Pioneering a chick embryo model to explore the intrauterine etiology of developmental dysplasia of the hip in oligohydramnios conditions.

OBJECTIVE: To explore the impact of oligohydramnios on fetal movement and hip development, given its association with developmental dysplasia of the hip (DDH) but unclear mechanisms. METHODS: Chick embryos were divided into four groups based on the severity of oligohydramnios induced by amniotic fluid aspiration (control, 0.2 mL, 0.4 mL, 0.6 mL). Fetal movement was assessed by detection of movement and quantification of residual amniotic fluid volume. Hip joint development was assessed by gross anatomic analysis, micro-computed tomography (micro-CT) for cartilage assessment, and histologic observation at multiple time points. In addition, a subset of embryos from the 0.4 mL aspirated group underwent saline reinfusion and subsequent evaluation. RESULTS: Increasing volumes of aspirated amniotic fluid resulted in worsening of fetal movement restrictions (e.g., 0.4 mL aspirated and control group at E10: frequency difference -7.765 [95% CI: -9.125, -6.404]; amplitude difference -0.343 [95% CI: -0.588, -0.097]). The 0.4 mL aspirated group had significantly smaller hip measurements compared to controls, with reduced acetabular length (-0.418 [95% CI: -0.575, -0.261]) and width (-0.304 [95% CI: -0.491, -0.117]) at day E14.5. Histological analysis revealed a smaller femoral head (1.084 ± 0.264 cm) and shallower acetabulum (0.380 ± 0.106 cm) in the 0.4 mL group. Micro-CT showed cartilage matrix degeneration (13.6% [95% CI: 0.6%, 26.7%], P = 0.043 on E14.5). Saline reinfusion resulted in significant improvements in the femoral head to greater trochanter (0.578 [95% CI: 0.323, 0.833], P = 0.001). CONCLUSIONS: Oligohydramnios can cause DDH by restricting fetal movement and disrupting hip morphogenesis in a time-dependent manner. Timely reversal of oligohydramnios during the fetal period may prevent DDH.

Are Generative Pretrained Transformer 4 Responses to Developmental Dysplasia of the Hip Clinical Scenarios Universal? An International Review.

OBJECTIVE: There is increasing interest in applying artificial intelligence chatbots like generative pretrained transformer 4 (GPT-4) in the medical field. This study aimed to explore the universality of GPT-4 responses to simulated clinical scenarios of developmental dysplasia of the hip (DDH) across diverse global settings. METHODS: Seventeen international experts with more than 15 years of experience in pediatric orthopaedics were selected for the evaluation panel. Eight simulated DDH clinical scenarios were created, covering 4 key areas: (1) initial evaluation and diagnosis, (2) initial examination and treatment, (3) nursing care and follow-up, and (4) prognosis and rehabilitation planning. Each scenario was completed independently in a new GPT-4 session. Interrater reliability was assessed using Fleiss kappa, and the quality, relevance, and applicability of GPT-4 responses were analyzed using median scores and interquartile ranges. Following scoring, experts met in ZOOM sessions to generate Regional Consensus Assessment Scores, which were intended to represent a consistent regional assessment of the use of the GPT-4 in pediatric orthopaedic care. RESULTS: GPT-4's responses to the 8 clinical DDH scenarios received performance scores ranging from 44.3% to 98.9% of the 88-point maximum. The Fleiss kappa statistic of 0.113 ( P = 0.001) indicated low agreement among experts in their ratings. When assessing the responses' quality, relevance, and applicability, the median scores were 3, with interquartile ranges of 3 to 4, 3 to 4, and 2 to 3, respectively. Significant differences were noted in the prognosis and rehabilitation domain scores ( P < 0.05 for all). Regional consensus scores were 75 for Africa, 74 for Asia, 73 for India, 80 for Europe, and 65 for North America, with the Kruskal-Wallis test highlighting significant disparities between these regions ( P = 0.034). CONCLUSIONS: This study demonstrates the promise of GPT-4 in pediatric orthopaedic care, particularly in supporting preliminary DDH assessments and guiding treatment strategies for specialist care. However, effective integration of GPT-4 into clinical practice will require adaptation to specific regional health care contexts, highlighting the importance of a nuanced approach to health technology adaptation. LEVEL OF EVIDENCE: Level IV.

