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Peroral endoscopic myotomy (POEM) is conducted for patients with esophageal motility disorders based on high-resolution manometry (HRM) findings. However, the impact of POEM on HRM findings and the associations between post-POEM HRM and outcomes have not been clarified. In a multicenter, observational, cohort study, patients with achalasia treated by POEM received follow-up HRM. Associations between patient characteristics, POEM procedures, and post-POEM HRM findings, including integrated relaxation pressure (IRP) and distal contractile integral (DCI), were investigated. Furthermore, POEM procedure outcomes were compared with post-POEM HRM findings. Of 2171 patients, 151 (7.0%) showed residual high post-POEM IRP (≥26 mm Hg; Starlet [Starmedical Ltd, Tokyo, Japan]). In a multivariate analysis, high pre-POEM IRPs (odds ratio [OR], 24.3) and gastric myotomy >2 cm (OR,.22) were found to be positive and negative predictive factors of high post-POEM IRPs, respectively. Peristalsis recovery (DCI ≥500 mm Hg/cm/s, at least 1 swallow; Starlet) was visible in 121 of 618 patients (19.6%) who had type II to III achalasia. High pre-POEM IRP (OR, 2.65) and DCI ≥500 (OR, 2.98) predicted peristalsis recovery, whereas esophageal dilation (OR,.42) predicted a risk of no recovery. Extended myotomy did not reveal a significant impact on peristalsis recovery. High or low post-POEM IRP and DCI did not increase the incidence of clinical failure, reflux esophagitis, or symptomatic GERD. Extended gastric myotomy decreased IRP values, whereas peristalsis recovery depended on the characteristics of achalasia. A residual high post-POEM IRP does not necessarily mean clinical failure. Routine HRM follow-up is not recommended after POEM. [Display omitted] [ABSTRACT FROM AUTHOR]

The etiology of chest pain in achalasia-related esophageal motility disorders and the frequency and risk factors of persistent chest pain after peroral endoscopic myotomy (POEM) remain unclear. A multicenter cohort study including 14 hospitals was conducted to elucidate the characteristics of patients with chest pain and the efficacy of POEM. Consecutive cases of achalasia-related esophageal motility disorders included 2294 (64.2%) and 1280 (35.8%) patients with and without chest pain, respectively. Among the 2107 patients with chest pain who underwent POEM, we observed complete remission in 1464 patients (69.5%) and nonremission in 643 patients (30.5%), including a partial response in 619 patients (29.4%) and resistance in 24 patients (1.1%). Multivariate analysis revealed that advanced age (odds ratio [OR],.28), male sex (OR,.70), prior treatment (OR, 1.39), and sigmoid type (OR,.65) were related to the prevalence of chest pain. Long disease duration (OR,.69) and esophageal dilation (OR,.79) were related to decreased severity. POEM improved patients' quality of life that was hindered by chest pain. Early onset (OR, 1.45), advanced age (OR,.58), male sex (OR,.79), prior treatment (OR, 1.37), and posterior myotomy (OR, 1.42) were associated with nonremission after POEM; high-resolution manometry (HRM) findings and myotomy length showed no statistical significance on pain etiology and persistence after POEM. The prevalence and severity of chest pain were dependent on age, sex, disease duration, prior treatment, and esophageal morphology rather than HRM findings. The efficacy of POEM is satisfactory; however, residual pain was often observed. Excessively long myotomy can be avoided, and anterior myotomy may be recommended. [ABSTRACT FROM AUTHOR]

Mesangial cells play an important role in inflammatory reactions in kidney. Although viral infections often trigger the worsening of chronic inflammatory renal diseases, the mechanisms are largely unknown. Melanoma differentiation-associated gene 5 (MDA5) is a member of RNA helicase family with a conserved Asp-Glu-x-His (DExH) box. In the present study, we examined the effect of polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA (dsRNA) that mimics viral dsRNAs, on MDA5 expression using primary culture of human mesangial cells. The cells were simply treated or transfected with poly IC; the former procedure is a model of cells exposed to viral dsRNA released from dying cells, and the latter is a model of entry of RNA virus into the cytoplasm. Expression levels of MDA5 mRNA in mesangial cells were increased about 70-100 fold in response to either treatment or transfection with poly IC. MDA5 protein expression was significantly induced as well. RNA interference experiments revealed that poly IC treatment induced MDA5 expression via Toll-like receptor 3 (TLR3) and interferon (IFN)-β, and that poly IC trasnfection induced MDA5 expression via another DExH box RNA helicase, retinoic acid-inducible gene-I (RIG-I), and IFN-β. Moreover, MDA5 induced by poly IC, in turn, increased the expression of a chemokine CXCL10. In addition, immunohistochemical staining demonstrated a high level of MDA5 expression in glomeruli, mainly in mesangial cells, of patients with severe lupus nephritis or proteinuric IgA nephropathy. MDA5 may be involved not only in physiological antiviral reactions but also in chronic inflammation in glomerular mesangial cells. [ABSTRACT FROM AUTHOR]