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Background: Acute myocardial infarction (AMI) is a severely life-threatening cardiovascular disease. Previous research has identified an association between the P2X7 receptor (P2X7R) and the development of atherosclerosis. However, the correlation of its expression with the clinical prognosis of patients with AMI remains unclear. The present study aimed to investigate the potential role of P2X7R in Chinese patients with AMI. Methods: Seventy-nine patients with AMI and 48 controls were consecutively enrolled in this prospective observational study. Circulating P2X7R mRNA expression levels and other clinical variables were determined upon admission to the hospital. Patients were followed up for 360 days, and the end-point was considered as the occurrence of major adverse cardiovascular events (MACE). Results: Circulating P2X7R mRNA expression level in peripheral blood mononuclear cells of patients with AMI were significantly higher than those in controls and had promising diagnostic ability of AMI with an area under the curve of 0.928. Furthermore, P2X7R was demonstrated to be correlated positively with the severity of coronary artery stenosis. Additionally, this is the first study to indicate that higher P2X7R mRNA expression is associated with a higher rate of MACE within 360 days after AMI. Conclusions: The present study showed that the circulating level of P2X7R was elevated in AMI patients and was closely associated with the severity of coronary artery stenosis and prognosis of AMI.

Aims His–Purkinje conduction system pacing (HPCSP) utilizing His (HBP) or left bundle branch pacing (LBBP) in patients with atrial fibrillation (AF) and wide QRS duration has not been well studied. We assessed the benefit of left bundle branch block (LBBB) correction during HPCSP in AF patients undergoing atrioventricular junction (AVJ) ablation with LBBB, compared with those with narrow QRS duration. Methods and results This is an observational study in consecutive patients with typical LBBB or narrow QRS duration in whom we attempted HPCSP after AVJ ablation for refractory AF with a left ventricular ejection fraction (LVEF) ≤ 50%. Echocardiographic responses and clinical outcomes were assessed at baseline and during 1 year of follow‐up. A total of 178 patients were enrolled, of which 170 achieved AVJ ablation + permanent HPCSP (age 69.3 ± 10.1 years; LVEF 34.3 ± 7.7%), 133 (78.2%) patients had a narrow QRS duration, and 37 (21.2%) had an LBBB. The QRS duration changed from a baseline of 159.7 ± 16.6 ms to a paced QRS duration of 110.4 ± 12.7 ms in the LBBB cohort and from 95.6 ± 10.4 to 100.8 ± 14.5 ms (both P

Aims His-bundle pacing (HBP) combined with atrioventricular node (AVN) ablation has been demonstrated to be effective in patients with atrial fibrillation (AF) and heart failure (HF) during medium-term follow-up and there are limited data on the risk analysis of adverse prognosis in this population. In this study, we aimed to evaluate the long-term performance of HBP following AVN ablation in AF and HF. Methods and results From August 2012 to December 2017, consecutive AF patients with HF and narrow QRS who underwent AVN ablation and HBP were enrolled. The clinical and echocardiographic data, pacing parameters, all-cause mortality, and heart failure hospitalization (HFH) were tracked. A total of 94 patients were enrolled (age 70.1 ± 10.5 years; male 57.4%). Acute HBP were achieved in 89 (94.7%) patients with successful permanent HBP combined with AVN ablation in 81 (86.2%) patients. Left ventricular ejection fraction (LVEF) improved from 44.9 ± 14.9% at baseline to 57.6 ± 12.5% during a median follow-up of 3.0 (IQR: 2.0–4.4) years (P Conclusion His-bundle pacing combined with AVN ablation was effective in patients with AF and drug-refectory HF. High PASP, high Scr, or low LVEF at baseline was independent predictors of composite endpoint of all-cause mortality or HFH.

PURPOSE: To evaluate the effectiveness of propranolol at mitigating FDG uptake in brown adipose tissue (BAT) of pediatric patients with known or suspected malignancies. METHODS: PET/CT scans of 3 cohorts of patients treated from 2005–2017 were scored for presence of FDG uptake by BAT at 7 sites: right or left neck/supraclavicular area, right or left axilla, anterior mediastinum, posterior thorax, and abdomen/pelvis. Uptake was scored as follows: 0-none, 1-mild uptake < liver, 2-moderate uptake = liver, 3-intense uptake > liver. Group 1 consisted of 323 patients (630 scans) who had no specific preparation to mitigate FDG uptake by BAT. Group 2 consisted of 345 patients (705 scans) who underwent only warming in an uptake room with a fixed temperature at 24°C. Group 3 consisted of 622 patients (1457 scans) who underwent warming. In Group 3, patients 8 years and older, 471 patients (1114 scans), were also pre-medicated with oral propranolol 60 minutes before injection of FDG. Generalized estimation equation, using the logit link method, was used to model the relationship between the incidence of BAT score > 0, in any site, as a function of age, sex, seasonal effect, and body surface area (BSA). RESULTS: In patients aged 8 years or older, the incidence of BAT uptake was 35 – 44% and declined to 15% with propranolol. BAT was most frequent in the neck (26%), axilla (18%), posterior thorax (18%), mediastinum (14%), and abdomen/pelvis (8%); BAT was less common in warm months (p=0.001). No substantial benefit was shown with pre-injection warming alone. No significant effect was found for age, sex, or BSA separately. When BAT uptake was present, it was usually intense. CONCLUSION: Propranolol preparation minimizes FDG uptake by BAT and should be considered routine for pediatric FDG PET/CT cancer-related protocols in children, adolescents, and young adults.

We performed left bundle pacing combined with atrioventricular nodal (AVN) ablation in a patient with persistent atrial fibrillation and refractory symptomatic heart failure. The major findings were new-onset intrinsic and paced QRS morphology of right bundle branch block (RBBB) pattern after AVN ablation which was performed at a more atrial site compared with the pacing site and the paced RBBB pattern could not be corrected regardless of the pacing output. Longitudinal dissociation cannot explain this observation, while anatomical separation could. We also confirm this was proximal left bundle pacing rather than His bundle pacing.

