Impact of HER2 on prognosis and benefit from adjuvant chemotherapy in stage II/III gastric cancer patients: a multicenter observational study.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a well-developed therapeutic target in breast and gastric cancer (GC). However, the impact of HER2 on survival and benefit from fluorouracil-based adjuvant chemotherapy remains unclear in patients with GC. MATERIALS AND METHODS: This multicenter cohort study involved 5622 consecutive stage II/III GC patients. HER2 expression was assessed prospectively via immunohistochemistry (IHC). The staining intensity was graded on a scale of 0 to 3+. An IHC score of 2+or 3+was defined as high expression, and a score of 3+was defined as overexpression. RESULTS: HER2 overexpression was independently associated with a lower 5-year overall survival (OS) in stage II [hazard ratio (HR), 2.10; 95% CI: 1.41-3.11], but not in stage III GC (HR, 1.00; 95% CI, 0.82-1.20). Further analysis revealed that stage II patients with high HER2 expression showed a poorer response to chemotherapy than stage II patients with low HER2 expression ( Pinteraction =0.024). The HRs for 5-year OS were 0.51 (95% CI, 0.38-0.70) for stage II patients with low HER2 expression, 0.58 (95% CI, 0.51-0.66) for stage III patients with low HER2 expression, 1.13 (95% CI, 0.61-2.09) for stage II patients with high HER2 expression, and 0.47 (95% CI, 0.36-0.61) for stage III patients with high HER2 expression. CONCLUSIONS: Fluorouracil-based adjuvant chemotherapy is insufficient for stage II GC patients with high HER2 expression, indicating that prospective trials are required to validate alternative HER2-targeted adjuvant therapies in the individuals above.

Efficacy of electrical stimulation on shoulder-hand syndrome after stroke: a systematic review and meta-analysis / 中国康复理论与实践

ObjectiveTo systematically evaluate the efficacy of electrical stimulation on shoulder-hand syndrome after stroke, and compare the curative effect of different electrical stimulation therapies. MethodsThe randomized controlled trials (RCT) about the effect of electrical stimulation on shoulder-hand syndrome after stroke were retrieved from eight databases, including PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and Wanfang data, from the establishment to February 14th, 2023. Two researchers selected and screened the literature, and evaluated the quality of methodology independently. RevMan 5.4 software and Stata 14.0 software were used for meta-analysis and network meta-analysis, respectively. ResultsA total of 18 RCT were selected, including 1 310 cases. Compared to conventional rehabilitation therapy alone, electrical stimulation combined with conventional rehabilitation therapy could improve the scores of Fugl-Meyer Assessment-Upper Extremities (MD = 8.17, 95%CI 6.90 to 9.45, P < 0.001) and modified Barthel Index (MD = 11.80, 95%CI 10.18 to 13.42, P < 0.001), and reduce the Visual Analogue Score (MD = -1.68, 95%CI -2.03 to -1.32, P < 0.001) and edema score (MD = -0.98, 95%CI -1.18 to -0.79, P < 0.001). The best effect of improving upper limb function followed as intermediate frequency electrotherapy, electroacupuncture, low frequency electrotherapy and routine rehabilitation therapy. The best effect of improving pain followed as electroacupuncture, intermediate frequency electrotherapy, low frequency electrotherapy and routine rehabilitation therapy. ConclusionElectrical stimulation therapy can relieve pain and edema of patients with shoulder-hand syndrome after stroke, and improve upper limb activity and activities of daily living. Intermediate frequency electrotherapy is the best in improving upper limb function, and electroacupuncture is the best in relieving pain.

The impact of coffee subtypes on incident cardiovascular disease, arrhythmias, and mortality: long-term outcomes from the UK Biobank.

