Comparing proficiency of obstetrics and gynaecology trainees with general surgery trainees using simulated laparoscopic tasks in Health Education England, North-West: a prospective observational study.

BACKGROUND: Training programmes for obstetrics and gynaecology (O&G) and general surgery (GS) vary significantly, but both require proficiency in laparoscopic skills. We sought to determine performance in each specialty. DESIGN: Prospective, observational study. SETTING: Health Education England North-West, UK. PARTICIPANTS: 47 surgical trainees (24 O&G and 23 GS) were subdivided into four groups: 11 junior O&G, 13 senior O&G, 11 junior GS and 12 senior GS trainees. OBJECTIVES: Trainees were tested on four simulated laparoscopic tasks: laparoscopic camera navigation (LCN), hand-eye coordination (HEC), bimanual coordination (BMC) and suturing with intracorporeal knot tying (suturing). RESULTS: O&G trainees completed LCN (p<0.001), HEC (p<0.001) and BMC (p<0.001) significantly slower than GS trainees. Furthermore, O&G found fewer number of targets in LCN (p=0.001) and dropped a greater number of pins than the GS trainees in BMC (p=0.04). In all three tasks, there were significant differences between O&G and GS trainees but no difference between the junior and senior groups within each specialty. Performance in suturing also varied by specialty; senior O&G trainees scored significantly lower than senior GS trainees (O&G 11.4±4.4 vs GS 16.8±2.1, p=0.03). Whilst suturing scores improved with seniority among O&G trainees, there was no difference between the junior and senior GS trainees (senior O&G 11.4±4.4 vs junior O&G 3.6±2.1, p=0.004). DISCUSSION: GS trainees performed better than O&G trainees in core laparoscopic skills, and the structure of O&G training may require modification. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05116332).

Surgical stress: the muscle and cognitive demands of robotic and laparoscopic surgery.

Introduction: Surgeons are among the most at-risk professionals for work-related musculoskeletal decline and experience high mental demands. This study examined the electromyographic (EMG) and electroencephalographic (EEG) activities of surgeons during surgery. Methods: Surgeons who performed live laparoscopic (LS) and robotic (RS) surgeries underwent EMG and EEG measurements. Wireless EMG was used to measure muscle activation in four muscle groups bilaterally (biceps brachii, deltoid, upper trapezius, and latissimus dorsi), and an 8-channel wireless EEG device was used to measure cognitive demand. EMG and EEG recordings were completed simultaneously during (i) noncritical bowel dissection, (ii) critical vessel dissection, and (iii) dissection after vessel control. Robust ANOVA was used to compare the %MVCRMS and alpha power between LS and RS. Results: Thirteen male surgeons performed 26 laparoscopic surgeries (LS) and 28 robotic surgeries (RS). Muscle activation was significantly higher in the right deltoid (p = 0.006), upper trapezius (left, p = 0.041; right, p = 0.032), and latissimus dorsi (left, p = 0.003; right, p = 0.014) muscles in the LS group. There was greater muscle activation in the right biceps than in the left biceps in both surgical modalities (both p = 0.0001). There was a significant effect of the time of surgery on the EEG activity (p <0.0001). A significantly greater cognitive demand was observed in the RS than in the LS with alpha, beta, theta, delta, and gamma (p = 0.002 - p <0.0001). Conclusion: These data suggest greater muscle demands in laparoscopic surgery, but greater cognitive demands in robotic surgery.

Should All Minimal Access Surgery Be Robot-Assisted? A Systematic Review into the Musculoskeletal and Cognitive Demands of Laparoscopic and Robot-Assisted Laparoscopic Surgery.

BACKGROUND: Surgeons are among the most at risk of work-related musculoskeletal health decline because of the physical demands of surgery, which is also associated with cognitive fatigue. Minimally invasive surgery offers excellent benefits to patients but the impact of robotic or laparoscopic surgery on surgeon well-being is less well understood. This work examined the musculoskeletal and cognitive demands of robot-assisted versus standard laparoscopic surgery. METHODS: Medline, Embase and Cochrane databases were systematically searched for 'Muscle strain' AND 'musculoskeletal fatigue' AND 'occupational diseases' OR 'cognitive fatigue' AND 'mental fatigue' OR 'standard laparoscopic surgery' AND 'robot-assisted laparoscopic surgery'. Primary outcomes measured were electromyographic (EMG) activity for musculoskeletal fatigue and questionnaires (NASA-TLX, SMEQ, or Borg CR-10) for cognitive fatigue. A systematic review was conducted in accordance with the Synthesis Without Meta-analysis (SWiM) Guidelines. The study was preregistered on Prospero ID: CRD42020184881. RESULTS: Two hundred and ninety-eight original titles were identified. Ten studies that were all observational studies were included in the systematic review. EMG activity was consistently lower in robotic than in laparoscopic surgery in the erector spinae and flexor digitorum muscles but higher in the trapezius muscle. This was associated with significantly lower cognitive load in robotic than laparoscopic surgery in 7 of 10 studies. CONCLUSIONS: Evidence suggests a reduction in musculoskeletal demands during robotic surgery in muscles excluding the trapezius, and this is associated with most studies reporting a reduced cognitive load. Robotic surgery appears to have less negative cognitive and musculoskeletal impact on surgeons compared to laparoscopic surgery.

