Search

2-year follow-up data from our randomised controlled trial showed that peroral endoscopic myotomy is associated with a significantly higher efficacy than pneumatic dilation as initial treatment of therapy-naive patients with achalasia. Here we report therapeutic success rates in patients treated with peroral endoscopic myotomy compared with pneumatic dilation at the 5-year follow-up.We did a multicentre, randomised controlled trial in six hospitals in the Netherlands, Germany, Italy, Hong Kong, and the USA. Adults aged 18-80 years with newly diagnosed symptomatic achalasia (based on an Eckardt score3) were eligible for inclusion. Patients were randomly assigned (1:1) to peroral endoscopic myotomy or pneumatic dilation using web-based randomisation with a random block size of 8 and stratification according to site. Randomisation concealment for treatment type was double blind until official study enrolment. Treatment was unmasked because of the different technical approach of each procedure. Patients in the pneumatic dilation group were dilated with a single series of 30-35 mm balloons. The need for subsequent dilations in the pneumatic dilation group, and the need for dilation after initial treatment in the peroral endoscopic myotomy group, was considered treatment failure. The primary outcome was therapeutic success (Eckardt score ≤3 in the absence of severe treatment-related complications and no need for retreatment). Analysis of the primary outcome was by modified intention to treat, including all patients randomly assigned to a group, excluding those patients who did not receive treatment or were lost to follow-up. Safety was assessed in all included patients. This study is registered at the Dutch Trial Registry, NTR3593, and is completed.Between Sept 21, 2012, and July 20, 2015, 182 patients were assessed for eligibility, 133 of whom were included in the study and randomly assigned to peroral endoscopic myotomy (n=67) or pneumatic dilation (n=66). 5-year follow-up data were available for 62 patients in the peroral endoscopic myotomy group and 63 patients in the pneumatic dilation group. 50 (81%) patients in the peroral endoscopic myotomy group had treatment success at 5 years, compared with 25 (40%) in the pneumatic dilation group, an adjusted absolute difference of 41% (95% CI 25-57; p0·0001). Reasons for failure were no initial effect of treatment (one patient in the peroral endoscopic myotomy group vs 12 patients in the pneumatic dilation group) and recurrent symptoms causing treatment failure (11 patients in the peroral endoscopic myotomy group [seven patients between 2 and 5 years] vs 25 patients in the pneumatic dilation group [nine patients between 2 and 5 years]); one patient in the pneumatic dilation group had treatment failure due to an adverse event. Proton-pump inhibitor use (mostly daily) was significantly higher after peroral endoscopic myotomy than after pneumatic dilation among patients still in clinical remission (23 [46%] of 50 patients vs three [13%] of 24 patients; p=0·008). 5-year follow-up endoscopy of patients still in clinical remission showed reflux oesophagitis in 14 (33%) of 42 patients in the peroral endoscopic myotomy group (12 [29%] grade A or B, two [5%] grade C or D) and two (13%) of 16 patients in the pneumatic dilation group (two [13%] grade A or B, none grade C or D; p=0·19). No intervention-related serious adverse events occurred between 2 and 5 years after treatment. The following non-intervention-related serious adverse events occurred between 2 and 5 years: a stroke (one [2%]) in the peroral endoscopic myotomy group; and death due to a melanoma (one [2%]) and dementia (one [2%]) in the pneumatic dilation group.Based on this study, peroral endoscopic myotomy should be proposed as an initial treatment option for patients with achalasia. Although our study has shown that peroral endoscopic myotomy has greater long-term efficacy with a low risk of major treatment-related complications, this should not lead to abandonment of pneumatic dilation from clinical practice. Ideally, all treatment options should be discussed with treatment-naive patients with achalasia and a shared decision should be made.Fonds NutsOhra and European Society of Gastrointestinal Endoscopy.

The effect of electrode orientation in an electrohydrodynamic (EHD) gas pump inside a square channel is experimentally examined for its effective use in thermal management. The two-stage gas pump w...

