Canonical effects of cytokines on glomerulonephritis: A new outlook in nephrology.

Glomerulonephritis (GN) is an important cause of renal inflammation resulting from kidney-targeted adaptive and innate immune responses and consequent glomerular damage. Given the lack of autoantibodies, immune complexes, or the infiltrating immune cells in some forms of GN, for example, focal segmental glomerulosclerosis and minimal change disease, along with paraneoplastic syndrome and a special form of renal involvement in some viral infections, the likeliest causative scenario would be secreted factors, mainly cytokine(s). Since cytokines can modulate the inflammatory mechanisms, severity, and clinical outcomes of GN, it is rational to consider the umbrella term of cytokine GN as a new outlook to reclassify a group of previously known GN. We focus here, particularly, on cytokines that have the central "canonical effect" in the development of GN.

NORTH AMERICAN EXPERT CONSENSUS ON THE POST-PROCEDURAL CARE OF PATIENTS AFTER PER-ORAL ENDOSCOPIC MYOTOMY USING A DELPHI PROCESS.

BACKGROUND AND AIMS: There is significant variability in the immediate post-operative and long-term management of patients undergoing per-oral endoscopic myotomy (POEM), largely stemming from the lack of high-quality evidence. We aimed to establish a consensus on several important questions on the after care of post-POEM patients through a modified Delphi process. METHODS: A steering committee developed an initial questionnaire consisting of 5 domains (33 statements): post-POEM admission/discharge, indication for immediate post-POEM esophagram, peri-procedural medications and diet resumption, clinic follow-up recommendations, and post-POEM reflux surveillance and management. A total of 34 experts participated in the 2 rounds of the Delphi process, with quantitative and qualitative data analyzed for each round to achieve consensus. RESULTS: A total of 23 statements achieved high degree of consensus. Overall, the expert panel agreed on the following: (1) same-day discharge after POEM can be considered in select patients, (2) a single dose of prophylactic antibiotics may be as effective as a short course, (3) a modified diet can be advanced as tolerated, (4) all patients should be followed in clinic and undergo objective testing for surveillance and management of reflux. Consensus could not be achieved on the indication of post-POEM esophagram to evaluate for leak. CONCLUSIONS: The results of this Delphi process established expert agreement on several important issues and provides a practical guidance on key aspects in the care of patients following POEM.

AGA Clinical Practice Update on Gastric Peroral Endoscopic Myotomy for Gastroparesis: Commentary.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding cognitive, procedural, and post-procedural aspects of performing gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis. METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are advanced endoscopists with expertise in treating patients by performing third-space endoscopy and gastric peroral endoscopic myotomy.

Evaluation of measurement errors in the Patient-Oriented Eczema Measure (POEM) outcome.

BACKGROUND: The Patient-Oriented Eczema Measure (POEM) is the recommended core outcome instrument for atopic dermatitis (AD) symptoms. POEM is reported by recalling the presence/absence of seven symptoms in the last 7 days. OBJECTIVE: To evaluate measurement errors in POEM recordings due to imperfect recall. METHODS: Using data from a clinical trial of 247 AD patients aged 12-65 years, we analysed the reported POEM score (r-POEM) and the POEM derived from the corresponding daily scores for the same seven symptoms without weekly recall (d-POEM). We quantified recall error by comparing the r-POEM and d-POEM for 777 patient-weeks collected from 207 patients, and estimated two components of recall error: (1) recall bias due to systematic errors in measurements and (2) recall noise due to random errors in measurements, using a bespoke statistical model. RESULTS: POEM scores have a relatively low recall bias, but a high recall noise. Recall bias was estimated at 1.2 points lower for the r-POEM on average than the d-POEM, with a recall noise of 5.7 points. For example, a patient with a recall-free POEM of 11 (moderate) could report their POEM score anywhere from 5 to 14 (with 95% probability) because of recall error. Model estimates suggested that patients tend to recall itch and dryness more often than experienced (positive bias of less than 1 day), but less often for the other symptoms (bleeding, cracking, flaking, oozing/weeping and sleep disturbance; negative bias ranging 1-4 days). CONCLUSIONS: In this clinical trial data set, we found that patients tended to slightly underestimate their symptoms when reporting POEM, with significant variation in how well they were able to recall the frequency of their symptoms every time they reported POEM. A large recall noise should be taken into consideration when interpreting POEM scores.

