Search

Background: In the surgical management of GERD, the traditional procedure is laparoscopic total (Nissen) fundoplication. However, partial fundoplication has been advocated as providing similar reflux control while potentially minimizing dysphagia. The comparative outcomes of different approaches to fundoplication are a topic of ongoing debate and long-term outcomes remain uncertain. This study aims to compare long-term gastroesophageal reflux disease (GERD) related outcomes following different fundoplication procedures. Methods: MEDLINE, EMBASE, PubMed, and CENTRAL databases were searched up to November 2022 to identify randomized controlled trials (RCTs) comparing different types of fundoplications reporting long-term (> 5 years) outcomes. The primary outcome was incidence of dysphagia. Secondary outcomes included incidence of heartburn/reflux, regurgitation, inability to belch, abdominal bloating, reoperation, and patient satisfaction. DataParty, which uses Python 3.8.10 was used to perform the network meta-analysis. We evaluated the overall certainty of evidence with the GRADE framework. Results: 13 RCTs were included, with 2063 patients across Nissen (360°), Dor (anterior 180°–200°), and Toupet (posterior 270°) fundoplications. Network estimates demonstrated that Toupet had lower incidence of dysphagia compared to Nissen (OR 0.285; 95% CrI 0.06–0.958). There were no differences in dysphagia between Toupet and Dor (OR 0.473, 95% CrI 0.072–2.835) or between Dor and Nissen (OR 1.689, 95% CrI 0.403–7.699). The three fundoplication types were comparable in all other outcomes. Conclusions: All three approaches of fundoplication share similar long-term outcomes, with the Toupet fundoplication likely providing the best long-term durability with lowest odds of developing postoperative dysphagia. [ABSTRACT FROM AUTHOR]

This study aims to assess the impact of endometrioma on embryo quality and cycle outcome in patients who undergo assisted reproductive technology (ART) treatment due to diminished ovarian reserve (DOR). Retrospective case–control study was conducted in women ≤ 40 years of age who underwent ART treatment caused by DOR, defined according to POSEIDON criteria, at a university-based infertility clinic between January 2015 and December 2020. Three groups of patients were selected: group A included patients with an idiopathic DOR, group B included patients with endometrioma(s) who underwent ovarian cystectomy, and group C included patients with endometrioma(s) without surgical treatment. A total of 351 women with DOR were included in the final analysis. Demographic characteristics, including age and AMH, were similar between the groups. Significant differences were observed among groups on mean number of MII oocytes retrieved (1.88 ± 1.59 vs. 2.84 ± 2.89 vs. 2.78 ± 2.41, respectively; p < 0.001) and mean number of embryos (1.04 ± 1.18 vs. 1.87 ± 2.01 vs. 1.66 ± 1.81, respectively; p < 0.001). However, the mean number of top-quality embryos, cycle cancellation, and live birth rates were similar between the groups. Clinical pregnancy (35 (26.5%) vs. 8 (18.2%) vs. 18 (42.9%), respectively; p = 0.038) and miscarriage rates (12 (9.1%) vs. 0 vs. 8 (19.0%), respectively; p = 0.009) were higher in endometrioma group without surgery. Women with DOR appear to have similar ART cycle outcomes regardless of the etiology, in terms of live birth rates. Infertility of endometrioma patients might be related to altered endometrium rather than to decreased oocyte quality. Cystectomy for endometrioma before IVF did not seem to affect the LBR. [ABSTRACT FROM AUTHOR]

Purpose: Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. However, the etiology of approximately 90% patients remains unknown. Diminished ovarian reserve (DOR) and poor ovarian response (POR) are related to POI in clinic. The main purpose of this review was to evaluate the roles of microRNAs (miRNAs) in the pathogenesis and therapeutic potential for POI, DOR and POR. Methods: A literature search was conducted using six databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and Wangfang Data) to obtain relevant studies. Results: This review enlightens expression profiles and functional studies of miRNAs in ovarian insufficiency in animal models and humans. Functional studies emphasized the role of miRNAs in steroidogenesis, granulosa cell proliferation/apoptosis, autophagy and follicular development by regulating target genes in specific pathways, such as the PI3K/AKT/mTOR, TGFβ, MAPK and Hippo pathways. Differentially expressed circulating miRNAs provided novel biomarkers for diagnosis and prediction, such as miR-22-3p and miR-21. Moreover, exosomes derived from stem cells restored ovarian function through miRNAs in chemotherapy-induced POI models. Conclusion: Differential miRNA expression profiles in patients and animal models uncovered the underlying mechanisms and biomarkers of ovarian insufficiency. Exosomal miRNAs can restore ovarian function against chemotherapy-induced POI, which needs further investigation to develop novel preventive and therapeutic strategies in clinical practice. [ABSTRACT FROM AUTHOR]

Background: The end-stage achalasia is a difficult condition to treat, for the esophageal diameter and conformation of the gullet, that may progress to a sigmoid shape. The aim of this study was to examine the outcome of Laparoscopic Heller-Dor in patients with end-stage achalasia, comparing them with patients who had mega-esophagus without a sigmoid shape. Methods: From 1992 to 2020, patients with a diagnosis of sigmoid esophagus, or radiological stage IV achalasia (the SE group), and patients with a straight esophagus larger than 6 cm in diameter, or radiological stage III achalasia (the NSE group), were all treated with LHD. The two groups were compared in terms of patients' symptoms, based on the Eckardt score, and on barium swallow, endoscopy and manometry performed before and after the treatment. The failure of the treatment was defined as an Eckardt score > 3, or the need for further treatment. Results: The study involved 164 patients: 73 in the SE group and 91 in the NSE group. No intra- or postoperative mortality was recorded. The median follow-up was 51 months (IQR 25–107). The outcome was satisfactory in 71.2% of patients in the SE group, and in 89% of those in the NSE group (p = 0.005). Conclusions: SE is certainly the worst condition of the disease and the final outcome of LHD, in term of symptom control, is inferior compared to NSE. Despite this, almost 3/4 of the SE patients experienced a significant relieve in symptoms after LHD, which may therefore still be the first surgical option to offer to these patients, before considering esophagectomy. [ABSTRACT FROM AUTHOR]