PURPOSE Stratum 1 of ACNS1123 (ClinicalTrials.gov identifier: NCT01602666 ), a Children’s Oncology Group phase II trial, evaluated efficacy of reduced-dose and volume of radiotherapy (RT) in children and adolescents with localized nongerminomatous germ cell tumors (NGGCTs). The primary objective was to evaluate the impact of reduced RT on progression-free survival (PFS) with a goal of preserving neurocognitive function. PATIENTS AND METHODS Patients received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide, as used in the Children’s Oncology Group predecessor study (ACNS0122; ClinicalTrials.gov identifier: NCT00047320 ). Patients who achieved a complete response (CR) or partial response (PR) with or without second-look surgery were eligible for reduced RT, defined as 30.6 Gy whole ventricular field and 54 Gy tumor-bed boost, compared with 36 Gy craniospinal irradiation plus 54 Gy tumor-bed boost used in ACNS0122. RESULTS A total of 107 eligible patients were enrolled. Median age was 10.98 years (range, 3.68 to 21.63) and 75% were male. Sixty-six of 107 (61.7%) achieved a CR or PR and proceeded to reduced RT. The 3-year PFS and overall survival and standard error values were 87.8% ± 4.04% and 92.4% ± 3.3% compared with 92% and 94.1%, respectively, in ACNS0122. There were 10 recurrences, prompting early study closure; however, after a retrospective central review, only disease in eight of 66 (12.1%) patients eligible for reduced RT subsequently progressed; six patients had distant spinal relapse alone and two had disease with combined local plus distant relapse. Serum and CSF α-fetoprotein and β-human chorionic gonadotropin levels were not associated with PFS. CONCLUSION Patients with localized NGGCT who achieved a CR or PR to chemotherapy and received reduced RT had encouraging PFS similar to patients in ACNS0122 who received full-dose craniospinal irradiation. However, the patterns of failure were distinct, with all patients having treatment failure in the spine.

Background The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3–21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. Methods Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. Results One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. Conclusions While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.

Background: Left bundle branch pacing (LBBP) is a novel physiological pacing and previous studies have confirmed the feasibility and safety of it. The incidence of complications in LBBP is relatively low as reported. Here we present a case of interventricular septal hematoma complicating LBBP lead implantation.Case summary: LBBP was achieved for treatment of high-grade atrioventricular block in a 67-year-old female. Chest pain began 1 h after implantation when the electrocardiogram showed ST-T changes. Then bedside echocardiography confirmed the formation of interventricular septal hematoma. Urgent coronary angiography showed the contrast agent retention and overflow in the interventricular septum. The symptom was relieved half an hour later. Echocardiogram performed 2 h later revealed the size of the hematoma was the same as before. The electrocardiography, coronary angiography and CTA confirmed the resolution of the hematoma at 1-month follow-up. Pacing parameters and cardiac function remained stable during 6-month follow-up.Conclusion: This is the first reported case describing the clinic features and management of interventricular septum hematoma complicating LBBP. The importance of routine echocardiograms after implantation for identifying the hematoma should be highlighted.

Because of its stability, hydrogen semiconductor sensor has become one of the most important means widely used in hydrogen monitoring. Sensor fault identification is of great significance. Traditional fault diagnosis methods, such as machine learning, are complicated in operation and network structure. In this paper, an improved method based on traditional CNN network is proposed for fault detection of hydrogen iron oxide sensors. Different from the previous method, it is not necessary to filter the data first, and the data will be converted into two-dimensional gray image as the input of the neural network. The excitation function of CNN network is optimized and combined with the wavelet analysis method, the wavelet basis function is used as the excitation function to detect and identify the fault. At the same time, different from the previous fault diagnosis methods, this paper has achieved good results in multi-fault detection and identification, and improved the accuracy of multi-fault diagnosis while avoiding the complex network structure.

His bundle pacing (HBP) can reverse left ventricular (LV) remodeling in patients with right ventricular (RV) pacing-induced cardimyopathy (PICM) but may be unable to correct infranodal atrioventricular block (AVB). Left bundle branch pacing (LBBP) results in rapid LV activation and may be able to reliably pace beyond the site of AVB. Our study was conducted to assess the feasibility, safety, and outcomes of permanent LBBP in infranodal AVB and PICM patients. Patients with infranodal AVB and PICM who underwent LBBP for cardiac resynchronization therapy (CRT) were included. Clinical evaluation and echocardiographic and electrocardiographic assessments were recorded at baseline and follow-up. Permanent LBBP upgrade was successful in 19 of 20 patients with a median follow-up duration of 12 months. QRS duration (QRSd) increased from 139.3 ± 28.0 ms at baseline to 176.2 ± 21.4 ms (P < 0.001) with right ventricular pacing (RVP) and was shortened to 120.9 ± 15.2 ms after LBBP (P < 0.001). The mean LBBP threshold was 0.7 ± 0.3 V at 0.4 ms at implant and remained stable during follow-up. The left ventricular ejection fraction (LVEF) increased from 36.3% ± 6.5% to 51.9% ± 13.0% (P < 0.001) with left ventricular end-systolic volume (LVESV) reduced from 180.1 ± 43.5 to 136.8 ± 36.7 ml (P < 0.001) during last follow-up. LBBP paced beyond the site of block, which results in a low pacing threshold with a high success rate in infranodal AVB patients. LBBP improved LV function with stable parameters over the 12 months, making it a reasonable alternative to cardiac resynchronization pacing via a coronary sinus lead in infranodal AVB and PICM patients.

Coupling among waveguides plays an important role in photonic integration, while it usually suffers from large wavelength dispersion and structural sensitivity that brings difficulties in broadband and robust photonic chip devices. Here, we report a new strategy of dispersion engineering of coupled waveguides by artificial gauge field (AGF) with curved trajectories, which gives rise to a dispersionless broadband coupler function in high-density silicon waveguides (waveguide pitch <λ/2). It is found that the artificial gauge field can generate an inverse dispersion to compensate for the dispersion of conventional waveguide coupling. As such, the coupling between the waveguides can be stable in a broad bandwidth. Based on this design, we demonstrate compact directional and 3dB couplers that show broadband dispersionless coupling of light with wavelength from 1400 to 1650 nm, which also exhibit robustness to considerably large structural variations ~150 nm (75% structural deviation). Furthermore, using the AGF coupler as the building block, we significantly demonstrate a three-level-cascaded waveguide network to route the broadband light to the desired ports, showing a tremendous advantage over the conventional counterparts. Our work exploits the artificial gauge field to integrated photonics and demonstrates the possibility of massive, broadband, robust and dense photonic integrations.

