PPARß/δ directs the therapeutic potential of mesenchymal stem cells in arthritis.

OBJECTIVES: To define how peroxisome proliferator-activated receptor (PPAR) ß/δ expression level in mesenchymal stem cells (MSCs) could predict and direct both their immunosuppressive and therapeutic properties. PPARß/δ interacts with factors such as nuclear factor-kappa B (NF-κB) and regulates the expression of molecules including vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1. Since these molecules are critical for MSC function, we investigated the role of PPARß/δ on MSC immunosuppressive properties. METHODS: We either treated human MSCs (hMSCs) with the irreversible PPARß/δ antagonist (GSK3787) or derived MSCs from mice deficient for PPARß/δ (PPARß/δ-/- MSCs). We used the collagen-induced arthritis (CIA) as model of immune-mediated disorder and the MSC-immune cell coculture assays. RESULTS: Modulation of PPARß/δ expression in hMSCs either using GSK3787 or hMSCs from different origin reveals that MSC immunosuppressive potential is inversely correlated with Ppard expression. This was consistent with the higher capacity of PPARß/δ-/- MSCs to inhibit both the proliferation of T lymphocytes, in vitro, and arthritic development and progression in CIA compared with PPARß/δ+/+ MSCs. When primed with proinflammatory cytokines to exhibit an immunoregulatory phenotype, PPARß/δ-/- MSCs expressed a higher level of mediators of MSC immunosuppression including VCAM-1, ICAM-1 and nitric oxide (NO) than PPARß/δ+/+ MSCs. The enhanced NO2 production by PPARß/δ-/- MSCs was due to the increased retention of NF-κB p65 subunit on the κB elements of the inducible nitric oxide synthase promoter resulting from PPARß/δ silencing. CONCLUSIONS: Our study is the first to show that the inhibition or knockdown of PPARß/δ in MSCs primes their immunoregulatory functions. Thus, the regulation of PPARß/δ expression provides a new strategy to generate therapeutic MSCs with a stable regulatory phenotype.

Educational value of surgical videos on transabdominal pre-peritoneal hernia repair (TAPP) on YouTube.

PURPOSE: Transabdominal pre-peritoneal hernia repair (TAPP) is a worldwide performed surgery. Surgical videos about TAPP uploaded on the web, with YouTube being the most frequently used platform, may have an educational purpose, which, however, remains unexplored. This study aims to evaluate the 20 most viewed YouTube videos on TAPP through the examination of four experienced surgeons and assess their conformity to the guidelines on how to report laparoscopic surgery videos. METHODS: On April 1st 2019, we searched for the 20 most viewed videos on TAPP on YouTube. Selected videos were evaluated on their overall utility and quality according to the Global Operative Assessment of Laparoscopic Skills-Groin Hernia (GOALS-GH) and the Laparoscopic surgery Video Educational Guidelines (LAP-VEGaS). RESULTS: Image quality was poor for 13 videos (65%), good for 6 (30%) and in high definition for 1 (5%). Audio and written commentary were present in 55% of cases, while no video presented a detailed preoperative case description. Only 35% of the videos had a GOALS-GH score > 15, indicating good laparoscopic skills. Overall video conformity to the LAP-VEGaS guidelines was weak, with a median value of 12.5% (5.4-18.9%). Concordance between the examiners was acceptable for both the overall video quality (Cronbach's Alpha 0.685) and utility (0.732). CONCLUSIONS: The most viewed TAPP videos available on YouTube in 2019 are not conformed to the LAP-VEGaS guidelines. Their quality and utility as a surgical learning tool are questionable. It is of upmost importance to improve the overall quality of free-access surgical videos due to their potential educational value.

Adult appendicitis: Clinical practice guidelines from the French Society of Digestive Surgery and the Society of Abdominal and Digestive Imaging.