AIMS: Epidemiological studies report the beneficial effects of habitual coffee consumption on incident arrhythmia, cardiovascular disease (CVD), and mortality. However, the impact of different coffee preparations on cardiovascular outcomes and survival is largely unknown. The aim of this study was to evaluate associations between coffee subtypes on incident outcomes, utilizing the UK Biobank. METHODS AND RESULTS: Coffee subtypes were defined as decaffeinated, ground, and instant, then divided into 0, <1, 1, 2-3, 4-5, and >5 cups/day, and compared with non-drinkers. Cardiovascular disease included coronary heart disease, cardiac failure, and ischaemic stroke. Cox regression modelling with hazard ratios (HRs) assessed associations with incident arrhythmia, CVD, and mortality. Outcomes were determined through ICD codes and death records. A total of 449 563 participants (median 58 years, 55.3% females) were followed over 12.5 ± 0.7 years. Ground and instant coffee consumption was associated with a significant reduction in arrhythmia at 1-5 cups/day but not for decaffeinated coffee. The lowest risk was 4-5 cups/day for ground coffee [HR 0.83, confidence interval (CI) 0.76-0.91, P < 0.0001] and 2-3 cups/day for instant coffee (HR 0.88, CI 0.85-0.92, P < 0.0001). All coffee subtypes were associated with a reduction in incident CVD (the lowest risk was 2-3 cups/day for decaffeinated, P = 0.0093; ground, P < 0.0001; and instant coffee, P < 0.0001) vs. non-drinkers. All-cause mortality was significantly reduced for all coffee subtypes, with the greatest risk reduction seen with 2-3 cups/day for decaffeinated (HR 0.86, CI 0.81-0.91, P < 0.0001); ground (HR 0.73, CI 0.69-0.78, P < 0.0001); and instant coffee (HR 0.89, CI 0.86-0.93, P < 0.0001). CONCLUSION: Decaffeinated, ground, and instant coffee, particularly at 2-3 cups/day, were associated with significant reductions in incident CVD and mortality. Ground and instant but not decaffeinated coffee was associated with reduced arrhythmia.

Sex-Related Differences in Atrial Remodeling in Patients With Atrial Fibrillation: Relationship to Ablation Outcomes.

BACKGROUND: Population studies have demonstrated a range of sex differences including a higher prevalence of atrial fibrillation (AF) in men and a higher risk of AF recurrence in women. However, the underlying reasons for this higher recurrence are unknown. This study evaluated whether sex-based electrophysiological substrate differences exist to account for worse AF ablation outcomes in women. METHODS: High-density electroanatomic mapping of the left atrium was performed in 116 consecutive patients with AF. Regional analysis was performed across 6 left atrium segments. High-density maps were created using a multipolar catheter (Biosense Webster) during distal coronary sinus pacing at 600 and 300 ms. Mean voltage and conduction velocity was determined. Complex fractionated signals and double potentials were manually annotated. RESULTS: Overall, 42 (36%) were female, mean age was 61±8 years and AF was persistent in 52%. Global mean voltage was significantly lower in females compared with males at 600 ms (1.46±0.17 versus 1.84±0.15 mV, P<0.001) and 300 ms (1.27±0.18 versus 1.57±0.18 mV, P=0.013) pacing. These differences were seen uniformly across the left atrium. Females demonstrated significant conduction velocity slowing (34.9±6.1 versus 44.1±6.9 cm/s, P=0.002) and greater proportion of complex fractionated signals (9.9±1.7% versus 6.0±1.7%, P=0.014). After a median follow-up of 22 months (Q1-Q3: 15-29), females had significantly lower single-procedure (22 [54%] versus 54 [75%], P=0.029) and multiprocedure (24 [59%] versus 60 [83%], P=0.005) arrhythmia-free survival. Female sex and persistent AF were independent predictors of single and multiprocedure arrhythmia recurrence. CONCLUSIONS: Female patients demonstrated more advanced atrial remodeling on high-density electroanatomic mapping and greater post-AF ablation arrhythmia recurrence compared with males. These changes may contribute to sex-based differences in the clinical course of females with AF and in part explain the higher risk of recurrence. Graphic Abstract: A graphic abstract is available for this article.

Experimental Models of Benign Prostatic Hyperplasia： A Review / 中国实验方剂学杂志

Benign prostatic hyperplasia （BPH） model， as a carrier of BPH， is vital for exploring the pathogenesis of the disease and evaluating the efficacy of corresponding drugs. This paper reviewed the in vivo and in vitro models of BPH， the modeling principles and methods， and evaluation indicators， and analyzed the advantages and disadvantages of different types of models. At present， the BPH model is getting closer to the clinical characteristics of human BPH， providing powerful support for the evaluation of drug efficacy. Furthermore， the model has been developed towards cytology to allow further research on the pathogenesis of BPH. The relevant testing indicators reflect the core pathological changes of BPH from different levels， providing a guarantee for further exploring the pathogenesis of BPH and the development of prevention and control drugs. However， no model can fully simulate the natural development process of human BPH， and each model and evaluation criterion has its unique advantages and limitations. In terms of model evaluation， most BPH models are assessed based on benign prostate enlargement （BPE）， and there is still a lack of reliable models to simulate BPH progression and combine with bladder dysfunction. In terms of indicator evaluation， symptom-reflected behavioral indicators are absent in the replication of BPH models in animals. The study of the BPH model in traditional Chinese medicine （TCM） only focuses on the replication and investigation of the "disease" model， rather than the "syndromes" and "signs"， which cannot simulate the syndrome differentiation and treatment under the guidance of the TCM theory. In view of the above deficiencies， we should further improve the modeling method based on clinical characteristics， explore the multifactor composite models， especially those of disease-syndrome combination suitable for basic research of TCM， replicate the model closing to disease development， and optimize the evaluation indicators， which is of great theoretical and practical significance to develop drugs for effective prevention and control of BPH.

