Biologic drugs hold immense promise for medical treatments, but their oral delivery remains a daunting challenge due to the harsh digestive environment and restricted gastrointestinal absorption. Here, inspired by the porcupinefish's ability to inflate itself and deploy its spines for defense, we proposed an intestinal microneedle robot designed to absorb intestinal fluids for rapid inflation and inject drug-loaded microneedles into the insensate intestinal wall for drug delivery. Upon reaching the equilibrium volume, the microneedle robot leverages rhythmic peristaltic contraction for mucosa penetration. The robot's barbed microneedles can then detach from its body during peristaltic relaxation and retain in the mucosa for drug releasing. Extensive in vivo experiments involving 14 minipigs confirmed the effectiveness of the intestinal peristalsis for microrobot actuation and demonstrated comparable insulin delivery efficacy to subcutaneous injection. The ingestible peristalsis-actuated microneedle robots may transform the oral administration of biologic drugs that primary relies on parenteral injection currently.

Cholecystectomy is the preferred option for symptomatic gallstones. Gallbladder-preserving cholecystolithotomy (GPC) is proposed to satisfy the specific surgical patients with high-risks, biliary deformity and suffered from concomitant gallstone and choledocholithiasis.

This review summarizes and compares the various GPC operations for cholelithiasis in some specific cases.

Transmural GPC mainly focuses on the gallstones, including endoscopic minimally invasive cholecystolithotomy (EMIC)-, natural orifice transluminal endoscopic surgery-, and endoscopic ultrasonography (EUS)-GPC. These GPC procedures potentially preserve gallbladder integrity and function after clearance of gallstones. Additionally, transmural GPC may overcome the disadvantages of cholecystectomy, including cosmetic considerations and postoperative complications. However, the stone recurrence rate of EMIC varies greatly from 4.92% to 40.0%, and based on limited studies, long-term adverse events due to gallbladder mucosa and natural lumen injury are largely unknown in transmural GPC. Thus, transmural GPC may be an alternative to cholecystectomy for surgical patients with high-risks and abnormal biliary anatomy. Endoscopic retrograde cholangiopancreatography-based transcystic GPC may be promising for some specific patients with concomitant gallstones and choledocholithiasis, since gallbladder integrity and function may be completely preserved as the gallbladder wall was hardly injured and the function of sphincter of Oddi was retained.

To compare adnexectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) versus laparoscopy.

Parallel group, 1:1 single-centre single-blinded randomised trial, designed as non-inferiority study with a margin of 15%.

Belgian teaching hospital.

Non-pregnant non-virgin women with an intact uterus and without obliteration of the pouch of Douglas scheduled to undergo removal of an adnexal mass assessed to be benign on ultrasound by IOTA criteria.

Randomisation to laparoscopy (control group) or vNOTES (experimental group). Stratification according to adnexal size. Blinding of participants and outcome assessors by sham incisions.

The primary outcome measure was adnexectomy by the allocated technique. Secondary outcomes included duration of surgery, pain scores and analgesics used, quality of life and adverse events.

We randomly assigned 67 participants (34 to the vNOTES group and 33 to the laparoscopy group). The primary end point was always reached in both groups: there were no conversions. We performed a sensitivity analysis for the primary outcome, assuming one conversion in the vNOTES group and no conversions in the laparoscopy group: the one-sided 95% upper limit for the differences in proportions of conversion was estimated as 13%, which is below the predefined non-inferiority margin of 15%. The secondary outcomes demonstrated a shorter duration of surgery, lower pain scores, lower total dose of analgesics and a trend for more adverse events in the vNOTES group.

vNOTES is non-inferior to laparoscopy for a successful adnexectomy without conversion. vNOTES allowed shorter operating times and less postoperative pain but there was a trend for more adverse events.

The first ever report of vaginal natural orifice transluminal endoscopic surgery (vNOTES) for benign gynaecological was reported in 2012. There has been an exponential uptake of the number of surgeons performing such procedures worldwide with no official guidance to ensure the safe implementation of this technique into gynaecological practice due its recency. The objective of this study is to report an international consensus-based statement to help guide a basis for adopting vNOTES into clinical practice.