INTRODUCTION: The French Society of Digestive Surgery (SFCD) and the Society of Abdominal and Digestive Imaging (SIAD) have collaborated to propose recommendations for clinical practice in the management of adult appendicitis. METHODS: An analysis of the literature was carried out according to the methodology of the French National Authority for Health (HAS). A selection was performed from collected references and then a manual review of the references listed in the selected articles was made in search of additional relevant articles. The research was limited to articles whose language of publication was English or French. Articles focusing on the pediatric population were excluded. Based on the literature review, the working group proposed recommendations whenever possible. These recommendations were reviewed and approved by a committee of experts. RESULTS: Recommendations about appendicitis in adult patients were proposed with regard to clinical, laboratory and radiological diagnostic modalities, treatment strategy for uncomplicated and complicated appendicitis, surgical technique, and specificities in the case of macroscopically healthy appendix, terminal ileitis and appendicitis in the elderly and in pregnant women. CONCLUSION: These recommendations for clinical practice may be useful to the surgeon in optimizing the management of acute appendicitis in adults.

A Reappraisal of Outcome of Elective Surgery After Successful Non-Operative Management of an Intra-Abdominal Abscess Complicating Ileocolonic Crohn's Disease: A Subgroup Analysis of a Nationwide Prospective Cohort.

BACKGROUND AND AIMS: Few prospective data exist on outcomes of surgery in Crohn's disease [CD] complicated by an intra-abdominal abscess after resolution of this abscess by antibiotics optionally combined with drainage. METHODS: From 2013 to 2015, all patients undergoing elective surgery for CD after successful non-operative management of an intra-abdominal abscess [Abscess-CD group] were selected from a nationwide multicentre prospective cohort. Resolution of the abscess had to be computed tomography/magnetic resonance-proven prior to surgery. Abscess-CD group patients were 1:1 matched to uncomplicated CD [Non-Penetrating-CD group] using a propensity score. Postoperative results and long-term outcomes were compared between the two groups. RESULTS: Among 592 patients included in the registry, 63 [11%] fulfilled the inclusion criteria. The abscess measured 37 ±â€…20 mm and was primarily managed with antibiotics combined with drainage in 14 patients and nutritional support in 45 patients. At surgery, a residual fluid collection was found in 16 patients [25%]. Systemic steroids within 3 months before surgery [p = 0.013] and the absence of preoperative enteral support [p = 0.001] were identified as the two significant risk factors for the persistence of a fluid collection. After propensity score matching, there was no significant difference between the Abscess-CD and Non-Penetrating-CD groups in the rates of primary anastomosis [84% vs 90% respectively, p = 0.283], overall [28% vs 15% respectively, p = 0.077] and severe postoperative morbidity [7% vs 7% respectively, p = 1.000]. One-year recurrence rates for endoscopic recurrence were 41% in the Abscess-CD and 51% in the Non-Penetrating-CD group [p = 0.159]. CONCLUSIONS: Surgery after successful non-operative management of intra-abdominal abscess complicating CD provides good early and long-term outcomes.

Antibiotics alone as an alternative to appendectomy for uncomplicated acute appendicitis in adults: Changes in treatment modalities related to the COVID-19 health crisis.

The massive inflow of patients with COVID-19 requiring urgent care has overloaded hospitals in France and impacts the management of other patients. Deferring hospitalization and non-urgent surgeries has become a priority for surgeons today in order to relieve the health care system. It is obviously not simple to reduce emergency surgery without altering the quality of care or leading to a loss of chance for the patient. Acute appendicitis is a very specific situation and the prevalence of this disease leads us to reconsider this particular disease in the context of the COVID-19 crisis. Indeed, while the currently recommended treatment for uncomplicated acute appendicitis is surgical appendectomy, the non-surgical alternative of medical management by antibiotic therapy alone has been widely evaluated by high-quality studies in the literature. Insofar as the main limitation of exclusively medical treatment of uncomplicated acute appendicitis is the risk of recurrent appendicitis, this treatment option represents an alternative of choice to reduce the intra-hospital overload in this context of health crisis. The aim of this work is therefore to provide physicians and surgeons with a practical guide based on a review of the literature on the medical treatment of uncomplicated acute appendicitis in adults, to offer this alternative treatment to the right patients and under good conditions, especially when access to the operating room is limited or impossible.

[Antibiotics alone as an alternative to appendectomy for uncomplicated acute appendicitis in adults: Changes in treatment modalities related to the COVID-19 health crisis]. / Crise sanitaire liée au COVID-19 : modalités du traitement de l'appendicite aiguë non compliquée de l'adulte par antibiothérapie seule comme alternative à l'appendicectomie.