Medium-term clinical efficacy of endoscopic antireflux mucosectomy on laryngopharyngeal reflux: a retrospective multicenter cohort study.

BACKGROUND AND AIMS: Studies on the effect of antireflux mucosectomy (ARMS) on laryngopharyngeal reflux disease (LPRD) are lacking. We conducted a multicenter retrospective study to explore the clinical efficacy of ARMS on LPRD. METHODS: We retrospectively analyzed the data of patients diagnosed with LPRD by oropharyngeal 24-hour Dx-pH monitoring who underwent ARMS. The effects of ARMS on LPRD were evaluated by comparing the 36-Item Short-Form Survey (SF-36), reflux symptom index (RSI), and 24-hour Dx-pH monitoring scores before and 1 year after surgery. Patients were divided into groups according to gastroesophageal flap valve (GEFV) grade to explore the effect of GEFV on prognosis. RESULTS: One hundred eighty-three patients were included in the study. The oropharyngeal pH monitoring results showed that the effective rate of ARMS was 72.1% (132/183). After surgery, the SF-36 score was higher (P = .000), RSI score was lower (P = .000), and the symptoms of constant throat clearing; difficulty swallowing food, liquids, and pills; coughing after eating or after lying down; troublesome or annoying cough; and breathing difficulties or choking episodes were significantly improved (P < .05). Upright reflux was dominant in GEFV grade I to III patients, and the SF-36, RSI, and upright Ryan index scores were significantly improved after surgery (P < .05). In GEFV grade IV patients, regurgitation was dominant in the supine position, and the above evaluation indexes were worse after surgery (P < .05). CONCLUSIONS: ARMS is effective for LPRD. The GEFV grade can predict the prognosis of surgery. ARMS is effective in GEFV grade I to III patients, but the effect is not exact in GEFV grade IV patients and may even be aggravated.

Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper GI tract in cirrhotic patients with esophagogastric varices: 10-year experience from a large tertiary center in China.

BACKGROUND AND AIMS: Treatment strategies for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and esophagogastric varices (EGVs) are complicated and risky. The aim of this study was to assess the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of such patients and explore optimal treatment strategies. METHODS: We retrospectively enrolled 15 patients with cirrhosis and EGV who underwent ESD for early cancers or precancerous lesions of the upper GI tract from January 2012 to December 2021 at our center. Clinical features, endoscopic findings, treatment methods, adverse events, and follow-up data were analyzed. RESULTS: Of the 15 patients, 1 had a platelet count <30 × 1000/mm3. Five were untreated for EGV, 1 was treated after ESD, 6 were treated before ESD, 1 was treated before and during ESD, and 2 were treated during ESD. The R0 resection rate was 100%. Of the 16 mucosal lesions, 15 were endoscopic resection bleeding (ERB)-0 or ERB-c1, and 1 was ERB-c2. No patient experienced deterioration in liver function. The only adverse events were fever in 2 patients and postoperative bleeding in 2 patients. During a median follow-up of 27 months, 1 patient's esophageal high-grade dysplasia recurred at 19 months. No death resulted from the ESD procedure, liver function injury, or GI tumor itself. CONCLUSIONS: ESD is an effective and safe treatment for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and EGV. The incidence of severe adverse events is very low due to the development of individualized clinical treatment strategies.

Numb inhibits migration and promotes proliferation of colon cancer cells via RhoA/ROCK signaling pathway repression.

Numb regulates cell proliferation and differentiation through endocytosis and ubiquitination of signaling molecules. Besides, Numb controls the migration of epithelial cells by regulating intercellular junctions. Studies have shown that Numb promotes or inhibits tumor progression in different tumors. However, its role and mechanism in colorectal cancer remain unclear. We found that the expression level of Numb in colon tumor tissues has a great variety in different patients. Numb expression was negatively correlated with TNM stage and lymph node metastasis but positively correlated with tumor size. Elevated expression of Numb was associated with a good prognosis. Inhibiting Numb expression promoted the migration and invasion of colon cancer cells induced by TGF-ß, up-regulated the expression of EMT-related molecule Snail, and prevented the expression of E-cadherin. We also found that Numb promoted the proliferation and clones formation while inhibiting colon cancer cells' late apoptosis. In addition, Numb inhibited the RhoA activation and ROCK inhibitor Y-27632 or interfered with ROCK expression, partially inhibiting Numb-regulated cell proliferation and migration. In vivo tumorigenesis assay in nude mice also found that Numb promoted the proliferation of colon cancer cells, inhibited the expression of E-cadherin, and strengthened the expression of Snail. In conclusion, our study found that Numb plays multiple roles in the occurrence and progression of colon cancer by regulating the RhoA/ROCK signaling pathway, which provides a new theoretical molecular basis for the pathogenesis of colon cancer.