Background: Manometry is the gold standard diagnostic test for achalasia. However, there are incidences where manometry cannot be obtained preoperatively, or the results of manometry is inconsistent with the patient's symptomatology. We aim to determine if intraoperative use of EndoFLIP can provide a diagnosis of achalasia and provide objective information during Heller myotomy and Dor fundoplication. Methods: To determine the intraoperative diagnostic EndoFLIP values for patients with achalasia, we determined the optimal cut-off points of the distensibility index (DI) between patients with a diagnosis of achalasia and patients with a diagnosis of hiatal hernia. To evaluate the usefulness of EndoFLIP values during Heller myotomy and Dor fundoplication, we obtained a cohort of patients with EndoFLIP values obtained after Heller myotomy and after Dor fundoplication as well as Eckardt score before and after surgery. Results: Our analysis of 169 patients (133 hiatal hernia and 36 achalasia) showed that patients with DI < 0.8 have a >99% probability of having achalasia, while DI > 2.3 have a >99% probability of having hiatal hernia. Patients with a DI 0.8–1.3 have a 95% probability of having achalasia, and patients with a DI of 1.4–2.2 have a 94% probability of having a hiatal hernia. There were 40 patients in the cohort to determine objective data during Heller myotomy and Dor fundoplication. The DI increased from a median of 0.7 to 3.2 after myotomy and decreased to 2.2 after Dor fundoplication (p < 0.001). The median Eckardt score went down from a median of 4.5 to 0 (p < 0.001). Conclusions: Our study shows that intraoperative use of EndoFLIP can facilitate the diagnosis of achalasia and is used as an adjunct to diagnose achalasia when symptoms are inconsistent. The routine use of EndoFLIP during Heller myotomy and Dor fundoplication provides objective data during the operation in a group of patients with excellent short-term outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To compare the surgical outcomes of redo laparoscopic Heller-Dor procedure and rescue peroral endoscopic myotomy for patients with failed Heller myotomy. Methods: We identified patients who had undergone redo laparoscopic Heller-Dor procedure or rescue peroral endoscopic myotomy from August 1996 to September 2019 and assessed the patients' characteristics, timed barium swallow results, symptom scores before/after surgery, surgical outcomes, and postoperative outcomes. Results: Eleven patients underwent redo laparoscopic Heller-Dor procedure, and 14 underwent rescue peroral endoscopic myotomy. Blood loss (p = 0.001) and intraoperative complications rate (p = 0.003) were lower and the operative time (p > 0.001) and observation period (p = 0.009) shorter in patients who underwent rescue peroral endoscopic myotomy than in patients who underwent redo laparoscopic Heller-Dor procedure. Patients who underwent rescue peroral endoscopic myotomy had a higher rate of postoperative reflux esophagitis (p = 0.033) than those who underwent redo laparoscopic Heller-Dor procedure. After the interventions, the dysphagia symptoms were improved for both groups. Furthermore, both groups expressed satisfaction with their respective procedures. Conclusions: Rescue peroral endoscopic myotomy was associated with better surgical outcomes than redo laparoscopic Heller-Dor for patients with failed Heller myotomy. However, rescue peroral endoscopic myotomy had higher rates of postoperative reflux esophagitis. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic Heller-myotomy with Dor-fundoplication (LHD) is the standard surgical treatment for achalasia; however, surgical outcomes over a period greater than 10 years have not been well-explored. The objective of this study was to evaluate the long-term outcomes of LHD for achalasia based on a single-center experience. Methods: Patients who underwent LHD between 1994 and 2019 were included. Of these, we excluded patients who had undergone foregut surgery or whose follow-up data were unavailable. Esophagogastroduodenoscopy (EGD) findings and postoperative persistent and/or recurrent symptoms had been assessed annually. Disease-free rates were calculated using Kaplan–Meier analysis. Results: A total of 530 patients (mean age 45.0 years with 267 men) were included. The median follow-up period was 50.5 months. More than 10 years' data were available in 78 patients (14.7%). The cumulative rates of freedom from dysphagia, vomiting, chest pain, and Eckardt score > 3 at 10 years after LHD were 80.1%, 97.5%, 96.3%, and 73.5%, respectively. Probability of esophagitis during 10 years after surgery was 34.4% of patients based on Kaplan–Meier estimation. Approximately 3/4th of patients who had post-LHD esophagitis showed mild esophagitis of Los Angeles classification grade A. Fifteen patients (2.8%) were required a revision of primary LHD. Six patients (1.2%) developed esophageal cancer with an incidence was as high as 219.8/100,000 person-year. All patients with esophageal cancer were found to have early stage tumors that were successfully resected. Conclusions: Symptomatic relief post-LHD lasted for over 10 years. The incidence rate of esophageal cancer was high. Regular EGD surveillance seems to be helpful for early detection of esophageal cancer early. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to explore whether β-EP in serum (sβ-EP) and follicular fluid (ffβ-EP) could predict the in vitro fertilization (IVF) outcomes of patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR). Methods: 90 PCOS women, 50 DOR women, and 100 women with normal ovarian function (control group), who were all undergoing an IVF-embryo transfer trial, were included in the study. Biochemical characteristics, anti-Mullerian hormone (AMH), sβ-EP, ffβ-EP, embryo formation, and pregnancy indicators were assessed in all women. The correlations of AMH and β-EP with oocyte quality were analyzed. Population-based and age-category stratified receiver operating characteristic (ROC) curve analysis of AMH and β-EP for predicting pregnancy and live birth were performed. Results: Compared with the control group, the PCOS group had higher antral follicle count, testosterone, luteinizing hormone, AMH, sβ-EP, and ffβ-EP, which were lower in the DOR group. Meanwhile, the PCOS and DOR groups had higher cycle cancellation and miscarriage rates, and lower high quality embryo numbers. Correlation analysis showed that the oocyte quality were positively correlated with AMH, sβ-EP, and ffβ-EP. The population-based and age-stratified ROC curve analysis showed that sβ-EP and ffβ-EP had high sensitivity and specificity to predict pregnancy and live birth. Meanwhile, age-stratified AMH enhanced the sensitivity for prediction of live birth after IVF. Conclusion: sβ-EP and ffβ-EP are different among women with PCOS, DOR, and normal ovarian function. β-EP can be used as a good predictor of clinical pregnancy and live birth after IVF. [ABSTRACT FROM AUTHOR]

Purpose: To compare the treatment results of needlescopic surgery with those of the conventional method for achalasia, using propensity score-matching. Methods: Propensity score-matching was performed based on five factors: age, gender, body mass index, extended form, and maximum expansion diameter, to extract 28 cases each for a needlescopic group and a conventional group. Results: There were no significant differences between the needlescopic group and the conventional group, in operative time (165 min vs. 170 min, p = 0.682), estimated blood loss (both ≒ 0 ml, p = 0.426), or post-operative hospital stay (4 vs. 4 days, p = 0.248). Although the follow-up period was significantly longer in the conventional group (6 vs. 105 months, respectively; p < 0.001), there was no difference in the post-operative symptom scores for difficulty in swallowing and chest pain or the degree of satisfaction (p = 0.563, p = 0.142, p = 0.342, respectively). Furthermore, there was no difference in the post-operative clearance rate, with both groups found to be favorable (p = 0.758, p = 0.790, p = 1.000, p = 1.000, respectively). Conclusions: The short-term results of needlescopic surgery for achalasia were good and equivalent to those of the conventional method. [ABSTRACT FROM AUTHOR]

Purpose: One diagnostic criterion of esophageal achalasia is that the integrated relaxation pressure (IRP) measured by high-resolution manometry (HRM) is at least 15 mmHg. Moreover, while the standard surgical treatment for esophageal achalasia is laparoscopic Heller-Dor surgery (LHD), there have been insufficient investigations concerning the surgical outcomes from the perspective of the preoperative IRP value. Methods: We split 121 cases in which LHD was performed as an initial treatment on patients with esophageal achalasia, into two categories according to the IRP median value, and performed a comparative investigation of the surgical outcomes with regard to the preoperative pathophysiology and symptoms. Results: The IRP median value was 29.6 mmHg. The high IRP group consisted of younger individuals and low BMI (p = 0.004 and p = 0.0273, respectively), and the percentage of Chicago classification Type II and III was high (p = 0.029) and the regurgitation score in the preoperative symptoms was high (p = 0.0043). However, no differences in the surgical outcomes were confirmed. Conclusion: In patients with esophageal achalasia, the degree of the preoperative IRP value affects the age, BMI, preoperative LESP, and preoperative regurgitation symptoms. However, there were no effects on the surgical outcomes, with the surgical outcomes being satisfactory, regardless of the IRP value. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the copy number variation (CNV) in the X-linked genes BCORL1, POF1B, and USP9X in idiopathic diminished ovarian reserve (DOR). Methods: This case-control study included 47 women, 26 with DOR and 21 in the control group. Age, weight, height, BMI, and FSH level were evaluated, as well as antral follicle count (AFC), oocyte retrieval after controlled ovarian stimulation, and metaphase II (MII) oocytes. The CNVs of BCORL1, USP9X, and POF1B genes were measured by quantitative real time PCR (qPCR) using two reference genes, the HPRT1 (X-linked) and MFN2 (autosomal). Protein–protein interaction network and functional enrichment analysis were performed using the STRING database. Results: The mean age was 36.52 ± 4.75 in DOR women and 35.38 ± 4.14 in control. Anthropometric measures did not differ between the DOR and control groups. DOR women presented higher FSH (p = 0.0025) and lower AFC (p <.0001), oocyte retrieval after COS (p = 0.0004), and MII oocytes (p <.0001) when compared to the control group. BCORL1 and POF1B did not differ in copy number between DOR and control. However, DOR women had more copies of USP9X than the control group (p = 0.028). Conclusion: The increase in the number of copies of the USP9X gene may lead to overexpression in idiopathic DOR and contribute to altered folliculogenesis and oocyte retrieval. [ABSTRACT FROM AUTHOR]

The article presents information about DOR BioPharma's development of an oral, enteric-coated form of the corticosteroid beclometasone diproprionate for treating as well as preventing gastrointestinal graft-versus-host disease. The company's efforts to establish clinical trials for the orBec® product and get approval from the U.S. Food and Drug Administration are discussed. Phase II and phase III randomized trial results indicate mortality is reduced with orBec®.

