Feasibility of full-thickness gastric resection using master and slave transluminal endoscopic robot and closure by overstitch: a preclinical study

Background

Gastric submucosal tumors are often treated by laparoscopic wedge resection. This study aimed to examine the feasibility of gastric full-thickness resection through a totally endoscopic approach using the master and slave transluminal endoscopic robot (MASTER), and closure of the luminal defect with an endoscopic suturing device.

Methods

The operation was performed in two live porcine models under general anesthesia. First, the anterior wall of the stomach was slung to the abdominal wall using a percutaneous suturing device. An imaginary 5-cm lesion was marked using a needle knife. After the initial mucosal incision was made using an IT knife, the MASTER was introduced through a long overtube. A circumferential mucosal incision was completed with the MASTER to expose the muscularis propria which was grasped and incised to the serosal layer by electrocautery applied through the hook of the MASTER. The full-thickness resection of the gastric wall was completed with retraction using the grasper and dissection using the hook. While the defect was being created, the luminal space was maintained with traction of the percutaneous sutures. The defect was closed with suture plication using an Apollo Overstitch device.

Results

Two full-thickness gastric resections were performed in two nonsurvival porcine models (body weight = 30 and 35 kg, respectively) using the MASTER. The total procedure time was 56 min for the first model and 70 min for the second model. The luminal view was maintained during the whole procedure, and there was no damage to surrounding organs throughout the whole procedure. The gastric defects were closed successfully using Overstitch, with satisfactory gastric distension and no gas leakage afterward.

Conclusion

The current experiment demonstrated the feasibility and safety of a totally endoscopic approach for the treatment of gastric submucosal tumors: full-thickness resection with the MASTER and successful closure of the defect using Overstitch.     

Making sense of the spectrum of glomerular disease associated with complement dysregulation

Over recent years, complement has emerged as a major player in the development of a number of glomerular diseases, including atypical haemolytic uraemic syndrome, membranoproliferative glomerulonephritis and the recently described C3 glomerulonephritis. Some patients and pedigrees show overlapping features of these conditions. Intriguingly, a few complement gene mutations are common to different disease phenotypes. In this review, we explore the evidence for complement dysregulation in these diseases and the clinical interface between them, and present a hypothesis to explain the variable phenotype associated with dysregulation of the alternative complement pathway.     

Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis

Summary

We completed a network meta-analysis of published papers to compare bisphosphonate gastrointestinal safety. We found that zoledronic acid had the highest chance of causing gastrointestinal adverse events. Etidronate had the highest chance of discontinuation due to an adverse event. No difference was found for serious adverse events.

Introduction

Bisphosphonates are first-line treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the primary reason for non-adherence. Little is known about the comparative GI safety of bisphosphonates.

Purpose

Leverage published clinical trial data to examine the comparative GI safety of bisphosphonates.

Methods

We completed a systematic review of all English-language clinical trials that assessed bisphosphonate safety and/or efficacy in primary osteoporosis through to 2012. Randomized, blinded, and controlled studies were eligible. The primary outcome was any GI-related AE. Subanalyses were completed for upper GI symptoms, serious GI, nausea, esophageal-related events, and discontinuation due to AE. A Bayesian-based network meta-analysis was completed to allow for indirect comparisons. Results were reported as the probability that a specific drug had the highest number of events.

Results

We identified 50 studies: 32 alendronate, 12 risedronate, 5 etidronate, and 7 zoledronic acid. Zoledronic acid had the highest probability of having the highest number of any GI AE (91 %) and nausea (70 %). Etidronate (70 %) and zoledronic acid (28 %) had the highest probability of having the greatest attrition due to AE. Etidronate had the highest probability (56 %) of having the greatest number of upper GI symptoms among oral bisphosphonates.

Conclusion

Zoledronic acid had the highest probability of causing the greatest number of GI AE, possibly related to nausea. These results question the assumption that annual zoledronic acid will translate into better adherence. Little difference was found between alendronate and risedronate for serious AE. More research into real-world implications of the comparative safety of bisphosphonates is needed.     

The effects of anxiety sensitivity,pain hypervigilance,and pain catastrophizing on quality of life outcomes of patients with chronic pain: a preliminary,cross-sectional analysis

Purpose

In the fear-avoidance model (FAM) of chronic pain, pain-related fear is one of the most prominent predictors of negative adjustment outcomes. While existing data point to the effects of anxiety sensitivity, pain hypervigilance, and pain catastrophizing on pain-related fear, the nature of their multivariate relationships remains unclear. This study explored the possible mediating role of pain hypervigilance in the relationship of anxiety sensitivity and pain catastrophizing with pain-related fear, and their effects on quality of life (QoL) outcomes within the FAM framework.

Methods

A sample of 401 Chinese patients with chronic musculoskeletal pain completed the standardized measures assessing the FAM components and QoL. Structural equation modeling (SEM) was used to evaluate six hypothesized models.