Comparison of flexible endoscopic needle knife septotomy and peroral endoscopic myotomy for treatment of Zenker's diverticulum.

BACKGROUND AND AIMS: Treatment of Zenker's diverticulum (ZD) has evolved from flexible endoscopic septotomy (FES) to peroral endoscopic myotomy (Z-POEM). In this study, we compare efficacy and safety of FES with a needle knife septotomy (FENKS) and Z-POEM for symptomatic ZD. METHODS: Consecutive patients at a single institution who underwent endoscopic ZD treatment by FENKS or Z-POEM were identified. Demographics, clinical characteristics, procedure technique, technical and clinical success, and adverse events (AEs) within 30 days were reviewed and compared between the two groups. AEs were classified by the AGREE classification. Baseline and post-procedure Dakkak and Bennett's (DB) scores were reported at 6, 12 and 24 months. Clinical success (DB score ≤1) was assessed by per-protocol (PP) and intention-to-treat analyses (ITT). RESULTS: 60 patients (55% M, mean 72±12 yrs.) underwent FENKS (n=21) or Z-POEM (n=39) between 2016 and 2023. Baseline clinical characteristics were similar and overall technical success was 98.3%. Clinical success by PP and ITT analyses at 6, 12 and 24 months after intervention were similar between both groups. The FENKS group had a higher prevalence (29% vs. 5%, p=0.018) and severity (p=0.032) of AEs and were more likely to be hospitalized after treatment (71% vs. 33%, p=0.007). During a median follow up of 18 months, reintervention was required for 5 (10%) in the FENKS (n=2, 9%) and Z-POEM (n=3, 7.6%) groups (p=1.0) a mean 7.6 ± 4.4 months after initial therapy. CONCLUSION: Treatment of ZD with Z-POEM appears to be safer than FENKS with similar short- and mid-term clinical success.

Efficacy and Safety of Gastric Peroral Endoscopic Myotomy Across Different Etiologies of Gastroparesis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Gastric Peroral Endoscopic Myotomy (G-POEM) is an emerging treatment for refractory gastroparesis. While its efficacy and safety have been analyzed in previous systematic reviews and meta-analyses, no studies have compared its effectiveness based on etiology. Our study aims to evaluate the efficacy and safety of G-POEM by etiologies of gastroparesis. METHODS: We conducted a comprehensive search in major databases until October 2023, focusing on the efficacy and safety of G-POEM by etiology. Our primary outcome was clinical success based on etiology, with additional subgroup analysis on pre-and post-GCSI scores based on etiology using standard meta-analysis methods and the random-effects model. Heterogeneity was assessed using I2% statistics. RESULTS: In our analysis of 15 studies (7 retrospective, 8 prospective) involving 982 patients (mean age 50.81 years, mean follow-up 21 months), post-surgical conditions were the most common etiology in G-POEM (290 cases), followed by idiopathic factors (287 cases) and diabetes (286 cases). Subgroup analysis revealed pooled clinical success rates of 65% (CI: 51-77; I2 = 46%) for diabetes, 70% (CI: 46-86; I2 = 73%) for post-surgical, and 60% (CI: 41-77; I2 = 68%) for idiopathic etiologies. Our research also indicated that G-POEM significantly improved GCSI scores: 1.7 (95% CI: -0.01 to 3.5, p = 0.052) for diabetes, 1.34 (95% CI: -0.07 to 2.62, p = 0.038) for post-surgical, and 1.5 (95% CI: 0.36 to 2.75, p = 0.01) for idiopathic patients. CONCLUSION: Based on this meta-analysis, G-POEM is effective and safe for treating refractory gastroparesis irrespective of the etiology, with significant improvements in clinical success rates and GCSI scores.

Malaysian joint societies' consensus recommendations on diagnosis and management of disorders of esophagogastric junction outflow.

