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INTRODUCTION:Achalasia is a primary motility disorder characterized by aperistalsis and failure of lower esophageal sphincter relaxation. Traditionally, treatment modalities have consisted of drug therapy, botulinum toxin injections, laparoscopic Heller myotomy, and balloon pneumatic dilatation. However, in the past several years, the novel technique peroral endoscopic myotomy (POEM) has gained popularity, as prior studies have suggested that it offers excellent short-term outcomes. In this study, we analyze the efficacy of POEM with a focus on both short-term and long-term outcomes.METHODS:This retrospective study utilized collected data at our tertiary referral center. A total of 71 patients underwent POEM. 18 patients were lost to follow-up post-procedure. 47 patients were included in the short-term assessment, defined as less than 6 months removed from the procedure, while 15 patients were included in the long-term assessment, defined as greater than or equal to 6 months removed from the procedure. Eckhardt score was assessed before POEM and afterwards for short-term follow-up and long-term follow-up.RESULTS:Mean age was 56.5 years old. 54% of patients were female. Mean short term follow-up time was 2.96 months. Mean long-term follow-up time was 13.0 (8-27) months. The mean pre-POEM Eckhardt score was 7.6. The mean short-term post-POEM Eckhardt score was 1.2 (P < 0.001) while the mean long-term post-POEM Eckhardt score was 1.8 (P < 0.001). There was no significant difference between short-term and long-term Eckhardt scores. Additionally, there were no adverse outcomes or effects in any of the 65 POEM cases.CONCLUSION:This study was one of the largest single-center studies that examining the efficacy and safety of POEM . Eckhardt scores decreased significantly after POEM, remained significantly decreased at longer-term follow-up, and there were no adverse outcomes. In short, this study supports that POEM is a safe, effective, and durable option for the treatment of achalasia.

INTRODUCTION:Peroral endoscopic myotomy (POEM) is a promising novel treatment modality for achalasia. Treatment success is usually determined by the patient's improvement in symptoms. A diagnostic tool during the POEM to evaluate effectiveness of the myotomy may aid in performing the POEM procedure optimally. One such diagnostic tool is the Endoluminal Functional Lumen Imaging Probe (FLIP), which uses impedance planimetry for real-time, intraoperative measurement of gastroesophageal junction diameter, compliance, distension, and surface area. Here we evaluate the efficacy of POEM using FLIP and compare changes in FLIP with those in Eckhardt scores.METHODS:This studied was performed at our tertiary care referral center. A total of 72 patients underwent POEM in this study. FLIP data was collected during the procedure with respect to the following variables: diameter, circumferential area, distention, and compliance. Eckhardt scores were assessed before and after POEM. Mean follow-up time was 2.96 months.RESULTS:Mean age was 57 years. 57% of patients were female. Mean diameter pre-POEM was 5.61 (SD = 2.20) mm and post-POEM was 10.57 (SD = 13.36) mm (n = 66). Mean circumferential area pre-POEM was 23.25 (SD = 10.67) mm2 and post-POEM was 61.89 (SD = 30.09) mm2 (n = 64). Mean distention pre-POEM was 1.31 (SD = 0.83) mm2/mmHg and post-POEM was 3.49 (SD = 1.85) mm2/mmHg (n = 63). Mean compliance pre-POEM was 84.99 (SD-83.33) mm3/mmHg and post-POEM was 117.76 (SD = 79.05) mm3/mmHg (n = 59). All P values were less than 0.01. There was a negative correlation between the changes in all FLIP measurements and Eckhardt scores before and after POEM.CONCLUSION:This study is one of the largest on patients undergoing POEM examined with FLIP. FLIP measurements may serve as an intraprocedural measurement of POEM efficacy. The fact that a negative correlation between FLIP and Eckhardt scores was achieved indicates that FLIP may be a prognostic indicator for POEM patients, although further follow up data will be needed to establish this.

Extant research shows that big data analytics (BDA) capability is often employed as a part of organizational resources to enhance firm performance. Drawing upon the resource-based view, dynamic capabilities, and contingency theory, this study endeavors to examine the alignment between BDA capability and a specific type of procurement strategies (i.e., supplier development) and its impact on firm performance. The study extends the BDA capability research by investigating the direct impact of BDA capability on supplier development and firm performance, respectively, and by exploring both mediating and moderating effects on the relationship between supplier development and firm performance. The main results show that a firm’s BDA capability has not only a direct positive significant impact on supplier development, but also a direct positive significant impact on its business performance. More importantly, the results indicate strong moderating and mediating effects of BDA capability on supplier development, which in turn affects the improvement of firm performance. Theoretical and managerial implications along with future research directions are provided in the end.