[Progress of researches on mechanisms of acupuncture therapy for lowering blood pressure].

Acupuncture treatment can regulate blood pressure (BP) through multiple levels and ways. In the present paper, we reviewed the progress of researches on the underlying mechanisms of acupuncture in lowering BP from 1) regulation of activities of the neuroendocrine, 2) improvement of metabolic abnormality, and 3) alternation of gene expression in the heart and BP-regulation-related centers of the brain. The neuroendocrine mechanism mainly involves the inhibition of neuroinflammatory reaction in some higher brain regions, reduction of neuronal apoptosis, and suppression of the sympathetic cardiovascular regulatory functional areas of the brain stem, regulation of neurotransmitters and autonomic balance, activation of brain areas related to BP regulation, and promotion of functional connection between brain networks. The improvement of metabolic abnormality mainly refers to amelioration of imbalance of intestinal flora and target metabolites related to hypertension. The alteration of gene expression mainly manifests as up- and down-regulation of expression of genes related to oxidative stress, inflammation and vascular endothelial function in the myocardium, hypothalamus, rostral ventrolateral medulla. We reviewed the new research progress on the mechanism of acupuncture for hypertension, in order to provide evidence and research ideas for the treatment of related cardiovascular diseases by using acupuncture therapy in the future.

Mogrol, an aglycone of mogrosides, attenuates ulcerative colitis by promoting AMPK activation.

BACKGROUND: Ulcerative colitis (UC) is a non-specific chronic inflammatory disease. The incidence of UC in China has been increasing in recent years. Mogrol is an aglycone of mogrosides. Studies have shown that mogrosides have anti-oxygenation, anti-inflammatory, and laxative effects as well as other biological activities. PURPOSE: To investigate the beneficial effects of mogrol on UC and identify its underlying mechanisms. STUDY DESIGN: We used the dextran sodium sulphate (DSS)-induced UC model in mice, TNF-α-damaged NCM460 colonic epithelial cells, macrophage cells THP-M stimulated with lipopolysaccharide (LPS) / adenosine triphosphate (ATP) and compound C (an AMPK inhibitor) to confirm the key role of AMPK (AMP-activated protein kinase) activation. METHODS: Histological evaluation, immunohistochemical staining, Western blot analysis, immunofluorescence assay and quantitative real time-PCR were used in the study. RESULTS: Oral administration of mogrol (5 mg/kg/daily) in vivo significantly attenuated pathological colonic damage, inhibited inflammatory infiltration and improved the abnormal expression of NLRP3 inflammasome in colonic mucosa via the AMPK and NF-κB signaling pathways. In vitro, mogrol protected against intestinal epithelial barrier dysfunction by activating AMPK in TNF-α-treated NCM460 cells and inhibited the production of inflammatory mediator in LPS-stimulated THP-M cells. Furthermore, mogrol's effects were reversed by compound C intervention in DSS-induced UC model. CONCLUSION: Mogrol exerts protective effects in experimental UC and inhibits production of inflammatory mediators through activation of AMPK-mediated signaling pathways.

Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin-induced peripheral neurotoxicity in stage II/III colorectal cancer.

BACKGROUND: Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin-based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin-induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy. METHODS: In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI-CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity (NCI-CTCAE or the oxaliplatin-specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3-year disease-free survival (DFS) and adverse events. RESULTS: There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 substantially decreased participant-reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3-year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms. CONCLUSION: Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977).

Dynamic Atrial Substrate During High-Density Mapping of Paroxysmal and Persistent AF: Implications for Substrate Ablation.