Purpose: The optimal management of achalasia in obese patients is unclear. For those who have undergone Heller myotomy and fundoplication, the long-term outcomes and their impressions following surgery are largely unknown. Methods: A retrospective review of patients who underwent laparoscopic Heller myotomy and Dor fundoplication (LHMDF) for achalasia was performed. From this cohort, Class 2 and 3 obese (BMI > 35 kg/m2) patients were identified for short- and long-term outcome analysis. Results: Between 2003 and 2015, 252 patients underwent LHMDF for achalasia, and 17 (7%) patients had BMI > 35 kg/m2. Pre-operative Eckardt scores varied from 2 to 9, and at short-term (2–4 week) follow-up, scores were 0 or 1. Ten (58%) patients had available long-term (2–144 months) follow-up data. Eckardt scores at this time ranged from 0 to 6. Symptom recurrence was worse for patients with BMI > 40 kg/m2 compared to patients with BMI < 40 kg/m2. BMI was largely unchanged at long-term follow-up regardless of pre-intervention BMI. Most patients were satisfied with surgery but would have considered a combined LHMDF and weight-loss procedure had it been offered. Conclusion: LHMDF for achalasia in obese patients is safe and effective in the short term. At long-term follow-up, many patients had symptom recurrence and experienced minimal weight loss. Discussing weight-loss surgery at the time LHMDF may be appropriate to ensure long-term achalasia symptom relief. [ABSTRACT FROM AUTHOR]

The Dor C shipwreck is the remains of a 60-t schooner that plied the Mediterranean during the last decades of the nineteenth century. The various building materials and ceramic ware found inside the shipwreck suggest an established commercial route between southern France and the Holy Land. Three metal objects were found in the bow area of the shipwreck: a lead pipe, an iron rigging hoop, and a brass wick housing. This study aims to understand their manufacturing processes, to propose possible dating and manufacturing locations, and to verify their use. The metallurgical investigation suggests that the objects were designated for marine use and manufactured using processes developed during the second half of the nineteenth century, probably post-1885, which supports the dating of the ship. The tonnage of the ship, the origin of her cargo, the provenance of some of the metal parts, and the location of the shipwreck, all suggest that her last voyage was a delivery of cargo from Marseilles to Dor. [ABSTRACT FROM AUTHOR]

Purpose: There is some debate about whether preoperative balloon dilation influences the outcomes of laparoscopic Heller-Dor surgery (LHD), with no consensus opinion as yet. Thus, we investigated if preoperative dilation influences the treatment outcomes of LHD for achalasia.Methods: The subjects of this study were 526 patients with achalasia who underwent LHD as an initial treatment between August 1994 and February 2017. The patients were roughly classified by the status of preoperative balloon dilation and matched with propensity scores for age, sex, BMI, morphologic type, and maximum esophageal transverse diameter. Consequently, 94 subjects each were assigned to the balloon dilation (BD) group and to the non-balloon dilation (non-BD) group. We evaluated patient backgrounds, surgical outcomes, and incidence of postoperative reflux esophagitis.Results: No differences were found in surgical time, intraoperative blood loss, incidence of intraoperative mucosal injury, or postoperative hospital stay between the BD and non-BD groups. The mean patient satisfaction was significantly higher in the non-BD group (4.9) than in the BD group (4.7) and the incidence of postoperative esophagitis was significantly lower in the non-BD group (1.1%) than in the BD group (7.4%).Conclusions: Preoperative balloon dilation had no effect on intraoperative complications but did increase the incidence of postoperative reflux esophagitis in patients undergoing LHD for achalasia. [ABSTRACT FROM AUTHOR]

Delaying childbearing age has become a trend in modern times, but it has also led to a common challenge in clinical reproductive medicine—diminished ovarian reserve (DOR). Since the mechanism behind DOR is unknown and its clinical features are complex, physicians find it difficult to provide targeted treatment. Many factors affect ovarian reserve function, and existing studies have shown that genetic variants, upstream regulatory genes, and changes in protein expression levels are present in populations with reduced ovarian reserve function. However, existing therapeutic regimens often do not target the genetic profile for more individualized treatment. In this paper, we review the types of genetic variants, mutations, altered expression levels of microRNAs, and other related factors and their effects on the regulation of follicular development, as well as altered DNA methylation. We hope this review will have significant implications for the future treatment of individuals with reduced ovarian reserve. [ABSTRACT FROM AUTHOR]

There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms. [ABSTRACT FROM AUTHOR]

Purpose: We compared the outcomes of Toupet fundoplication with those of Dor fundoplication in patients with achalasia who underwent laparoscopic Heller myotomy. Methods: Seventy-two patients with achalasia and dysphagia underwent laparoscopic Heller myotomy with fundoplication performed by a single surgeon. Heller-Toupet fundoplication (HT) was performed in 30 patients, and Heller-Dor fundoplication (HD) was done in 42. The symptoms and esophageal function were retrospectively assessed in both groups. Results: The dysphagia scores significantly decreased after both the HT and HD procedures, and did not differ significantly between them. The incidence of reflux symptoms was significantly higher after HT (26.7 %) than after HD (7.1 %). The lower esophageal sphincter (LES) resting pressure significantly decreased after both HT and HD. Upon endoscopic examination, the incidence of reflux esophagitis was significantly higher after HT (38.5 %) than after HD (8.8 %). During esophageal pH monitoring, the fraction time at pH <4 was similar in the patients who underwent HT and HD. Conclusions: Laparoscopic Heller myotomy provided significant improvements in the dysphagia symptoms of achalasia patients, regardless of the type of fundoplication. The incidences of reflux symptoms and reflux esophagitis were higher after HT than after HD. However, the results of pH monitoring did not differ between the procedures. [ABSTRACT FROM AUTHOR]

Purpose: Decreased ovarian reserve function is mainly characterized by female endocrine disorders and fertility decline. Follicular fluid (FF) exosomal microRNAs (miRNAs) have been shown to regulate the function of granulosa cells (GCs). The present study explored differentially expressed miRNAs (DEmiRNAs) in patients with diminished ovarian reserve (DOR). Methods: FF was collected from 12 DOR patients and 12 healthy controls. DEmiRNAs between the two groups were identified and analyzed using high-throughput sequencing technology and validated by real-time quantitative PCR (RT-qPCR). Results: A total of 592 DEmiRNAs were identified using high-throughput miRNA sequencing, of which 213 were significantly upregulated and 379 were significantly downregulated. The sequencing results were further validated by RT-qPCR. These DEmiRNA target genes were mainly involved in the cancer pathway, phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, regulation of actin cytoskeleton signaling pathway, and biological processes related to protein binding, nucleoplasm, cytoplasm, and cell membrane. Conclusion: FF exosomal miRNAs are significantly differentially expressed in DOR patients versus non-DOR patients, underscoring their crucial role in regulating the pathogenesis of DOR. [ABSTRACT FROM AUTHOR]

A 31-year-old man, referred to our hospital for investigation of dysphagia, was found to have a spindle-shaped lower esophagus on a contrasted esophagram. The dysphagia was initially treated conservatively, but after 4 years of unsatisfactory control, he requested surgery. Our surgical team has been performing laparoscopic Heller-Dor fundoplication for achalasia since August, 1994, and 265 patients have undergone this procedure so far. Based on our experience, we decided to perform Heller-Dor fundoplication through a single incision for this patient. The operative time was 236 min with minimal blood loss and there were no perioperative complications. His postoperative course was uneventful and he was discharged on postoperative day 4, completing the clinical pathway used for conventional laparoscopic Heller-Dor fundoplication. [ABSTRACT FROM AUTHOR]