Disorders of esophagogastric junction (EGJ) outflow, including achalasia and EGJ outflow obstruction, are motility disorders characterized by inadequate relaxation of lower esophageal sphincter with or without impaired esophageal peristalsis. Current guidelines are technical and less practical in the Asia-Pacific region, and there are still massive challenges in timely diagnosis and managing these disorders effectively. Therefore, a Malaysian joint societies' task force has developed a consensus on disorders of EGJ outflow based on the latest evidence, while taking into consideration the practical relevance of local and regional context and resources. Twenty-one statements were established after a series of meetings and extensive review of literatures. The Delphi method was used in the consensus voting process. This consensus focuses on the definition, diagnostic investigations, the aims of treatment outcome, non-surgical or surgical treatment options, management of treatment failure or relapse, and the management of complications. This consensus advocates the use of high-resolution esophageal manometry for diagnosis of disorders of EGJ outflow. Myotomy, via either endoscopy or laparoscopy, is the preferred treatment option, while pneumatic dilatation can serve as a secondary option. Evaluation and management of complications including post-procedural reflux and cancer surveillance are recommended.

Toll-Like Receptor 7-Expressed Macrophages Are Involved in the Pathogenesis of Esophageal Achalasia and Esophagogastric Junction Outflow Obstruction.

INTRODUCTION: Esophageal achalasia is a typical esophageal motility disorder (EMD). Although viral infections have been hypothesized to play a role in the pathogenesis of esophageal achalasia, its etiology remains unclear. This study used esophageal muscle layer specimens collected during per-oral endoscopic myotomy (POEM) procedures to investigate the association between esophageal achalasia and esophagogastric junction outflow obstruction (EGJOO) and pattern recognition receptors. METHODS: Patients with esophageal achalasia and EGJOO who underwent POEM were allocated to the EMD group. Biopsies of the inner circular muscle were conducted during the POEM procedure. The control group comprised individuals diagnosed with esophageal squamous cell carcinoma who underwent surgical resection. Expression of pattern recognition receptors, including Toll-like receptor (TLR) 7, was examined by polymerase chain reaction. Immunohistochemical staining was performed to determine TLR7 expression sites in the esophageal muscle layer, and the relationship between TLR7 mRNA expression and clinical score was investigated. RESULTS: Our analysis revealed a notable upregulation of TLR7 mRNA levels within the muscle layer of esophageal achalasia and EGJOO, in contrast to those of control specimens. In contrast, the correlation between TLR7 and clinical score was not significant. Immunohistochemical staining revealed increased numbers of TLR7-expressing macrophages between the muscle layers. CONCLUSIONS: TLR7-expressing macrophages are involved in the innate immune response underlying esophageal achalasia and EGJOO. This result will lead to the elucidation of new pathogenetic mechanisms and the development of novel therapeutic targets.

Factors associated with peroral endoscopic myotomy for achalasia outcomes: systematic review and meta-analysis.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging effective treatment for achalasia. However, a significant proportion of patients do not respond well to the treatment. After over a decade of clinical practice, potential risk factors associated with POEM failure have been identified. This meta-analysis aimed to summarize the evidence of risk factors for POEM failure. METHODS: A systematic literature search was conducted on PubMed, Embase, Web of Science, and Cochrane Library from inception to June 10th, 2022. We included English studies that reported POEM outcomes in achalasia patients and identified risk factors for POEM failure. Relevant information was extracted and analyzed using fixed- or randomized-effect models to pool the effect size. RESULTS: A total of 27 studies comprising 9371 patients with achalasia were included in this review. The pooled failure rate was 8% (90% CI 7%-10%). We identified sigmoid esophagus (OR 1.90, 95% CI 1.45-2.47), type I achalasia (OR 1.30, 95% CI 1.04-1.63), and type III achalasia (OR 1.26, 95% CI 0.89-1.78) were associated with a worse clinical response. Conversely, type II achalasia was associated with a better response (OR 0.59, 95% CI 0.47-0.75). Prior treatment with Heller myotomy (OR 5.75, 95% CI 3.97-8.34) and prior balloon dilation (OR 1.18, 95% CI 1.07-1.29) were also associated with a higher risk of clinical failure. CONCLUSION: Our meta-analysis results demonstrated that sigmoid esophagus, manometric achalasia subtype, and prior treatment were associated with POEM failure. This information could be used to guide treatment decisions and improve the success rate of POEM in achalasia patients.

