Assessing the effect of Maillard reaction products on the functionality and antioxidant properties of Amaranth-red seaweed blends.

Plant-based proteins, represented by amaranth in our study, embrace a potential as an ingredient for the functional-food formulation. However, their efficacy is hindered by inherent limitations in solubility, emulsification, and antioxidant traits. The Maillard reaction, a complex chemical-process resulting in a diverse array of products, including Maillard conjugates and Maillard reaction products (MRPs), can employ variable effects on these specific attributes. To elucidate the influence of this reaction and the MRPs on the aforementioned properties, we used a complex blend of dehydrated seaweed Gracilaria and amaranth protein to create a conjugate-MRP blend. Our investigations revealed that the resultant incorporation enhanced solubility, emulsification, and antioxidant properties, while the intermediates formed did not progress to advanced glycation stages. This change is likely attributed to the dual effect of conjugates that altered the secondary protein structure, while the generation and/or preservation of MRPs post ultrasonication and spray drying enhanced its antioxidant potential.

Understanding the Treatment Algorithm of Patients with Metastatic Pancreatic Neuroendocrine Neoplasms: A Single-Institution Retrospective Analysis Comparing Outcomes of Chemotherapy, Molecular Targeted Therapy, and Peptide Receptor Radionuclide Therapy in 255 Patients.

BACKGROUND: The number of therapeutic options for patients with pancreatic neuroendocrine neoplasms (PNEN) has increased, but the optimal therapeutic algorithm has not been defined due to lack of randomised trials comparing different modalities. METHODS: We performed a retrospective study in patients with metastatic PNEN treated with ≥1 line of systemic therapy. The relationship between baseline characteristics, treatment type, and time to treatment failure (TTF), time to progression (TTP), and overall survival (OS) was analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Two hundred and fifty-five patients with metastatic PNEN had 491 evaluable lines of therapy. Independent predictors of TTF included treatment type, Ki-67, tumour grade, and chromogranin A. To reduce selection bias, a subgroup of 114 patients with grade 2 (G2) metastatic pancreatic neuroendocrine tumours (PNET) was analysed separately. These patients had received 234 lines of treatment (105 chemotherapy, 82 molecular targeted therapy, and 47 peptide receptor radionuclide therapy [PRRT]). In the G2 cohort, TTF and TTP were superior for PRRT compared with both chemotherapy and molecular targeted therapy. OS in the G2 cohort was also superior for those that had received PRRT compared with those that had not (median 84 vs. 56 months; HR 0.55, 95% CI: 0.31-0.98, p = 0.04). CONCLUSIONS: This study suggests that PRRT is associated with superior clinical outcomes relative to other systemic therapies for G2 metastatic PNET. Prospective studies are required to confirm these observations.

Robotic simulation experience in undergraduate medical education: a perspective.

Robotic surgery has been one of the most revolutionary advancements in surgery, and demand is anticipated to grow. The performance of robotic surgery has seen an exponential increase in recent years. This is largely due to the benefits offered by robotics, including shorter hospital stays and recovery times, improved visualisation, and fewer postoperative complications. However, due to its expense, only a few specialist centres in the UK offer these techniques, making exposure amongst medical students limited. As final-year medical students, our exposure to simulated robotic surgery gave us a greater appreciation of the associated challenges, such as depth perception, a lack of haptic feedback, and movement economy. Compared to other techniques, robotic simulators provide a greater range of performance measures, allowing one to better adapt to the learning curve. We believe that increasing the exposure of medical students to robotics will be beneficial, allowing future doctors to better inform patients and inspire the next generation of robotic surgeons.

Treatment of Refractory Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common disorder that is treated with lifestyle modification, weight loss, and medications, such as proton pump inhibitors (PPIs). An empiric course of PPI therapy is an effective and cost-effective strategy for the management of GERD. However, in some patients, PPI therapy and lifestyle changes are inadequate to control symptoms. When there is persistence of symptoms despite empiric therapy, patients are labeled as having refractory GERD. This label underestimates the wide differential diagnosis of foregut pathology that can mimic symptoms of GERD. A careful history of symptoms, response to PPI therapy, adherence, compliance, and timing helps elucidate if medication has been helping. When patients are refractory, alternative etiologies of GERD must be considered. Many of these alternatives can be determined on an upper endoscopy or with complementary testing, such as high-resolution esophageal manometry or gastric emptying testing as symptoms dictate. When an alternative cause is not found and index endoscopy is normal, additional testing with either traditional pH or impedance testing can be completed based on prior examination results and response to therapy. Further therapy, including medical, endoscopic, or surgical, can then be targeted at the etiology.