The massive inflow of patients with COVID-19 requiring urgent care has overloaded hospitals in France and impacts the management of other patients. Deferring hospitalization and non-urgent surgeries has become a priority for surgeons today in order to relieve the health care system. It is obviously not simple to reduce emergency surgery without altering the quality of care or leading to a loss of chance for the patient. Acute appendicitis is a very specific situation and the prevalence of this disease leads us to reconsider this particular disease in the context of the COVID-19 crisis. Indeed, while the currently recommended treatment for uncomplicated acute appendicitis is surgical appendectomy, the non-surgical alternative of medical management by antibiotic therapy alone has been widely evaluated by high-quality studies in the literature. Insofar as the main limitation of exclusively medical treatment of uncomplicated acute appendicitis is the risk of recurrent appendicitis, this treatment option represents an alternative of choice to reduce the intra-hospital overload in this context of health crisis. The aim of this work is therefore to provide physicians and surgeons with a practical guide based on a review of the literature on the medical treatment of uncomplicated acute appendicitis in adults, to offer this alternative treatment to the right patients and under good conditions, especially when access to the operating room is limited or impossible.

[Postoperative imaging of the pancreas and duodenum]. / Imagerie post-opératoire du pancréas et du duodénum.

Pancreatic surgery is a frequent therapeutic approach for benign and malignant conditions. CT has become the imaging method of reference to detect early postoperative complications and to detect recurrent disease during long-term follow-up. Knowledge of the normal postoperative anatomy is essential for accurate interpretation of CT scans. The purpose of this paper is to illustrate the normal and abnormal CT appearances of common surgical procedures involving the pancreas.

[Evidence-based ways of colorectal anastomotic complications prevention in the setting of digestive deep endometriosis resection: CNGOF-HAS Endometriosis Guidelines]. / Moyens de prévention des complications anastomotiques digestives dans la chirurgie de l'endométriose profonde, RPC Endométriose CNGOF-HAS.

Management of deep pelvic and digestive endometriosis can lead to colorectal resection and anastomosis. Colorectal anastomosis carries risks for dreaded infectious and functional morbidity. The aim of the study was to establish, regarding the published data, the role of the three most common used surgical techniques to prevent such complications: pelvic drainage, diverting stoma, epiplooplasty. Even if many studies and articles have focused on colorectal anastomotic leakage prevention in rectal cancer surgery data regarding this topic in the setting of endometriosis where lacking. Due to major differences between the two situations, patients, diseases the use of the conclusions from the literature have to be taken with caution. In 4 randomized controlled trials the usefulness of systematic postoperative pelvic drainage hasn't been demonstrated. As this practice is not systematically recommended in cancer surgery, its interest is not demonstrated after colorectal resection for endometriosis. There is a heavy existing literature supporting systematic diverting stoma creation after low colorectal anastomosis for rectal cancer. Keeping in mind the important differences between the two situations, the conclusions cannot be directly extrapolated. In endometriosis surgery after low rectal resection, stoma creation must be discussed and the patient must be informed and educated about this possibility. Even if widely used there is no data supporting the role of epiplooplasty in colorectal anastomotic complication prevention? The place for epiplooplasty in preventing rectovaginal fistula occurrence in case of concomitant resection hasn't been studied.

[Strategies and surgical management of endometriosis: CNGOF-HAS Endometriosis Guidelines]. / Synthèse des stratégies et prise en charge chirurgicale de l'endométriose, RPC Endométriose CNGOF-HAS.

The article presents French guidelines for surgical management of endometriosis. Surgical treatment is recommended for mild to moderate endometriosis, as it decreases pelvic painful complaints and increases the likelihood of postoperative conception in infertile patients (A). Surgery may be proposed in symptomatic patients with ovarian endometriomas which diameter exceeds 20mm. Cystectomy allows for better postoperative pregnancy rates when compared to ablation using bipolar current, as well as for lower recurrences rates when compared to ablation using bipolar current or CO2 laser. Ablation of ovarian endometriomas using bipolar current is not recommended (B). Surgery may be employed in patients with deep endometriosis infiltrating the colon and the rectum, with good impact on painful complaints and postoperative conception. In these patients, laparoscopic route increases the likelihood of postoperative spontaneous conception when compared to open route. When compared to conservative rectal procedures (shaving or disc excision), segmental colorectal resection increases the risk of postoperative stenosis, requiring additional endoscopic or surgical procedures. In large deep endometriosis infiltrating the rectum (>20mm length of bowel infiltration), conservative rectal procedures do not improve postoperative digestive function when compared to segmental resection. In patients with bowel anastomosis, placing anti-adhesion agents on contact with bowel suture is not recommended, due to higher risk of bowel fistula (C). Various other recommendations are proposed in the text, however, they are based on studies with low level of evidence.