Simultaneous Examination of Eosinophil Infiltration in Esophageal Mucosa and Muscle in Patients with Achalasia: Direct Biopsy of the Esophageal Muscle at Per-oral Endoscopic Myotomy.

BACKGROUND: The relationship between eosinophilic esophagitis (EoE) and achalasia is not completely understood. There have been reports of eosinophilic infiltration of all esophageal layers in patients with achalasia. However, a routine endoscopic biopsy of the muscular layer is usually not feasible. We evaluate the safety and efficacy of muscle layer biopsy during per-oral endoscopic myotomy (POEM) as well as the prevalence of eosinophilic infiltration of the esophageal mucosa and muscular layer in patients with achalasia. PATIENTS AND METHODS: All enrolled patients had diagnosed achalasia and had simultaneous biopsies of the muscular layer at the middle esophagus and distal esophageal sphincter as well as the mucosal layer of the proximal and distal esophagus during POEM. All POEM procedures took place from August 2018 to December 2018 or September 2019 to November 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. Eosinophilic infiltration in the biopsy specimen was examined. KEY RESULTS: Twenty consecutive patients (65% female, age range: 21-84) with a pre-procedure Eckardt score of >6 were enrolled during the study period, with the duration of their achalasia ranging from 1 to 32 years. Eighteen patients had clinical symptomatic improvement after POEM, as defined by an Eckardt score <3. Endoscopic examination did not reveal any signs of eosinophilic esophagitis. Pathologic examination of biopsies revealed eosinophilic infiltration in three of 20 patients (15%) in the distal esophageal mucosa (all <15 eosinophils/HPF) and none in the proximal esophageal mucosa. There was no eosinophilic infiltration in the distal esophageal sphincter and the middle esophageal muscle. No complication was noted due to muscle biopsy. CONCLUSIONS AND INFERENCES: Submucosal tunneling during POEM provides a safe access for direct esophageal muscle biopsy. This is the first report of the simultaneous biopsy of the esophageal mucosa and muscle in patients with achalasia. Contrary to all previously published studies, the association of esophageal eosinophilic infiltration and achalasia was not observed in this small sample study. Based on our findings, immune or autoimmune reaction rather than direct eosinophilic infiltration in the muscle is more likely the cause of achalasia.

Quantification of Interstitial Cells of Cajal in the Gastric Muscle of Patients with Gastroparesis at Per-Oral Endoscopic Pyloromyotomy: A Novel Approach for Future Research in Pathogenesis of Gastroparesis.

BACKGROUND: The role of Interstitial Cells of Cajal (ICC) in the pathogenesis of gastroparesis has been suggested by previous studies due to their involvement in the transmission of neuronal signaling to the smooth muscles of the GI tract. However, studies have been limited by the inability to obtain a gastric muscle sample, since routine endoscopy can only biopsy the mucosa. We present a new technique of muscle biopsy during per-oral endoscopic pyloromyotomy (GPOEM), a novel endoscopic procedure for treatment of gastroparesis. PATIENTS AND METHODS: All enrolled patients had diagnosed gastroparesis and had biopsies of the muscular layer at the antrum/pylorus during POEM. All GPOEM procedures took place from August 2019 to December 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. ICC in the biopsy specimen was examined and quantitated. RESULTS: Through this method, we readily expose the gastric muscle of 21 patients through dissection of a gastric submucosal tunnel during GPOEM and provide reliable muscle sample for ICC quantification. Average number of ICC were higher in clinical responders (88 ICC ± 63 vs. 39 ICC ± 24, p = 0.02), defined as those who experienced significant improvement in nausea and vomiting symptoms after GPOEM. CONCLUSIONS: This study provides a reliable novel biopsy method for safely biopsy gastric muscle for quantitating the number of gastric ICC in patients with gastroparesis. The number of ICC may be related to the outcome of GPOEM therapy. However, further studies with larger number of patients are needed to confirm the results.