WHAT IS KNOWN AND OBJECTIVE Drug-induced immune haemolytic anaemia (DIIHA) is rare and difficult to diagnose. In diabetic patients, the diagnosis of DIIHA is even harder. In the current study, we report on two cases of ceftizoxime-induced immune haemolytic anaemia in diabetic patients. CASE DESCRIPTION Two diabetic patients (suffering from type 1 and type 2 diabetes mellitus, respectively) presented with rapid reduction in haemoglobin levels when exposed to ceftizoxime (2g q12h). They both achieved symptom improvement after switching to another antibiotic. WHAT IS NEW AND CONCLUSION The persistently reduced haemoglobin levels in diabetic patients may contribute to DIIHA. Reviewing patients' medical records might provide some valuable clues as to the causes of DIIHA.

PURPOSE: Most pediatric spinal tumors are low-grade gliomas (LGGs). Characterization of these tumors has been difficult given their heterogeneity and rare incidence. The objective was to characterize such tumors diagnosed at our institution. METHODS: Spinal tumors diagnosed in our pediatric patients between 1984 and 2014 were reviewed retrospectively. Demographics, presentation, pathology, imaging, management, and sequelae were examined. RESULTS: Forty patients had spinal LGG tumors, 24 (62%) of which were pilocytic astrocytomas. The most common initial presentations were pain (n=15), partial extremity paralysis (n=13), and ataxia (n=11), with the diagnosis frequently delayed by months (median=5.9 months, range=4 days-6.2 years). Twenty-nine patients had some tumor resection, and 8 required adjuvant therapy with chemotherapy (n=4) or radiation (n=4) post-resection. Ten other patients received only biopsy for histologic diagnosis, who were treated with chemotherapy (n=4) or radiation (n=5) post biopsy. Tumor progression was noted in 16 patients (2 after gross-total resection; 10, partial resection; and 4, biopsy). During the evaluation period, 3 patients died secondary to tumor progression. BRAF status could have shortened progression-free survival: patients with BRAFV600E mutations (n=3) all experienced progression within 10 months. Long-term sequelae of the disease/treatment were mostly residual neurologic deficits (paresthesia, paralysis), chemotherapy-induced hearing loss, and scoliosis. CONCLUSIONS: Spinal LGG is a rare entity with significant long-term effects. Although surgery is the most common initial treatment option, more in-depth analysis of molecular biomarkers may improve stratification and prognostication.

In this letter, a compact self-decoupled antenna structure is proposed for the fifth-generation multiple-input--multiple-output (MIMO) operation in mobile terminals. The antenna structure consists of two adjacent antenna elements, which are placed very close (1.2 mm or 0.014λ) to each other and located on the same side of the system ground plane. By sharing one common grounding branch for the two adjacent antenna elements, a compact self-decoupled antenna pair can be obtained. The MIMO antenna system is optimized to operate in the 3.5 GHz (3.4–3.6 GHz) band with isolation better than –17 dB. An antenna prototype is fabricated, and good agreement between simulation and measurement is obtained.

Background Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory, as measured by verbal recall. Methods Eighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores. Results Median neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope = −0.01 standard deviation [SD]/year, P < 0.001), total recall (slope = −0.09 SD/y, P = 0.005), and long-delay recall (slope = −0.01 SD/y, P = 0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope = −0.001 SD/y, P = 0.019) or left hippocampus (slope = −0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = −0.002, P = 0.025). In children Conclusion In this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.

Background Low-grade gliomas (LGGs) and low-grade glioneuronal tumors (LGGNTs) diagnosed during the first year of life carry unique clinical characteristics and challenges in management. However, data on the treatment burden, outcomes, and morbidities are lacking. Methods A retrospective study of LGGs and LGGNTs diagnosed in patients younger than 12 months at St. Jude Children's Research Hospital (1986-2015) was conducted. Results For the 51 patients (including 31 males), the mean age at diagnosis was 6.47 months (range, 0.17-11.76 months), and the mean follow-up period was 11.8 years (range, 0.21-29.19 years). Tumor locations were hypothalamic/optic pathway (61%), hemispheric (12%), brainstem (12%), cerebellar (8%), and spinal (8%). There were 41 patients with histological diagnoses: 28 had World Health Organization grade 1 tumors, 6 had grade 2 tumors, and 7 had an LGG/LGGNT not definitively graded. Forty-one patients required an active intervention at diagnosis. Throughout their treatment course, 41 patients eventually underwent tumor-directed surgeries (median, 2 surgeries; range, 1-6), 39 received chemotherapy (median, 2 regimens; range, 1-13), and 21 received radiotherapy. Forty patients experienced disease progression (median, 2 progressions; range, 1-18). Ten patients died of progression (n = 5), malignant transformation (n = 2), a second cancer (n = 2), or a shunt infection (n = 1). The 10-year overall survival, progression-free survival, and radiation-free survival rates were 85% ± 5.3%, 16.9% ± 5.3%, and 51.2% ± 7.5%, respectively. Forty-nine patients experienced health deficits (eg, endocrinopathies, obesity, seizures, visual/hearing impairments, neurocognitive impairments, and cerebrovascular disease). Predictors of progression and toxicities were defined. Conclusions Infantile LGG/LGGNT is a chronic, progressive disease universally associated with long-term morbidities and requires multidisciplinary intervention.

Background and PurposeThe profibrotic and proinflammatory effects induced by doxorubicin (DOX) are key processes in the development of serious heart damage. Lack of effective drugs and the unclear mechanisms of its side effects limit the clinical treatment of DOX-induced cardiac injury. This study aimed to explore the protective role of LCZ696 and the potential mechanism of Toll-like receptor 2 (TLR2) in doxorubicin-induced cardiac failure.Experimental ApproachDOX (5 mg/kg/week, three times) was used to establish a chronic cardiomyopathy mouse model. Heart function tests, pathology examinations and molecular biology analyses were used to explore the effects of LCZ696 and TLR2 deficiency in vivo and in vitro. Computational docking was applied to predict the key residues for protein-ligand interaction.Key ResultsThe EF% declined, and the LVIDd, pro-fibrosis marker levels and NF-κB related inflammatory response increased in the chronic cardiomyopathy group induced by DOX. LCZ696 treatment and TLR2 deficiency reversed these heart damage in vivo. In H9C2 cells, pre-treatment with LCZ696 and TLR2 knockdown suppressed the DOX-induced high expression of profibrotic and proinflammatory markers. Moreover, DOX notably increased the TLR2-MyD88 interaction in vivo and in vitro, which was inhibited by LCZ696. Finally, we demonstrated the direct interaction between DOX and TLR2 via hydrogen bonds on Pro-681 and Glu-727 and Pro-681 and Ser-704 may be the key residues by which LCZ696 affects the interaction between DOX and TLR2.Conclusion and ImplicationsLCZ696 prevents DOX-induced cardiac dilation failure, fibrosis and inflammation by reducing the formation of TLR2-MyD88 complexes. LZC696 may be a potential effective drug to treat DOX-induced heart failure.