Background: The type of fundoplication that should be performed in conjunction with Heller myotomy for esophageal achalasia is controversial. We prospectively compared anterior fundoplication (Dor) with partial posterior fundoplication (Toupet) in patients undergoing laparoscopic Heller myotomy. Methods: A multicenter, prospective, randomized-controlled trial was initiated to compare Dor versus Toupet fundoplication after laparoscopic Heller myotomy. Outcome measures were symptomatic GERD scores (0-4, five-point Likert scale questionnaire) and 24-h pH testing at 6-12 months after surgery. Data are mean ± SD. Statistical analysis was by Mann-Whitney U test, Wilcoxon signed rank test, and Freidman's test. Results: Sixty of 85 originally enrolled and randomized patients who underwent 36 Dor and 24 Toupet fundoplications had follow-up data per protocol for analysis. Dor and Toupet groups were similar in age (46.8 vs. 51.7 years) and gender (52.8 vs. 62.5% male). pH studies at 6-12 months in 43 patients (72%: Dor n = 24 and Toupet n = 19) showed total DeMeester scores and % time pH < 4 were not significant between the two groups. Abnormal acid reflux was present in 10 of 24 Dor group patients (41.7%) and in 4 of 19 Toupet patients (21.0%) ( p = 0.152). Dysphagia and regurgitation symptom scores improved significantly in both groups compared to preoperative scores. No significant differences in any esophageal symptoms were noted between the two groups preoperatively or at follow-up. SF-36 quality-of-life measures changed significantly from pre- to postoperative for five of ten domains in the Dor group and seven of ten in the Toupet patients (not significant between groups). Conclusion: Laparoscopic Heller myotomy provides significant improvement in dysphagia and regurgitation symptoms in achalasia patients regardless of the type of partial fundoplication. Although a higher percentage of patients in the Dor group had abnormal 24-h pH test results compared to those of patients who underwent Toupet, the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

AA Dor is an eclipsing, close, post common-envelope binary (PCEB) consisting of a sdOB primary star and an unseen secondary with an extraordinary small mass (M2 ≈ 0.066 M⊙)—formally a brown dwarf. The brown dwarf may have been a former planet which survived a common envelope (CE) phase and has even gained mass. A recent determination of the components' masses from results of NLTE spectral analysis and subsequent comparison to evolutionary tracks shows a discrepancy compared to masses derived from radial-velocity and the eclipse curves. Phase-resolved high-resolution and high-SN spectroscopy was carried out in order to investigate this problem. We present results of a NLTE spectral analysis of the primary, an analysis of its orbital parameters, and discuss possible evolutionary scenarios. [ABSTRACT FROM AUTHOR]

Intermittent, normobaric hypoxia confers robust cardioprotection against ischemia-induced myocardial infarction and lethal ventricular arrhythmias. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) have been implicated in cardioprotective phenomena, but their roles in intermittent hypoxia are unknown. This study examined the contributions of DOR and ROS in mediating intermittent hypoxia-induced cardioprotection. Mongrel dogs completed a 20 day program consisting of 5–8 daily, 5–10 min cycles of moderate, normobaric hypoxia (FIO2 0.095–0.10), with intervening 4 min room air exposures. Subsets of dogs received the DOR antagonist naltrindole (200 μg/kg, sc) or antioxidant N-acetylcysteine (250 mg/kg, po) before each hypoxia session. Twenty-four hours after the last session, the left anterior descending coronary artery was occluded for 60 min and then reperfused for 5 h. Arrhythmias detected by electrocardiography were scored according to the Lambeth II conventions. Left ventricles were sectioned and stained with 2,3,5-triphenyl-tetrazolium-chloride, and infarct sizes were expressed as percentages of the area at risk (IS/AAR). Intermittent hypoxia sharply decreased IS/AAR from 41 ± 5 % (n = 12) to 1.8 ± 0.9 % (n = 9; P < 0.001) and arrhythmia score from 4.1 ± 0.3 to 0.7 ± 0.2 (P < 0.001) vs. non-hypoxic controls. Naltrindole (n = 6) abrogated the cardioprotection with IS/AAR 35 ± 5 % and arrhythmia score 3.7 ± 0.7 (P < 0.001 vs. untreated intermittent hypoxia). N-acetylcysteine (n = 6) interfered to a similar degree, with IS/AAR 42 ± 3 % and arrhythmia score 4.7 ± 0.3 (P < 0.001 vs. untreated intermittent hypoxia). Without the intervening reoxygenations, hypoxia (n = 4) was not cardioprotective (IS/AAR 50 ± 8 %; arrhythmia score 4.5 ± 0.5; P < 0.001 vs. intermittent hypoxia). Thus DOR, ROS and cyclic reoxygenation were obligatory participants in the gradually evolving cardioprotection produced by intermittent hypoxia. [ABSTRACT FROM AUTHOR]

Our objective was to establish the efficiency of single-incision laparoscopic Heller myotomy and Dor fundoplication (SILHD) as treatment for esophageal achalasia. A 58-year-old man underwent SILHD for achalasia. The left triangular ligament was retracted using a suture thread and fixed to the body surface, providing a good operative field at the cardia. We performed a 7-cm long myotomy, extending 2 cm into the gastric wall, using a tissue-sealing device or L-shaped electrocautery. Oral intake resumed on postoperative day 1, and hospital stay was 4 days. No morbidity was observed. Based on our experience, we believe that the SILHD can be performed safely and seems to offer at least short-term benefits for selected patients with esophageal achalasia, when performed by surgeons experienced in laparoscopic and esophageal surgery. [ABSTRACT FROM AUTHOR]

We present an on-going study of CoRoT 102931335. Our preliminary results indicate that the target is an eclipsing binary system with an orbital period of $3{.\!\!\vphantom{0}^{\mathrm{d}}}979$ and a primary component pulsating in the frequency range 0.6–0.8 c/d. The results of a ground-based follow-up program provided four-colour Strömgren photometry and allowed us to infer the spectral class and the primary effective temperature. We devised and applied an iterative procedure to disentangle the effects of binarity from those of pulsations and could test that a detailed binary modelling is essential for the purpose. Our results suggest that the pulsating component of CoRoT 102931335 could be a γ Dor variable, a rare occurrence in an eclipsing system. [ABSTRACT FROM AUTHOR]

Background: The type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller's cardiomyotomy (LHCM) in Achalasia cardia is controversial. We compared Angle of His accentuation and Dor fundoplication in a randomized controlled trial. Methods: From May 2010 to October 2013, 62 patients undergoing LHCM were randomized to receive either Dor fundoplication (Dor group) or Angle of His accentuation (AOH group) as an anti-reflux procedure. Symptomatic outcome was evaluated using modified Mellow and Pinkas scale for dysphagia and modified DeMeester's score for regurgitation and heartburn. Achalasia-specific quality-of-life (QOL) questionnaire was used to assess quality of life. The primary outcome was symptomatic relief and the secondary outcome was postoperative heartburn. Statistical analysis was done using SPSS software. Results: All the procedures were completed laparoscopically with no mortality. Morbidity was similar in the two groups (6.4 %). Median operative time was higher in Dor group (170 vs 130 min). At a median follow-up of 21 months relief of dysphagia, regurgitation, and heartburn was seen in 87, 90.3, and 90.3 % patients in Dor group versus 93.5, 96.7, and 77.4 % in AOH group patients with significant improvement in symptom scores. Improvement was similar in both groups with no statistically significant difference in the symptom scores ( p = 0.48 for dysphagia, p = 0.37 for regurgitation, and p = 0.19 for heartburn). The QOL improved in both groups [62.3 to 12.3 ( p = 0.02) in Dor group and 63.9-13 ( p = 0.02) in AOH group] with no statistically significant difference between the two groups ( p = 0.96). There was no statistically significant difference in the postoperative heartburn between the two groups ( p = 0.19). Conclusion: Laparoscopic Heller's cardiomyotomy with either Angle of His accentuation or Dor fundoplication leads to similar improvement in symptoms and quality of life. [ABSTRACT FROM AUTHOR]