Lymphoepithelial carcinoma is rare in the salivary glands, with an incidence of 0.4%. The most commonly affected site is the parotid gland, followed by the submandibular gland. Lymphoepithelial carcinoma in the sublingual gland has been reported only four times in the existing English-language literature. Such tumours are characterized by the presence of a poorly differentiated carcinoma that is surrounded and infiltrated by lymphocytes, and they are strongly associated with Epstein–Barr virus infection, patient ethnicity, and prominent radiosensitivity. Wide surgical excision combined with adjuvant therapy has been suggested as the first-choice therapeutic regimen. This report describes the case of a 34-year-old Indonesian woman who was evaluated and treated in Taipei Medical University Hospital. She had a tumour that presented as a painless swelling on the floor of the mouth. The diagnosis was confirmed by conducting an incisional biopsy, and a wide surgical excision with bilateral supraomohyoid neck dissection and free flap reconstruction was performed. The patient also underwent adjuvant chemoradiotherapy. No evidence of local recurrence or distant metastasis was detected during the 6 months of follow-up. Subsequently, the patient returned to her home country, and further follow-ups were not conducted.

An electrohydrodynamic (EHD) gas pump inside a square channel is experimentally evaluated for its effectiveness in flow delivery. The gas pump with three sets of electrode assemblies (separately wi...

In Parkinson's disease (PD), oropharyngeal dysphagia is common and clinically relevant. The neurophysiology of dysphagia in PD is complex and incompletely understood. The aim of the study was to determine the changes in oropharyngeal deglutitive pressure dynamics in PD and to correlate these with clinical characteristics including dysphagia and PD severity. In prospective consecutive series of 64 patients with PD [mean age: 66.9 ± 8.3 (SD)], we evaluated dysphagia severity clinically as well as with Sydney Swallow Questionnaire (SSQ) and Swallow Quality-of-Life Questionnaire (SWAL-QOL). PD severity was assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). We used high-resolution pharyngeal impedance manometry (HRPIM) to objectively evaluate swallow function and compared data from 23 age-matched healthy controls [mean age 62.3 ± 9.1 (SD)]. Metrics assessed were upper esophageal sphincter (UES), integrated relaxation pressure (IRP), relaxation time (RT), maximum opening (MaxAdm), and pharyngeal intrabolus pressure (IBP) and pharyngeal contractility (PhCI). Mean MDS-UPDRS score was positively associated with dysphagia severity on SSQ and SWAL-QOL. HRPIM in PD compared with controls showed impaired UES relaxation parameters, with shorter RT, and elevated IRP and IBP. MaxAdm was not affected. The overall pharyngeal contractility was significantly higher in PD. Only the IBP and IRP were associated with PD severity and only IBP was significantly associated with dysphagia severity. UES dysfunction leading to increased flow resistance is common in patients with PD and correlates with dysphagia severity. Increased flow resistance may suggest impaired UES relaxation and/or impaired neuromodulation to bolus volume.

Vitiligo is an acquired depigmentation disease of the skin due to melanocyte destruction. A shared pathogenesis affecting melanocytes in the cochlea has been postulated. However, the association between vitiligo and sensorineural hearing loss (SNHL) is unclear.To identify the association between vitiligo and SNHL.This retrospective, nationwide cohort study included patients with vitiligo and age-, sex- and comorbidities-matched controls (propensity score matching; 1:4 ratio) from the National Health Insurance Research Database in Taiwan from 1 January 2000 to 31 December 2013.In total, 13 048 patients with vitiligo and 52 192 controls were included. SNHL developed in 0.61% patients with vitiligo and 0.29% controls. After adjusting for sex, age and comorbidities, a significant association between vitiligo and SNHL was found (adjusted hazard ratio, 2.18; 95% CI, 1.66-2.86). The other risk factors for developing SNHL included increased age, male sex, hyperlipidaemia, coronary artery disease and diffuse connective tissue diseases. In subgroup analysis, the association between vitiligo and SNHL remained significant in almost all the subgroups.A 2.2-fold increased risk of developing SNHL was found in patients with vitiligo. Proper referral to otologists for early screening and closer follow-up of SNHL should be considered for patients with vitiligo, especially for patients with older age.

Esophageal ambulatory reflux monitoring is the current gold standard for the diagnosis of gastroesophageal reflux disease (GERD). In order to facilitate standardized procedure and improve diagnostic accuracy, clinical guidelines for ambulatory esophageal reflux monitoring were developed based on thorough literature search and working group conference by experts in gastrointestinal motility. Indications, contraindications, methodology, and reporting of ambulatory esophageal reflux monitoring were discussed in these clinical guidelines.