Background: Higher serum gamma-glutamyltransferase (GGT) is associated with high risk of hypertension. We aimed to examine the association between sex-specific serum GGT levels and incident of hypertension in a Chinese population without metabolic syndrome.Methods: Participants who were free of hypertension and metabolic syndrome from the First Affiliated Hospital of Wenzhou Medical University between 2009 and 2014 were included. Participants were grouped into sex-specific quartiles of GGT levels (Q1–Q4) defined as: ≤19, 20–26, 27–38, and ≥39 U/L for male; ≤12, 13–15, 16–19, and ≥20 U/L for female. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of hypertension according to sex-specific quartiles of GGT levels. Kaplan–Meier analysis and interaction analysis were conducted.Results: Among 38,806 participants included (average age 36.0 years, 54.0% men), 4,505 of them developed hypertension. In the overall study population, using Q1 as the reference group, participants in Q2, Q3, and Q4 showed a higher risk of developing hypertension, with HRs (95% CIs) of 1.126 (1.029–1.232), 1.187 (1.083–1.302), and 1.300 (1.182–1.431), respectively (P < 0.001), after adjusting for known confounders. Sex-specific analysis showed that the adjusted HRs for participants in Q4 (reference: Q1) were greater in females [1.321 (1.100–1.586, P < 0.001)] than in males [1.268 (1.133–1.420, P < 0.001)] (P for interaction = 0.047). Moreover, interaction analysis showed that this association was consistently observed when the participants were stratified by age, body mass index, and fatty liver status.Conclusion: Among Chinese adults without metabolic syndrome, serum GGT level was positively associated with incidence of hypertension, and the association was stronger in females than in males.

Background Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes. Methods We present results from children with recurrent/progressive OPHGs treated on a PBTC (Pediatric Brain Tumor Consortium) phase II trial evaluating efficacy of selumetinib (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase II dose (25mg/m2/dose BID) for a maximum of 26 courses. Results Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease, and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%), and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia, and rash. Conclusions Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes.

Background: Early reports suggest adverse events following proton therapy (PT) for childhood cancer are more prevalent. We evaluated treatment-failure and toxicity following Pencil Beam Scanning (PBS)-PT in children. Methods: The single-institution Phase IV trial screened 856 children, of which 528 were eligible for PBS-PT, and 500 enrolled in SJPROTON1 from 2017–2020. The median follow-up was 2.1 years (range 1.1-4.4). The primary objective was the cumulative incidence (CI) of ≥grade 3 non-hematologic, PBS-PT attributable toxicity by CTCAE v4.0. Additional outcomes included PBS-PT toxicity attributable hospitalization, procedures, and treatment-related mortality. Toxicities including necrosis, vasculopathy, neurologic deficits, and fracture/osteoradionecrosis were further characterized (any grade). Competing risk regression was used to evaluate predictors of ≥grade 3 PBS-PT attributable toxicity. Findings: At two years, the event-free survival was 73.2% (95% CI, 68.9%-77.8%). Distant and local failure predominated with a 2-year CI of 16.5% (95% CI 13.1-20.4) and 6.8% (95% CI 4.6-9.5) respectively. The 4 year CI of ≥grade 3 toxicity was 24.5%; including necrosis (3.7%), neurologic deficit (2.9%), and fracture/osteoradionecrosis (0.79%). The rates of PBS-PT-toxicity attributable hospitalization and procedures were 3.9% and 7.6%. Predictors of any ≥grade 3 toxicity included baseline total toxicity burden (TTB) (HR 1.043, 95% CI 1.012-1.07, p=0.007), and mixed photon/PBS-PT (HR 2.62, 95% CI 1.51-4.54, p=0.006) in CNS patients, and pelvic radiotherapy (HR 4.25, 95% CI 1.08-16.72, p=0.038), and TTB (HR 1.1, 95% CI 1.04-1.16, p=0.002) in non-CNS patients. Interpretation: PBS-PT yields a low incidence of toxicity, but subsets are at increased risk, and may require additional procedures or hospitalization. Funding: This work was supported by ALSAC and Cancer Center Core Grant CA21765. Declaration of Interest: None to declare. Ethical Approval: The SJPROTON1 trial was reviewed and approved by the Institutional Review Board at St. Jude. Informed consent was obtained from the parent, caregiver, or patient, with assent from the patient, as appropriate.

BackgroundDiabetes and cancer are both multifactorial diseases, and epidemiologic evidence indicates that diabetes may be associated with the incidence of certain types of cancer. In diabetes the risk of pancreatic cancer is increased significantly. However, whether certain diabetes treatment being related with the risk of pancreatic cancer remains unclear. In this report, we presented a case of pancreatic ductal adenocarcinoma in a diabetic patient in China after being treated with liraglutide, a novel glucagon-like peptide-1 (GLP-1) analog.Case reportA 71-year-old Han Chinese man who had had a type 2 diabetes for 25 years presented at the endocrinology department with discomfort in the left upper quadrant of abdomen for 10 days. The patient’s vital signs and laboratory findings were unremarkable except for the elevated level of carbohydrate antigen (CA19-9). The upper abdomen routine enhanced computed tomography (CT) scan showed low density of the pancreatic body and tail, and the histopathological result of the pancreatic biopsy samples was pancreatic ductal adenocarcinoma with regional lymph node metastasis. We reviewed his former medical records and found that liraglutide was added to his hypoglycemic treatment regimen 20 months ago. At that time, the level of tumor biomarkers and upper abdomen routine CT were unremarkable. We estimated the causality between liraglutide and pancreatic cancer by the Naranjo Adverse Drug Reaction Probability scale and WHO-Uppsala Monitoring Centre (WHO-UMC) system, and the causality turned out to be possible.ConclusionOur report suggests that liraglutide may be related with the genesis and development of pancreatic cancer and also highlights the importance of regular checkups in diabetic patients treated with liraglutide. However, our report has some notable limitations, and further longer-term follow-up trials with larger sample should be conducted in future to assess the causality between liraglutide and pancreatic cancer.

