Postoperative Dysphagia Following Esophagogastric Fundoplication: Does the Timing to First Dilation Matter?

Background Postoperative dysphagia after anti-reflux surgery typically resolves in a few weeks. However, even after the initial swelling has resolved at 6 weeks, dysphagia can persist in 30% of patients necessitating esophageal dilation. The purpose of this study was to investigate the effect of esophageal dilation on postoperative dysphagia, the recurrence of reflux symptoms, and the efficacy of pneumatic dilations on postoperative dysphagia. Methods A prospectively collected database was reviewed for patients who underwent partial/complete fundoplication with/without paraesophageal hernia repair between 2006 and 2014. Patient age, sex, BMI, DeMeester score, procedure type, procedure duration, length of stay, postoperative dysphagia, time to first pneumatic dilation, number of dilations, and the need for reoperations were collected. Results The study included 902 consecutive patients, 71.3% females, with a mean age of 57.8 ± 14.7 years. Postoperative dysphagia was noted in 26.3% of patients, of whom 89% had complete fundoplication (p < 0.01). Endoscopic dilation was performed in 93 patients (10.3%) with 59 (63.4%) demonstrating persistent dysphagia. Recurrent reflux symptoms occurred in 35 (37.6%) patients who underwent endoscopic dilation. Patients who underwent a dilation for symptoms of dysphagia were less likely to require a revisional surgery later than patients who had dysphagia but did not undergo a dilation before revisional surgery (17.2% vs 41.7%, respectively, p < 0.001) in the 4-year follow-up period. The duration of initial dilation from surgery was inversely related to the need for revisional surgery (p = 0.047), while more than one dilation was not associated with additive benefit. Conclusion One attempt at endoscopic dilation of the esophagogastric fundoplication may provide relief in patients with postoperative dysphagia and can be used as a predictive factor for the need of revision. However, there is an increased risk for recurrent reflux symptoms and revisional surgery may ultimately be indicated for control of symptoms

How are Bariatric Patients Coping During the COVID-19 Pandemic? Analysis of Factors Known to Cause Weight Regain Among Postoperative Bariatric Patients

Background The global coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc on society. Bariatric patients are more prone to severe infection due to their high body mass index (BMI) and are more vulnerable to the effects of isolation, such as depression or disruption of their health habits. Objectives To quantify the impact of self-quarantine on bariatric patients and self-quarantine’s relationship with weight gain. Setting Academic hospital, United States. Methods A 30-item survey examining several known contributors to weight regain was distributed among the postoperative bariatric patients of our clinic. Changes in eating habits, exercise, depression, social support, loneliness, and anxiety were studied, among others. Results A total of 208 patients completed the survey (29.3% response rate). A large percentage of patients reported increases in their depression (44.2%), loneliness (36.2%), nervousness (54.7%), snacking (62.6%), loss of control when eating (48.2%), and binge eating (19.5%) and decreases in their social support (23.2%), healthy food eating (45.5%), and activity (55.2%). Difficulty in accessing vitamins was reported by 13%. Patients more than 18 months out of surgery regained more than 2 kg during an average of 47 days. Risk factors for weight regain were found to be loss of control when eating, increases in snacking and binge eating, reduced consumption of healthy food, and reduced physical activity. Conclusion Bariatric patients are negatively affected by the COVID-19 pandemic and subsequent social isolation on many levels. This patient population is vulnerable to crisis situations; thus, additional intervention is needed to address behaviors that lead to weight regain

Multicenter, Prospective, Longitudinal Study of the Recurrence, Surgical Site Infection, and Quality of Life After Contaminated Ventral Hernia Repair Using Biosynthetic Absorbable Mesh: The COBRA Study