OBJECTIVES: This study sought to determine the impact of rate and direction on left atrial (LA) substrate. BACKGROUND: The extent to which substrate mapped in sinus rhythm varies according to cycle length and direction of wave front propagation is unknown. METHODS: A total of 73 consecutive patients with atrial fibrillation (AF) underwent electroanatomic LA mapping before pulmonary vein isolation using multipolar catheter during distal coronary sinus (CS) pacing at 600 ms and 300 ms. Additional maps were created during left superior pulmonary vein pacing at 300 ms. Bipolar voltage, conduction velocity (CV), and complex signals were determined. RESULTS: Mean age was 61 ± 9 years, 67% were men, and 53% had persistent AF. Global mean voltage was lower with CS pacing at 300 ms compared with 600 ms (1.56 ± 0.47 mV vs. 1.74 ± 0.48 mV; p < 0.001). This was seen in all LA segments. Global CV was reduced (30.4 ± 13.0 cm/s vs. 38.6 ± 14.0 cm/s; p < 0.001) with greater complex signals at 300 ms (8.9% vs. 5.3%; p < 0.005). Compared with CS pacing, left superior pulmonary vein pacing demonstrated highly regional changes with decreased voltage (1.04 ± 0.43 mV vs. 1.47 ± 0.53 mV; p = 0.01) and CV (24.4 ± 13.0 cm/s vs. 39.9 ± 16.6 cm/s; p = 0.008), and greater complex signals posteriorly. Longer AF duration in paroxysmal AF (p = 0.02) and shorter duration in persistent AF (p = 0.015) and left ventricular ejection fraction (p = 0.016) were independent predictors of voltage change. CONCLUSIONS: In patients with AF, variation in cycle length and direction of wave front activation produce both generalized and regional changes in voltage, CV, and complex fractionation, resulting in significant changes in substrate maps. This study highlights the potential limitations of static low-voltage maps to identify the AF ablation target zone.

[Prewarming effect of transcutaneous acupoint electrical stimulation preconditioning in patients undergoing elective video-assisted thoracoscopic lobectomy].

OBJECTIVE: To observe the prewarming effect of transcutaneous acupoint electrical stimulation (TAES) preconditioning of Dazhui (GV14) and Mingmen (GV4) in patients undergoing elective video-assisted thoracoscopic lobectomy, so as to determine whether TAES can improve intraoperative hypothermia. METHODS: A total of 80 patients undergoing elective video-assisted thoracoscopic lobectomy were randomly divided into TAES group (40 cases) and control group (40 cases). Before surgery, all the patients were transferred to the fixed area of an anesthetic preparation room by using a surgery cart carrying the same temperature sheets and quilts before surgery. TAES (2 Hz/100 Hz, 20-30 mA) was applied to Dazhui (GV14) and Mingmen (GV4) for 30 min for patients of the TAES group and the same sheet electrodes of EA stimulator were only attached to GV14 and GV 4 without electrical current transmission for patients in the control group. Then, these patients in the two groups were transferred to the operation room and treated by total intravenous anesthesia, and their anesthetic depth was monitored with bispectral index (BIS, between 45-60) and end-tidal carbon dioxide tension (PETCO2, between 30-45 mmHg). The auricular tympanic temperature was monitored, and when the temperature was below 35.5 ℃, forced-air blanket was used to warm the patient as the remedial measure. The same temperature of operation room, surgical drape, infusion solution and pleural lavage fluid were controlled. The patients' body temperature in the preparation room and operation room during surgery, incidence of hypothemia, blood pressure (BP), heart rate (HR), duration of anesthesia, duration of operation, blood loss volume, urine output, total infusion volume, recovery (awaking) time, and chills during recovery were recorded. RESULTS: The body temperature of patients in the TAES group was significantly higher than that in the control group at the time of entering the operation room (P<0.05). The incidence of chills during recovery was obviously lower in the TAES group (3/40,7.5%) than in the control group (7/40, 17.5%, P<0.05), and the recovery time was significantly shorter in the TAES group than in the control group (P<0.05). There were no significant differences between the two groups in the incidence of intraoperative hypothermia, the duration of anesthesia and operation, blood loss volume, urine output, total infusion volume, BP and HR (P>0.05). CONCLUSION: TAES preconditioning of GV14 and GV4 can produce prewarming effect before anesthesia, shorten the awaking time and reduce the incidence of chills in the recovery period in patients undergoing elective video-assisted thoracoscopic lobectomy.

Atrial Remodeling Following Catheter Ablation for Atrial Fibrillation-Mediated Cardiomyopathy: Long-Term Follow-Up of CAMERA-MRI Study.