orBec® is an oral enteric-coated tablet formulation of the corticosteroid beclometasone, which has been developed by Enteron Pharmaceuticals, a subsidiary of Corporate Technology Development (now DOR BioPharma). orBec® is being developed for the treatment of gastrointestinal graft-versus-host disease (GVHD) and an NDA has been filed in the US. DOR BioPharma has also filed an MAA in Europe for the same indication. orBec® is designed to reduce the need for systemic immunosuppressive drugs, thereby improving the outcome of bone marrow and stem cell transplantation. DOR BioPharma may seek a marketing partner in the US and elsewhere for orBec® in GVHD and will seek a partner for other potential indications of the drug. In December 2001, Corporate Technology Development was acquired by Endorex Corporation (now DOR BioPharma). In October 1998, Enteron Pharmaceuticals (DOR BioPharma) entered into an exclusive, worldwide, royalty bearing license agreement with George B. McDonald, MD, including the right to grant sublicenses, for the rights to the intellectual property and know-how relating to orBec®. In January 2007, DOR BioPharma received $U53 million under a non-binding letter of intent from Sigma-Tau Pharmaceuticals. The agreement grants Sigma-Tau an exclusive right to negotiate terms and conditions for a possible business transaction or strategic alliance regarding orBec® and potentially other DOR pipeline compounds until 1 March 2007. Under the terms of the agreement, Sigma-Tau purchased $US 1 million of DOR's common stock, with an additional $US2 million paid in cash. If no agreement is reached by 1 March 2007, DOR will return the $US2 million to Sigma-Tau within 60 days. DOR BioPharma received an unsolicited proposal from Cell Therapeutics, Inc. to acquire DOR BioPharma in January 2007. Because of the non-binding agreement already signed with Sigma-Tau, DOR BioPharma's board of directors cannot consider Cell Therapeutics' merger proposal at this time. orBec® has been filed for approval in the US for the treatment of gastrointestinal GVHD. The US FDA accepted the NDA filing and has established a target date of 21 July 2007 for completion of review of the NDA. In November 2006, the EMEA determined that the MAA for orBec® for the treatment of gastrointestinal GVHD is complete and that the review process has begun. The data provided in the MAA and NDA submissions demonstrate that orBec® safely provides a lower risk of mortality compared with the current standard of care. Both filings are supported by data from two rndomised, double-blinded, placebo-controlled clinical trials. The first was a 129-patient pivotal phase lU clinical trial for orBec® conducted at 16 bone marrow/stem cell transplant centres in the US and France. The second trial was a 60-patient phase II clinical trial conducted at the Fred Hutchinson Cancer Research Centre. In the primary endpoint of its pivotal trial, time to treatment failure through day 50, orBec® failed to achieve statistical significance (p-value 0.1177). However, orBec® did achieve statistical significance in the secondary endpoints of time to treatment failure through day 80, and a reduction in mortality compared with placebo. In this trial, patient survival at the prespecified endpoint of 200 days post-transplant showed a statistically significant 66% reduction in mortality among patients randomised to orBec®. DOR BioPharma believes the primary endpoint was not achieved due to a higher than expected rate of treatment failures during the initial 10 days in both treatment groups. The mortality benefit in favour of orBec® was confirmed in a retrospective analysis of the phase II study, in which there was a 55% reduction in mortality at 200 days post-transplant.… [ABSTRACT FROM AUTHOR]

Background: Our prior randomized controlled trial of Heller myotomy alone versus Heller plus Dor fundoplication for achalasia from 2000 to 2004 demonstrated comparable postoperative resolution of dysphagia but less gastroesophageal reflux after Heller plus Dor. Patient-reported outcomes are needed to determine whether the findings are sustained long-term.Methods: We actively engaged participants from the prior randomized cohort, making up to six contact attempts per person using telephone, mail, and electronic messaging. We collected patient-reported measures of dysphagia and gastroesophageal reflux using the Dysphagia Score and the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) instrument. Patient-reported re-interventions for dysphagia were verified by obtaining longitudinal medical records.Results: Among living participants, 27/41 (66%) were contacted and all completed the follow-up study at a mean of 11.8 years postoperatively. Median Dysphagia Scores and GERD-HRQL scores were slightly worse for Heller than Heller plus Dor but were not statistically different (6 vs 3, p = 0.08 for dysphagia, 15 vs 13, p = 0.25 for reflux). Five patients in the Heller group and 6 in Heller plus Dor underwent re-intervention for dysphagia with most occurring more than five years postoperatively. One patient in each group underwent redo Heller myotomy and subsequent esophagectomy. Nearly all patients (96%) would undergo operation again.Conclusions: Long-term patient-reported outcomes after Heller alone and Heller plus Dor for achalasia are comparable, providing support for either procedure. [ABSTRACT FROM AUTHOR]

High risk preterm newborns are exposed to unavoidable painful experiences in Neonatal Intensive Care Units. In spite of their biological immaturity, they are able to perceive and react to pain stimuli. Repetitive exposure to pain has a negative impact on the development and may increase the infant's vulnerability, affecting self-regulatory processes. Biobehavioral reactivity to pain is an indicator of self-regulation and it is associated to the child's temperament. Preterm infants need pharmacological and non-pharmacological strategies for pain relieving. Moreover, they need a context of synchronic interaction with their parents which must be adapted to their temperament characteristics. Health professionals may play an important role in supporting external regulation for those infants, promoting pain relief and preventing development problems. [ABSTRACT FROM AUTHOR]

Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy ( τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log ( τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of E values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase E values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells. [ABSTRACT FROM AUTHOR]

With the movement towards recovery-oriented mental health (MH) services, individuals with MH lived-experience are increasingly employed as peer providers (peers). Peers are unique in that they bring knowledge from experience and eye-level connection to service users that enhance the quality of services and humanize MH systems' culture. In Israel, hundreds of peers are employed in various roles and settings across the MH system. However, peer integration into MH services faces challenges. One issue involves the use of self-disclosure (SD) in MH services which varies with explicitness across roles and settings. This study sought to understand perspectives and experiences regarding peers' SD (use & sharing of knowledge from experience) among different stakeholders in MH health services. Six focus groups and 4 semi-structured interviews (N = 42) were conducted as a part of a larger international project (UPSIDES; ERC Horizon 2020, Moran et al., Trials 21:371, 2020). Data was transcribed verbatim and analyzed using thematic analysis. Four categories and 7 themes were identified regarding current perspectives and experiences with peers' SD in MH organizations: (i) Restrained or cautious organizational approach to SD; (ii) Attitudes of peers to SD approach; (iii) The influence of designated peer roles on SD; and (iv) Unwarranted SD of peers working in traditional roles. The findings reveal that peers' SD in MH services is a complex process. Organizational approaches were often controlling of non-designated peers' SD practices; participants had diverse attitudes for and against peers' SD; SD occurred according to personal preferences, specific peer role and the director's approach to peers' SD; Conflictual SD dilemmas emerged in relation to service users and staff. SD sometimes occurs unwarrantely due to ill mental health. The presence of peer-designated roles positively impacts peers' SD. We interpret the current mix of views and general conduct of peer SD practice in statutory MH services as related to three aspects: 1. The presence of a traditional therapeutic SD model vs. a peer SD model – with the former currently being dominant. 2. Insufficient proficiency and skill development in peers' SD. 3. Stigmatic notions about peer SD among service users and staff. Together, these aspects interrelate and sometimes create a negative cycle create tension and confusion. A need to develop professionalism of peer SD in statutory services is highlighted alongside enhancing staff and service user acknowledgement of the value of peer SD. Developing peer-designated roles can positively impacts peer SD in MH statutory services. Training, support, and organizational interventions are required to further support for peer-oriented SD and the enhancement of a person-centered and recovery orientation of MH services. [ABSTRACT FROM AUTHOR]

Peripheral sensorimotor stimming activity, such as rocking and fidgeting, is widely considered irrelevant to and even distracting from learning. In this critical-pedagogy conceptual paper, we argue that stimming is an intrinsic part of adaptive functioning, interaction, and cognitive dynamics. We submit that when cultural resources build from students’ own sensorimotor dynamics, rather than subjugating them to hegemonic corporeal norms, learners’ intrinsic sensorimotor behaviors may be embraced and empowered as mental activity. This call for transformative inclusive pedagogy is of particular importance for neurodivergent children whose sensorimotor engagements have historically been ostracized as disruptive. Following a conceptual analysis of stimming that builds on a range of neuro-cognitive empirical studies drawing on post-cognitivist embodied cognition theory, we imagine inclusive educational futures that disrupt sedentary instructional design to elevate minoritized learners’ sensorimotor activity. As proof of concept, we present an example inclusive embodied activity, balance board math, a pedagogical tool designed to elicit stimming as thinking. We propose a set of design heuristics for realizing stimming’s pedagogical potential. [ABSTRACT FROM AUTHOR]