Fluoride increases the susceptibility of developmental dysplasia of the hip via increasing capsular laxity triggered by cell apoptosis and oxidative stress in vivo and in vitro.

The etiology of developmental dysplasia of the hip (DDH) is multifactorial, including breech presentation and hip capsular laxity. In particular, hip laxity is the main contributor to DDH by changing the ratio and distribution of collagens. Also, fluoride (F) affects collagens from various tissue besides bone and tooth. To investigate the association of DDH and excessive F intake, we conducted this research in lab on cell and animal model simultaneously. We established animal model of combination of DDH and F toxicity. The incidence of DDH in each group was calculated, and hip capsules were collected for testing histopathological and ultrastructural changes. The primary fibroblasts were further extracted from hip capsule and treated with F. The expression of collagen type I and III was both examined in vivo and in vitro, and the level of oxidative stress and apoptosis was also tested identically. We revealed that the incidence of DDH increased with F concentration. Furthermore, the oxidative stress and apoptosis levels of hip capsules and fibroblasts both increased after F exposure. Therefore, this study shows that excessive F intake increases susceptibility to DDH by altering hip capsular laxity in vivo and in vitro respectively. We believe that F might be a risk factor for DDH by increasing hip laxity induced by triggering fibroblast oxidative stress and apoptosis.

The Association of Asymmetric Skinfolds and the Diagnosis of Developmental Dysplasia of the Hip in Infants.

BACKGROUND: The clinical finding of asymmetric skinfolds (ASF) in infants is used to indicate the possibility of developmental dysplasia of the hip (DDH). The association of ASF and a diagnosis of DDH remains unknown. PURPOSE: To determine the association of ASF in the gluteal and femoral regions with a diagnosis of DDH. METHODS: The correlation of ASF and other physical examination findings with DDH was compared retrospectively. The medical records of infants who underwent DDH screening in the clinic were analyzed. The physical examination findings were reviewed and categorized as ASF, clunk of the hip, limb-length discrepancy, hip abduction limitation, combined conditions of musculoskeletal disorders, and regular screening for DDH. The hip conditions were classified by Graf's ultrasound method. Type IIb and higher classifications were defined as DDH. The diagnosed rate and severity of DDH based on physical examination findings were calculated and compared. RESULTS: Clinical data of 3266 infants aged up to 6 months were reviewed, and 194 infants were diagnosed with DDH by ultrasound examination. ASF was the most common indication for DDH screening (64.5%; 2107/3266). However, this was poorly correlated with a diagnosis of DDH (4.79%; P < .0001). No difference was found between the Graf classification severity and various indications ( P = .079). IMPLICATIONS FOR PRACTICE: Clinicians should recognize that, although ASF is the most common reason for DDH screening in infants, ASF does not correlate with a diagnosis of DDH. IMPLICATIONS FOR RESEARCH: Additional research should examine the relationship between DDH and ASF in other populations.

Long-term Outcome of Gastric Per-Oral Endoscopic Pyloromyotomy in Treatment of Gastroparesis.