This study sought to assess the predictive value of the proposed electrocardiogram and intracardiac electrogram characteristics for confirmation of left bundle branch (LBB) capture.Previously proposed criteria to distinguish left bundle branch pacing (LBBP) and left ventricular septum (LVS) pacing (LVSP) have not been fully validated.A His bundle pacing lead, an LBBP lead, and a multielectrode catheter at the LVS were placed. Direct LBB capture was defined as demonstration of retrograde His potential on the His bundle pacing lead and/or anterograde left conduction system potentials on the multielectrode catheter during LBBP. The routinely used parameters-His, LBB potential, time from stimulus to peak ventricular activation (Stim-LVAT), and paced QRS morphology during LVSP and LBBP at various depths and outputs were analyzed.Thirty patients (21 non-left bundle branch block [LBBB], 9 LBBB) who demonstrated direct LBB capture using the defined criteria were included. The proportion of paced right bundle branch block was 100% during LBB capture in all patients compared to 23.4% in non-LBBB and 44.4% in LBBB during LVSP. LBB potential was recorded in all patients during intrinsic rhythm (non-LBBB group) or His corrective pacing in LBBB. Paced QRS duration was longer during selective LBBP compared to nonselective LBBP or LVSP only. All patients with characteristics of selective LBBP or abrupt decrease in Stim-LVAT of ≥10 ms demonstrated LBB capture.Direct LBB capture can be confirmed by recording retrograde His potential and anterograde left conduction system potentials. Abrupt decrease in Stim-LVAT of ≥10 ms and demonstration of selective LBBP could be used as simple criteria to confirm LBB capture.

Introduction: Left bundle branch pacing (LBBP) is a novel pacing method and has been proven to have low and stable pacing thresholds. However, data on large numbers of patients with long-term follow-up is still needed to evaluate its feasibility and safety. Hypothesis: To evaluate the feasibility and safety of LBBP in a large sample with long-term follow up. Methods: This study prospectively enrolled 632 consecutive patients with left bundle branch block, AV block or sick sinus syndrome with attempted LBBP from April 2017 to July 2019. Pacing parameters, ECG, echocardiographic measurements, complications were assessed at implant, and during follow-up of 1, 6, 12 and 24 months. Results: LBBP was successful in 618/632 (97.8%) patients according to the strict criteria for LBB capture. Mean follow-up time was 17.8±6.9 months. LBB capture threshold at implant was 0.65±0.27 mV@0.5ms and 0.71±0.35 mV@0.5ms at 2-year follow-up (n=166). Left ventricular ejection fraction were improved in QRS≥120ms and Conclusions: Feasibility and safety of LBBP were confirmed by this large sample size and long-term follow-up study. It is a reliable physiologic method for standards pacing indications.

Introduction: Antiarrhythmic drug therapy can affect pacemaker parameters in both the atrial and ventricular myocardium. It is not known whether antiarrhythmic drugs impact His bundle pacing/sensing parameters and His to ventricle (H-V) intervals following permanent His bundle pacing (HBP). The aims of the study were to prospectively determine the influence of rhythm and rate-controlling drugs on pacing parameters and H-V conduction after His bundle lead implantation and to assess the impact of rhythm and rate-controlling drugs on the safety of HBP.Materials and Methods: Patients (N = 140) with QRS duration < 120 ms who met permanent pacing indications were prospectively enrolled. Propafenone, lidocaine, and adenosine were injected intravenously after implantation of 3,830 lead during the procedure. Metoprolol succinate, amiodarone, and digoxin were taken orally for 1 month. Pacing parameters before and after drug intervention was measured, including His capture threshold, sensing and impedance, H-V interval, and conduction.Results: There were no statistically significant differences in His bundle pacing thresholds, impedance, and sensing after drug intervention at implantation or during a 2-month follow-up (P > 0.05). The HV interval was not affected except in the large-dose propafenone group where HV interval prolonged (P = 0.001). All patients maintained 1:1 H-V conduction following drug administration.Conclusion: There was no adverse impact on the HBP parameters or H-V conduction after the administration of commonly used dosage of rhythm and rate-controlling drugs. The drugs were safe in patients with permanent His bundle pacing.

It is well recognized that a high burden of right ventricular pacing results in deleterious clinical outcomes over the long term. His bundle pacing can achieve optimal ventricular synchronization; however, relatively high pacing thresholds, low R-wave amplitudes, and the long-term performance have been concerns. Recently, left ventricular (LV) septal endocardium pacing (LVSP) has demonstrated improved acute haemodynamics. Another novel technique of intraseptal left bundle branch pacing (LBBP) via transvenous approach has been adopted rapidly and has demonstrated its feasibility and effectiveness. This article reviews the clinical application and differences between LVSP and LBBP. Compared with LVSP, LBBP has strict criteria for left conduction system capture and lead location. In addition to LV septal capture it also stimulates the proximal left bundle branch, resulting in rapid and physiological LV activation. With a uniformity and standardization of the implant procedure and definitions, it may be possible to achieve widespread application of this form of physiological pacing.

Left bundle branch pacing (LBBP) is a novel method for delivering cardiac resynchronization therapy (CRT). We compared on-treatment outcomes with His bundle pacing (HBP) and biventricular pacing (BVP) in this nonrandomized observational study.Consecutive patients with left-ventricular ejection fraction (LVEF) ≤ 40% and typical left bundle branch block (LBBB) referred for CRT received BVP, HBP, or LBBP. QRS duration, pacing threshold, LVEF, and New York Heart Association (NYHA) class were assessed.One hundred thirty-seven patients were recruited: 49 HBP, 32 LBBP, and 54 BVP; 2 did not receive CRT. The majority of patients had nonischemic cardiomyopathy. Mean paced QRS duration was 100.7 ± 15.3 ms, 110.8 ± 11.1 ms, and 135.4 ± 20.2 ms during HBP, LBBP, and BVP, respectively. HBP and LBBP demonstrated a similar absolute increase (Δ) in LVEF (+23.9% vs +24%, P = 0.977) and rate of normalized final LVEF (74.4% vs 70.0%, P = 0.881) at 1-year follow-up. This was significantly higher than in the BVP group (Δ LVEF +16.7% and 44.9% rate of normalized final LVEF, P0.005). HBP and LBBP also demonstrated greater improvements in NYHA class compared with BVP. LBBP was associated with higher R-wave amplitude (11.2 ± 5.1 mV vs 3.8 ± 1.9 mV, P0.001) and lower pacing threshold (0.49 ± 0.13 V/0.5 ms vs 1.35 ± 0.73 V/0.5 ms, P 0.001) compared with HBP.LBBP appears to be a promising method for delivering CRT. We observed similar improvements in symptoms and LV function with LBBP and HBP. These improvements were significantly greater than those seen in patients treated with BVP in this nonrandomized study. These promising findings justify further investigation with randomized trials.