The clinical significance of an abnormal free light chain (FLC) test, performed due to unspecific complains in the absence of a known plasma cell dyscrasia (PCD) or lymphoproliferative disease (LPD), is not fully elucidated. We investigated the importance of an abnormal FLC ratio (FLC-R) in this setting. Patients registered in the Maccabi Healthcare Services database, tested for FLC during 2007–2023 without previously documented PCD/LPD or increased total protein (TP) level, were reviewed. Demographics, co-morbidities, and laboratory tests were recorded. FLC-R was defined as normal (0.26–1.65) or slightly (slAb 0.1–0.26/1.65–4), moderately (mAbn 0.1–0.05/4–8) and significantly abnormal (sigAb- < 0.05 or > 8). Factors associated with PCD/LPD and overall survival were identified. In total, 8,661 patients, 2,215 (25.6%) with abnormal FLC-R [2,090 (24.1%)-slAb, 65 (0.75%)-mAbn and 60 (0.7%)-sigAb], were analyzed. Almost none had anemia nor acute renal failure. 14% had concomitant increased immunoglobulins. Within a median follow-up of 52 months, 943 were diagnosed with PCD (816-MGUS, 127-MM/Amyloidosis/plasmacytoma) and 48 with LPD. Median time to PCD and LPD were 19 and 28 months. Multivariate analysis found slAb (HR = 1.8, CI95%:1.53–2.12, p < 0.001), mAbn (HR = 6.3, CI95%:4.16–9.53, p < 0.001), and sigAb FLC (HR = 10.4, CI95%:7.0–15.35, p < 0.001), to be associated with PCD/LPD diagnosis. Decreased IgG, increased IgA, and concomitant comorbidities predicted PCD, whereas increased IgM predicted LPD. Older age, male gender, anemia, decreased albumin, increased IgG and concomitant comorbidities, predicted shorter survival. Our large study emphasizes the independent clinical significance of abnormal FLC-R as a predictor of PCD/LPD diagnosis even in patients with normal TP level, promoting early detection of PCD/LPD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether androgen conversion rates after supplementation with dehydroepiandrosterone (DHEA) differ, and whether differences between patients with diminished ovarian reserve (DOR) are predictive of pregnancy chances in association with in vitro fertilization (IVF). Methods: In a prospective cohort study we investigated 213 women with DOR, stratified for age (≤38 or >38 years) and ovarian FMR1 genotypes/sub-genotypes. All women were for at least 6 weeks supplemented with 75 mg of DHEA daily prior to IVF, between initial presentation and start of 1st IVF cycles. Levels of DHEA, DHEA-sulfate (DHEAS), total T (TT) and free T (FT) at baseline () and IVF cycle start () were then compared between conception and non-conception cycles. Results: Mean age for the study population was 41.5 ± 4.4 years. Forty-seven IVF cycles (22.1 %) resulted in clinical pregnancy. Benefits of DHEA on pregnancy rates were statistically associated with efficiency of androgen conversion from DHEA to T and amplitude of T gain. Younger women converted significantly more efficiently than older females, and selected FMR1 genotypes/sub-genotypes converted better than others. FSH/androgen and AMH/androgen ratios represent promising new predictors of IVF pregnancy chances in women with DOR. Conclusions: DOR at all ages appears to represent an androgen-deficient state, benefitting from androgen supplementation. Efficacy of androgen supplementation with DHEA, however, varies depending on female age and FMR1 genotype/sub-genotype. Further clarification of FMR1 effects should lead to better individualization of androgen supplementation, whether via DHEA or other androgenic compounds. [ABSTRACT FROM AUTHOR]

Purpose: A symbiotic relationship between ovarian granulosa cells (GC) and the developing oocyte is critical. Genetic modulations in GC's can lead to reproductive insufficiency, highlighting the role of GC's in reproductive competence. Utilizing gene expression analyses in cumulus GC's, we attempt to enhance our understanding of mechanisms that may contribute to poor reproductive capacity in young women with diminished ovarian reserve (DOR). Methods: We measured gremlin 1 (GREM1) gene expression in GC's from infertile women <38 years undergoing in vitro fertilization in the context of DOR. Results: GREM1, a member of the differential screening-selected gene aberrative in neuroblastoma (DAN) family of genes known for its highly regulated expression pattern during folliculogenesis and a downstream effecter of oocyte-derived growth and differentiation factor 9, was down-regulated 3-fold (−3.08) in women with DOR versus control; down-regulation was confirmed by qRT-PCR (−4.02). Conclusion: This is the first demonstration linking differential expression of Gremlin with etiology of infertility in women. [ABSTRACT FROM AUTHOR]

Non-thyroidal illness is characterized by low tri-iodothyronine (T3) serum level under acute-phase conditions. We studied hepatic gene expression of the newly identified thyroid hormone receptor (TR) cofactor DOR/TP53INP2 together with TRs in a rat model of aseptic abscesses induced by injecting intramuscular turpentine-oil into each hind limb. A fast (4-6 h) decrease in the serum level of free thyroxine and free T3 was observed. By immunohistology, abundant DOR protein expression was detected in the nuclei of hepatocytes and ED-1 (mononuclear phagocytes), CK-19 (biliary cells), and SMA (mesenchymal cells of the portal tract) cells. DOR signal was reduced with a minimum at 6-12 h after the acute-phase reaction (APR). Immunohistology also showed a similar pattern of protein expression in TRα1 but without a significant change during APR. Transcripts specific for DOR, nuclear receptor co-repressor 1 (NCoR-1), and TRβ1 were down-regulated with a minimum at 6-12 h, whereas expression for TRα1 and TRα2 was slightly and significantly up-regulated, respectively, with a maximum at 24 h after APR was initiated. In cultured hepatocytes, acute-phase cytokines interleukin-1β (IL-1β) and IL-6 down-regulated DOR and TRβ1 at the mRNA level. Moreover, gene expression of DOR and TRs (TRα1, TRα2, and TRβ1) was up-regulated in hepatocytes by adding T3 to the culture medium; this up-regulation was almost completely blocked by treating the cells with IL-6. Thus, TRβ1, NCoR-1, and the recently identified DOR/TP53INP2 are abundantly expressed and down-regulated in liver cells during APR. Their down-regulation is attributable to the decreased serum level of thyroid hormones and most probably also to the direct action of the main acute-phase cytokines. [ABSTRACT FROM AUTHOR]

Abstract  A 41-year-old woman was admitted due to dysphagia and weight loss of 6 kg. An upper gastrointestinal radiographic contrast study demonstrated an S-shaped lower esophagus with a peak transverse diameter of 65 mm. Moreover, an epiphrenic diverticulum was also detected in the lower part of the esophagus (50 × 40 mm). The measurement of intraesophageal pressure showed a lower esophageal sphincter pressure of 80 mmHg and a lower esophageal sphincter length of 31 mm. Esophageal clearance assessment via a timed barium esophagogram demonstrated impaired contrast clearance, with a rate of 26% at 5 min. A laparoscopic Heller myotomy, Dor fundoplication, and diverticular introversion suturing were performed. The postoperative course was uneventful and the patient was discharged on day 4. At the 2-year follow-up, no dysphagia was present. This is the first report of a laparoscopic diverticuloplasty using an introversion buried suture with a Heller myotomy and Dor fundoplication for achalasia complicated by an epiphrenic diverticulum. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic training demands practice. The transfer of laparoscopic skills from training models to real surgical procedures has been proven. The global operative assessment of laparoscopic skills (GOALS) score is a 5-item global rating scale developed to evaluate laparoscopic skills by direct observation. This scale has been used to demonstrate construct validity of several laparoscopic training models. Here, we present a low-cost model of laparoscopic Heller-Dor for advanced laparoscopic training. The aim of this study was to determine the capability of a training model for laparoscopic Heller-Dor to discriminate between different levels of laparoscopic expertise.Methods: The performance of two groups with different levels of expertise, novices (<30 laparoscopic procedures PGY1-2) and experts (>300 laparoscopic procedures PGY4-5) was assessed. All participants were instructed to perform two tasks (esophageal myotomy and fundoplication). All the performances were recorded in a digital format. A laparoscopic expert who was blinded to subject's identity evaluated the recordings using the GOALS score. Autonomy, one of the five items of GOALS, was removed since the evaluator and the trainee did not have interaction. The time required to finish each task was also recorded. Performance was compared using the Mann-Whitney U test (p < 0.05 was significant).Results: Twenty subjects were evaluated: ten in each group, using the GOALS score. The mean total GOALS score for novices was 7.5 points (SD: 1.64) and 13.9 points (SD: 1.66) for experts (p < 0.05).The expert group was superior in each domain of the GOALS score compared to novices: depth perception (mean: 3.3 vs 2 p < 0.05), bimanual dexterity (mean 3.4 vs 2.1 p < 0.05), efficiency (mean 3.4 vs 1.7 p < 0.05) and tissue handling (mean 3.6 vs 1.7 p < 0.05). With regard to time, experts were superior in task 1 (mean 9.7 vs 14.9 min p < 0.05) and task 2 (mean 24 vs 47.1 min p < 0.05) compared to novices.Conclusions: The laparoscopic Heller-Dor training model has construct validity. The model may be used as a tool for training of the surgical resident. [ABSTRACT FROM AUTHOR]

