Should an Interval Appendicectomy Be Performed by a Minimally Invasive Gynaecologist?

Objective: We aimed to explore the abnormal pathology findings in appendix specimens removed based on intraoperative abnormal appearance during elective surgery for benign gynaecological conditions by a minimally invasive gynaecologist, as well as the associated complication rate.

Materials And Methods: This retrospective cohort study was conducted in a tertiary referral surgical centre for benign gynaecological conditions between the years 2004-2023. It included patients who underwent appendicectomy by a trained minimally invasive gynaecologist based on observations during surgery for benign gynaecological conditions.

Intrafascial Colpotomy, Edge-to-Edge Closure, and Peritoneal Graft Technique for Minimizing Mesh Erosion in Concurrent Robotic Hysterectomy and Sacrocolpopexy.

Introduction And Hypothesis: Sacrocolpopexy (SCP) is a recognized treatment for apical pelvic organ prolapse (POP). However, mesh erosion remains a concern, particularly when performed with concomitant hysterectomy. This video presents data on one case of a modified technique aimed at potentially minimizing mesh erosion in robotic SCP.

Implementation and outcomes in benign gynecological surgery with HUGO™ RAS system 12 months initial experience.

We share our experience with the Hugo™ Robotic-Assisted Surgery system in benign gynecological surgeries. We retrospectively analyzed patients who underwent elective robotic surgeries for benign gynecological conditions at our surgical center from February 2023 to February 2024. Data collected included patient demographics, surgery indications, and outcomes.

The Versius Variation: A Novel Technique for Robotic Training.

Objective: To describe a novel technique, the "Versius variation," that enables trainee surgeons to actively participate in robotic surgery by controlling the camera and assistant arm at the robotic console while the primary surgeon performs a traditional laparoscopic operation.

Design: This is a descriptive study of a hybrid Laparo-robotic technique that integrates robotic training into conventional laparoscopic surgery.

Setting: The study was conducted at the Sydney Women's Endosurgery Centre (SWEC).

Nerve-sparing surgery in deep endometriosis: Has its time come?

Nerve-sparing (NS) surgery was first introduced for the treatment of deep endometriosis (DE) 20 years ago, drawing on established neuroanatomy and success from oncological applications. It aims to identify and preserve autonomic nerve fibres, reduce iatrogenic nerve injury, and minimize postoperative visceral dysfunction, without compromising the therapeutic effectiveness against endometriosis. The evolution of NS surgical techniques over the past two decades has been supported by an expanding body of literature on anatomical details, dissection techniques, and functional outcomes.

A cysteine-specific solubilizing tag strategy enables efficient chemical protein synthesis of difficult targets.

We developed a new cysteine-specific solubilizing tag strategy a cysteine-conjugated succinimide. This solubilizing tag remains stable under common native chemical ligation conditions and can be efficiently removed with palladium-based catalysts. Utilizing this approach, we synthesized two proteins containing notably difficult peptide segments: interleukin-2 (IL-2) and insulin.

Omniligase-1-Mediated Phage-Peptide Library Modification and Insulin Engineering.

Chemical and enzymatic modifications of peptide-displayed libraries have been successfully employed to expand the phage display library. However, the requirement of specific epitopes and scaffolds has limited the scope of protein engineering using phage display. In this study, we present a novel approach utilizing omniligase-1-mediated selective and specific ligation on the phage pIII protein, offering a high conversion rate and compatibility with commercially available phage libraries.

Treatment of rectosigmoid endometriosis by laparoscopic reverse submucosal dissection (LRSD): The Sydney partial thickness discoid excision technique.

Background: Laparoscopic reverse submucosal dissection (LRSD) is a standardised surgical technique for removal of rectosigmoid endometriosis which optimises the anatomical dissection plane for excision of endometriotic nodules.

Aim: This cohort study assesses the outcomes of the first cohort of women treated by LRSD, for deeply infiltrating rectosigmoid endometriosis.

Materials And Methods: Primary outcomes assessed were complication rate as defined by the Clavien-Dindo system, and completion of the planned LRSD.

Serine-mediated hydrazone ligation displaying insulin-like peptides on M13 phage pIII.

Phage display has emerged as a tool for the discovery of therapeutic antibodies and proteins. However, the effective display and engineering of structurally complex proteins, such as insulin, pose significant challenges due to the sequence of insulin, which is composed of two peptide chains linked by three disulfide bonds. In this study, we developed a new approach for the display of insulin-like peptides on M13 phage pIII, employing N-terminal serine-mediated hydrazone ligation.

Supramolecular approaches for insulin stabilization without prolonged duration of action.

Aggregation represents a significant challenge for the long-term formulation stability of insulin therapeutics. The supramolecular PEGylation of insulin with conjugates of cucurbit[7]uril and polyethylene glycol (CB[7]‒PEG) has been shown to stabilize insulin formulations by reducing aggregation propensity. Yet prolonged duration of action, arising from sustained complex formation in the subcutaneous depot, limits the application scope for meal-time insulin uses and could increase hypoglycemic risk several hours after a meal.