Transverse versus longitudinal mucosal incision during POEM for esophageal motility disorders: a randomized trial.

BACKGROUND: Longitudinal incision is the commonly used incision for entry into the submucosal space during peroral endoscopic myotomy (POEM) for esophageal motility disorders. Transverse incision is another alternative for entry and retrospective data suggest it has less operative time and chance of gas-related events. METHODS: This was a single-center, randomized trial conducted at a tertiary care hospital. Patients undergoing POEM for esophageal motility disorders were randomized into group A (longitudinal incision) and group B (transverse incision). The primary objective was to compare the time needed for entry into the submucosal space. The secondary objectives were to compare the time needed to close the incision, number of clips required to close the incision, and development of gas-related events. The sample size was calculated as for a non-inferiority design using Kelsey method. RESULTS: Sixty patients were randomized (30 in each group). On comparing the 2 types of incisions, there was no difference in entry time [3 (2, 5) vs 2 (1.75, 5) min, p = 0.399], closure time [7 (4, 13.5) vs 9 (6.75, 19) min, p = 0.155], and number of clips needed for closure [4 (4, 6) vs 5 (4, 7), p = 0.156]. Additionally, the gas-related events were comparable between the 2 groups (capnoperitoneum needing aspiration-5 vs 2, p = 0.228, and development of subcutaneous emphysema-3 vs 1, p = 0.301). CONCLUSION: This randomized trial shows comparable entry time, closure time, number of clips needed to close the incision, and gas-related events between longitudinal and transverse incisions. REGISTRATION NUMBER: CTRI/2021/08/035829.

Outcomes after per-oral endoscopic myotomy for Zenker's diverticula (Z-POEM) and correlation with impedance planimetry (FLIP).

INTRODUCTION: Zenker's diverticulum (ZD) is a false pulsion diverticulum of the cervical esophagus. It is typically found in older adults and manifests with dysphagia. The purpose of this study is to describe our experience with Per-oral endoscopic myotomy for Zenker's (Z-POEM) and intraoperative impedance planimetry (FLIP). METHODS: We performed a single institution retrospective review of patients undergoing Z-POEM in a prospective database between 2014 and 2022. Upper esophageal sphincter (UES) distensibility index (DI, mm2/mmHg) was measured by FLIP before and after myotomy. The primary outcome was clinical success. Secondary outcomes included technical failure, adverse events, and quality of life as assessed by the gastroesophageal health-related quality of life (GERD-HRQL), reflux severity index (RSI), and dysphagia score. A statistical analysis of DI was done with the paired t-test (p < 0.05). RESULTS: Fifty-four patients underwent Z-POEM, with FLIP measurements available in 30 cases. We achieved technical success and clinical success in 54/54 (100%) patients and 46/54 patients (85%), respectively. Three patients (6%) experienced contained leaks. Three patients were readmitted: one for aforementioned contained leak, one for dysphagia, and one post-operative pneumonia. Three patients with residual dysphagia underwent additional endoscopic procedures, all of whom had diverticula > 4 cm. Following myotomy, mean DI increased by 2.0 ± 1.7 mm2/mmHg (p < 0.001). In those with good clinical success, change in DI averaged + 1.6 ± 1.1 mm2/mmHg. Significant improvement was found in RSI and GERD-HRQL scores, but not dysphagia score. CONCLUSION: Z-POEM is a safe and feasible for treatment of ZD. We saw zero cases of intraoperative abandonment. We propose that large diverticula (> 4 cm) are a risk factor for poor outcomes and may require additional endoscopic procedures. An improvement in DI is expected after myotomy, however, the ideal range is still not known.

Long-term efficacy of peroral endoscopic myotomy for achalasia under different criteria.

