergoing CFAE ablation (HR 2.003; 95% CI 1.262 to 3.180; P=0.003) in the index procedure were independent predictors for recurrent atrial tachyarrhythmia. CONCLUSIONS: The 10-year outcomes of single RFCA in non-paroxysmal AF were unsatisfactory. Enlarged LA, presence of NPV triggers, and undergoing CFAE ablation in the index procedure independently predicted single-procedure recurrence. Multiple procedures are required to achieve adequate rhythm control.

The Beneficial Effects of Beta Blockers on the Long-Term Prognosis of Patients With Premature Atrial Complexes.

AIMS: Premature atrial complexes (PACs) have been reported to increase the risk of adverse cardiovascular outcomes. Beta blockers at low dosages may help to reduce PAC symptoms, but it is unclear whether they can improve long-term outcomes. METHODS: Patients enrolled from a Holter cohort in a medical referral center were stratified into high-burden (≥100 beats/24 h) and low-burden (<100 beats/24 h) sub-cohorts, and propensity score matching between treatment groups and non-treatment groups was conducted for each sub-cohort. RESULTS: In the high-burden sub-cohort, after propensity score matching, the treatment group and non-treatment group respectively had 208 and 832 patients. The treatment group had significantly lower mortality rates than the non-treatment group [hazard ratio (HR) = 0.521, 95% confidence interval (CI) = 0.294-0.923, p = 0.025], but there was no difference in new stroke (HR = 0.830, 95% CI = 0.341-2.020, p = 0.681), and new atrial fibrillation (HR = 1.410, 95% CI = 0.867-2.292, p = 0.167) events. In the low-burden sub-cohort, after propensity score matching, there were 614 patients in the treatment group and 1,228 patients in the non-treatment group. Compared to the non-treatment group, up to 40% risk reduction in mortality was found in the treatment group (HR = 0.601, 95% CI = 0.396-0.913, p = 0.017), but no differences in new stroke (HR =0.969, 95% CI = 0.562-1.670, p = 0.910) or atrial fibrillation (HR = 1.074, 95% CI = 0.619-1.863, p = 0.800) were found. CONCLUSIONS: Beta blockers consistently decreased long-term mortality in high-burden and low-burden patients. Interestingly, this effect was not achieved through reduction of new-onset stroke or AF, and further research is warranted.

"Pin Method" for Endoscopic Lumbar Interbody Fusion.

BACKGROUND: Endoscopic lumbar interbody fusion using a cage can have a similar fusion rate as minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) or open lumbar interbody fusion. Direct visual control during cage insertion is the key to prevent neural structure incarceration in endoscopic lumbar interbody fusion. Creating a track with any kind of retractor or cannula for cage insertion under fluoroscopic guidance is not safe enough, because the retractor and cannula can create many blind spots and can displace during cage insertion. METHOD: The pin method utilizes two flexible metallic guide pins inserted from the skin incision through the annulotomy site into the disk space until the anterior longitudinal ligament is reached under direct endoscopic monitoring. The two guide pins could be oriented parallel or perpendicular or even reduce to one or increase to many as needed to serve as a sliding track and a see-through barrier to prevent neural incarceration. RESULTS AND CONCLUSION: Two cases of L4/L5 grade 2 spondylolisthesis with neurogenic claudication were treated with endoscopic lumbar interbody fusion with 1-year follow-up, and the visual analog scale (VAS) score, Oswestry Disability Index (ODI) score, EuroQol five-dimensional questionnaire (EQ-5D, %) score, and modified Macnab score all improved greatly in both. The author developed an original, cheap, accessible, and safe method called the "pin method," which can be used in both full-endoscopic and biportal surgery and can apply to various approaches and has no limitation on the size and shape of the cage.

Treatment of Pathologic Peritrochanteric Fractures Using Sliding Hip Screws Augmented with Cerclage Reconstruction Plates.

We proposed a new method to augment the traditional sliding hip screw (SHS) with cerclage reconstruction plates to treat pathologically impending and actual peritrochanteric fractures as well as to revise open reductions and internal fixations to increase the construct strength against the shearing force, thus reducing the implant failure rate. In this retrospective study, patients with peritrochanteric pathology with at least two years of follow-up who underwent augmentation with cerclage reconstruction plates (modified SHS) and conventional SHS between 1 May 2015 and 31 May 2017 were divided into groups A (n = 12) and B (n = 28), respectively. Demographic data, surgery duration, blood loss, complications, and local radiotherapy were analyzed. The average surgery duration was significantly longer in group A (p = 0.013). The estimated intraoperative and perioperative blood losses were not significantly different between the groups. The implant survival rates were not significantly different under competing risk analysis. The success rate of a revision surgery with modified SHS was excellent, and implant survival time was >2 years, as observed with the previous SHS constructs. Subtrochanteric region involvement and a postoperative visual analog scale ≥4 could be risk factors of implant failure and revision surgery. This technique can be an alternative treatment for difficult pathologic peritrochanteric fractures, especially those with previous plating failure.

Comparison of lesion characteristics between conventional and high-power short-duration ablation using contact force-sensing catheter in patients with paroxysmal atrial fibrillation.

BACKGROUND: Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. METHODS: Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25-30 W, force-time integral = 400 g s, n = 40) or with HPSD (power control: 40-50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. RESULTS: 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P < 0.01). In the conventional group, most type A lesions were at the right pulmonary vein (RPV) posterior wall (50.2%) whereas in the HPSD group, most type A lesions were at the RPV anterior wall (44.0%) (P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03). CONCLUSION: Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation.

Improvement of p-Type AlGaN Conductivity with an Alternating Mg-Doped/Un-Doped AlGaN Layer Structure.

