Metformin (
) is a synthetic derivative of guanidine, isolated from the extracts of
, a plant with a prominent antidiabetic effect. Since its discovery more than 50 years ago, metformin represents a ...worldwide milestone in treatment of patients with type 2 diabetes (T2D). Recent evidence in humans indicates novel pleiotropic actions of metformin which span from its consolidated role in T2D management up to various regulatory properties, including cardio- and nephro-protection, as well as antiproliferative, antifibrotic, and antioxidant effects. These findings, together with ground-breaking studies demonstrating its ability to prolong healthspan and lifespan in mice, provided the basis for defining metformin as a potential
molecule. Moreover, emerging
and
evidence support the novel hypothesis that metformin can exhibit immune-modulatory features. Studies suggest that metformin interferes with key immunopathological mechanisms involved in systemic autoimmune diseases, such as the T helper 17/regulatory T cell balance, germinal centers formation, autoantibodies production, macrophage polarization, cytokine synthesis, neutrophil extracellular traps release, and bone or extracellular matrix remodeling. These effects may represent a powerful contributor to antiaging and anticancer properties exerted by metformin and, from another standpoint, may open the way to assess whether metformin can be a candidate molecule for clinical trials involving patients with immune-mediated diseases. In this article, we will review the available preclinical and clinical evidence regarding the effect of metformin on individual cells of the immune system, with emphasis on immunological mechanisms related to the development and maintenance of autoimmunity and its potential relevance in treatment of autoimmune diseases.
Background
Although several non-randomized studies comparing robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) recently demonstrated that the two operative techniques could ...be equivalent in terms of safety outcomes and short-term oncologic efficacy, no definitive answer has arrived yet to the question as to whether robotic assistance can contribute to reducing the high rate of postoperative morbidity.
Methods
Systematic literature search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases. Prospective and retrospective studies comparing RPD and OPD as surgical treatment for periampullary benign and malignant lesions were included in the systematic review and meta-analysis with no limits of language or year of publication.
Results
18 non-randomized studies were included for quantitative synthesis with 13,639 patients allocated to RPD (
n
= 1593) or OPD (
n
= 12,046). RPD and OPD showed equivalent results in terms of mortality (3.3% vs 2.8%;
P
= 0.84), morbidity (64.4% vs 68.1%;
P
= 0.12), pancreatic fistula (17.9% vs 15.9%;
P
= 0.81), delayed gastric emptying (16.8% vs 16.1%;
P
= 0.98), hemorrhage (11% vs 14.6%;
P
= 0.43), and bile leak (5.1% vs 3.5%;
P
= 0.35). Estimated intra-operative blood loss was significantly lower in the RPD group (352.1 ± 174.1 vs 588.4 ± 219.4;
P
= 0.0003), whereas operative time was significantly longer for RPD compared to OPD (461.1 ± 84 vs 384.2 ± 73.8;
P
= 0.0004). RPD and OPD showed equivalent results in terms of retrieved lymph nodes (19.1 ± 9.9 vs 17.3 ± 9.9;
P
= 0.22) and positive margin status (13.3% vs 16.1%;
P
= 0.32).
Conclusions
RPD is safe and feasible as surgical treatment for malignant or benign disease of the pancreatic head and the periampullary region. Equivalency in terms of surgical radicality including R0 curative resection and number of harvested lymph nodes between the two groups confirmed the reliability of RPD from an oncologic point of view.
From its beginning in December 2019, the coronavirus disease 2019 outbreak has spread globally from Wuhan and is now declared a pandemic by the World Health Organization. The sheer scale and severity ...of this pandemic is unprecedented in the modern era. Although primarily a respiratory tract infection transmitted by direct contact and droplets, during aerosol‐generating procedures, there is a possibility of airborne transmission. In addition, emerging evidence suggests possible fecal–oral spread of the virus. Clinical departments that perform endoscopy are faced with daunting challenges during this pandemic. To date, multiple position statements and guidelines have been issued by various professional organizations to recommend practices in endoscopic procedures. This article aims to summarize and discuss available evidence for these practices, to provide guidance for endoscopy to enhance patient safety, avoid nosocomial outbreaks, protect healthcare personnel, and ensure rational use of personal protective equipment. Responses adapted to national recommendations and local infection control guidelines and tailored to the availability of medical resources are imminently needed to fight the coronavirus disease 2019 pandemic.