A growing body of evidence has indicated that behaviors of cancers are defined by not only intrinsic activities of tumor cells but also tumor-infiltrating immune cells (TIICs) in the tumor microenvironment. However, it still lacks a well-structured and comprehensive analysis of TIICs and its therapeutic value in esophageal cancer (EC). The proportions of 22 TIICs were evaluated between 150 normal tissues and 141 tumor tissues of EC by the CIBERSORT algorithm. Besides, correlation analyses between proportions of TIICs and clinicopathological characters, including age, gender, histologic grade, tumor location, histologic type, LRP1B mutation, TP53 mutation, tumor stage, lymph node stage, and TNM stage, were conducted. We constructed a risk score model to improve prognostic capacity with 5 TIICs by least absolute shrinkage and selection operator (lasso) regression analysis. The risk score=−1.86∗plasma+2.56∗T cell follicular helper−1.37∗monocytes−3.64∗activated dendritic cells−2.24∗resting mast cells (immune cells in the risk model mean the proportions of immune cell infiltration in EC). Patients in the high-risk group had significantly worse overall survival than these in the low-risk group (HR: 2.146, 95% CI: 1.243-3.705, p=0.0061). Finally, we identified Semustine and Sirolimus as two candidate compounds for the treatment of EC based on CMap analysis. In conclusion, the proportions of TIICs may be important to the progression, prognosis, and treatment of EC.

PURPOSE: Low-grade gliomas (LGG) are a heterogeneous group of brain tumors, which are often assumed to have a benign course. Yet, children diagnosed and treated for LGG in infancy are at increased risk for neurodevelopmental disruption. We sought to investigate neuropsychological outcomes of infants diagnosed with LGG. METHODS: Between 1986 and 2013, 51 patients were diagnosed with LGG before 12 months of age and managed at St. Jude Children’s Research Hospital. Twenty-five of the 51 patients received a cognitive assessment (68% male; 6.8 ± 3.3 months at diagnosis; 10.5 ± 4.8 years at latest assessment). Approximately half the patients received radiation therapy (n = 12; aged 4.0 ± 3.0 years at radiation therapy), with a median of 2 chemotherapy regimens (range = 0 – 5) and 1 tumor directed surgery (range = 0 – 5). RESULTS: The analyses revealed performance below age expectations on measures of IQ, memory, reading, mathematics, and fine motor functioning as well as parent-report of attention, executive, and adaptive functioning. Following correction for multiple comparisons, a greater number of chemotherapy regimens was associated with lower scores on measures of IQ and mathematics. More tumor directed surgeries and presence of visual field loss were associated with poorer dominant hand fine motor control. Radiation therapy exposure was not associated with decline in neuropsychological performance. CONCLUSIONS: Children diagnosed with LGG in infancy experience substantial neuropsychological deficits. Treatment factors, including number of chemotherapy regimens and tumor directed surgeries, may increase risk for neurodevelopmental disruption and need to be considered in treatment planning.

As an alternative to antiarrhythmic drugs and catheter ablation of atrial fibrillation (AF) for rate and rhythm control, pacing combined with atrioventricular node (AVN) ablation is suitable for many AF patients with heart failure (HF) who suffer from symptoms despite optimal medical therapy or have failed AF ablation. Studies have demonstrated His bundle pacing in conjunction with AVN ablation to treat refractory AF patients with HF provide long-term clinical benefits. Here we introduce the clinical application and procedures of His bundle pacing and AVN ablation.

Tectal glioma (TG) is a rare low-grade tumor occurring predominantly in the pediatric population. There has been no detailed analysis of molecular alterations in TG. Risk factors associated with inferior outcome and long-term sequelae of TG have not been well-documented. We retrospectively studied TGs treated or referred for review at St. Jude Children’s Research Hospital (SJCRH) between 1986 and 2013. Longitudinal clinical data were summarized, imaging and pathology specimen centrally reviewed, and tumor material analyzed with targeted molecular testing and genome-wide DNA methylation profiling. Forty-five patients with TG were included. Twenty-six (57.8%) were male. Median age at diagnosis was 9.9 years (range, 0.01–20.5). Median follow-up was 7.6 years (range, 0.5–17.0). The most common presenting symptoms were related to increased intracranial pressure. Of the 22 patients treated at SJCRH, 19 (86%) required cerebrospinal fluid diversion and seven (32%) underwent tumor-directed surgery. Five patients (23%) received radiation therapy and four (18%) systemic therapy. Ten-year overall and progression-free survival were 83.9 ± 10.4% and 48.7 ± 14.2%, respectively. Long-term morbidities included chronic headaches, visual symptoms and neurocognitive impairment. Lesion ≥3cm2, contrast enhancement and cystic changes at presentation were risk factors for progression. Among those with tumor tissue available, 83% showed growth patterns similar to pilocytic astrocytoma and 17% aligned best with diffuse astrocytoma. BRAF duplication (a marker of KIAA1549-BRAF fusion) and BRAF V600E mutation were detected in 25% and 7.7%, respectively. No case had histone H3 K27M mutation. DNA methylation profile of TG was distinct from other brain tumors. In summary, TG is an indolent, chronic disease with unique clinical and molecular profiles and associated with long term morbidities. Large size, contrast enhancement and cystic changes are risk factors for progression.

In this paper, a wideband end-fire dipole antenna and array based on liquid crystal polymer (LCP) is proposed for fifth-generation (5G) applications. Meandered or bent arm is adopted in the dipole antenna design to reduce its size. Meanwhile, a director is added in front of the dipole, which not only improves the gain, but also generates a new resonance to expand the bandwidth. The simulated results show a wide bandwidth from 22.5 GHz to 30.2GHz with end-fire radiation and good beam steering characteristic. Two antenna prototypes, including an antenna element and an array are fabricated and the experimental results demonstrate good agreement with the simulated ones.

ObjectivesHis bundle pacing (HBP) can potentially correct left bundle branch block (LBBB). We aimed to assess the efficacy of HBP to correct LBBB and long-term clinical outcomes with HBP in patients with heart failure (HF).MethodsThis is an observational study of patients with HF with typical LBBB who were indicated for pacing therapy and were consecutively enrolled from one centre. Permanent HBP leads were implanted if the LBBB correction threshold was ResultsIn 74 enrolled patients (69.6±9.2 years and 43 men), LBBB correction was acutely achieved in 72 (97.3%) patients, and 56 (75.7%) patients received permanent HBP (pHBP) while 18 patients did not receive permanent HBP (non-permanent HBP), due to no LBBB correction (n=2), high LBBB correction thresholds (n=10) and fixation failure (n=6). The median follow-up period of pHBP was 37.1 (range 15.0–48.7) months. Thirty patients with pHBP had completed 3-year follow-up, with LVEF increased from baseline 32.4±8.9% to 55.9±10.7% (p0.05).ConclusionspHBP improved LVEF, LVESV and NYHA Class in patients with HF with typical LBBB.