Microbial dysbiosis has been implicated in the development of atopic dermatitis (AD). The risk of development of AD following early-life infections remains unclear.To investigate the impact of early-life infections on AD development.This population-based nested case-control study was conducted using the Taiwan's National Health Insurance Research Database. A total of 5454 AD patients and 16 362 control subjects without AD were identified, for the period 1997 to 2013. Demographic characteristics, comorbidities and maternal factors were compared. Adjusted odds ratio (aOR) was calculated to examine the associations between early-life infections and subsequent AD by conditional stepwise logistic regression analysis.Mean age was 2.6 ± 2.9 years in both groups. Overall infections (41.8% vs. 28.9%) before the diagnosis of AD were more common in AD patients than in control subjects (P 0.001). Infectious diseases [aOR, 1.40; 95% confidence interval (CI), 1.29-1.51], skin infections (aOR, 1.55; 95% CI, 1.40-1.71) and systemic antibiotic exposure (aOR 1.67, 95% CI 1.55-1.79) before AD diagnosis were independently associated with AD development on multivariate analyses. These results were consistent across observation periods (0-1, 1-2 and2 years after birth) and sensitivity analyses after redefining the index date as 3 or 6 months before the date of AD diagnosis. Other independent risk factors included asthma, allergic rhinitis, intussusception and neonatal hyperbilirubinemia. No association with subsequent AD was found for maternal age at delivery, Caesarean delivery or prenatal antibiotic exposure.Infections in early life are associated with AD development in infancy and early childhood.

Background Prokinetic is the first-line conventional treatment for functional dyspepsia (FD) in Asia despite potential adverse events. Chinese herbal medicine (CHM) may be an effective and safe substitution. This network meta-analysis (NMA) aimed to evaluate the comparative effectiveness of different CHM formulae for FD against prokinetics. Methods Seven international and Chinese databases were searched from their inception to July 2020 for randomised controlled trials (RCTs) on CHM versus prokinetics. Data from each RCT were first pooled using random-effect pairwise meta-analyses and illustrated as risk difference (RD) or standardised mean difference (SMD) with 95% confidence interval (CI). Random-effect NMAs were then performed to evaluate the comparative effectiveness of CHM formulae and displayed as RD with 95% CI or SMD with 95% credible interval (CrI). The GRADE partially contextualised framework was applied for NMA result interpretation. Results Twenty-six unique CHM formulae were identified from twenty-eight RCTs of mediocre quality. Pairwise meta-analyses indicated that CHM was superior to prokinetics in alleviating global symptoms at 4-week follow-up (pooled RD: 0.14; 95% CI: 0.10–0.19), even after trim and fill adjustment for publication bias. NMAs demonstrated that Modified Zhi Zhu Decoction may have a moderate beneficial effect on alleviating global symptoms at 4-week follow-up (RD: 0.28; 95% CI: − 0.03 to 0.75). Xiao Pi Kuan Wei Decoction may have a large beneficial effect on alleviating postprandial fullness (SMD: − 2.14; 95% CI: − 2.76 to 0.70), early satiety (SMD: − 3.90; 95% CI: − 0.68 to − 0.42), and epigastric pain (SMD: − 1.23; 95% CI: − 1.66 to − 0.29). No serious adverse events were reported. Conclusion Modified Zhi Zhu Decoction and Xiao Pi Kuan Wei Decoction may be considered as an alternative for patients unresponsive to prokinetics. Confirmatory head-to-head trials should be conducted to investigate their comparative effectiveness against prokinetics.

Rosai-Dorfman病是一种少见的良性组织细胞增生性疾病，多发生于淋巴结，原发于肺孤立性Rosai-Dorfman病十分罕见，本文报道1例32岁男性，体检发现右肺下叶结节行右中下肺叶切除术，右下叶支气管根部见肿块，大小4.0 cm×3.5 cm×2.5 cm，灰白灰黄色，质硬，界尚清。低倍镜下见肺组织结构破坏，淡染区和深染区明暗相间分布。高倍镜下见淡染区主要为体积增大的组织细胞呈簇状分布，胞质淡染嗜酸性或空泡状，胞质内可见吞噬一至数枚形态完整的淋巴细胞。深染区主要是成熟的浆细胞和淋巴细胞。免疫组织化学组织细胞S-100蛋白、CD68及CD163阳性。分子检测KRAS基因G12D突变。术后随访21个月无复发。肺Rosai-Dorfman病术前常被误诊为肺癌，病理诊断需要与多个疾病鉴别，免疫组织化学S-100蛋白对正确诊断有帮助。.