The role of extended venous thromboembolism prophylaxis for major urological cancer operations.

OBJECTIVES: Venous thromboembolism (VTE), consisting of both pulmonary embolism (PE) and deep vein thromboses (DVT), remains a well-recognised complication of major urological cancer surgery. Several international guidelines recommend extended thromboprophylaxis (ETP) with LMWH, whereby the period of delivery is extended to the post-discharge period, where the majority of VTE occurs. In this literature review we investigate whether ETP should be indicated for all patients undergoing major urological cancer surgery, as well procedure specific data that may influence a clinician's decision. METHODS: We performed a search of six databases (PubMed, Cochrane, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and British Nursing Index (BNI)) from inception to June 2019, for studies looking at adult patients who received VTE prophylaxis after surgery for a major urological malignancy. RESULTS: Eighteen studies were analysed. VTE risk is highest in open and robotic Radical Cystectomy (RC) (2.6-11.6%) and ETP demonstrates a significant reduction in risk of VTE, but not a significant difference in Pulmonary Embolism (PE) or mortality. Risk of VTE in open Radical Prostatectomy (RP) (0.8-15.7%) is comparable to RC, but robotic RP (0.2-0.9%), open partial/radical nephrectomy (1.0-4.4%) and robotic partial/radical nephrectomy (0.7-3.9%) were lower risk. It has not been shown that ETP reduces VTE risk specifically for RP or nephrectomy. CONCLUSION: The decision to use ETP is a fine balance between variables such as VTE incidence, bleeding risk and perioperative morbidity/mortality. This balance should be assessed for each specific procedure type. While ETP still remains of net benefit for open RP as well as open and robotic RC, the balance is closer for minimally invasive RP as well as radical and partial nephrectomy. Due to a lack of procedure specific evidence for the use of ETP, adherence with national guidelines remains poor. Therefore, we advocate further studies directly comparing ETP vs standard prophylaxis, for specific procedure types, in order to allow clinicians to make a more informed decision in future.

Challenging the Current Risk Factors of Appendiceal Neuroendocrine Neoplasms: Can They Accurately Predict Local Lymph Nodal Invasion? Results from a Large Case Series.

BACKGROUND: Appendiceal neuroendocrine neoplasms (ANEN) are uncommon entities, which run mostly an indolent course. Appendicectomy alone is usually curative, except for in a selected group of patients that are deemed to be at risk of loco-regional metastases, in whom a completion right hemicolectomy (RHC) is recommended. The current "Guidelines" criteria for the latter have been controversial, and may result in overtreatment, which is concerning for a young patient population. OBJECTIVE: The aim of this study is to evaluate the prognostic value of the current criteria in identifying more accurately those at-risk patients. METHODS: This was a retrospective study of the 263 cases of ANEN referred for advice or management to a tertiary referral unit over a 10-year period. Seventy-two patients underwent RHC, based on criteria, suggested by International Guidelines. Each one of those was assessed to identify whether it correlated with lymph node invasion (LNI) at the RHC surgical specimen. RESULTS: Tumour grade (p < 0.001), vascular (p = 0.044) and lymph vessel invasion (p < 0.001) were all found to be statistically significant independent risk factors for LNI identified following RHC, whilst tumour size (p = 0.375) and mesoappendiceal invasion (MAI) (p = 0.317) were not statistically significant. However, deep MAI and tumour size >2 cm showed a correlation with each other on LNI positive subgroup analysis. Location in appendiceal base made LNI more likely but again was not significant (p = 0.133). CONCLUSIONS: Higher tumour grade and lymphovascular invasion should be considered as the most important risk prognosticators. Surprisingly, tumour size was not found to be significant in our cohort. Further international multicentre studies with large numbers of patients are needed to fully validate those data.

Advances in the Diagnosis and Treatment of GERD: New Tricks for an Old Disease.