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease. In our meta-analysis, we aimed to assess the correlation of NAFLD and four surrogate markers of subclinical atherosclerosis. PubMed, Embase, and the Cochrane Library were searched up until April 2017. Original studies investigating the association between NAFLD and subclinical atherosclerosis were included. The outcome data were extracted and pooled for the effect estimate by using a random-effects model. We used the Newcastle-Ottawa Quality Assessment Scale to assess the quality of the included studies. Of the 434 initially retrieved studies, 26 studies involving a total of 85,395 participants (including 29,493 patients with NAFLD) were included in this meta-analysis. The Newcastle-Ottawa Quality Assessment Scale scores suggested the included studies were of high quality. The pooled effects estimate showed that subjects with NAFLD exhibited a significant independent association with subclinical atherosclerosis compared to the non-NAFLD group (odds ratio, 1.60; 95% confidence interval, 1.45-1.78). Subgroup analysis suggested that the presence of NAFLD yielded a remarkable higher risk of increased carotid artery intima-media thickness/plaques, arterial stiffness, coronary artery calcification, and endothelial dysfunction with odds ratios (95% confidence interval) of 1.74 (1.47-2.06), 1.56 (1.24-1.96), 1.40 (1.22-1.60), and 3.73 (0.99-14.09), respectively. Conclusion: Our meta-analysis revealed a close link between NAFLD and subclinical atherosclerosis in light of four different indices. Patients with NAFLD might benefit from screening and surveillance of early atherosclerosis, which would facilitate the prediction of potential cardiovascular disease burden, risk stratification, and appropriate intervention in the long term. (Hepatology Communications 2018;2:376-392).

Background Hearing loss may occur in patients with posterior fossa low-grade glioma who undergo surgery. Methods We retrospectively reviewed 217 patients with posterior fossa low-grade glioma, including 115 for whom results of hearing tests performed after surgery and before chemotherapy or radiation therapy were available. We explored the association of UHL with age at diagnosis, sex, race, tumor location, extent of resection, posterior fossa syndrome, ventriculoperitoneal shunt placement, and histology. Results Of the 115 patients, 15 (13.0%: 11 male, 6 black, 8 white, 1 multiracial; median age 7 years [range, 1.3–17.2 years]) had profound UHL after surgery alone or before receiving ototoxic therapy. Median age at tumor diagnosis was 6.8 years (range, 0.7–14.1 years), and median age at surgery was 6.8 years (range, 0.7–14.1 years). Patients with UHL had pathology characteristic of pilocytic astrocytoma (n = 10), ganglioglioma (n = 4), or low-grade astrocytoma (n = 1). Of these 15 patients, 4 underwent biopsy, 1 underwent gross total resection, 1 underwent near-total resection, and 9 underwent subtotal resection. UHL was more frequent in black patients than in white patients (OR 7.3, P = .007) and less frequent in patients who underwent gross total resection or near-total resection than in those who underwent subtotal resection (OR 0.11, P = .02). Conclusions Children undergoing surgery for posterior fossa low-grade glioma are at risk for UHL, which may be related to race or extent of resection. These patients should receive postoperative audiologic testing, as earlier intervention may improve outcomes.

Aiming at the problem that targets are difficult to detect in the marine reverberation environment, this paper studies traditional PCI methods, AR pre-whitening methods, and low-rank matrix decomposition methods, but because traditional PCI methods are difficult to rank, AR pre-whitening methods are difficult to determine the order, and low-rank Matrix factorization method is slow in calculation speed. Based on this research, this paper proposes an anti-reverberation method based on PCI-SVM. This method combines Principal Component Inversion (PCI) and Support Vector Machine (SVM), first obtains the eigenvalues by the principal component inversion algorithm, and then uses the support vector machine to classify and rank the eigenvalues, thereby receiving active sonar the received echo signal is decomposed into subspace to realize the separation of reverberation subspace. This paper uses this method to process simulation data, lake trial data, and sea trial data separately and compares the data processing results with the direct matched filtering method. The comparison results show that the reverberation data processed by the PCI-SVM method has signal detection capabilities Increase by 3.8 dB, 12 dB, and 1.9 dB respectively. At the same time, the PCI-SVM method is compared with the traditional AR anti-reverberation method and PCI anti-reverberation method. The comparison results show that the PCI-SVM method adopted in this paper has better robustness and anti-reverberation ability.

PURPOSE The primary objective of this study is to determine the EFS and OS of children with gross total and near totally resected ependymoma (EPN) treated with post-operative focal radiation therapy (RT) followed by randomization to either RT alone or RT + 4 cycles of maintenance chemotherapy with vincristine, cisplatin, cyclophosphamide and etoposide. Secondary objectives include estimating the EFS and OS of children not randomized, evaluation of neurobehavioral and quality of life (QoL) endpoints, and EPN biomarkers. RESULTS 479 patients enrolled, 451 were eligible. Of 325 eligible randomized patients, 161 were randomized to RT alone and 164 to RT + maintenance chemotherapy. Age range (1–21 years, median 4.9 years). The planned primary analysis was based on intent-to-treat, irrespective of actual treatment received. Based on the data available as of 12/31/2019, estimated 3-year EFS in the RT + maintenance chemotherapy vs. RT arms were 78% vs. 72%, respectively, which did not meet statistical criteria to establish the benefit of maintenance chemotherapy post RT (1-sided log-rank p-value=0.074). Due to significant noncompliance (30.5% in the RT + maintenance vs 4.3% in the RT arm), a planned secondary “as treated” analysis was performed. With median follow-up of 42.6 months among patients without events, the 3 year EFS estimates for patients who received any chemotherapy (n=114) vs. those who received RT only (n=196) were 80% vs. 71%, respectively (1-sided p-value = 0.0121). CONCLUSION Early results in this randomized trial suggest that there may be some EPN patients who benefit from maintenance chemotherapy. Genomic analyses are ongoing.