The consensus-based statement was developed amongst 39 international experts using the Delphi methodology over three successive rounds. Consensus was pre-defined as an agreement of 80% or more by the experts. Consensus sought over eight key concepts pertaining to vNOTES including patient selection, perioperative management, surgical technique, instruments, anatomy, training, registries and trials and definition of the surgical technique. Recommendations from an expert anaesthetist and urogynaecologist were also sought to give a broader perspective with respect to the implementation of vNOTES.

Fifty nine international surgeons were invited to participate and 39 (66%) agreed to participate based on being involved in a minimum of 20 vNOTES procedures. They were from 13 countries across 5 continents (Europe, North America, South America, Australia and Asia). Participation was 100% on all three rounds. Overall, consensus was reached in 50 of the 56 questions (89%) with the remaining 6 questions where consensus was not reached pertaining to the domain of patient selection.

An international expert based vNOTES statement is presented here to help guide adoption of vNOTES based on the experience of early adopters. Consensus was achieved on most components of this consensus statement. Given the recency of this technique, until high-level evidence becomes available, this statement provides an appropriate guidance to the safe implementation of vNOTES into gynaecological practice.

Few researchers have investigated the use of multiple physiological enhancers combined with synthetic carriers to augment delivery of nutraceuticals. The current work describes the development of an oral delivery system termed a bioactive association platform (BAP) capable of delivering nutraceutical actives from a formulation framework specifically for enhancing the in vitro and in vivo performance of model vitamin, cholecalciferol (Vitamin D₃). Synthesis of a novel triple vitamin minitablet and an optimized bile salt/lipase alginate-glycerin film provided unique oral components for inclusion in a BAP capsule. Component validation and physicochemical characterizations included comparative ex vivo permeability, chemical structure mapping, thermodynamic analysis and magnetic resonance imaging. In vitro dissolution studies of the BAP produced an area under the dissolution curve (AUC) for cholecalciferol release that was 28% greater than a conventional comparator product. A total of 84.01% of cholecalciferol was released from the BAP within 3 h versus only 59% from a comparator. Ex vivo permeation studies revealed superior cholecalciferol membrane diffusion from the triple vitamin minitablet BAP component. In vivo performance showed a greater mean change from baseline cholecalciferol to peak plasma levels (C_max) from the BAP compared to the comparator (55.66 versus 46.05 ng/mL). Cholecalciferol bioavailability was improved in vivo with an AUC_0-inf from the BAP that was 3.2× greater than the conventional product. The BAP was also superior at improving and maintaining serum levels of the main metabolite, 25-hydroxyvitamin D₃, compared to the conventional system. In vitro and in vivo results thus confirmed improvements in cholecalciferol dissolution, membrane permeability and plasma drug levels. The study results position the BAP as an ideal oral vehicle for enhanced delivery of cholecalciferol.

NOTES is a technique in which an operation is performed within the body without a skin incision by using a natural body orifice to provide access. The principal challenge of transgastric NOTES procedures is still the feasibility and safety of access closure. Currently, there are very limited data regarding the closure of transgastric NOTES in humans, and the standard method and device for closure has not been defined. Herein, we evaluate the feasibility and safety of gastric closure after NOTES procedures in humans with the over-the-scope clip (OTSC).

Review of collected data of patients underwent transgastric NOTES in prospective clinical studies between April 2010 and March 2014 focused on the gastric closure with the OTSC.

A total of 43 patients underwent transgastric

36 patients with an acute appendicitis, six patients with a prophylactic bilateral salpingo-oophorectomy, and one patient with uterus myomatosus. In all 43 cases, the incision of the gastric wall and the endoscopic access to the abdominal cavity succeeded without any difficulty. After performing transgastric procedures, it was possible to close the access by OTSC in all cases. There were all in all three adverse events: one major (Clavien-Dindo Grade III) and two minor (Clavien-Dindo Grades I and II).

Even if we could show for the first time in more than 40 consecutive patients that there is a safe approach for closing the transgastric access, it is absolutely necessary that further investigation in clinical settings has to be done to establish clear indications and guidelines for the use of transgastric NOTES.