BACKGROUND: Peroral endoscopic myotomy (POEM) has emerged as a widely accepted treatment for achalasia, with limited studies for over 2 years. Additionally, traditional measurements of achalasia after POEM have deficiencies. The study aimed to analyze the long-term outcomes of POEM under different criteria. METHODS: Patients with achalasia who received POEM between November 2012 and March 2021 were recruited. Patients and characteristics were shown, and risk factors related to two novel definitions of recurrence, symptomatic reflux, and reflux esophagitis were analyzed. RESULTS: Three hundred and twenty-one patients were included. At a median follow-up of 52 months, twenty-three failures happened (7.17%) under the modified criterion, and forty-seven failures occurred (14.64%) under the normal standard. Hospitalization (P = 0.027) and esophageal myotomy length (P = 0.039) were significantly associated with long-term efficacy under the modified and normal criteria, respectively. Fifty-two patients (16.20%) reported reflux symptoms and endoscopy performed in 88 patients revealed reflux esophagitis in 22 cases (25.00%). There were no predictors in the analysis of symptomatic reflux and gender (P = 0.010), LESP (P = 0.013), IRP (P = 0.015), and the esophageal myotomy length (P = 0.032) were statistically related to reflux esophagitis. CONCLUSION: POEM is an extremely safe and effective treatment for achalasia with long-term follow-up. Shorter hospitalization and shorter esophageal myotomy length may decrease the incidence of recurrence under the modified and normal criteria, respectively. Long-term outcomes of POEM are unpredictable. No risk factors were related to symptomatic reflux, and male patients with low preoperative LESP and IRP needed relatively shorter esophageal myotomy to prevent reflux esophagitis.

Using impedance planimetry to define the end of a peroral endoscopic myotomy.

INTRODUCTION: Peroral endoscopic myotomy (POEM) is a minimally invasive endoscopic option for management of achalasia. Adequate distal myotomy is necessary for relief of symptoms, but when too long may also increase risk of reflux. The objective of this study is to evaluate clinical outcomes after POEM and final length of gastric myotomy using impedance planimetry (EndoFLIP). METHODS: A retrospective review of 34 consecutive patients undergoing POEM with EndoFLIP were included. EndoFLIP measurements, including esophagogastric junction distensibility index (DI), minimum diameter (Dmin), and cross-sectional area (CSA) were recorded at 30- and 40-mL balloon-fill pre- and post- myotomy. The myotomy was considered complete when DI ≥ 3.4 mm2/mmHg. Postoperative Eckardt score (ES) was determined at initial postoperative visit and most recent follow-up. Linear and logistic regression were used to evaluate the association between gastric myotomy length and post-myotomy EndoFLIP measurements on postoperative ES and GERD. Wilcoxon rank-sum test was used to compare gastric myotomy lengths and EndoFLIP parameters in relation to clinical success and development of GERD, and paired t-test to compare EndoFLIP measurements and ES pre- and post-myotomy. RESULTS: Final length of gastric myotomy measured 1 cm in 1 (2.9%), 1.5 cm in 11 (32.4%), 2.0 cm in 19 (55.9%), and 2.5 cm in 3 (8.8%) patients. Mean preoperative ES was 6.6 ± 2.2. All patients achieved ES < 3 postoperatively, which was maintained in 88.5% of patients at a median of 7.5 months of follow-up. Gastric myotomy length and post-myotomy EndoFLIP values were not associated with postoperative Eckardt scores or GERD. DISCUSSION: Early and late symptom relief was achieved in 100 and 88.5% of patients, respectively, at a gastric myotomy length of 1-2.5 cm. Using EndoFLIP to define a completed myotomy at DI of 3.4 mm2/mmHg yielded variable lengths of gastric myotomy.

Short-term symptomatic outcomes of GERD in patients with gastroparesis after gastric per oral endoscopic pyloromyotomy.