Results

Results of SEM showed adequate data-model fit [comparative fit indexes (CFIs) ranging from 0.92 to 0.94] on models which specified pain hypervigilance as mediator of anxiety sensitivity and pain catastrophizing with pain-related fear on two QoL outcomes (QoL-Physical and QoL-Mental). Results consistent with net suppression effects of pain catastrophizing on anxiety sensitivity were found in SEM when both anxiety sensitivity and pain catastrophizing were included in the same full model to predict QoL-Physical (CFI = 0.95; Sobel z = 8.06, p < 0.001) and QoL-Mental (CFI = 0.93; Sobel z = 8.31, p < 0.001).

Conclusions

These cross-sectional analyses gave results consistent with pain hypervigilance, mediating the relationship of pain catastrophic cognition and anxiety sensitivity with pain-related fear. The net suppression effects of pain catastrophizing point to anxiety sensitivity, enhancing the effect of pain catastrophic cognition on pain hypervigilance. These findings elucidate how the interdependence of dispositional factors might influence pain adjustment and functioning.     

Optimization of GPR40 Agonists for Type 2 Diabetes

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Clinical services for obstructive sleep apnea patients in pharmacies: the Australian experience

Background In Australia, certain pharmacies have undertaken a role in the management of the chronic sleep disorder, obstructive sleep apnea. The perspectives of pharmacy staff involved in this niche clinical service have never been formally collated on a national scale. The experiences of Australian pharmacies could provide a template for pharmacies in other health systems to adopt similar roles. Objective To provide an overview of the perspectives of pharmacy staff involved in Continuous Positive Airway Pressure (CPAP) and sleep apnea-related services. Specifically, to describe clinical and structural elements, explore benefits and barriers, investigate viability, and gauge perspectives on future directions. Setting Australian community pharmacies involved in CPAP and sleep apnea-related services. Method Cross-sectional mail survey. A questionnaire designed to meet the study objectives was developed by the researchers and mailed to all pharmacies in Australia providing CPAP services during the period of study recruitment. Pharmacies were identified through the distributor lists of the major CPAP manufacturers and a comprehensive Internet search. Non-responders were contacted in two subsequent recruitment rounds. Main outcome measure Self-reported sleep apnea service specifics. Results A response rate of 55 % was achieved (n = 106 questionnaires valid for data entry). Benefits of providing a CPAP service included meeting patient and community needs, and professional satisfaction. Barriers included the cost of CPAP equipment to patients and lack of time. A majority of pharmacies (71 %) reported the service was financially viable despite most (63 %) not charging a ‘fee for service.’ Respondents expressed the view that CPAP provision should remain a specialist area of practice within the pharmacy profession. Key areas identified for improvement within the service were: (1) Staff training and knowledge (2) Promotion of the service and increasing public awareness (3) Infrastructure and expansion (4) Inter-professional collaboration and communication (5) Patient follow-up. Conclusion The provision of CPAP and sleep apnea-related services can be a viable and rewarding experience for pharmacists. The role may need to remain a specialised area for those willing to invest significantly in the service—in time, staff, resources and finances.     

Crosstalk between circadian rhythms and the microbiota

Circadian rhythms influence daily molecular oscillations in gene/protein expression and aspects of biology and physiology, including behaviour, body temperature and sleep–wake cycles. These circadian rhythms have been associated with a number of metabolic, immune and microbial changes that correlate with health and susceptibility to disease, including infection. While light is the main inducer of circadian rhythms, other factors, including the microbiota, can have important effects on peripheral rhythms. The microbiota have been of significant interest to many investigators over the past decade, with the development of molecular techniques to identify large numbers of species and their function. These studies have shown microbial associations with disease susceptibility, and some of these have demonstrated that alterations in microbiota cause disease. Microbial circadian oscillations impact host metabolism and immunity directly and indirectly. Interestingly, microbial oscillations also regulate host circadian rhythms, and the host circadian rhythms in turn modulate microbial composition. Thus, it is of considerable interest and importance to understand the crosstalk between circadian rhythms and microbiota and especially the microbial influences on the host. In this review, we aim to discuss the role of circadian microbial oscillations and how they influence host immunity. In addition, we discuss how host circadian rhythms can also modulate microbial rhythms. We also discuss potential connections between microbes and circadian rhythms and how these may be used therapeutically to maximize clinical success.     

Efficient Polymer Solar Cells Based on New Random Copolymers with Porphyrin‐Incorporated Side Chains

Two new wide bandgap block copolymers (PL1 and PL2) with porphyrin‐incorporated side chains are designed and used as electron donors for solution‐processed bulk heterojunction polymer solar cells. The photophysical, electrochemical, and photovoltaic properties, charge transport mobility and film morphology of these two block copolymers are investigated. Detailed investigations reveal that the different alkyl groups and electron‐withdrawing substituents on the porphyrin pendant units have significant influence on the polymer solubility, absorption energy level, band gap, and charge separation in the bulk‐heterojunction thin films, and thus the overall photovoltaic performances. Organic photovoltaic devices derived from these copolymers and ([6,6]‐phenyl‐C₇₁‐butyric acid methyl ester) (PC₇₁BM) acceptor show the best power conversion efficiencies of 5.83% and 7.14%, respectively. These results show that the inclusion of a certain proportion of side chain porphyrin group as a pendant in the traditional donor‐acceptor (D‐A) type polymer can broaden the molecular absorption range and become a full‐color absorbing molecule. The size of the porphyrin pendant also has an obvious effect on the properties of the molecule.