Using molecular beam epitaxy, we prepared seven p-type AlGaN samples of ~25% in Al content, including six samples with Mg-doped/un-doped AlGaN alternating-layer structures of different layer-thickness combinations, for comparing their p-type performances. Lower sheet resistance and higher effective hole mobility are obtained in a layer-structured sample, when compared with the reference sample of uniform Mg doping. The improved p-type performance in a layer-structured sample is attributed to the diffusion of holes generated in an Mg-doped layer into the neighboring un-doped layers, in which hole mobility is significantly higher because of weak ionized impurity scattering. Among the layer-structured samples, that of 6/4 nm in Mg-doped/un-doped thickness results in the lowest sheet resistance (the highest effective hole mobility), which is 4.83 times lower (4.57 times higher) when compared with the sample of uniform doping. The effects of the Mg-doped/un-doped layer structure on p-type performance in AlGaN and GaN are compared.

Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome.

Premature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose-response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

Clinical significance of J waves with respect to substrate characteristics and ablation outcomes in patients with arrhythmogenic right ventricular cardiomyopathy.

AIMS: J-wave syndrome in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to an increased risk of ventricular arrhythmia. We investigated the significance of J waves with respect to substrate manifestations and ablation outcomes in patients with ARVC. METHODS AND RESULTS: Forty-five patients with ARVC undergoing endocardial/epicardial mapping/ablation were studied. Patients were classified into two groups: 13 (28.9%) and 32 (71.1%) patients with and without J waves, respectively. The baseline characteristics, electrophysiological features, ventricular substrate, and recurrent ventricular tachycardia/fibrillation (VT/VF) were compared. Among the 13 patients with J waves, only the inferior J wave was observed. More ARVC patients with J waves fulfilled the major criteria of ventricular arrhythmias (76.9% vs. 21.9%, P = 0.003). Similar endocardial and epicardial substrate characteristics were observed between the two groups. However, patients with J waves had longer epicardial total activation time than those without (224.7 ± 29.9 vs. 200.8 ± 21.9 ms, P = 0.005). Concordance of latest endo/epicardial activation sites was observed in 29 (90.6%) patients without J waves and in none among those with J waves (P < 0.001). Complete elimination of endocardial/epicardial abnormal potentials resulted in the disappearance of the J wave in 8 of 13 (61.5%) patients. The VT/VF recurrences were not different between ARVC patients with and without J waves. CONCLUSION: The presence of J waves was associated with the discordance of endocardial/epicardial activation pattern in terms of transmural depolarization discrepancy in patients with ARVC.

The Burden of Ventricular Premature Complex Is Associated With Cardiovascular Mortality.

BACKGROUND: Ventricular premature complex (VPC) is one of the most common ventricular arrhythmias. The presence of VPC is associated with an increased risk of heart failure (HF). METHOD: We designed a single-center, retrospective, and large population-based cohort to clarify the role of VPC burden in long-term prognosis in Taiwan. We analyzed the database from the National Cheng Kung University Hospital-Electronic Medical Record (NCKUH-EMR) and NCKUH-Holter (NCKUH-Holter). A total of 19,527 patients who underwent 24-h Holter ECG monitoring due to palpitation, syncope, and clinical suspicion of arrhythmias were enrolled in this study. RESULTS: The clinical outcome of interests involved 5.65% noncardiovascular death and 1.53% cardiovascular-specific deaths between 2011 and 2018. Multivariate Cox regression analysis, Fine and Gray's competing risk model, and propensity score matching demonstrated that both moderate (1,000-10,000/day) and high (>10,000/day) VPC burdens contributed to cardiovascular death in comparison with a low VPC burden (<1,000/day). CONCLUSION: A higher VPC burden via Holter ECG is an independent risk factor of cardiovascular mortality.

Successful trans-septal ablation of a left concealed accessory pathway in a patient receiving surgical mitral valve repair and mechanical aortic valve replacement.

We presented a case of severe aortic regurgitation and moderate mitral regurgitation s/p aortic valve replacement and mitral valve repair. Deterioration of tachyarrhythmia attacks was noted. In EP study, left lateral accessory pathway with orthodromic atrioventricular reentrant tachycardia was identified. We successfully ablated the accessory pathway by trans-septal approach. Even though trans-septal approach currently is a daily routine of invasive interventional electrophysiologists, in this case, we want to emphasize and illustrate the distance between true mitral annulus and coronary sinus. Unrecognizing this concept could result in efficacy and safety of catheter-based therapy.

Altered balance control in thoracic adolescent idiopathic scoliosis during obstructed gait.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity during adolescence, leading to altered postural control with compromised stability. To identify the effects of AIS on whole-body balance control during obstacle-crossing, 14 adolescents with Lenke 1 thoracic AIS and 14 healthy controls were compared in terms of the inclination angle (IA) of the body's center of mass (COM) relative to the center of pressure (COP), the rate of change of IA (RCIA) and the jerk index of IA. Between-side comparisons were also performed for the AIS group. The patients showed less smooth COM-COP motion in the sagittal plane with significantly increased anterior RCIA and IA jerk index during crossing with either the concave side (p = 0.001) or the convex side (p = 0.001) leading when compared to healthy controls. In the frontal plane, the patients showed close-to-zero RCIA (p = 0.002) while crossing with the leading limb, with an increased IA magnitude (p = 0.039) only while crossing with the concave-side limb leading. The patients with Lenke 1 thoracic AIS were found to cross obstacles with altered, compromised COM-COP control in both sagittal and frontal planes when compared to healthy controls. The results suggest that the thoracic spinal deformity in Lenke 1 AIS affects the whole-body balance control during obstacle-crossing, which should be monitored for signs of increased risk of loss of balance in the management of such patient groups.