Gastroparesis (Gp) patients often have gastroesophageal reflux disease (GERD). Management of GERD in Gp patients is a challenge. Many studies have shown that gastric peroral endoscopic pyloromyotomy (G-POEM or POP) is moderately effective in reducing nausea and vomiting in patients with Gp. This study aims to determine whether G-POEM can improve GERD in Gp Patients. Patients who underwent G-POEM from July 2021 to October 2022 were enrolled in the study. GERD Health-Related Quality of Life (GERD HRQL) and Reflux Symptom Index (RSI) were used to assess patients' GERD before and after G-POEM. The use of proton pump inhibitors (PPIs) before and after G-POEM were also documented. The Gastroparesis Cardinal Symptom Index (GCSI) was used to assess the severity of Gp before and after G-POEM. A 'Welch two-sample t-test' was used to find differences in GERD HRQL (health-related quality of life) and RSI scores before and after the procedure. Pearson's chi-square test was used to find differences for use of PPI before and after G-POEM. Twenty-three consecutive refractory Gp patients with 30% male (average age 63.2) and 70% female patients (average age 53.9) were enrolled. Of these, 14 had diabetes, 3 had a history of surgery, and 6 had idiopathic Gp. The mean follow-up was 41 days (range 7-61 days). There was a significant decrease in the mean GERD HRQL score from 16.5 to 6.5 after G POEM with a P-value <0.0001 (95% level of significance) and a significant decrease in mean RSI score from 15.3 to 5.2 after G-POEM with P-value <0.0001 (95% level of significance). The proportion of use of PPI before GPOEM was 0.91, and the proportion of PPI use after GPOEM was 0.43 (P = 0.0008). The mean GCSI pre- and post-GPOEM were 3.53 and 1.59, respectively. Eighteen had clinical success in Gp as defined by decreased mean GCSI score greater than 1. In this short-term outcome study, 87% of patients' GERD HRQL scores and RSI scores decreased after G-POEM. These findings indicate that GPOEM not only effectively reduces Gp symptoms but also improves GERD symptoms leading to decreased or more effective use of PPI in these patients. To our knowledge, this is the first study to comprehensively show G-POEM significantly improves GERD. Further studies with a larger patient population and long-term outcomes are needed.

Impact of peroral endoscopic myotomy on the endoscopic pressure study integrated system.

OBJECTIVES: The endoscopic pressure study integrated system (EPSIS) is an endoscopic diagnostic system utilized for evaluation of lower esophageal sphincter function. Although previous studies have determined that EPSIS was effective as a tool for the diagnosis of achalasia, it remains uncertain if EPSIS can detect significant changes before and after peroral endoscopic myotomy (POEM), which is the premier treatment for achalasia. This study aimed to evaluate the effectiveness of EPSIS as an objective diagnostic tool for assessing the clinical effect of POEM. METHODS: We conducted a retrospective analysis of patients who underwent POEM from January 2022 to December 2023. The patients underwent EPSIS preoperatively and 2 months postoperatively. Intragastric pressure (IGP) parameters, including the maximum IGP, IGP difference, and waveform gradient were compared pre- and post-POEM. These parameters also were compared between two groups: the postoperative gastroesophageal reflux disease (GERD) group and the non-GERD group. RESULTS: A total of 50 patients were analyzed. The mean maximum IGP was significantly lower postoperatively than preoperatively (15.0 mmHg vs. 19.8 mmHg, P < 0.001). The mean IGP difference and waveform gradient were also significantly lower postoperatively than preoperatively (8.0 mmHg vs. 12.2 mmHg, P < 0.001; and 0.26 mmHg/s vs. 0.43 mmHg/s, P < 0.001, respectively). The mean postoperative waveform gradient was significantly lower in the GERD group (17 patients, 34%) than in the non-GERD group (33 patients, 66%) (0.207 mmHg vs. 0.291 mmHg, P = 0.034). CONCLUSION: The results supported the use of EPSIS as an effective diagnostic tool for assessing the effect of POEM.

Achalasia: laparoscopic Heller myotomy with fundoplication versus peroral endoscopic myotomy-a systematic review and meta-analysis.