PURPOSE OF REVIEW: Gastroesophageal reflux disease (GERD) is a common diagnosis encountered by both primary care providers and specialists, but despite its prevalence, there are limitations in the current diagnostic tests for GERD. Once an accurate diagnosis is made, treatment options can be offered, and this field continues to burgeon with options. In this review, we seek to review the recent advances in GERD diagnostics and subsequent treatment options. RECENT FINDINGS: Novel impedance markers and novel techniques (mucosal impedance testing, salivary pepsin, high-resolution manometry, and narrow-band imaging) have shown promise in diagnosing GERD. Advances in medical therapy, including potassium-competitive acid blockers and bile acid sequestrants, along with advances in invasive therapy (transoral incisionless fundoplication, endoscopic radiofrequency, electrical stimulation of the LES, and magnetic sphincter augmentation) have provided additional options for therapy for GERD beyond PPI and anti-reflux surgery. Novel impedance markers and techniques will provide further clarity on mucosal integrity and the barrier function allowing improved diagnostic accuracy of GERD. Improvements in medical and invasive therapy will expand GERD therapy.

MTG16 is a tumor suppressor in colitis-associated carcinoma.

MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example, Mtg16-/- mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models. MTG16 is also underexpressed in patients with moderate/severe ulcerative colitis. Based on these findings, we postulated that MTG16 might protect against colitis-associated carcinogenesis. MTG16 was downregulated at the protein and RNA levels in patients with inflammatory bowel disease and in those with colitis-associated carcinoma. Mtg16-/- mice subjected to inflammatory carcinogenesis modeling exhibited worse colitis and increased tumor multiplicity and size. Loss of MTG16 also increased severity of dysplasia, apoptosis, proliferation, DNA damage, and WNT signaling. Moreover, transplantation of WT marrow into Mtg16-/- mice failed to rescue the Mtg16-/- protumorigenic phenotypes, indicating an epithelium-specific role for MTG16. While MTG dysfunction is widely appreciated in hematopoietic malignancies, the role of this gene family in epithelial homeostasis, and in colon cancer, was unrealized. This report identifies MTG16 as an important modulator of colitis and tumor development in inflammatory carcinogenesis.

BVES regulates c-Myc stability via PP2A and suppresses colitis-induced tumourigenesis.

OBJECTIVE: Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. However, the functional impact of BVES loss on tumourigenesis is unknown. Here we define the in vivo role of BVES in colitis-associated cancer (CAC), its cellular function and its relevance to patients with IBD. DESIGN: We determined BVES promoter methylation status using an Infinium HumanMethylation450 array screen of patients with UC with and without CAC. We also measured BVES mRNA levels in a tissue microarray consisting of normal colons and CAC samples. Bves-/- and wild-type mice (controls) were administered azoxymethane (AOM) and dextran sodium sulfate (DSS) to induce tumour formation. Last, we used a yeast two-hybrid screen to identify BVES interactors and performed mechanistic studies in multiple cell lines to define how BVES reduces c-Myc levels. RESULTS: BVES mRNA was reduced in tumours from patients with CAC via promoter hypermethylation. Importantly, BVES promoter hypermethylation was concurrently present in distant non-malignant-appearing mucosa. As seen in human patients, Bves was underexpressed in experimental inflammatory carcinogenesis, and Bves-/- mice had increased tumour multiplicity and degree of dysplasia after AOM/DSS administration. Molecular analysis of Bves-/- tumours revealed Wnt activation and increased c-Myc levels. Mechanistically, we identified a new signalling pathway whereby BVES interacts with PR61α, a protein phosphatase 2A regulatory subunit, to mediate c-Myc destruction. CONCLUSION: Loss of BVES promotes inflammatory tumourigenesis through dysregulation of Wnt signalling and the oncogene c-Myc. BVES promoter methylation status may serve as a CAC biomarker.

Recent advances in diagnostic testing for gastroesophageal reflux disease.

INTRODUCTION: Gastroesophageal reflux disease (GERD) has a large economic burden with important complications that include esophagitis, Barrett's esophagus, and adenocarcinoma. Despite endoscopy, validated patient questionnaires, and traditional ambulatory pH monitoring, the diagnosis of GERD continues to be challenging. Areas covered: This review will explore the difficulties in diagnosing GERD with a focus on new developments, ranging from basic fundamental changes (histology and immunohistochemistry) to direct patient care (narrow-band imaging, impedance, and response to anti-reflux surgery). We searched PubMed using the noted keywords. We included data from full-text articles published in English. Further relevant articles were identified from the reference lists of review articles. Expert commentary: Important advances in novel parameters in intraluminal impedance monitoring such as baseline impedance monitoring has created some insight into alternative diagnostic strategies in GERD. Recent advances in endoscopic assessment of esophageal epithelial integrity via mucosal impedance measurement is questioning the paradigm of prolonged ambulatory testing for GERD. The future of reflux diagnosis may very well be without the need for currently employed technologies and could be as simple as assessing changes in epithelia integrity as a surrogate marker for GERD. However, future studies must validate such an approach.