Characterisation of the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with avian influenza A H7N9 virus, which emerged in China in early 2013. We obtained information about laboratory-confirmed cases of avian influenza A H7N9 virus infection reported as of May 28, 2013, from an integrated database built by the Chinese Center for Disease Control and Prevention. We estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit for patients who required hospital admission for medical reasons. We also used information about laboratory-confirmed cases detected through sentinel influenza-like illness surveillance to estimate the symptomatic case fatality risk. Of 123 patients with laboratory-confirmed avian influenza A H7N9 virus infection who were admitted to hospital, 37 (30%) had died and 69 (56%) had recovered by May 28, 2013. After we accounted for incomplete data for 17 patients who were still in hospital, we estimated the fatality risk for all ages to be 36% (95% CI 26–45) on admission to hospital. Risks of mechanical ventilation or fatality (69%, 95% CI 60–77) and of admission to an intensive care unit, mechanical ventilation, or fatality (83%, 76–90) were high. With assumptions about coverage of the sentinel surveillance network and health-care-seeking behaviour for patients with influenza-like illness associated with influenza A H7N9 virus infection, and pro-rata extrapolation, we estimated that the symptomatic case fatality risk could be between 160 (63–460) and 2800 (1000–9400) per 100 000 symptomatic cases. Human infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection. Chinese Ministry of Science and Technology; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; US National Institute of Allergy and Infectious Disease; and the US National Institutes of Health.

HER2 is an established therapeutic biomarker in advanced or recurrent endometrial serous carcinoma. Current clinical guidelines recommend HER2 testing exclusively in this endometrial carcinoma (EC) subtype; however, the full spectrum of ECs harboring HER2 amplification remains ill-defined. The present study characterizes the clinicopathologic and molecular features of HER2-amplified ECs across all histologic subtypes. Retrospective analysis of our institutional cohort of 2,042 ECs subjected to targeted clinical massively parallel sequencing identified 77 (3.8%) cases with HER2 amplification, a group comprised of serous (n = 29), endometrioid (low-grade, n = 2, high-grade, n = 1) and clear cell (n = 4) carcinomas, carcinosarcomas (n = 18) and high-grade ECs with ambiguous features (HGEC, n = 23). A co-existing TP53 mutation was identified in 94% (72/77) of HER2-amplified ECs. Other recurrent genetic alterations included amplification of CCNE1 (22%) and ERBB3 (10%), FBXW7 mutations or deletions (13%), and mutations in PIK3CA (40%) and PPP2R1A (13%). The HER2 immunohistochemistry score was 2+ or 3+ for all evaluable cases (n = 61). Apart from carcinosarcomas, which often showed lower HER2 expression, particularly in the sarcomatous component, HER2 immunohistochemical staining pattern and intensity were similar across EC subtypes. Intratumor heterogeneity in HER2 expression was common and correlated with genetic heterogeneity as detected by fluorescence in-situ hybridization. These results demonstrate the frequent co-occurrence of HER2 amplification with TP53 mutation and high-grade histology, rather than being specific to serous carcinoma, per se. Overall, these findings suggest that HER2 targeted therapy may be more broadly applicable to all high-grade EC histotypes and consideration should be given to expanding therapeutic eligibility.

PurposeThe purpose of this study is to examine how supply chain strategy affects a firm's sustainability performance and how the strength of that relationship is influenced by managerial authentic leadership (AL) and its associated impact on interorganizational citizenship behavior (ICB).Design/methodology/approachBuilding on the intersection of three theories: organizational ambidexterity, AL and ICB, a mediated moderation model is developed and tested using structural equation modeling based on the responses from a cross-sectional survey administered by the authors.FindingsThe results reveal that an ambidextrous supply chain strategy is positively related to firm sustainability performance and this relationship is strengthened by AL. Furthermore, this study finds that this moderating relationship is partially mediated by ICB.Originality/valueTo the best of the authors’ knowledge, this paper is among the first to empirically test the effect of supply chain ambidexterity on sustainability performance by explicitly considering how leadership characteristics can both directly and indirectly affect the efficacy of this relationship. The findings complement existing literature by providing novel insights into the ability of firm supply chain strategy to affect sustainability performance.

PurposeThe purpose of this study is to examine the extent to which a firm is able to leverage its information system (IS) innovativeness to improve supply chain resilience through developing and employing its analytics capability. It further considers how this mediating effect of analytics capability can be enhanced by internal and external integration.Design/methodology/approachBuilding on the logic of organizational information processing theory, a mediated moderation model is developed and tested using structural equation modeling and partial least squares regression based on survey responses from 247 working professionals.FindingsThe results indicate that IS innovativeness improves a firm’s supply chain resilience through enhanced analytics capability, with higher levels of internal and external integration further strengthening the effects of this mediating relationship.Originality/valueThis study is among the first to empirically test the effects of IS innovativeness and analytics capability on supply chain resilience and to examine the impacts of internal and external integration as key factors affecting the strength of these relationships. The findings complement existing literature through providing new insights into the linkage between IS strategy and supply chain resilience and highlighting the importance of relationships throughout the supply chain to enhance the efficacy of a firm’s analytics capability within this domain.

Traditional gene expression deconvolution methods assess a limited number of cell types, therefore do not capture the full complexity of the tumor microenvironment (TME). Here, we integrate nine deconvolution tools to assess 79 TME cell types in 10,592 tumors across 33 different cancer types, creating the most comprehensive analysis of the TME. In total, we found 41 patterns of immune infiltration and stroma profiles, identifying heterogeneous yet unique TME portraits for each cancer and several new findings. Our findings indicate that leukocytes play a major role in distinguishing various tumor types, and that a shared immune-rich TME cluster predicts better survival in bladder cancer for luminal and basal squamous subtypes, as well as in melanoma for RAS-hotspot subtypes. Our detailed deconvolution and mutational correlation analyses uncover 35 therapeutic target and candidate response biomarkers hypotheses (including CASP8 and RAS pathway genes).