Observation of high energy and very high emission from Gamma Ray Bursts (GRBs) is crucial to study the gigantic explosion and the underline processes. With a large field-of-view and almost full duty cycle, the Water Cherenkov Detector Array (WCDA), a sub-array of the Large High Altitude Air Shower Observatory (LHAASO), is appropriate to monitor the very high energy emission from unpredictable transients such as GRBs. Nevertheless, the main issue for an extensive air shower array is the high energy threshold which limits the horizon of the detector. To address this issue a new trigger method is developed in this article to lower the energy threshold of WCDA for GRB observation. The proposed method significantly improves the detection efficiency of WCDA for gamma-rays around the GRB direction at 10-300 GeV. The sensitivity of the WCDA for GRB detection with the new trigger method is estimated. The achieved sensitivity of the quarter WCDA array above 10 GeV is comparable with that of Fermi-LAT. The data analysis process and corresponding fluence upper limit for GRB 190719C is presented as an example.

The present work investigated the effect of Ag additives on the consumption of cathode Cu pad under electromigration in a current-stressed Cu/Sn3.5Ag/Cu flip-chip structure. The consumption rate of a cathode Cu pad in a pure Sn system is faster than that of a cathode Cu pad in a Sn3.5Ag system at 80℃ by a factor of 10. Using the kinetics of the consumption equation, the activation energy in the consumption of a cathode Cu pad was calculated. The activation energy (0.65 eV) of the consumption of a cathode Cu pad in a Cu/Sn3.5Ag/Cu flip-chip structure under electromigration (EM) is slightly greater than that (0.62 eV) of the consumption of a cathode Cu pad in a Cu/Sn/Cu flip-chip structure under EM. The dissolution of Cu flux is discussed, and the possible effect of Ag additives on the consumption rate of a cathode Cu pad under EM is proposed. The Ag additives reduced the deficiency of Cu solubility in a solder matrix near the cathode Cu/solder interface, which is the main factor in the reduction of Cu pad consumption. Moreover, the Ag3Sn phase forming on the cathode Cu6Sn5 interface protects Cu6Sn5 from dissolving into the Sn3.5Ag solder matrix under EM.

The main scientific goal of LHAASO-WCDA is to survey gamma-ray sources with energy from 100 GeV to 30 TeV. To observe high-energy shower events, especially to measure the energy spectrum of cosmic rays from 100 TeV to 10 PeV, a dynamic range extension system (WCDA++) is designed to use a 1.5-inch PMT with a dynamic range of four orders of magnitude for each cell in WCDA-1. The dynamic range is extended by using these PMTs to measure the effective charge density in the core region of air shower events, which is an important parameter for identifying the composition of primary particles. The system has been running for more than one year. In this paper, the details of the design and performance of WCDA++ are presented.

The impact behavior and energy absorption of two types of composite tubes, fabricated from carbon fabrics by the resin transfer molding and from carbon prepregs by the lay-up method, were investigated experimentally and numerically. In impact tests, outward-splaying crush caps with different fillet radii were used. Different types of crushing behavior of the tubes were simulated by the finite-element analysis, including a progressive failure function and considering the possibility of delamination. A comparison with experimental results confirmed that, the finite-element analysis was able to well predict the crushing behavior of the composite tubes, showing that the specific energy absorption of the prepreg composite tubes was always about 20% lower than that of the braided ones.

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 105 and 109 GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Introduction Functional dyspepsia (FD) is diagnosed based on self-reported symptoms and negative upper gastrointestinal endoscopic findings. The Rome criteria were not adopted as a diagnostic instrument in clinical guidelines due to their complexity. Different guidelines used relatively simple symptom assessment schemes with contents that vary significantly. A previously evaluated short Reference Standard may serve as a more standardised tool for guidelines. We evaluated its diagnostic accuracy against the Rome IV criteria in a cross-sectional study in Hong Kong. Methods A total of 220 dyspeptic patients sampled consecutively from a tertiary hospital and the community completed the Rome IV diagnostic questionnaire, which was translated into Cantonese-Chinese, and the Reference Standard. Sensitivity, specificity, positive and negative likelihood ratios (LRs), and area under the receiver operating characteristics curve (AUC), with 95% confidence intervals (CIs), were calculated. Results Among the participants, 160 (72.7%) fulfilled the Reference Standard with negative upper gastrointestinal endoscopic results. The Reference Standard identified patients with Rome IV-defined FD with 91.1% (95% CI 82.6%–96.4%) sensitivity and 37.6% (95% CI 29.6%–46.1%) specificity. The positive and negative LRs were 1.46 (95% CI 1.26–1.69) and 0.24 (95% CI 0.11–0.49), respectively. The AUC value was 0.64 (95% CI 0.59–0.69). Conclusions The Reference Standard can rule out patients without Rome IV-defined FD. It may be used as an initial screening tool for FD in settings where the use of the Rome IV criteria is impractical. It may also provide a uniform definition and diagnostic rule for future updates of clinical guidelines.