Association Between Response to Acid-Suppression Therapy and Efficacy of Antireflux Surgery in Patients With Extraesophageal Reflux.

BACKGROUND & AIMS: The effectiveness of antireflux surgery (ARS) varies among patients with extraesophageal manifestations of gastroesophageal reflux disease (GERD). By studying a cohort of patients with primary extraesophageal symptoms and abnormal physiologic markers for GERD, we aimed to identify factors associated with positive outcomes from surgery, and compare outcomes to those with typical esophageal manifestations of GERD. METHODS: We performed a retrospective cohort study to compare adult patients with extraesophageal and typical reflux symptoms who underwent de novo ARS from 2004 through 2012 at a tertiary care center. All 115 patients (79 with typical GERD and 36 with extraesophageal manifestations of GERD) had evidence of abnormal distal esophageal acid exposure based on pH testing or endoscopy. The principle outcome was time to primary symptom recurrence after surgery, based on patient reports of partial or total recurrence of symptoms at follow-up visits. Patients were followed up for a median duration of 66 months (interquartile range, 52-77 mo). RESULTS: The median time to recurrence of symptoms in the overall cohort was 68 months (11.5 months in the extraesophageal cohort vs >132 months in the typical cohort). Symptom recurrence after ARS was associated with having primarily extraesophageal symptoms (adjusted hazard ratio, 2.34; 95% confidence interval, 1.31-4.17) and poor preoperative symptom response to acid-suppression therapy (AST) (hazard ratio, 3.85; 95% confidence interval, 2.05-7.22). Patients with primary extraesophageal symptoms who had a full or partial preoperative AST response experienced lower rates of symptom recurrence compared to patients with poor AST response (P < .01). The rate of symptom recurrence was lowest among patients with primary typical reflux symptoms who had a partial or full symptom response to AST (P < .01). The severity of acid reflux on pH testing, symptom indices, severity of esophagitis, and hiatal hernia size were not associated with symptom response. CONCLUSIONS: In a retrospective study, we found the effectiveness of ARS to be less predictable in patients with extraesophageal symptoms of GERD than in patients with typical GERD. Response to AST before surgery was associated with ARS effectiveness in patients with extraesophageal reflux symptoms. Caution should be exercised when advocating ARS for patients with extraesophageal symptoms that do not respond to AST.

Clinical management of achalasia: current state of the art.

Achalasia is a primary disorder of esophageal motility. It classically presents with dysphagia to both solids and liquids but may be accompanied by regurgitation and chest pain. The gold standard for the diagnosis of achalasia is esophageal motility testing with manometry, which often reveals aperistalsis of the esophageal body and incomplete lower esophageal sphincter relaxation. The diagnosis is aided by complimentary tests, such as esophagogastroduodenoscopy and contrast radiography. Esophagogastroduodenoscopy is indicated to rule out mimickers of the disease known as "pseudoachalasia" (eg, malignancy). Endoscopic appearance of a dilated esophagus with retained food or saliva and a puckered lower esophageal sphincter should raise suspicion for achalasia. Additionally, barium esophagography may reveal a dilated esophagus with a distal tapering giving it a "bird's beak" appearance. Multiple therapeutic modalities aid in the management of achalasia, the decision of which depends on operative risk factors. Conventional treatments include medical therapy, botulinum toxin injection, pneumatic dilation, and Heller myotomy. The last two are defined as the most definitive treatment options. New emerging therapies include peroral endoscopic myotomy, placement of self-expanding metallic stents, and endoscopic sclerotherapy.

Consequences of bariatric surgery on oesophageal function in health and disease.

Obesity is a continuing epidemic with substantial associated morbidity and mortality. Owing to the limitations of lifestyle modifications and pharmacological options, bariatric surgery has come to the forefront as an efficient method of achieving sustained weight loss and decreasing overall mortality in comparison with nonsurgical interventions. The most frequently performed bariatric operations are either purely restrictive, such as laparoscopic adjustable gastric band (LAGB) and laparoscopic sleeve gastrectomy (LSG), or restrictive-malabsorptive, such as the Roux-en-Y gastric bypass (RYGB). Each operation results in weight loss, but can also have unintended effects on the health of the oesophagus. Specifically, operations might lead to oesophageal dilation or the development of GERD. LAGB is the best-studied procedure with notable evidence for postoperative worsening of GERD and pseudo-achalasia, which increases lower oesophageal pressure and causes aperistalsis. In some studies, LSG initiates not only a worsening of GERD, but also the formation of de novo GERD in patients without preoperative GERD symptoms. RYGB demonstrates the most profound evidence for improvement of GERD symptoms and preservation of oesophageal motility. Future high-quality studies will be required to better understand the interaction between bariatric surgery and oesophageal disease.

Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay.

Gastroesophageal reflux disease (GERD) is a condition that develops when there is reflux of stomach contents, which typically manifests as heartburn and regurgitation. These esophageal symptoms are well recognized; however, there are extra-esophageal manifestations of GERD, which include asthma, chronic cough, laryngitis and sinusitis. With the rising incidence of asthma, there is increasing interest in identifying how GERD impacts asthma development and therapy. Due to the poor sensitivity of endoscopy and pH monitoring, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. If unresponsive, diagnostic testing with pH monitoring off therapy and/or impedance/pH monitoring on therapy, may be reasonable in order to assess for baseline presence of reflux with the former and exclude continued acid or weakly acid reflux with the latter tests. PPI-unresponsive asthmatics, without overt regurgitation, usually have either no reflux or causes other than GERD. In this group, PPI therapy should be discontinued. In those with GERD as a contributing factor acid suppressive therapy should be continued as well as optimally treating other etiologies requiring concomitant treatment. Surgical fundoplication is rarely needed but in those with a large hiatal hernia, moderate-to-severe reflux by pH monitoring surgery might be helpful in eliminating the need for high-dose acid suppressive therapy.

Impact of Weight Loss Surgery on Esophageal Physiology.

Bariatric surgery has come to the forefront of weight loss treatment due to its complex interactions via anatomic, physiologic, and neurohormonal changes leading to sustained weight loss. Unlike lifestyle and pharmacologic options, which fail to show long-term sustained weight loss, bariatric surgery has been shown to decrease overall mortality and morbidity. Bariatric surgery can be purely restrictive, such as laparoscopic adjustable gastric band (LAGB) or laparoscopic sleeve gastrectomy (LSG), or restrictive-malabsorptive, such as Roux-en-Y gastric bypass (RYGB). These surgeries cause specific anatomic changes that promote weight loss; however, they also have unintended effects on the esophagus, particularly in terms of gastroesophageal reflux disease (GERD) and esophageal motility. Via restrictive surgery, LAGB has been widely reported to cause significant weight loss, although studies have also shown an increase and worsening of GERD as well as elevated rates of esophageal dilation, aperistalsis, and alterations in lower esophageal sphincter pressure. Along with LAGB, LSG has shown not only a worsening of GERD, but also the formation of de novo GERD in patients who were asymptomatic before the operation. In a restrictive-malabsorptive approach, RYGB has been reported to improve GERD and preserve esophageal motility. Bariatric surgery is a burgeoning field with immense implications on overall mortality. Future randomized, controlled trials are needed to better understand which patients should undergo particular surgeries, with greater emphasis on esophageal health and prevention of GERD and esophageal dysmotility.

Outcomes of hook of hamate fracture excision in high-level amateur athletes.

PURPOSE: To determine the overall long-term postoperative clinical and functional results of high-level amateur athletes after hook of hamate excision, based on complications; return to sport; Disabilities of the Arm, Shoulder, and Hand (DASH) score; and a self-reported questionnaire. METHODS: We evaluated 11 patients representing 12 cases of hook of hamate excision. All patients were high-level amateur athletes (rising collegiate or collegiate level). We performed a retrospective chart review to elicit information pertaining to the patient's injury. We assessed long-term postoperative outcomes with a self-reported questionnaire, the DASH form, and the DASH Sport/Performing Arts Module form. RESULTS: All patients successfully returned to full participation in their respective sports an average of 6 weeks after surgery. The average postoperative DASH score was less than 1, and all patients scored a 0 on the DASH Sports form. There was a significant improvement in preoperative pain after surgical intervention. There was no significant difference between preinjury and postoperative performance scores. Finally, every patient was very satisfied with the surgical outcome. There was only 1 postoperative complication in which a patient developed transient ulnar nerve paresthesias, which completely resolved by 6 weeks after surgery. CONCLUSIONS: Surgical excision of hook of hamate fractures in high-level amateur athletes allows for successful return to sports participation at preinjury performance levels, achievement of normal function as measured by validated objective outcome measures, significant reduction in pain, and high overall patient satisfaction. We consider surgical excision to be a safe and effective technique to restore normal function and hasten return to play for high-level amateur athletes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.