The perioperative care of colorectal cancer (CRC) patients includes antibiotics. Although antibiotics do provide a certain protection against infections, they do not eliminate them completely, and ...they do carry risks of microbial resistance and disruption of the microbiome. Probiotics can maintain the microbiome's balance postoperatively by maintaining intestinal mucosal integrity and reducing bacterial translocation (BT). This review aims to assess the role of probiotics in the perioperative management of CRC patients. The outcomes were categorised into: postoperative infectious and non-infectious complications, BT rate analysis, and intestinal permeability assessment. Fifteen randomised controlled trials (RCTs) were included. There was a trend towards lower rates of postoperative infectious and non-infectious complications with probiotics versus placebo. Probiotics reduced BT, maintained intestinal mucosal permeability, and provided a better balance of beneficial to pathogenic microorganisms. Heterogeneity among RCTs was high. Factors that influence the effect of probiotics include the species used, using a combination vs. single species, the duration of administration, and the location of the bowel resection. Although this review provided evidence for how probiotics possibly operate and reported notable evidence that probiotics can lower rates of infections, heterogeneity was observed. In order to corroborate the findings, future RCTs should keep the aforementioned factors constant.
Purpose
Rectal cancer surgery presents challenges in achieving good oncological results and preserving functional outcomes. Different surgical approaches, including open, laparoscopic, robotic and ...transanal techniques, have been employed, but there is a lack of consensus on the optimal approach, particularly in terms of functional results. This study aims to assess bowel function and to compare outcomes of patients that had undergone surgery for mid-low rectal cancer across different surgical approaches.
Method
This is an international, multicentre, prospective cohort study. Inclusion criteria are patients diagnosed with rectal cancer below the peritoneal reflection, eligible for different surgical approaches for total mesorectal excision (TME). Data will be collected using validated questionnaires assessing bowel, sexual and urinary function, and quality of life (QOL). Secondary outcomes include short-term postoperative results. Data will be collected at baseline and 6, 12 and 24 months after index surgery or stoma reversal surgery.
Conclusion
This study will provide insights into the impact of different approaches for TME on bowel, sexual and urinary function, and overall QOL of patients undergoing rectal cancer surgery. The findings will provide important information to optimise the surgical strategy and to improve patient care in this population.
Trial registration
ClinicalTrials.gov, NCT04936581 (registered 23 June 2021).
Introduction
There has been a constant increase in the number of published surgical videos with preference for open-access sources, but the proportion of videos undergoing peer-review prior to ...publication has markedly decreased, raising questions over quality of the educational content presented. The aim of this study was the development and validation of a standard framework for the appraisal of surgical videos submitted for presentation and publication, the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool.
Methods
An international committee identified items for inclusion in the LAP-VEGaS video assessment tool and finalised the marking score utilising Delphi methodology. The tool was finally validated by anonymous evaluation of selected videos by a group of validators not involved in the tool development.
Results
9 items were included in the LAP-VEGaS video assessment tool, with every item scoring from 0 (item not presented in the video) to 2 (item extensively presented in the video), with a total marking score ranging from 0 to 18. The LAP-VEGaS video assessment tool resulted highly accurate in identifying and selecting videos for acceptance for conference presentation and publication, with high level of internal consistency and generalisability.
Conclusions
We propose that peer review in adherence to the LAP-VEGaS video assessment tool could enhance the overall quality of published video outputs.
Graphic Abstract
Purpose
Anal intraepithelial neoplasia (AIN) is the accepted precursor of anal squamous cell carcinoma (ASCC). There has long been a hypothesis that treating AIN may prevent ASCC. Many different ...treatment modalities have been suggested and studied. We conducted this systematic review to evaluate their efficacy and the evidence as to whether we can prevent ASCC by treating AIN.
Methods
MEDLINE and EMBASE were electronically searched using relevant search terms. All studies investigating the use of a single treatment for AIN that reported at least one end outcome such as partial or complete response to treatment, recurrence after treatment and/or ASCC diagnosis after treatment were included.
Results
Thirty studies were included in the systematic review investigating 10 treatment modalities: 5% imiquimod, 5-fluorouracil, cidofovir, trichloroacetic acid, electrocautery, surgical excision, infrared coagulation, radiofrequency ablation, photodynamic therapy and HPV vaccination. All treatment modalities demonstrated some initial regression of AIN after treatment; however, recurrence rates were high especially in HIV-positive patients. Many of the studies suffered from significant bias which prevented direct comparison.
Conclusions
Although the theory persists that by inducing the regression of AIN, we may be able to reduce the risk of ASCC, there was no clinical evidence within the literature advocating that treating AIN does prevent ASCC.
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