梭形细胞血管瘤（spindle cell hemangioma）是1986年首次提出的一种罕见病变，好发于青年四肢远端皮下软组织。镜下观察可见海绵状血管区、实性梭形细胞区、裂隙状血管区及乳头结构，极易误诊为其他血管源性肿瘤。本文报道1例发生在67岁女性患者胸骨的梭形细胞血管瘤，随访9个月余，病情稳定，无复发征象。.

Typically, Sn cannot be finished on Ni and Ag surfaces via the immersion process. In this work, through galvanic reaction, immersion Sn finish was processed on an immersion Ag finish coexisting with a Ni surface. Herein, the detailed mechanism of the reduction of Sn2+ ions on the immersion Ag surface through galvanic reaction is reported. Through transmission electron microscopy and X-ray diffraction analysis, the uncommon Ag4Sn phase, instead of the common Ag3Sn phase, was confirmed to form during the Sn immersion of the Ag immersion layer. The Ag4Sn phase was found to form between the Ag grains in the immersion Sn layer. The mixed Ag/Ag4Sn structure in the immersion Sn layer can be explained by the galvanic reaction. The preferred formation of the Ag4Sn during the Sn immersion of the Ag immersion layer is discussed from the viewpoint of thermodynamics. The changes in the Gibbs free energy of the formation of the Ag3Sn and Ag4Sn phases were calculated as − 3.67 and − 8.89 kJ/mol, respectively. This confirms that the Ag4Sn phase is the favorable phase formed in the immersion Sn over the immersion Ag layer.

Background Chinese medicine (CM) modalities, including acupuncture and Chinese herbal medicine (CHM), are popular palliative interventions among patients with cancer, but further clinical research is required to assess their effectiveness and safety. Objective To prioritize top ten important CM clinical research questions from patients with cancer, cancer survivors and caregivers' perspectives via a face-to-face prioritization workshop in Hong Kong. Methods A list of 25 CM clinical research questions for cancer palliative care, which were identified from existing systematic reviews (SRs) and overview of SRs, was presented to 17 participants (patients with cancer [n = 5], cancer survivors [n = 6] and caregivers [n = 6]). The participants were then invited to establish consensus on prioritizing top ten research questions. Results Among the top ten priorities, five (50%) focused on acupuncture and related therapies, while five (50%) were on CHM. The three most important research priorities were (i) manual acupuncture plus opioids for relieving pain; (ii) CHM for improving quality of life among patients receiving chemotherapy; and (iii) concurrent use of CHM plus loperamide for reducing stomatitis. Conclusion The top ten participant-endorsed CM clinical research priorities for cancer palliative care can guide local researchers on future direction. They can also inform local research funders on patient-centred allocation of limited funding. Under limited research funding, the most important co-prioritized research question from professional and patient perspectives may be addressed first. Patient or public contribution Patients with cancer, cancer survivors and caregivers participated in conduct of the study to prioritize CM clinical research questions.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons—cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3–6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators. Observations of γ-rays with energies up to 1.4 PeV find that 12 sources in the Galaxy are PeVatrons, one of which is the Crab Nebula.

The data of 33 patients with adult-onset still's disease (AOSD)-associated macrophage activation syndrome (MAS) were retrospectively collected from January 2013 to December 2020 in Peking Union Medical College Hospital. Hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, macrophage activation syndrome/juvenile idiopathic arthritis (MS-Score) and hemophagocytic syndrome diagnostic score (HScore) were used to diagnose AOSD-associated MAS, respectively. The time of diagnosis of AOSD-associated MAS by MS-Score was 19.0 (4.5, 31.0) days [收集2013年1月至2020年12月在北京协和医院出院诊断为成人Still病（AOSD）合并巨噬细胞活化综合征（MAS）的33例患者的临床资料，分析比较分别应用噬血细胞性淋巴组织细胞增多症（HLH）-2004标准、巨噬细胞活化综合征/幼年特发性关节炎评分（MS-Score）和HLH诊断评分（HScore）确诊MAS的时间。结果发现，应用MS-Score确诊MAS的时间［