Background Non-alcoholic fatty liver disease (NAFLD) is the one of the most common form of chronic liver disease in China, so it is important to apply bio-marker in predict the development of NAFLD. Aims This study aims to evaluate association between plateletcrit (PCT) and non-alcoholic fatty liver disease (NAFLD) in Chinese female adults. Methods NAFLD was defined as per ultrasound in this study and 9737 NAFLD-free female subjects from Wenzhou People's Hospital were followed for five years in average in the study. The determination of NAFLD PCT quartiles (Q1 to Q4) were defined: 0–0.16, 0.17–0.18, 0.19–0.21, ≥ 0.22. With Q1 used as reference, 95% confidence intervals (CIs) and hazard ratios (HRs) in different models were computed across each quartile. Results From Q1 to Q4, the incidence ratios (95% CIs) were 8.30 (7.14–9.47), 11.51 (10.12–12.89), 12.68 (11.47–13.89) and 16.46 (15.03–17.88). Simply considering PCT, in the longitudinal population, values in Q2, Q3 and Q4 had HRs (95% CIs) are 1.51 (1.25–1.84), 1.72 (1.44–2.06) and 2.34 (1.96–2.79) versus Q1. After adjusting for all known confounding variables, values in Q2, Q3 and Q4 had HRs (95% CIs) of 1.31 (1.08–1.60), 1.30 (1.09–1.56) and 1.54 (1.29–1.84) in females compared with Q1. Conclusions We reported that elevated serum PCT levels are considered as an independently significant predictor for NAFLD development in females. The high PCT level contributes to the development of NAFLD.

BACKGROUND Left bundle branch pacing (LBBP) is emerging as a novel option for physiological ventricular pacing. The impact of current of injury (COI) at left bundle branch (LBB) has not been previously evaluated. METHODS Consecutive patients with QRS duration less than 120 milliseconds referred for LBBP in whom LBB potentials were recorded were included from August 2018 to March 2019. We recorded LBB COI during LBBP and assessed its impact on the pacing parameters and complications during implantation and at short term follow-up. RESULTS A total of 115 patients with an identifiable LBB potential at implant were included. LBB COI was confirmed in 77 (67.0%) of these patients. Three types of LBB COI were observed. LBB was captured in all patients at a pacing threshold less than 1.5 V/0.5 ms in COI(+) patients, while present in only 29 patients without an LBB COI(-) (100% vs 76.3%; P

Background His bundle pacing (HBP) has been shown to correct left bundle branch block (LBBB), however it often requires high pacing output and the success rate is variable. Objective To assess the feasibility and safety of left bundle branch area pacing (LBBAP) in patients with LBBB. Methods From Apr 2014 to Aug 2018, patients with LBBB from multicenters indicated for CRT or pacing therapy were included. LBBAP was performed by advancing the MDT 3830 lead deep into the septum about 1 cm distal to the His bundle region (Figure 1F). Pacing characteristics, success rate, threshold and R-wave amplitude were assessed. Results A total of 94 patients aged 68.3±10.7 y with the native QRS duration of 167.2±17.2 ms were included. In 92 patients, LBBAP was successfully achieved and demonstrated RBBB pattern during unipolar tip pacing (UTP), with the paced QRS duration of 116.4±12.6ms (Figure 1C). Fusion of LBBAP and native conduction via the RBB eliminated RBBB and resulted in an average QRS duration of 103.2±10.1 ms (Figure 1D). LBB potential could be recorded from the LBB lead during correction of LBBB by HBP in 21 patients who used two leads method (His lead and LBB lead, Figure 1B). Output dependent selective and non-selective LBBAP were demonstrated in 48 patients (Figure 1C, D). The LBB capture threshold by UTP was 0.53±0.18V/0.5ms at acute and 0.62±0.17V/0.5ms at 6 months and 0.65±0.2V/0.5ms at 1 year. The R-wave amplitude were 11.4±5.2mV, 12.4±5.8mV and 12.0±5.8mV at acute, 6 month and 1 year. During follow-up, only one patient had an increase in LBB capture threshold to 2.5V/0.5ms at 3 months and there were no other complications such as dislodgment, infections, embolism or stroke associated with the implantation. Conclusion Permanent LBBAP is feasible and safe in patients with LBBB.

Background The application of His bundle pacing (HBP) on patients with distal AV block should be of concern.Left bundle branch Aera pacing (LBBA pacing), pacing immediately beyond the site of block will be considered. Purpose To access the clinical benefits and safety of LBBA pacing in patients with atrioventricular (AV) block. Methods One hundred and thiry nine patients diagnosed with AVB were included. The Select Secure lead (model 3830; Medtronic) was used. Characteristics of LBB capture are summarized as following: 1) The paced QRS morphology of RBBB pattern during unipolar tip pacing; 2) Usually, LBB potential could be recorded; 3) If higher output pacing shortened the times abruptly and the times remain constant. Pacing parameters (threshold, R-wave amplitude and impedance) and Echocardiographic measurements were assessed during follow-up. Results All patients were success achieved LBBA pacing. The detailed baseline characteristic and follow-up were shown in the Table. Threshold, R-wave amplitude and impedance remained stable during follow -up. Echocardiographic measurements showed that LBB pacing did not affect the cardiac function. There was no LV septum penetration and dislodgment. Conclusion LBBA pacing had ideal pacing parameters and preserve cardiac function and may be an excellent alternative to HBP or RVP. Acknowledgement/Funding Key R&D Program of Zhejiang (2019C03012), Major Project of the Science and Technology of Wenzhou (ZS2017010)

Objective This study was performed to investigate the association of the admission hemoglobin level with the incidence of in-hospital cardiac arrest (IHCA) in patients with acute coronary syndrome (ACS) complicated by cardiogenic shock (CS). Methods In this retrospective study, we reviewed the medical records of consecutive patients with ACS complicated by CS admitted to the coronary care unit from January 2014 to October 2017. Logistic regression models were carried out to evaluate the association between hemoglobin and the incidence of IHCA. Interaction and subgroup analyses were also performed. Results In total, 211 patients were included in the study, and 61 (28.9%) patients developed IHCA. In the multivariable analysis, hemoglobin was a strong independent predictor of IHCA (odds ratio, 0.971; 95% confidence interval, 0.954–0.989). In the fully adjusted model, patients in the higher hemoglobin tertile were less likely to develop IHCA than patients in the lowest hemoglobin tertile (odds ratio, 0.194; 95% confidence interval, 0.071–0.530). The relationship remained stable in most subgroups except patients aged ≥70 years. Conclusion In patients with ACS complicated by CS, the incidence of IHCA is related to the hemoglobin concentration, and a high hemoglobin concentration is a protective factor against the development of IHCA.