OBJECTIVES: This study sought to determine the long-term right atrial (RA) electrical and structural changes in a subgroup from the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-Magnetic Resonance Imaging) study. BACKGROUND: Catheter ablation (CA) is successful in restoring ventricular function in patients with atrial fibrillation (AF) and otherwise unexplained cardiomyopathy, as demonstrated in the randomized study of CA versus rate control (CAMERA-MRI). It is unknown if this is associated with atrial remodeling. METHODS: Detailed electroanatomical (EA) mapping of the RA using CARTO3 and a force sensing catheter was performed at initial CA and electively at least 12 months after CA in patients with >90% reduction in AF burden following ablation. Bipolar voltage, fractionation, and conduction velocity were collected in 4 segments together with echo and cardiac magnetic resonance imaging. RESULTS: Fifteen patients (mean age 59.1 ± 6.8 years) underwent repeat RA EA mapping. At a mean follow-up of 23.4 ± 11.9 months, left ventricular (LV) ejection fraction improved from 33.6 ± 3.2% to 54.1 ± 3.2% (p = 0.001), RA area decreased from 28.4 ± 2.0 cm2 to 20.8 ± 1.2 cm2 (p < 0.001), and left atrial area decreased from 32.9 ± 2.3 cm2 to 26.8 ± 1.4 cm2 (p = 0.007). On EA mapping, RA bipolar voltage increased from 1.6 ± 0.1 mV to 1.9 ± 0.1 mV (p = 0.04). Tissue voltage increased across all regions, which achieved statistical significance at the posterior (p = 0.002) and septal (p = 0.01) segments. There was a significant decrease in complex fractionated electrograms from 21.7 ± 3.5% to 8.3 ± 1.8% (p = 0.002); however, no significant change occurred in global or regional conduction velocities (p = 0.5). CONCLUSIONS: Recovery of atrial electrical and structural changes was observed following restoration of sinus rhythm and recovery of LV function in patients who underwent CA for persistent AF and LV systolic dysfunction. The randomized CAMERA MRI study demonstrated significant improvement in LV systolic function with AF ablation compared with rate control. The present study demonstrated reverse electrical and structural atrial recovery in concert with recovery of LV systolic function at 2 years post-AF ablation. This may partially explain the long-term success of CA in patients with AF and otherwise unexplained cardiomyopathy.

Moderate alcohol consumption is associated with atrial electrical and structural changes: Insights from high-density left atrial electroanatomic mapping.

BACKGROUND: Regular alcohol intake is an important modifiable risk factor associated with atrial fibrillation (AF) and left atrial (LA) dilation. OBJECTIVE: The purpose of this study was to determine the impact of different degrees of alcohol consumption on atrial remodeling using high-density electroanatomic mapping. METHODS: We enrolled 75 patients before AF ablation to undergo high-density LA mapping (CARTO, Biosense Webster) using a multipolar catheter. The Confidense algorithm was used to create maps during distal coronary sinus pacing at 600 ms. Bipolar voltage and complex atrial activity were assessed, and isochronal activation maps were created to determine global conduction velocity (CV). Patients were classified as lifelong nondrinkers, mild drinkers (2-7 drinks/week), or moderate drinkers (8-21 drinks/week). RESULTS: High-density electroanatomic mapping (mean 1016 ± 445 points per patient) was performed on 25 lifelong nondrinkers, 25 mild drinkers (4.4 ± 2.3 drinks/week), and 25 moderate drinkers (14.0 ± 4.2 drinks/week). Moderate drinkers had significantly lower mean global bipolar voltages (1.53 ± 0.62 mV vs 1.89 ± 0.45 mV; P = .02), slower CV (33.5 ± 14.4 cm/s vs 41.7 ± 12.1 cm/s; P = .04), and a higher proportion of complex atrial potentials (7.8% ± 4.7% vs 4.5% ± 2.7%; P = .004) compared to nondrinkers. Global voltage and CV did not differ significantly in mild drinkers, but there was a significant increase in global complex potentials (6.6% ± 4.6%; P = .04) and regional low-voltage zones (<0.5 mV) in the septum and lateral wall (P <.05) compared with nondrinkers. CONCLUSION: Regular moderate alcohol consumption, but not mild consumption, is an important modifiable risk factor for AF associated with lower atrial voltage and conduction slowing. These electrical and structural changes may explain the propensity to AF in regular drinkers.

Biatrial Electrical and Structural Atrial Changes in Heart Failure: Electroanatomic Mapping in Persistent Atrial Fibrillation in Humans.