OBJECTIVE: The aim of the study was to evaluate biosynthetic absorbable mesh in single-staged contaminated (Centers for Disease Control class II and III) ventral hernia (CVH) repair over 24 months. BACKGROUND: CVH has an increased risk of postoperative infection. CVH repair with synthetic or biologic meshes has reported chronic biomaterial infections and high hernia recurrence rates. METHODS: Patients with a contaminated or clean-contaminated operative field and a hernia defect at least 9 cm had a biosynthetic mesh (open, sublay, retrorectus, or intraperitoneal) repair with fascial closure (n = 104). Endpoints included overall Kaplan-Meier estimates for hernia recurrence and postoperative wound infection rates at 24 months, and the EQ-5D and Short Form 12 Health Survey (SF-12). Analyses were conducted on the intent-to-treat population, and health outcome measures evaluated using paired t tests. RESULTS: Patients had a mean age of 58 years, body mass index of 28 kg/m, 77% had contaminated wounds, and 84% completed 24-months follow-up. Concomitant procedures included fistula takedown (n = 24) or removal of infected previously placed mesh (n = 29). Hernia recurrence rate was 17% (n = 16). At the time of CVH repair, intraperitoneal placement of the biosynthetic mesh significantly increased the risk of recurrences (P ≤ 0.04). Surgical site infections (19/104) led to higher risk of recurrence (P < 0.01). Mean 24-month EQ-5D (index and visual analogue) and SF-12 physical component and mental scores improved from baseline (P < 0.05). CONCLUSIONS: In this prospective longitudinal study, biosynthetic absorbable mesh showed efficacy in terms of long-term recurrence and quality of life for CVH repair patients and offers an alternative to biologic and permanent synthetic meshes in these complex situations

Chylous ascites in the setting of internal hernia: a reassuring sign

BACKGROUND: Chylous ascites is often reported in cases with lymphatic obstruction or after lymphatic injuries such as intraabdominal malignancies or lymphadenectomies. However, chylous ascites is also frequently encountered in operations for internal hernias. We sought to characterize the frequency and conditions when chylous ascites is encountered in general surgery patients. METHODS: Data from patients who underwent operations for CPT codes related to open and laparoscopic abdominal and gastrointestinal surgery in our tertiary hospital from 2010 to 2019 were reviewed. Patients with the postoperative diagnosis of internal hernia were identified and categorized into three groups: Internal Hernia with chylous ascites, non-chylous ascites, and no ascites. Demographics, prior surgical history, CT findings, source of internal hernia, open or laparoscopic surgery, and preoperative labs were recorded and compared. RESULTS: Fifty-six patients were found to have internal hernias and were included in our study. 80.3% were female and 86% had a previous Roux-en-Y gastric bypass procedure (RYGBP). Laparoscopy was the main approach for all groups. Ascites was present in 46% of the cases. Specifically, chylous ascites was observed in 27% of the total operations and was exclusively (100%) found in patients with gastric-bypass history. Furthermore, it was more commonly associated with Petersen's defect (p < 0.001), while the non-chylous fluid group was associated with herniation through the mesenteric defect (p < 0.001). CONCLUSIONS: Chylous ascites is a common finding during internal hernia operations. Unlike other more morbid conditions, identification of chylous ascites during an internal hernia operation appears innocuous. However, in the context of a patient with a history of RYGBP, the presence of chylous fluid signifies the associated small bowel obstruction is likely related to an internal hernia through a patent Petersen's defect

The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study

Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCα), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies

Population policies and education: exploring the contradictions of neo-liberal globalisation

The world is increasingly characterised by profound income, health and social inequalities (Appadurai, 2000). In recent decades development initiatives aimed at reducing these inequalities have been situated in a context of increasing globalisation with a dominant neo-liberal economic orthodoxy. This paper argues that neo-liberal globalisation contains inherent contradictions regarding choice and uniformity. This is illustrated in this paper through an exploration of the impact of neo-liberal globalisation on population policies and programmes. The dominant neo-liberal economic ideology that has influenced development over the last few decades has often led to alternative global visions being overlooked. Many current population and development debates are characterised by polarised arguments with strongly opposing aims and views. This raises the challenge of finding alternatives situated in more middle ground that both identify and promote the socially positive elements of neo-liberalism and state intervention, but also to limit their worst excesses within the population field and more broadly. This paper concludes with a discussion outling the positive nature of middle ground and other possible alternatives

Ancient evolutionary origin of vertebrate enteric neurons from trunk-derived neural crest