BACKGROUND & AIMS: Gastric per oral endoscopic pyloromyotomy (GPOEM) is a promising treatment for gastroparesis. There are few data on the long-term outcomes of this procedure. We investigated long-term outcomes of GPOEM treatment of patients with refractory gastroparesis. METHODS: We conducted a retrospective case-series study of all patients who underwent GPOEM for refractory gastroparesis at a single center (n = 97), from June 2015 through March 2019; 90 patients had more than 3 months follow-up data and were included in our final analysis. We collected data on gastroparesis cardinal symptom index (GCSI) scores (measurements of postprandial fullness or early satiety, nausea and vomiting, and bloating) and SF-36 questionnaire scores (measures quality of life). The primary outcome was clinical response to GPOEM, defined as a decrease of at least 1 point in the average total GCSI score with more than a 25% decrease in at least 2 subscales of cardinal symptoms. Recurrence was defined as a return to baseline GCSI or GCSI scores of 3 or more for at least 2 months after an initial complete response. The secondary outcome was the factors that predict GPOEM failure (no response or gastroparesis recurrence within 6 months). RESULTS: At initial follow-up (3 to 6 months after GPOEM), 73 patients (81.1%) had a clinical response and significant increases in SF-36 questionnaire scores (indicating increased quality of life) whereas 17 patients (18.9%) had no response. Six months after GPOEM, 7.1% had recurrence. At 12 months, 8.3% of patients remaining in the study had recurrence. At 24 months, 4.8% of patients remaining in the study had a recurrence. At 36 months, 14.3% of patients remaining in the study had recurrence. For patients who experienced an initial clinical response, the rate of loss of that response per year was 12.9%. In the univariate and multivariate regression analysis, a longer duration of gastroparesis reduced the odds of response to GPOEM (odds ratio [OR], 0.092; 95% CI, 1.04-1.3; P = .001). On multivariate logistic regression, patients with high BMIs had increased odds of GPOEM failure (OR, 1.097; 95% CI, 1.022-1.176; P = .010) and patients receiving psychiatric medications had a higher risk of GPOEM failure (OR, 1.33; 95% CI, 0.110-1.008; P = .052). CONCLUSIONS: In retrospective analysis of 90 patients who underwent GPOEM for refractory gastroparesis, 81.1% had a clinical response at initial follow-up of their procedure. 1 year after GPOEM, 69.1% of all patients had a clinical response and 85.2% of initial responders maintained a clinical response. Patients maintained a clinical response and improved quality of life for as long as 3 years after the procedure. High BMI and long duration gastroparesis were associated with failure of GPOEM.

WISP-2, an upregulated gene in hip cartilage from the DDH model rats, induces chondrocyte apoptosis through PPARγ in vitro.

Chondrocyte apoptosis plays an important role in the developmental dysplasia of the hip (DDH) development. It has been found that WNT1 inducible signaling pathway protein 2 (WISP-2) and peroxisome proliferator-activated receptor γ (PPARγ) are involved in cell apoptosis. In this study, we performed the straight-leg swaddling DDH rat model and we found that cartilage degradation and chondrocyte apoptosis were remarkably increased in DDH rats in vivo. Moreover, we found that WISP-2 was upregulated in hip acetabular cartilage of DDH rats compared to control rats. Next, the effects of WISP-2 on chondrocyte apoptosis and its possible underlying mechanism were examined in vitro. The lentivirus-mediated gain- and loss-of-function experiments of WISP-2 and peroxisome proliferator-activated receptor γ (PPARγ) for cell viability and apoptosis were performed in primary rat chondrocytes. The results showed that the overexpression of WISP-2 induced chondrocyte apoptosis, and knockdown of WISP-2 could suppress the chondrocyte apoptosis induced by advanced glycation end products (AGE). Additionally, WISP-2 could negatively regulate the expression of PPARγ in chondrocytes. Moreover, the knockdown of PPARγ promoted chondrocyte apoptosis and overexpression of PPARγ abated the increased apoptosis and decreased cell viability of chondrocytes induced by WISP-2. This study demonstrated that WISP-2 might contribute to chondrocyte apoptosis of hip acetabular cartilage through regulating PPARγ expression and activation, which may play an important role in the development of DDH.

Prevalence and Risk Factors of Burnout Among Chinese Pediatric Orthopedic Surgeons.

BACKGROUND: Burnout is an occupational hazard among Chinese pediatric orthopedists, characterized by extreme physical and emotional exhaustion, and reduced professional efficacy; however, it has yet to be studied among this group of professionals in China. Our study aimed to assess the levels of burnout in Chinese pediatric orthopedists, and to identify the potential risk factors for burnout. METHODS: A 32-question, anonymous, cross-sectional survey was conducted from August to September 2019. Overall, 1392 Chinese pediatric orthopedists participated in the survey. RESULTS: Seven hundred valid questionnaires (50.3% response rate) were retrieved from 387 (55.3%) and 313 (44.7%) full-time and part-time pediatric orthopedists, respectively. Overall, 73.7% of the participants experienced burnout, of which 64.7% and 9.0% had some and severe burnout symptoms, respectively. The burnout levels significantly differed based on age (P=0.005), years in service (P=0.006), professional rank (P=0.03), weekly working hours (P<0.001), and monthly income (P=0.03). A binary logistic regression model showed that longer weekly working hours (adjusted odds ratio=1.29, 95% confidence interval: 1.09-1.52, P=0.004) was a risk factor for burnout, while higher monthly income (adjusted odds ratio=0.78, 95% confidence interval: 0.64 to 0.95, P=0.02) was protective against burnout, suggesting that younger pediatric orthopedists were more susceptible. No significant difference between full-time and part-time pediatric orthopedists or between sexes was detected in the adjusted analysis. CONCLUSIONS: Chinese pediatric orthopedists have a relatively high rate of burnout. Younger pediatric orthopedists have a greater chance of experiencing burnout. These results highlight the need for further policies, especially focused on younger pediatric orthopedists, to assist in better developing Chinese pediatric orthopedics. LEVEL OF EVIDENCE: Level: IV.