OBJECTIVES: This study sought to characterize the biatrial substrate in heart failure (HF) and persistent atrial fibrillation (PeAF). BACKGROUND: Atrial fibrillation (AF) and HF frequently coexist; however, the contribution of HF to the biatrial substrate in PeAF is unclear. METHODS: Consecutive patients with PeAF and normal left ventricular (NLV) systolic function (left ventricular ejection fraction [LVEF] >55%) or idiopathic cardiomyopathy (LVEF ≤45%) undergoing AF ablation were enrolled. In AF, pulmonary vein (PV) cycle length (PVCL) was recorded via a multipolar catheter in each PV and in the left atrial appendage for 100 consecutive cycles. After electrical cardioversion, biatrial electroanatomic mapping was performed. Complex electrograms, voltage, scarring, and conduction velocity were assessed. RESULTS: Forty patients, 20 patients with HF (mean age: 62 ± 8.9 years; AF duration: 15 ± 11 months; LVEF: 33 ± 8.4%) and 20 with NLV (mean age: 59 ± 6.7 years; AF duration: 14 ± 9.1 months; p = 0.69; mean LVEF: 61 ± 3.6%; p < 0.001), were enrolled. HF reduced biatrial tissue voltage (p < 0.001) with greater voltage heterogeneity (p < 0.001). HF was associated with significantly more biatrial fractionation (left atrium [LA]: 30% vs. 9%; p < 0.001; right atrium [RA]: 28% vs. 11%; p < 0.001), low voltage (<0.5 mV) (LA: 23% vs. 6%; p = 0.002; RA: 20% vs 11%; p = 0.006), and scarring (<0.05 mV) in the LA (p = 0.005). HF was associated with a slower average PVCL (185 vs. 164 ms; p = 0.016), which correlated significantly with PV antral bipolar voltage (R = -0.62; p < 0.001) and fractionation (R = 0.46; p = 0.001). CONCLUSIONS: HF is associated with significantly reduced biatrial tissue voltage, fractionation, and prolongation of PVCL. Advanced biatrial remodeling may have implications for invasive and noninvasive rhythm control strategies in patients with AF and HF.

A comparison of the electrophysiologic and electroanatomic characteristics between the right and left atrium in persistent atrial fibrillation: Is the right atrium a window into the left?

INTRODUCTION: The right atrium (RA) is readily accessible; however, it is unclear whether changes in the RA are representative of the LA. We performed detailed biatrial electroanatomic mapping to determine the electrophysiological relationship between the atria. METHODS AND RESULTS: Consecutive patients with persistent AF underwent biatrial electroanatomical mapping with a contact force catheter acquiring points with a CF >10 g prior to ablation. Points were analyzed for tissue voltage, complex electrograms, low voltage (<0.5 mV), scar (<0.05 mV), and conduction velocity (CV). Forty patients (mean age 59 ± 9.2 years, AF duration 12.9 ± 9.2 months, LA area: 28 ± 5.2, RA area: 25 ± 6.4 mm2 , LVEF: 44 ± 15%) underwent mapping during CS pacing. Bipolar voltage (R = 0.57, P <0.001), unipolar voltage (R = 0.68, P <0.001), low voltage (<0.5 nV) (R = 0.48, P = 0.002), fractionation (R = 0.73, P <0.001), and CV (R = 0.49, P = 0.001) correlated well between atria. There was no difference in global bipolar voltage (LA 1.89 ± 0.77 vs. RA 1.77 ± 0.57 mV, P = 0.57); complex electrograms (LA 20% vs. RA 20%, P = 0.99) or low voltage (LA 15% vs. RA 16%, P = 0.84). Global unipolar voltage was significantly higher in the LA compared to the RA (2.95 ± 1.14 vs. 2.28 ± 0.65 mV, P = 0.002) and CV was significantly slower in the RA compared to the LA (0.93 ± 0.15 m/s vs. 1.01 ± 0.19 m/s, P = 0.001). CONCLUSION: AF is associated with remodeling processes affecting both atria. The more accessible RA provides an insight into the biatrial process associated with AF in various disease states without trans-septal access.

[Effect of Transcutaneous Acupoint Electrical Stimulation on Hemodynamic Fluctuation Caused by Loosing Tourniquet in Elderly Patients Undergoing Knee Joint Replacement].

OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) on hemodynamic fluctuation caused by loosing tourniquet in the elderly patients undergoing knee joint replacement. METHODS: A total of 60 ASA (America Society Anesthesiologist) I or II elderly patients for elective knee joint replacement surgery were randomly divided into control group (30 cases) and TAES group (30 cases). Patients of both groups were treated by intravenous anesthesia, and monitored with bispectral index (BIS, between 45－60) for anesthesia depth, stroke volume variation (SVV) for fluid management, mean arterial pressure (MAP) and cardiac index (CI) for hemodynamic fluctuation evaluation, and with analgesia nociception index (ANI, between 50－70) for remifentanil dosage adjustment. TAES (2 Hz/100 Hz, 8－20 mA) was applied to bilateral Xinshu (BL 15), Feishu (BL 13), Neiguan (PC 6) and Hegu (LI 4) acupoints for 30 min first (followed by anesthesia induction and operation), and given continuously until 15 min after tourniquet loosing. Patients of the control group were only given with electrodes attachment without electrical stimulation. The levels of MAP, CI, and arterial blood pH, PaCO2, PaO2, base excess (BE) and lactic acid (Lac) 1 min before, and 5 and 15 min after tourniquet loosing, and the dosages of remifentanil and ephedrine after tourniquet loosing were recorded. RESULTS: The changed levels of MAP, CI and blood Lac at 5 min after tourniquet loosing (relevant to the baseline levels), and blood Lac content at 15 min after tourniquet loosing (relevant to 5 min after tourniquet loosing) were significantly lower in the TAES group than in the control group (P<0.05), but the levels of MAP and CI at 15 min after tourniquet loosing (relevant to 5 min following tourniquet loosing) were significantly higher in the TAES group than in the control group (P<0.05), suggesting an improvement of blood pressure, cardiac function and substance metabolism after TAES. Moreover, the dosages of remifentanil and ephedrine after tourniquet loosing were considerably lower in the TAES group than in the control group (P<0.05), suggesting a better stabilization of hemodynamics after TAES. No significant differences were found between the two groups in the levels of blood pH, PaCO2, PaO2 and BE at 5 and 15 min after tourniquet loosing (P>0.05). CONCLUSIONS: TAES has a positive effect on hemodynamics fluctuation caused by loosing tourniquet in the aged patients undergoing knee joint replacement.

Determining the Optimal Dose of Adenosine for Unmasking Dormant Pulmonary Vein Conduction Following Atrial Fibrillation Ablation: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study.

INTRODUCTION: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: The significance of adenosine induced dormant pulmonary vein (PV) conduction in atrial fibrillation (AF) ablation remains controversial. The optimal dose of adenosine to determine dormant PV conduction is yet to be systematically explored. METHODS AND RESULTS: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: Consecutive patients undergoing index AF ablation received 3 adenosine doses (12, 18, and 24 mg) in a randomized blinded order, immediately after pulmonary vein isolation (PVI). Electrophysiological (PR prolongation, AV block (AVB) and PV reconnection) and hemodynamic (BP) parameters were measured. A total, 339 doses (113/dose) assessed 191 PVs in 50 patients (66% male, 72% PAF, 52% hypertensive). Dormant PV conduction occurred in 28% of patients (16.5% [32] of PVs). All cases were associated with AVB (AVB: PV reconnection vs. no PV reconnection 100% vs. 83%, P = 0.007). AVB occurred more frequently at 24 mg versus 12 mg (92% vs. 82%, P = 0.019) but not versus 18 mg (91%, P = 0.62). AVB duration progressed between 12 mg (12.0 ± 8.9 seconds), 18 mg (16.1 ± 9.1 seconds, P = 0.001), and 24 mg (19.0 ± 9.3 seconds, P < 0.001) doses. MBP fell further at 24 mg (ΔMBP: 27 ± 12 mmHg) and 18 mg (26 ± 13 mmHg) doses compared to 12 mg (22 ± 10 mmHg vs., P < 0.001). A significant reduction in AVB in patients >110 kg (65% vs. 91% in 70-110 kg group, P < 0.001) in response to adenosine was seen. CONCLUSION: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: An adenosine dose producing AVB is required to unmask dormant PV conduction. AVB is significantly reduced in patients >110 kg. Weight and dosing variability may in part explain the conflicting results of studies evaluating the clinical utility of adenosine in PVI.

Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies.

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.

Extraction, Antimicrobial, and Antioxidant Activities of Crude Polysaccharides from the Wood Ear Medicinal Mushroom Auricularia auricula-judae (Higher Basidiomycetes).