[Management of endometriosis: CNGOF-HAS practice guidelines (short version)]. / Prise en charge de l'endométriose : recommandations pour la pratique clinique CNGOF-HAS (texte court).

First-line investigations to diagnose endometriosis are clinical examination and pelvic ultrasound. Second-line investigations include pelvic examination performed by a referent clinician, transvaginal ultrasound performed by a referent echographist, and pelvic MRI. It is recommended to treat endometriosis when it is symptomatic. First-line hormonal treatments recommended for the management of painful endometriosis are combined with hormonal contraceptives or levonorgestrel 52mg IUD. There is no evidence to recommend systematic preoperative hormonal therapy for the unique purpose of preventing the risk of surgical complications or facilitating surgery. After endometriosis surgery, combined hormonal contraceptives or levonorgestrel SIU 52mg are recommended as first-line therapy in the absence of desire of pregnancy. In case of initial treatment failure, recurrence, or multiple organ involvement by endometriosis, medico-surgical and multidisciplinary discussion is recommended. The laparoscopic approach is recommended for the surgical treatment of endometriosis. HRT may be offered in postmenopausal women operated for endometriosis. In case of infertility related to endometriosis, it is not recommended to prescribe anti-gonadotropic hormone therapy to increase the rate of spontaneous pregnancy, including postoperatively. The possibilities of fertility preservation should be discussed with the patient in case of surgery for ovarian endometrioma.

Management of endometriosis: CNGOF/HAS clinical practice guidelines - Short version.

First-line diagnostic investigations for endometriosis are physical examination and pelvic ultrasound. The second-line investigations are: targeted pelvic examination performed by an expert clinician, transvaginal ultrasound performed by an expert physician sonographer (radiologist or gynaecologist), and pelvic MRI. Management of endometriosis is recommended when the disease has a functional impact. Recommended first-line hormonal therapies for the management of endometriosis-related pain are combined hormonal contraceptives (CHCs) or the 52mg levonorgestrel-releasing intrauterine system (IUS). There is no evidence base on which to recommend systematic preoperative hormonal therapy solely to prevent surgical complications or facilitate surgery. After surgery for endometriosis, a CHC or 52mg levonorgestrel-releasing IUS is recommended as first-line treatment when pregnancy is not desired. In the event of failure of the initial treatment, recurrence, or multiorgan involvement, a multidisciplinary team meeting is recommended, involving physicians, surgeons and other professionals. A laparoscopic approach is recommended for surgical treatment of endometriosis. HRT can be offered to postmenopausal women who have undergone surgical treatment for endometriosis. Antigonadotrophic hormonal therapy is not recommended for patients with endometriosis and infertility to increase the chances of spontaneous pregnancy, including postoperatively. Fertility preservation options must be discussed with patients undergoing surgery for ovarian endometriomas.

["Designer baby" changed to French for "double hope baby"]. / Du "bébé médicament" au "bébé du double espoir".

Scientific advances during the last decades regarding potential intervention on embryos arouse many questions in society to prepare the ground concerning the limits that should be set for these practices. For the first time in 1994, a parliamentary proceeding allowed the definition of a French model of bioethics through laws of the same name. These laws, among others, authorized in a well and strictly defined setting the practice of preimplantation genetic diagnosis (PGD). Because of technical progress concerning PGD, new questions arose, especially concerning the accomplishment of designer babies. The French Chamber of Representatives came in with a new law that banishes the concept of designer babies and replaces it with another concept: double hope babies, in French "bébé du double espoir". A first hope of a pregnancy giving birth to a healthy child and the second being that this child conceived with the aid of PGD could help treat an elder brother. Because of the issuing of two specific laws in a ten years interval, France occupies a privileged place in a Europe where bioethical issues continue to be debated, particularly PGD.