There are various therapeutic options for achalasia. Nevertheless, peroral endoscopic myotomy (POEM) and laparoscopic Heller myotomy with fundoplication (LHM) are distinguished by their efficacy and low incidence of complications. Compare POEM and LHM regarding several outcomes in patients with achalasia. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An exhaustive literature search was performed using PubMed, Web of Science, and Cochrane Library databases. Studies comparing several outcomes between POEM and LHM in patients with achalasia were included. Data on clinical success, operative time, intraoperative complications, length of stay, reintervention rates, postoperative pain, overall complications, occurrence of GERD symptoms, use of proton bomb inhibitors and esophagitis were extracted. Quality assessment of the included studies was performed using the MINORS scale. We included 20 retrospective observational studies with a combined total of 5139 participants. The results demonstrated that there was no statistically significant difference in terms of intraoperative complications, postoperative complications, reintervention rate, occurrence of GERD symptoms, GERD HRQL, use of proton pump inhibitors, and esophagitis between POEM and LHM groups. Conversely, POEM was associated with higher clinical success and shorter operative time, length of stay, and postoperative pain. This meta-analysis concludes that both POEM and LHM, are effective and safe treatments for achalasia. However, POEM demonstrates better results regarding clinical success, operative time, length of stay, postoperative pain, and a tendency towards lower recurrence.

Association of gastric myotomy length in peroral endoscopic myotomy (POEM) with gastro-esophageal junction distensibility measured by Endoluminal Functional Lumen Imaging Probe (EndoFLIP).

BACKGROUND: Endoluminal Functional Lumen Imaging Probe (EndoFLIP) is a device that measures gastro-esophageal junction (GEJ) distensibility. However, it is not demonstrated that GEJ distensibility increases proportionally with varying gastric myotomy length in peroral endoscopic myotomy (POEM). This study aimed to investigate the association between gastric myotomy length in POEM and intraoperative EndoFLIP findings. METHODS: This single-center, retrospective cohort study included patients who underwent POEM with intraoperative EndoFLIP from December 2019 to January 2023. Using EndoFLIP, minimal balloon diameter and its distensibility index (DI) were measured pre- and post-myotomy. Primary and secondary outcomes were the post-myotomy EndoFLIP findings at 30 ml and 40 ml volume fills. RESULTS: The study included 44 patients (mean age 53.1 years, 50% female). Chicago classification included achalasia type I (39%), II (41%), III (9%), hypercontractile esophagus (2%), and EGJOO (9%). The mean esophageal myotomy length was 7.5 ± 2.2 cm and gastric myotomy was 2.1 ± 0.6 cm. Simple linear regression analyses indicated that for each 1 cm increase in gastric myotomy length, the DI at 30 ml volume fill was estimated to increase by 2.0 mm2/mmHg (p < 0.05, R2 = 0.41), the minimal diameter at 30 ml volume fill was estimated to increase by 2.4 mm (p < 0.05, R2 = 0.48), and the minimal diameter at 40 ml volume fill was estimated to increase by 1.3 mm (p < 0.05, R2 = 0.09). CONCLUSIONS: This study demonstrates a significant linear relationship between gastric myotomy length and GEJ distensibility measured by EndoFLIP during POEM. These findings may be useful in clinical practice by enabling EndoFLIP to help calibrate a desired gastric myotomy length to achieve optimal DI and minimal diameter.

High-fat diet, but not duration of lactation, increases mammary gland lymphatic vessel function and subsequent growth of inflammatory breast cancer cells.

Inflammatory breast cancer (IBC) presents as rapid-onset swelling and breast skin changes caused by tumor emboli in the breast and breast skin lymphatics. IBC has been linked with obesity and duration of breastfeeding, but how these factors affect IBC tumor progression is not clear. We modeled the simultaneous effects of diet and weaning in mice on in vivo lymphatic function; on IBC tumor growth; and on aspects of the mammary gland microenvironment before and after IBC (SUM149) xenograft inoculation. We hypothesized that weaning status and diet would have synergistic effects on lymphatic function and the breast microenvironment to enhance IBC tumor growth. Changes in lymphatic structure and function were characterized with in vivo near-infrared fluorescence (NIRF) imaging. Mice were fed either a high-fat diet (HFD; 60 kcal%) or a normal/low-fat diet (LFD; 10 kcal%), bred twice, and subjected to either normal-duration nursing (NW) or forced weaning (FW). SUM149 IBC tumors were implanted at 14 months; images were obtained before and after implantation. Multiparous mice fed HFD showed increased pre-tumor lymphatic pulsing in both the FW and NW groups relative to mice fed LFD. HFD promoted tumor growth independent of weaning time (P = 0.04). Pre-tumor lymphatic pulsing was associated with tumor volume at 8 weeks (P = 0.02) and was significantly correlated with expression of the lymphatic tracking ligand CCL21 (P = 0.05, Table 1). HFD significantly increased the numbers of monocyte-derived IBA1+, CD163+, and CD11c+ cells (P < 0.0001, P < 0.0001, P = 0.0005) in the contralateral, non-tumor-bearing mammary gland. Numbers of lymphangiogenic podoplanin+/IBA1+ macrophages were increased in the ducts of HFD and FW mice (all P < 0.003). HFD in nulliparous mice had a similar increase in lymphatic pulsing at 14 weeks (P = 0.006), indicating that this functional change was independent of parity. We conclude that HFD induced increases in mammary gland lymphatic function, assessed as pulsing rate before tumor initiation, and correlated with inflammation in the mammary gland and increased SUM149 tumor growth. The relationship between diet, lymphatic pulsing, and tumor growth warrants further investigation.