We consider first-passage percolation on with independent and identically distributed weights whose common distribution is absolutely continuous with a finite exponential moment. Under the assumption that the limit shape has more than 32 extreme points, we prove that geodesics with nearby starting and ending points have significant overlap, coalescing on all but small portions near their endpoints. The statement is quantified, with power-law dependence of the involved quantities on the length of the geodesics. The result leads to a quantitative resolution of the Benjamini–Kalai–Schramm midpoint problem. It is shown that the probability that the geodesic between two given points passes through a given edge is smaller than a power of the distance between the points and the edge. We further prove that the limit shape assumption is satisfied for a specific family of distributions. Lastly, related to the 1965 Hammersley–Welsh highways and byways problem, we prove that the expected fraction of the square {−n,...,n}2 which is covered by infinite geodesics starting at the origin is at most an inverse power of n. This result is obtained without explicit limit shape assumptions. [ABSTRACT FROM AUTHOR]

Background: There is no consensus regarding the type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller cardiomyotomy (LHCM). The aim of this study was to compare Angle of His accentuation (AOH) with Dor Fundoplication (Dor) as an adjunct to LHCM.Methods: A total of 110 patients with achalasia cardia presenting for LHCM from March 2010 to July 2015 were randomized to Dor and AOH. Symptom severity, achalasia-specific quality of life (ASQOL), new onset heartburn, and patient satisfaction were assessed using standardized scores preoperatively, at 3, 6 months, and then yearly. The primary outcome was relief of esophageal symptoms while secondary outcomes were new onset heartburn and ASQOL.Results: Both groups were comparable with respect to the baseline demographic characteristics. There was no conversion to open and no mortality in either group. Median operative time was 128 min in AOH and 144 min in Dor group (p < 0.01). Mean follow-up was 36 months and was available in 98% patients. There was significant improvement in esophageal symptoms in both groups with no statistically significant difference between the two groups (p > 0.05). There was no difference in cumulative symptom scores between the two groups over the period of follow-up. New onset heartburn was seen in 11% in AOH and 9% in Dor group. Mean ASQOL score improved in both groups with no difference between the two groups (p = 0.83). Patient satisfaction was similar in both groups.Conclusion: AOH is similar to Dor as an adjunct to LHCM in safety and efficacy and can be performed in shorter time.Clinical Registration Number: CTRI: REF/2014/06/007146. [ABSTRACT FROM AUTHOR]

Benign and malignant diseases of the upper gastrointestinal tract show gender-specific differences. The frequent gastroesophageal reflux disease is a prime example: men have an erosive reflux disease more often than women and are also younger at the time of onset. The rate of progression to a metaplastic Barrett's esophagus is also higher in men. In the case of achalasia, there are indications that surgical treatment by laparoscopic Heller's myotomy and semifundoplication 180° according to Dor leads to a markedly better improvement in the symptoms in women compared to men, although they showed a more pronounced dilation of the tubular esophagus. The female hormone status influences the localization and histopathology of adenocarcinoma of the esophagogastric junction and gastric carcinoma. Premenopausal and postmenopausal carcinomas differ significantly in women. In addition, high microsatellite instability (MSI high) is more frequent in women and is associated with a generally significantly better prognosis. The MSI high gastric carcinomas of women show better survival than MSI high carcinomas of men. The future inclusion of gender-specific aspects in studies of the upper gastrointestinal tract is desirable in order to generate adequate data and to enable differentiated treatment stratification in the future. [ABSTRACT FROM AUTHOR]

Purpose: Diminished ovarian reserve (DOR) is associated with compromised fertility that affects approximately 10% of couples. Gene mutations are implicated in the pathogenesis of DOR. Here, we aimed to assess the clinical and genetic characteristics of two sisters with impaired fertility history. The two sisters showed DOR and suffered from recurrent pregnancy loss (RPL) in natural pregnancy and in vitro fertilization-embryo transfer (IVF-ET). Methods: Whole exome sequencing (WES) was performed for the proband and pathogenic variants detected were validated by Sanger sequencing in all available family members. Minigene assay was performed to evaluate the impact of sequence variants on splicing effect. Results: Two novel heterozygous variants on the HFM1 gene, c.1978-2A > C and c.2680 + 3_2680 + 4delAT, were observed in the two patients. The genotype of their parents was all heterozygous, while the unaffected sister and brother did not carry the variants. Both variants could produce alternative transcripts compared to wild-type counterparts, which might result in protein dysfunction. Conclusion: Our results demonstrated that the pathogenic splicing variants in HFM1 are associated with DOR in these two sisters. Mutations in HFM1 may contribute to RPL and poor IVF-ET outcomes because of descending quality and quantity of oocytes. The study enriched the genetic defect spectrum of DOR and understanding of the roles of HFM1 in female reproduction. [ABSTRACT FROM AUTHOR]

Background: The significance of laparoscopic Heller myotomy and Dor fundoplication (LHD) for the treatment of achalasia in relation to the severity of the lesion has not been sufficiently assessed.Methods: Of patients who were diagnosed with achalasia from August 1994 to February 2004, 55 individuals who underwent LHD served as subjects. The therapeutic effects of LHD were assessed in terms of operation time, intraoperative complications, postoperative hospital stay, and symptom improvement in relation to morphologic type (spindle type, Sp; flask type, Fk; and sigmoid type, Sig). Degree of symptomatic improvement was classified into four grades: excellent, good, fair, and poor.Results: Breakdown of morphologic type was as follows: Sp, n = 29; Fk, n = 18; and Sig, n = 8. Excluding one patient for whom conversion to open surgery was required, median average operation time for 54 patients was 160 min. As to intraoperative complications, esophageal mucosal perforation was seen in nine of the 55 patients (16%); however, conversion to open surgery could be avoided by suturing the affected area. Moreover, intraoperative bleeding of at least 100 g was seen in five of the 55 patients (9%), with one Fk patient requiring conversion to open surgery and transfusion. Median postoperative hospital stay was 8 days. Degree of dysphagia relief was excellent in 45 patients (83%), good in eight patients (15%), and fair in one patient (2%). Excellent improvement was obtained in 90%, 88%, and 50% in Sp, Fk, and Sig patients, respectively. Reflux esophagitis was seen in two patients, and was treated with a proton pump inhibitor.Conclusions: The results of the present study suggest that classification of morphologic type is a useful parameter in predicting postoperative outcome in achalasia. In order to achieve excellent symptomatic relief, surgery for achalasia should be recommended for but not limited to Sp and Fk types. [ABSTRACT FROM AUTHOR]