Development of acetabular anteversion in children with normal hips and those with developmental dysplasia of the hip: a cross-sectional study using magnetic resonance imaging.

Background and purpose - Acetabular anteversion (AA) is related to hip function. Most previous studies were based on radiographic investigations that determine osseous acetabular anteversion (OAA). But children's acetabulum is mostly composed of cartilage; the cartilaginous acetabular anteversion (CAA) represents the real anteversion of the acetabulum. We measured OAA and CAA in children of various ages using MRI, and compared the developmental patterns between children with normal hips and those with developmental dysplasia of the hip (DDH).Patients and methods - The OAA and CAA were measured on MRI cross-sections of the hips in 293 children with normal hips (average age 8 years), and in 196 children with DDH (average age 34 months). Developmental patterns of OAA and CAA in children with normal hips were determined through age-based cross-sectional analysis. Differences in OAA and CAA between children with normal hips and those with DDH were compared.Results - Normal OAA increased from mean 8.7° (SD 3.2) to 12° (3.0) during the first 2 years of life and remained unchanged until 9 years of age. From 9 to 16 years, the OAA showed a minimal increase of 2°-3°. The normal CAA increased rapidly from a mean of 12° (3.1) to 15° (2.7) within the first 2 years of life, and remained constant at 15° (SD 3.4) until 16 years of age. The age-matched average OAA in the normal and DDH cases was 11° (3.2) and 15° (3.0), respectively (p < 0.001). The age-matched average CAA in normal and DDH cases was 17° (4.2) and 23° (4.5), respectively (p < 0.001). Similarly, there was a significant difference in OAA and CAA between the uninvolved hips in unilateral DDH and normal cases (p < 0.001).Interpretation - The CAA was fully formed at birth in normal children, and remained unchanged until adulthood, whereas the OAA increased with age. The OAA and CAA were both over-anteverted in DDH children. MRI evaluation is of importance in children during skeletal development when planning hip surgery.

SIRT2, a direct target of miR-212-5p, suppresses the proliferation and metastasis of colorectal cancer cells.

The aberrant expression of human sirtuin 2 (SIRT2) has been detected in various types of cancer; however, the biological roles, underlying mechanisms and clinical significance of SIRT2 dysregulation in human colorectal cancer (CRC) remain unclear. The results of this study demonstrate that compared with paired normal tissues, SIRT2 expression is significantly decreased in CRC tissues. SIRT2 loss has been correlated with clinicopathological characteristics, including distant metastasis, lymph node metastasis and American Joint Committee on Cancer (AJCC) stage; this loss serves as an independent factor that indicates a poor prognosis for patients with CRC. Further gain- and loss-of-function analyses have demonstrated that SIRT2 suppresses CRC cell proliferation and metastasis both in vivo and in vitro. Mechanistically, miR-212-5p was identified to directly target the SIRT2 3'-untranslated region (3'-UTR), leading to SIRT2 down-regulation. The ectopic expression of SIRT2 reverses the effect of miR-212-5p overexpression on CRC cell colony formation, invasion, migration and proliferation. Clinically, an inverse correlation was found between miR-212-5p and SIRT2 expression. High miR-212-5p expression has been found to result in a poor prognosis and aggressive clinicopathological characteristics in patients with CRC. Taken together, these results suggest that SIRT2, targeted by miR-212-5p, acts as a tumour suppressor in CRC and that the miR-212-5p/SIRT2 axis is a promising prognostic factor and potential therapeutic target in CRC.