Prevalence and burden of atopic dermatitis involving the head, neck, face, and hand: A cross sectional study from the TARGET-DERM AD cohort.

BACKGROUND: Atopic dermatitis (AD) is severely burdensome, and there has been poor characterization of any differences in impact based on the area affected. OBJECTIVE: To estimate the prevalence and HRQoL impact of head/face/neck/hand (HFNH) involvement among patients with moderate-to-severe atopic dermatitis. METHODS: All TARGET-DERM AD registry patients with moderate/severe Investigator Global Assessment (vIGA-AD) were assessed using the Patient Oriented SCORing Atopic Dermatitis, Patient Oriented Eczema Measure (POEM) and the (Children's) Dermatology Life Quality Index ((C)DLQI). RESULTS: 541 participants met the criteria (75.0% adults) and 84% (N = 453) reported HFNH involvement. HFNH and non-HFNH involved participants had similar characteristics; 55.2% female and 46.9% White. Compared to the non-HFNH involved, the involved had severe vIGA-AD (28.5% vs 16.3%, P = .02) and higher median body surface area affected (15% vs 10%, P ≤ .01) and were twice as likely to have higher (C)DLQI and POEM scores. LIMITATIONS: This was an analysis of real-world and patient reported outcome data. CONCLUSION: Real-world HFNH involved AD patients were associated with significantly worse quality of life, POEM/(C)DLQI, and more severe disease. Detailed assessments of specific areas affected by AD are needed to personalize treatment.

Characteristics of the esophageal microbiome in patients with achalasia and its changes before and after peroral endoscopic myotomy: A pilot study.

BACKGROUND AND AIM: Achalasia often presents with chronic food stasis and fermentation in the esophageal lumen, which may lead to alterations of the esophageal microbiome, with associated mucosal inflammation and dysplastic changes. The study aims to evaluate the characteristics of the esophageal microbiome in achalasia and changes of the esophageal microbiome before and after peroral endoscopic myotomy (POEM). METHODS: This is a prospective case-control study. This study enrolled patients with achalasia and asymptomatic subjects as control group. Endoscopic brushing for esophageal microbiome collection was performed in all subjects, with additional follow-up endoscopy and brushing 3 months after POEM in achalasia patients. The composition of the esophageal microbiome was determined and compared between (1) achalasia patients and asymptomatic controls and (2) achalasia patients before and after POEM. RESULTS: Thirty-one achalasia patients (mean age 53.5 ± 16.2 years; male 45.2%) and 15 controls were analyzed. We observed a distinct esophageal microbial community structure in achalasia patients, with increased Firmicutes and decreased Proteobacteria when compared with the control group at the phylum level. The discriminating enriched genera in achalasia patients were Lactobacillus, followed by Megasphaera and Bacteroides, and the amount of Lactobacillus was associated with the severity of achalasia. Twenty patients were re-examined after POEM, and a high prevalence of erosive esophagitis (55%) was noted, alongside an increase in genus Neisseria and decrease in Lactobacillus and Bacteroides. CONCLUSIONS: The altered esophageal microenvironment in achalasia leads to dysbiosis with a high abundance of genus Lactobacillus. Increased Neisseria and decreased Lactobacillus were observed after POEM. The long-term effect of microbial changes warrants further study.