Postoperative bilateral vertebral artery dissection: a case report.

With the improvement of medical imaging and surgical techniques, surgery on cervical vertebral is more frequent. Some cases of complications of this type of surgery have been described. We report a case of postoperative bilateral vertebral artery dissection. It concerns a 58 year-old woman who suffered from a left cervico-brachial C6 neuralgia with paresthesiae of the thumb. She underwent discectomy at C5-C6 and C6-C7 followed by setting up intersomatic cages. In subsequent days, an irreversible coma developed. Supra-aortic echographic study revealed bilateral vertebral artery thrombosis. CT scan revealed ischemic lesions of the brain stem and cerebellum. Cerebral death was declared five days after the operation. Autopsy was performed to determine whether death was the consequence of the intervention. The cause of death was determined to be ischemic brain injury of the brain stem and cerebellum resulting from bilateral traumatic occlusion of the vertebral arteries caused by the surgery.

[Laparoscopy: incisional hernias]. / Coelioscopie: les éventrations sur orifices de trocarts.

Post-laparoscopics incisionals hernias are among the serious complications of laparoscopy, however they are probably under-reported. We undertook a literature review to discuss their main characteristics. We emphasized on the need of controlled studies regarding their prevention measures.

[Umbilical hernias treatment by the "stamp mesh technique"]. / Les hernies ombilicales : traitement par la technique de la prothèse << timbre-poste >>.

We describe an original technique for umbilical hernia repair ("stamps mesh technique") during which no umbilical ring widening is carried out. A non-absorbable mesh is positioned in the preperitoneal space.

[Surgery and transfusion in Jehovah's witness patient. Medical legal review]. / Chirurgie et transfusion chez les patients témoins de Jéhovah. Mise au point médico-légale.

The religious convictions of the witnesses of Jehovah leads them to refuse transfusion of blood, of its major components and of blood sparing procedures breaking the physical contact between the patient and his blood. We recall the rules of good practice in case of elective surgery concerning exhaustive information of the patient within multidisciplinary team associating anesthetist and surgeon advised by the forensic pathologist. This consultation must, to our point of view, be concluded by a report which summarizes what is accepted or not by the patient. This report will be initialed by the patient. This consultation can never lead the physician to swear to never use a transfusion whatever the circumstances. In case of emergency if and only some conditions are met (everything was made to convince the patient, vital emergency, no therapeutic choice, therapeutic care adapted to the patient heath status), the physician can be brought to overpass the patient's will to not receive blood transfusion. Current jurisprudence has, to date, never recognized as faulty the physicians having practiced such transfusions whenever they took place within a precise framework.

[Management of umbilical hernia in cirrhotic patients]. / Prise en charge de la hernie ombilicale du cirrhotique.

The treatment of umbilical hernia in the setting of cirrhosis poses unique and specific management problems due to the pathophysiology of cirrhotic ascites. The high intra-abdominal pressures generated by ascites when applied to areas of parietal weakness are the cause of hernia formation and enlargement. Successful surgical treatment depends on minimization or elimination of ascites. Umbilical rupture and hernia strangulation are the most life-threatening complications of umbilical hernia with ascites and they demand urgent surgical intervention. In non-emergency situations, medical therapy to control ascites should precede hernia repair. When ascites is refractory to medical therapy, treatment will vary depending on whether transplantation is an option. In liver transplantation candidates, hernia repair can be performed at the end of the transplantation procedure. If transplanation is not envisaged, concomitant treatment of both ascites and hernia is best achieved by placement of a peritoneo-venous shunt at the time of the parietal repair.

[Hematoma of the abdominal large right muscles: diagnosis and treatment]. / Hématome des muscles grands droits de l'abdomen: diagnostic et traitement.

Rectus sheath hematoma is an uncommon event, and exception post-trauma hematoma, affects predisposed patients. The typical clinical case combine abdominal pain, a palpable mass, and parietal eccymosis appearing when a patient under anticoagulant therapy coughs. Diagnosis is confirmed by abdominal ultrasonography or CT scan. Surgical treatment is indicated only in complicated forms.