We show that for any set A ⊆ [ 0 , 1 ] n with Vol (A) ≥ 1 / 2 there exists a line ℓ such that the one-dimensional Lebesgue measure of ℓ ∩ A is at least Ω (n 1 / 4) . The exponent 1/4 is tight. More generally, for a probability measure μ on R n and 0 < a < 1 define L (μ , a) : = inf A ; μ (A) = a sup ℓ line | ℓ ∩ A | where | · | stands for the one-dimensional Lebesgue measure. We study the asymptotic behavior of L (μ , a) when μ is a product measure and when μ is the uniform measure on the ℓ p ball. We observe a rather unified behavior in a large class of product measures. On the other hand, for ℓ p balls with 1 ≤ p ≤ ∞ we find that there are phase transitions of different types. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the long-term outcome and quality of life (QoL) data, and to assess the potential influence of age and different conservative procedures on laparoscopic surgery.Background: Current therapies for achalasia can palliate dysphagia, but other symptoms may persist, making it difficult to quantify and compare. To understand if they could influence results, we analyzed short- and long-term results and correlated them to age and previous conservative treatments using a specific QoL test.Methods: Functional examinations (endoscopy, 24-hr pH manometry, upper GI X-rays) and the gastrointestinal quality of life index (GIQLI) were used before and after a laparoscopic Heller-Dor myotomy. Data were analyzed by the Mann-Whitney U test, Wilcoxon signed rank test, and Spearman's rho coefficient for bivariate correlations (p < 0.05).Results: From January 1996 to January 2004, 31 consecutive patients out of 35 diagnosed with achalasia, in clinical stages I-III, were operated on by laparoscopy . Two groups were identified using the break point of 70 years of age, (20 younger and 15 older) and two subgroups according to the conservative therapy performed (20, none; 15, some). Patients underwent a clinical manometry evaluation at six and 12 months, and then yearly, and pH-metry at six, 24, and 60 months. In 78% of patients dysphagia disappeared and the incidence of reflux was 13%. Age and previous treatments did not influence surgical outcome. Patients completed a GIQLI questionnaire before surgery, six months after surgery, and then yearly (for five years). The median preoperative GIQLI score was 78 (range 38-109) out of a theoretical maximum score of 144. At a median follow-up of 49 months (range 24-72 months), the score had significantly improved to 115 (range 71-140). There was no significant statistical difference between the groups.Conclusions: Laparoscopic Heller-Dor myotomy is an effective palliation for achalasia; the long-term outcome is not significantly affected by preoperative conservative treatments or by the age of the patients. The GIQLI questionnaire is a reliable instrument to compare the impact of achalasia symptoms on health-related QoL before and after surgery. [ABSTRACT FROM AUTHOR]

Background: The addition of a Dor antireflux procedure reduces the risk of pathologic gastroesophageal reflux (GER) by ninefold following laparoscopic Heller myotomy for achalasia. It is not clear, however, how these benefits compare with the increased cost of the fundoplication. The objective of this study was to estimate the cost-effectiveness of Heller myotomy plus Dor fundoplication compared with Heller alone in patients with achalasia.Methods: We conducted a cost-utility analysis using the Markov simulation model to examine the two treatment alternatives. The model estimated the total expected costs of each strategy over a 10-year time horizon. Data for the model were derived from our randomized clinical trial. The strategies were compared using the method of incremental cost-effectiveness analysis.Results: The incidence of pathologic GER was 47.6% (10 of 21 patients) in the Heller group and 9.1% (2 of 22 patients) in the Heller plus Dor group using an intention-to-treat analysis (p = 0.005). Heller plus Dor was associated with a significant reduction in the risk of GERD (relative risk 0.11; 95% confidence interval 0.02-0.59; p = 0.01). The cost of surgery was significantly higher for Heller plus Dor than for Heller alone (mean difference $942; p = 0.04), secondary to a longer operating room time (mean difference 40 min; p = 0.01). At a time horizon of 10 years, when proton pump inhibitor (PPI) therapy costs are considered, the cost-utility analysis demonstrates that Heller plus Dor surgery is associated with a total cost of $6,861 per patient and a quality-adjusted life expectancy of 9.9 years, whereas Heller-alone surgery is associated with a cost of $9,541 per patient and a quality-adjusted life expectancy of 9.5 years.Conclusions: In achalasia patients, Heller myotomy plus Dor fundoplication is preferred to Heller alone because it is both more effective in preventing postoperative GERD and more cost-effective at a time horizon of 10 years. [ABSTRACT FROM AUTHOR]

Our study focuses on analysing the coronal, transition and chromospheric activity of four rapidly rotating stars located within 50 pc in the solar neighborhood. We have used the multi-wavelength capabilities of AstroSat to investigate the outer atmospheres of AB Dor, BO Mic, DG CVn and GJ 3331. These stars, classified as M and K type active stars, are known for their short rotation periods, leading to increased surface magnetic activity. Our soft X-ray observations provide the coronal properties, such as emission measures, temperatures and elemental coronal abundances. We reported the detection of X-ray flares from AB Dor, BO Mic and DG CVn, while UV light curves reveal flares in both BO Mic and DG CVn. [ABSTRACT FROM AUTHOR]

Introduction: Delineating subthalamic nucleus (STN) boundaries using microelectrode recordings (MER) and trajectory history is a valuable resource for neurosurgeons, aiding in the accurate and efficient positioning of deep brain stimulation (DBS) electrodes within the STN. Here, we aimed to assess the application of artificial intelligence, specifically Hidden Markov Models (HMM), in the context of STN localization. Methods: A comprehensive search strategy was employed, encompassing electronic databases, including PubMed, EuroPMC, and MEDLINE. This search strategy entailed a combination of controlled vocabulary (e.g., MeSH terms) and free-text keywords pertaining to “artificial intelligence,” “machine learning,” “deep learning,” and “deep brain stimulation.” Inclusion criteria were applied to studies reporting the utilization of HMM for predicting outcomes in DBS, based on structured patient-level health data, and published in the English language. Results: This systematic review incorporated a total of 14 studies. Various machine learning compared wavelet feature to proposed features in diagnosing the STN, with the HMM yielding a diagnostic odds ratio (DOR) of 838.677 (95% CI: 203.309–3459.645). Similarly, the K-Nearest Neighbors (KNN) model produced parameter estimates, including a diagnostic odds ratio of 25.151 (95% CI: 12.270–51.555). Meanwhile, the support vector machine (SVM) model exhibited parameter estimates, with a DOR of 13.959 (95% CI: 10.436–18.671). Conclusions: MER data demonstrates significant variability in neural activity, with studies employing a wide range of methodologies. Machine learning plays a crucial role in aiding STN diagnosis, though its accuracy varies across different approaches. [ABSTRACT FROM AUTHOR]

Objectives: To assess the diagnostic performance of ultrafast magnetic resonance imaging (UF-DCE MRI) in differentiating benign from malignant breast lesions. Materials and methods: A comprehensive search was conducted until September 1, 2023, in Medline, Embase, and Cochrane databases. Clinical studies evaluating the diagnostic performance of UF-DCE MRI in breast lesion stratification were screened and included in the meta-analysis. Pooled summary estimates for sensitivity, specificity, diagnostic odds ratio (DOR), and hierarchic summary operating characteristics (SROC) curves were pooled under the random-effects model. Publication bias and heterogeneity between studies were calculated. Results: A final set of 16 studies analyzing 2090 lesions met the inclusion criteria and were incorporated into the meta-analysis. Using UF-DCE MRI kinetic parameters, the pooled sensitivity, specificity, DOR, and area under the curve (AUC) for differentiating benign from malignant breast lesions were 83% (95% CI 79–88%), 77% (95% CI 72–83%), 18.9 (95% CI 13.7–26.2), and 0.876 (95% CI 0.83–0.887), respectively. We found no significant difference in diagnostic accuracy between the two main UF-DCE MRI kinetic parameters, maximum slope (MS) and time to enhancement (TTE). DOR and SROC exhibited low heterogeneity across the included studies. No evidence of publication bias was identified (p = 0.585). Conclusions: UF-DCE MRI as a stand-alone technique has high accuracy in discriminating benign from malignant breast lesions. Clinical relevance statement: UF-DCE MRI has the potential to obtain kinetic information and stratify breast lesions accurately while decreasing scan times, which may offer significant benefit to patients. Key Points: • Ultrafast breast MRI is a novel technique which captures kinetic information with very high temporal resolution. • The kinetic parameters of ultrafast breast MRI demonstrate a high level of accuracy in distinguishing between benign and malignant breast lesions. • There is no significant difference in accuracy between maximum slope and time to enhancement kinetic parameters. [ABSTRACT FROM AUTHOR]