Short-term outcomes of double versus single pyloromyotomy at peroral endoscopic pyloromyotomy in the treatment of gastroparesis (with video).

BACKGROUND AND AIMS: The prevalence of gastroparesis (Gp), a chronic debilitating disorder, and resulting hospitalizations are increasing. Gastric peroral endoscopic pyloromyotomy (POP or GPOEM) is a novel technique in the treatment of refractory Gp. Despite the initial promising results of GPOEM, one-third of patients do not exhibit any clinical response. Furthermore, loss of clinical response was reported in several studies. No response or loss of response after GPOEM may be related to inadequate myotomy. The aim of our study is to examine whether double pyloromyotomy at GPOEM is superior to single pyloromyotomy. METHOD: A retrospective case-controlled study of patients who underwent GPOEM for refractory Gp at our tertiary care institution between June 2015 and March 2018 was performed. Because the follow-up time for the single myotomy group was much longer than that of the double myotomy group, we matched the length of follow-up for the single myotomy group to that of the double myotomy group. The outcomes were measured by the changes in the Gastroparesis Cardinal Symptom Index (GCSI) before and 3 to 6 months after the procedure. Adverse events and other procedural and clinical parameters were also compared. RESULTS: Ninety patients underwent GPOEM (55 single and 35 double pyloromyotomy). The mean age was 47 ± 14 years, and the mean duration of symptoms was 5.3 ± 4.4 years. The average GCSI score was 3.8 before the GPOEM, and the average GCSI score 6 months after procedure was 1.8. Thirty-seven of 55 (67%) patients who underwent single pyloromyotomy achieved clinical response compared with 30 of 35 (86%) patients who underwent double pyloromyotomy. There were no significant differences for procedure time, postoperative pain, or length of hospital stay between the 2 groups. There was no difference in adverse events in the 2 pyloromyotomy groups. CONCLUSION: Double pyloromyotomy is a safe and feasible technique during GPOEM. Clinical success was higher in patients undergoing double pyloromyotomy compared with single pyloromyotomy in this nonrandomized, short-term follow-up study. Long-term studies are needed to further confirm our results.

Relationship between laryngopharyngeal reflux disease and gastroesophageal reflux disease based on synchronous esophageal and oropharyngeal Dx-pH monitoring.

PURPOSE: To use the synchronous esophageal and oropharyngeal Dx-pH monitoring analysis to investigate the relationship between LPRD and GERD. MATERIALS AND METHODS: Synchronous esophageal and oropharyngeal Dx-pH monitoring, electronic gastroscopy, reflux symptom index (RSI) and gastroesophageal reflux questionnaire (Gerd-Q) were collected from 514 consecutive patients and comparative analysis was done. RESULTS: A total of 85 patients had positive Ryan score and 251 cases had positive DeMeester or acid exposure time percent (AET) ≥4.2%. Moreover, 61.2% (52/85) of all LPRD cases were pure LPRD without GERD. There was no statistical difference in the acid exposure to oropharynx between pure LPRD group and LPRD+GERD group (U test, P > 0.05). Furthermore, there were no statistical differences in the other esophageal reflux data between pure GERD without LPRD group and LPRD+GERD group (U test, P > 0.05) apart from the number of episodes, which was higher in the pure GERD group than in LPRD+GERD group (U test, P = 0.027). Additionally, 149 patients were diagnosed with reflux esophagitis by electronic gastroscopy. No significant difference in the acid exposure to oropharynx was seen between different grades of reflux esophagitis (U test, P > 0.05). Among the LPRD patients, 32 cases (37.6%) were negative for Gerd-Q, Dx-pH esophageal probe and gastroscopy. CONCLUSION: The results of synchronous esophageal and oropharyngeal Dx-pH monitoring demonstrated that LPRD and GERD could co-exist as separate medical conditions. Our data suggest that some LPRD are not accompanied by GERD, and that LPRD is not secondary to severe GERD.

Gastric Peroral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of Life, and Reduces Health Care Use For Patients With Gastroparesis.