The enteric nervous system of jawed vertebrates arises primarily from vagal neural crest cells that migrate to the foregut and subsequently colonize and innervate the entire gastrointestinal tract. Here we examine development of the enteric nervous system in the basal jawless vertebrate the sea lamprey (Petromyzon marinus) to gain insight into its evolutionary origin. Surprisingly, we find no evidence for the existence of a vagally derived enteric neural crest population in the lamprey. Rather, labelling with the lipophilic dye DiI shows that late-migrating cells, originating from the trunk neural tube and associated with nerve fibres, differentiate into neurons within the gut wall and typhlosole. We propose that these trunk-derived neural crest cells may be homologous to Schwann cell precursors, recently shown in mammalian embryos to populate post-embryonic parasympathetic ganglia, including enteric ganglia. Our results suggest that neural-crest-derived Schwann cell precursors made an important contribution to the ancient enteric nervous system of early jawless vertebrates, a role that was largely subsumed by vagal neural crest cells in early gnathostomes

Carotid intima-medial thickness measured on multiple ultrasound frames: evaluation of a DICOM-based software system

United Kingdo

Design, expression and characterization of mutants of fasciculin optimized for interaction with its target, acetylcholinesterase

Predicting mutations that enhance protein–protein affinity remains a challenging task, especially for high-affinity complexes. To test our capability to improve the affinity of such complexes, we studied interaction of acetylcholinesterase with the snake toxin, fasciculin. Using the program ORBIT, we redesigned fasciculin's sequence to enhance its interactions with Torpedo californica acetylcholinesterase. Mutations were predicted in 5 out of 13 interfacial residues on fasciculin, preserving most of the polar inter-molecular contacts seen in the wild-type toxin/enzyme complex. To experimentally characterize fasciculin mutants, we developed an efficient strategy to over-express the toxin in Escherichia coli, followed by refolding to the native conformation. Despite our predictions, a designed quintuple fasciculin mutant displayed reduced affinity for the enzyme. However, removal of a single mutation in the designed sequence produced a quadruple mutant with improved affinity. Moreover, one designed mutation produced 7-fold enhancement in affinity for acetylcholinesterase. This led us to reassess our criteria for enhancing affinity of the toxin for the enzyme. We observed that the change in the predicted inter-molecular energy, rather than in the total energy, correlates well with the change in the experimental free energy of binding, and hence may serve as a criterion for enhancement of affinity in protein–protein complexes

Clostridial Glucosylating Toxins Enter Cells via Clathrin-Mediated Endocytosis

Clostridium difficile toxin A (TcdA) and toxin B (TcdB), C. sordellii lethal toxin (TcsL) and C. novyi α-toxin (TcnA) are important pathogenicity factors, which represent the family of the clostridial glucosylating toxins (CGTs). Toxin A and B are associated with antibiotic-associated diarrhea and pseudomembraneous colitis. Lethal toxin is involved in toxic shock syndrome after abortion and α-toxin in gas gangrene development. CGTs enter cells via receptor-mediated endocytosis and require an acidified endosome for translocation of the catalytic domain into the cytosol. Here we studied the endocytic processes that mediate cell internalization of the CGTs. Intoxication of cells was monitored by analyzing cell morphology, status of Rac glucosylation in cell lysates and transepithelial resistance of cell monolayers. We found that the intoxication of cultured cells by CGTs was strongly delayed when cells were preincubated with dynasore, a cell-permeable inhibitor of dynamin, or chlorpromazine, an inhibitor of the clathrin-dependent endocytic pathway. Additional evidence about the role of clathrin in the uptake of the prototypical CGT family member toxin B was achieved by expression of a dominant-negative inhibitor of the clathrin-mediated endocytosis (Eps15 DN) or by siRNA against the clathrin heavy chain. Accordingly, cells that expressed dominant-negative caveolin-1 were not protected from toxin B-induced cell rounding. In addition, lipid rafts impairment by exogenous depletion of sphingomyelin did not decelerate intoxication of HeLa cells by CGTs. Taken together, our data indicate that the endocytic uptake of the CGTs involves a dynamin-dependent process that is mainly governed by clathrin