Antagonistic Insulin Derivative Suppresses Insulin-Induced Hypoglycemia.

Insulin derivatives provide new functions that are distinctive from native insulin. We investigated insulin modifications on the C-terminal A chain with insulin receptor (IR) peptide binders and presented a full and potent IR antagonist. We prepared insulin precursors featuring a sortase A (SrtA) recognition sequence, LPETGG, at the C-terminal A chain and used a SrtA-mediated ligation method to synthesize insulin derivatives.

Supramolecular Protein Stabilization with Zwitterionic Polypeptide-Cucurbit[7]uril Conjugates.

Protein aggregation is an obstacle for the development of new biopharmaceuticals, presenting challenges in shipping and storage of vital therapies. Though a variety of materials and methods have been explored, the need remains for a simple material that is biodegradable, nontoxic, and highly efficient at stabilizing protein therapeutics. In this work, we investigated zwitterionic polypeptides prepared using a rapid and scalable polymerization technique and conjugated to a supramolecular macrocycle host, cucurbit[7]uril, for the ability to inhibit aggregation of model protein therapeutics insulin and calcitonin.

End-to-End Approach to Surfactant Selection, Risk Mitigation, and Control Strategies for Protein-Based Therapeutics.

A survey performed by the AAPS Drug Product Handling community revealed a general, mostly consensus, approach to the strategy for the selection of surfactant type and level for biopharmaceutical products. Discussing and building on the survey results, this article describes the common approach for surfactant selection and control strategy for protein-based therapeutics and focuses on key studies, common issues, mitigations, and rationale. Where relevant, each section is prefaced by survey responses from the 22 anonymized respondents.

Surface-Induced Protein Aggregation and Particle Formation in Biologics: Current Understanding of Mechanisms, Detection and Mitigation Strategies.

Protein stability against aggregation is a major quality concern for the production of safe and effective biopharmaceuticals. Amongst the different drivers of protein aggregation, increasing evidence indicates that interactions between proteins and interfaces represent a major risk factor for the formation of protein aggregates in aqueous solutions. Potentially harmful surfaces relevant to biologics manufacturing and storage include air-water and silicone oil-water interfaces as well as materials from different processing units, storage containers, and delivery devices.

Improved Handling of Peptide Segments Using Side Chain-Based "Helping Hand" Solubilizing Tools.

Maintaining high, or even sufficient, solubility of every peptide segment in chemical protein synthesis (CPS) remains a critical challenge; insolubility of just a single peptide segment can thwart a total synthesis venture. Multiple approaches have been used to address this challenge, most commonly by employing a chemical tool to temporarily improve peptide solubility. In this chapter, we discuss chemical tools for introducing semipermanent solubilizing sequences (termed helping hands) at the side chains of Lys and Glu residues.

Modifying insulin to improve performance.

A platform to enable precise modifications of insulin could improve drug functionality.

Synthesis and Characterization of Phenylboronic Acid-Modified Insulin With Glucose-Dependent Solubility.

Glucose-responsive insulin represents a promising approach to regulate blood glucose levels. We previously showed that attaching two fluorophenylboronic acid (FPBA) residues to the C-terminal B chain of insulin glargine led to glucose-dependent solubility. Herein, we demonstrated that relocating FPBA from B chain to A chain increased the baseline solubility without affecting its potency.

Symmetric and asymmetric receptor conformation continuum induced by a new insulin.

Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes and biochemical properties. Here, we report an active humanized cone snail venom insulin with an elongated A chain and a truncated B chain, and use cryo-electron microscopy (cryo-EM) and protein engineering to elucidate its interactions with the human insulin receptor (IR) ectodomain. We reveal how an extended A chain can compensate for deletion of B-chain residues, which are essential for activity of human insulin but also compromise therapeutic utility by delaying dissolution from the site of subcutaneous injection.

Nucleation in Protein Aggregation in Biotherapeutic Development: A look into the Heart of the Event.

In spite of extensive research, protein aggregation still remains one of the most difficult phenomena to be understood in the field of biologics research and development. Protein aggregation is a complex process which results in the formation of a variety of supramolecular protein structures. Nucleation is the core step that initiates the cascade of molecular events leading to the formation of protein aggregates.

Stress Factors in Primary Packaging, Transportation and Handling of Protein Drug Products and Their Impact on Product Quality.

Protein-based biologic drugs encounter a variety of stress factors during drug substance (DS) and drug product (DP) manufacturing, and the subsequent steps that result in clinical administration by the end user. This article is the third in a series of commentaries on these stress factors and their effects on biotherapeutics. It focuses on assessing the potential negative impact from primary packaging, transportation, and handling on the quality of the DP.