BACKGROUND & AIMS: Gastric peroral endoscopic pyloromyotomy (GPOEM) is becoming a promising treatment option for patients with refractory gastroparesis. We aimed to systematically assess the efficacy of GPOEM and its effects on health care use. METHODS: We performed a retrospective study on 30 patients with refractory gastroparesis who underwent GPOEM from June 2015 through July 2017 at a tertiary center. We compared outcomes with those of 7 patients with refractory gastroparesis who did not undergo the procedure (controls). The primary outcomes were patient-reported reductions in symptoms, based on the gastroparesis cardinal symptom index (GCSI), and increases in 8 aspects of quality of life, based on Short Form 36 (SF-36) scores. Data were collected on the day of the procedure (baseline) and at 1 month, 6 months, 12 months, and 18 months afterward. Secondary outcomes included visits to the emergency department or hospitalization for gastroparesis-related symptoms. RESULTS: GPOEM was technically successful in all patients and significantly reduced GCSI scores in repeated-measure analysis of variance (F2.044, 38.838 = 22.319; P < .0005). The mean score at baseline was 3.5 ± 0.6, at 1 month after GPOEM was 1.8 ± 1.0 (P < .0005), at 6 months after was 1.9 ± 1.2 (P < .0005), at 12 months after was 2.6 ± 1.5 (P < .026), and at 18 months after was 2.1 ± 1.3 (P < .016). GPOEM was associated with improved quality of life: 77.8%, 76.5%, and 70% of patients had significant increases in SF-36 scores, compared with baseline, at 1 month, 6 months, and 12 months after GPOEM, respectively (F1.71,18.83 = 14.16; P < .0005). Compared with controls, patients who underwent GPOEM had significant reductions in GCSI, after we controlled for baseline score and duration of the disease (F1,31 = 9.001; P = .005). Patients who received GPOEM had significant reductions in number of emergency department visits (from 2.2 ± 3.1 times/mo at baseline to 0.3 ± 0.8 times/mo; P = .003) and hospitalizations (from 1.7 ± 2 times/mo at baseline to 0.2 ± 0.4 times/mo; P = .0002). CONCLUSIONS: In a retrospective study of patients who underwent GPOEM for refractory gastroparesis, we found the procedure significantly improved symptoms, increased quality of life, and reduced health care use related to gastroparesis.

Current Status of Endoscopic Resection of Gastric Subepithelial Tumors.

Most gastrointestinal (GI) subepithelial tumors (SETs) are identified incidentally during endoscopic examination and are located in the stomach. Some SETs are malignant or have the potential to become malignant. Tumors originating from deeper layers, such as the muscularis propria or serosa, are not easy to diagnose and resect. Current guidelines recommend yearly endoscopic surveillance of SETs smaller than 2 cm. This recommendation may not be cost-effective in managing GI SETs. Endoscopic resection results not only in obtaining sufficient tissue for pathological diagnosis but also in resection and curing the tumor. Many different endoscopic methods for resection of GI SETs have been published in the literature. To avoid confusion, we have divided these methods into standard endoscopic submucosal dissection, modified endoscopic submucosal dissection, submucosal tunneling endoscopic resection, and nonexposed and exposed endoscopic full-thickness resection. These procedures offer less invasive approaches than surgery for resection of GI SETs and may be the most cost-effective in taking care of patients with GI SETs.

Gastric per-oral endoscopic myotomy for refractory gastroparesis: a detailed description of the procedure, our experience, and review of the literature.

BACKGROUND AND AIMS: Gastric per-oral endoscopic myotomy (G-POEM) was introduced four years ago as an investigational procedure for refractory gastroparesis. The safety and efficacy were currently evaluated. With our recent studies on G-POEM, we share our experience and knowledge through the discussion of a detailed description of the procedure and review of the literature. To our knowledge, this is the first systemic review on this new therapeutic endoscopic procedure. METHODS: The indications and contraindications, various aspects of the procedure, and efficacy assessment are discussed based on our experience and current available data. RESULTS: Preoperative preparation, detailed description of the procedure, post-procedural care, and results in the literature are presented. The procedure is safe and effective. 70-80% of patients have significant improvement in overall symptoms and quality of life in short-term (6 months) follow-up, as assessed by Gastric Cardinal Symptom Index and Short Form 36. CONCLUSIONS: G-POEM is a feasible and effective procedure for refractory gastroparesis based on early and limited data. Well-designed prospective studies are expected to advance and evaluate this new procedure in the future.