In this study, crude polysaccharides of culinary-medicinal mushroom Auricularia auricular-judae were extracted by hot water extraction and alcohol precipitation, and their antimicrobial and antioxidant activities were investigated. An optimum extraction condition was obtained at a ratio of liquid to solid 70 mL/g, temperature 90°C, time 4 h and extraction number 4. Accordingly, the best yield of crude polysaccharides was 6.89% with 76.12% in purity. Some bacteria and fungi were used for antimicrobial studies. It was found that crude A. auricula-judae had great antimicrobial activities against Escherichia coli and Staphylococcus aureus, but no activities on the others. The inhibitory diameters of antimicrobial zones for the two were 5.55 ± 0.182 and 9.84 ± 0.076 mm, respectively. Moreover, crude A. auricula-judae had significant antioxidant activities in scavenging free radicals, reducing power assays, and Fe2+ chelating ability assay. Results revealed that crude A. auricula-judae has a great potential as antimicrobial and antioxidant, and it can be a supplementary food for human health.

Impact of Catheter Contact Force on Human Left Atrial Electrogram Characteristics in Sinus Rhythm and Atrial Fibrillation.

BACKGROUND: During left atrial mapping, optimal contact parameters minimizing variation secondary to catheter contact are not established. METHODS AND RESULTS: Across 30 patients undergoing first-time atrial fibrillation ablation, 1965 stable mapping points (1409 atrial fibrillation, 556 sinus rhythm), comprising 8-s contact force (CF) and bipolar electrogram data were analyzed. Points were taken in groups at locations with CF or catheter orientation actively changed between acquisitions. Complexes were less positive at higher CF (Spearman ρ, -0.2; P<0.005, both rhythms). Increasing CF at a location significantly increased complex size, but only where initial CF was <10 g, and if the change was ≥4.5 g in sinus rhythm and ≥8 g in atrial fibrillation (P<0.0005, both rhythms): if initial CF was ≥10 g, no change was observed, regardless of CF change (P>0.05, both). Atrial ectopics during sinus rhythm were observed more frequently when CF was ≥10 g (P<0.0005). Increasing CF at a location was associated with an increase in the complex fractionated atrial electrogram interval confidence level score, but only if initial CF was <10 g and CF increased ≥8 g (P=0.003). The dominant frequency and organization index were unaffected by CF (P>0.1 for both). Changing catheter orientation from perpendicular to parallel in atrial fibrillation was associated with smaller, more positive complexes (P=0.001 for both), but no changes in complex fractionated atrial electrogram scores, dominant frequency or organization index (P>0.08 for each). CONCLUSIONS: During left atrial electrogram mapping, including complex fractionated atrial electrogram but not spectral parameter mapping, CF and catheter orientation influence results: consequently, mapping CFs should be ≥10 g to negate the influence of CF. CLINICAL TRIALS REGISTRATION: URL: http://clinicaltrials.gov/. Unique identifier: NCT01587404.

The transesophageal echo probe may contribute to esophageal injury after catheter ablation for paroxysmal atrial fibrillation under general anesthesia: a preliminary observation.

INTRODUCTION: The transesophageal echo probe (TEE) is commonly used before and during atrial fibrillation (AF) ablation under general anesthesia (GA). We sought to determine the potential contribution of the TEE probe to esophageal injury after pulmonary vein isolation (PVI) alone for paroxysmal AF. METHODS AND RESULTS: Seventy-six patients undergoing PVI with TEE, PVI/TEE, 16 undergoing PVI without TEE (PVI/No TEE), and 27 undergoing TEE without any left atrial ablation (TEE/No LA ablation) under GA were included. Posterior wall ablation was power (20-25 W) and time limited (electrogram attenuation or ≤30 s). Esophageal capsule endoscopy (n = 206) was performed pre- and post-procedure and at 2 weeks. Esophageal lesions were seen in 30% of PVI/TEE, 0% of patients in the PVI/No TEE (P = 0.009), and 22% of TEE/No LA ablation groups (P = 0.47 vs. PVI/TEE). There were no instances of esophageal bleeding, perforation, or need for gastrointestinal intervention. Self-resolving dysphagia was the only reported symptom (5%). All lesions healed within 2 weeks. There was no significant difference in the location or morphological appearance of esophageal lesions seen in the PVI/TEE versus TEE/No LA ablation groups. CONCLUSIONS: Esophageal lesions were seen in 30% of patients undergoing PVI alone under GA with use of TEE and in a similar proportion (22%) of patients undergoing TEE in the absence of left atrial ablation. This study makes the preliminary observation that one must be cognizant of the TEE probe as a potential contributor to esophageal injury after AF ablation. Larger studies are needed to confirm these findings.