The Impact of Prehabilitation on Patient Outcomes in Hepatobiliary, Colorectal, and Upper Gastrointestinal Cancer Surgery: A PRISMA-Accordant Meta-analysis.

OBJECTIVE: To determine the impact of prehabilitation on hospital length of stay, functional capacity, complications, and mortality after surgery in patients with hepatobiliary, colorectal, and upper gastrointestinal cancer. BACKGROUND: "Prehabilitation" encompasses exercise, nutrition, and psychosocial interventions to optimize health before surgery. The benefits of prehabilitation are ill-defined. METHODS: Medline, Embase and Cochrane Databases were searched systematically for the terms "prehabilitation AND exercise," "perioperative care AND cancer surgery," and "colorectal AND hepatobiliary AND hepatopancreatobiliary AND esophagogastric AND recovery AND outcomes." Primary outcomes analyzed were hospital length of stay, functional capacity, significant postoperative complications (Clavien Dindo ≥ III), and mortality. A meta-analysis was conducted on the effect of all-modality prehabilitation for patients with colorectal, hepatopancreatobiliary and upper gastrointestinal cancer surgery using the raw mean difference, risk difference, and a random-effects model. RESULTS: Three hundred and seventy seven original titles were identified. Fifteen studies (randomized controlled trials; n = 9 and uncontrolled trials; n = 6) were included in the meta-analysis. Prehabilitation reduced hospital length of stay by 1.78 days versus standard care (95% CI: -3.36, -0.20, P < 0.05). There was no significant difference in functional capacity with prehabilitation determined using the 6-minute walk test (P = 0.816) and no significant reduction in postoperative complications (P = 0.378) or mortality rates (P = 0.114). CONCLUSIONS: Prehabilitation was associated with reduced hospital length of stay but had no effect on functional capacity, postoperative complications, or mortality rates. Thus, prehabilitation should be recommended to accelerate recovery from cancer surgery, demonstrated by reduced hospital length of stay.

Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans.

Sarcopenia, the age-related decline of muscle, is a significant and growing public health burden. C. elegans, a model organism for investigating the mechanisms of ageing, also displays sarcopenia, but the underlying mechanism(s) remain elusive. Here, we use C. elegans natural scaling of lifespan in response to temperature to examine the relationship between mitochondrial content, mitochondrial function, and sarcopenia. Mitochondrial content and maximal mitochondrial ATP production rates (MAPR) display an inverse relationship to lifespan, while onset of MAPR decline displays a direct relationship. Muscle mitochondrial structure, sarcomere structure, and movement decline also display a direct relationship with longevity. Notably, the decline in mitochondrial network structure occurs earlier than sarcomere decline, and correlates more strongly with loss of movement, and scales with lifespan. These results suggest that mitochondrial function is critical in the ageing process and more robustly explains the onset and progression of sarcopenia than loss of sarcomere structure.

Degenerin channel activation causes caspase-mediated protein degradation and mitochondrial dysfunction in adult C. elegans muscle.

BACKGROUND: Declines in skeletal muscle structure and function are found in various clinical populations, but the intramuscular proteolytic pathways that govern declines in these individuals remain relatively poorly understood. The nematode Caenorhabditis elegans has been developed into a model for identifying and understanding these pathways. Recently, it was reported that UNC-105/degenerin channel activation produced muscle protein degradation via an unknown mechanism. METHODS: Generation of transgenic and double mutant C. elegans, RNAi, and drug treatments were utilized to assess molecular events governing protein degradation. Western blots were used to measure protein content. Cationic dyes and adenosine triphosphate (ATP) production assays were utilized to measure mitochondrial function. RESULTS: unc-105 gain-of-function mutants display aberrant muscle protein degradation and a movement defect; both are reduced in intragenic revertants and in let-2 mutants that gate the hyperactive UNC-105 channel. Degradation is not suppressed by interventions suppressing proteasome-mediated, autophagy-mediated, or calpain-mediated degradation nor by suppressors of degenerin-induced neurodegeneration. Protein degradation, but not the movement defect, is decreased by treatment with caspase inhibitors or RNAi against ced-3 or ced-4. Adult unc-105 muscles display a time-dependent fragmentation of the mitochondrial reticulum that is associated with impaired mitochondrial membrane potential and that correlates with decreased rates of maximal ATP production. Reduced levels of CED-4, which is sufficient to activate CED-3 in vitro, are observed in unc-105 mitochondrial isolations. CONCLUSIONS: Constitutive cationic influx into muscle appears to cause caspase degradation of cytosolic proteins as the result of mitochondrial dysfunction, which may be relevant to ageing and sarcopenia.

Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development.

Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1 gene that encodes the only glutathione reductase protein in this model organism. By using green fluorescent protein reporters we demonstrate that gsr-1 produces two GSR-1 isoforms, one located in the cytoplasm and one in the mitochondria. gsr-1 loss of function mutants display a fully penetrant embryonic lethal phenotype characterized by a progressive and robust cell division delay accompanied by an aberrant distribution of interphasic chromatin in the periphery of the cell nucleus. Maternally expressed GSR-1 is sufficient to support embryonic development but these animals are short-lived, sensitized to chemical stress, have increased mitochondrial fragmentation and lower mitochondrial DNA content. Furthermore, the embryonic lethality of gsr-1 worms is prevented by restoring GSR-1 activity in the cytoplasm but not in mitochondria. Given the fact that the thioredoxin redox systems are dispensable in C. elegans, our data support a prominent role of the glutathione reductase/glutathione pathway in maintaining redox homeostasis in the nematode.

The integrin-adhesome is required to maintain muscle structure, mitochondrial ATP production, and movement forces in Caenorhabditis elegans.

The integrin-adhesome network, which contains >150 proteins, is mechano-transducing and located at discreet positions along the cell-cell and cell-extracellular matrix interface. A small subset of the integrin-adhesome is known to maintain normal muscle morphology. However, the importance of the entire adhesome for muscle structure and function is unknown. We used RNA interference to knock down 113 putative Caenorhabditis elegans homologs constituting most of the mammalian adhesome and 48 proteins known to localize to attachment sites in C. elegans muscle. In both cases, we found >90% of components were required for normal muscle mitochondrial structure and/or proteostasis vs. empty vector controls. Approximately half of these, mainly proteins that physically interact with each other, were also required for normal sarcomere and/or adhesome structure. Next we confirmed that the dystrophy observed in adhesome mutants associates with impaired maximal mitochondrial ATP production (P < 0.01), as well as reduced probability distribution of muscle movement forces compared with wild-type animals. Our results show that the integrin-adhesome network as a whole is required for maintaining both muscle structure and function and extend the current understanding of the full complexities of the functional adhesome in vivo.

Protective role of DNJ-27/ERdj5 in Caenorhabditis elegans models of human neurodegenerative diseases.

AIMS: Cells have developed quality control systems for protection against proteotoxicity. Misfolded and aggregation-prone proteins, which are behind the initiation and progression of many neurodegenerative diseases (ND), are known to challenge the proteostasis network of the cells. We aimed to explore the role of DNJ-27/ERdj5, an endoplasmic reticulum (ER)-resident thioredoxin protein required as a disulfide reductase for the degradation of misfolded proteins, in well-established Caenorhabditis elegans models of Alzheimer, Parkinson and Huntington diseases. RESULTS: We demonstrate that DNJ-27 is an ER luminal protein and that its expression is induced upon ER stress via IRE-1/XBP-1. When dnj-27 expression is downregulated by RNA interference we find an increase in the aggregation and associated pathological phenotypes (paralysis and motility impairment) caused by human ß-amyloid peptide (Aß), α-synuclein (α-syn) and polyglutamine (polyQ) proteins. In turn, DNJ-27 overexpression ameliorates these deleterious phenotypes. Surprisingly, despite being an ER-resident protein, we show that dnj-27 downregulation alters cytoplasmic protein homeostasis and causes mitochondrial fragmentation. We further demonstrate that DNJ-27 overexpression substantially protects against the mitochondrial fragmentation caused by human Aß and α-syn peptides in these worm models. INNOVATION: We identify C. elegans dnj-27 as a novel protective gene for the toxicity associated with the expression of human Aß, α-syn and polyQ proteins, implying a protective role of ERdj5 in Alzheimer, Parkinson and Huntington diseases. CONCLUSION: Our data support a scenario where the levels of DNJ-27/ERdj5 in the ER impact cytoplasmic protein homeostasis and the integrity of the mitochondrial network which might underlie its protective effects in models of proteotoxicity associated to human ND.