Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial.

Rationale: Management of first episodes of primary spontaneous pneumothorax remains the subject of debate. Objectives: To determine whether first-line simple aspiration is noninferior to first-line chest tube drainage for lung expansion in patients with complete primary spontaneous pneumothorax. Methods: We conducted a prospective, open-label, randomized noninferiority trial. Adults aged 18-50 years with complete primary spontaneous pneumothorax (total separation of the lung from the chest wall), recruited at 31 French hospitals from 2009 to 2015, received simple aspiration (n = 200) or chest tube drainage (n = 202) as first-line treatment. The primary outcome was pulmonary expansion 24 hours after the procedure. Secondary outcomes were tolerance of treatment, occurrence of adverse events, and recurrence of pneumothorax within 1 year. Substantial discordance in the numerical inputs used for trial planning and the actual trial rates of the primary outcome resulted in a reevaluation of the trial analysis plan. Measurement and Main Results: Treatment failure occurred in 29% in the aspiration group and 18% in the chest tube drainage group (difference in failure rate, 0.113; 95% confidence interval [CI], 0.026-0.200). The aspiration group experienced less pain overall (mean difference, -1.4; 95% CI, -1.89, -0.91), less pain limiting breathing (frequency difference, -0.18; 95% CI, -0.27, -0.09), and less kinking of the device (frequency difference, -0.05; 95% CI, -0.09, -0.01). Recurrence of pneumothorax was 20% in this group versus 27% in the drainage group (frequency difference, -0.07; 95% CI, -0.16, +0.02). Conclusions: First-line management of complete primary spontaneous pneumothorax with simple aspiration had a higher failure rate than chest tube drainage but was better tolerated with fewer adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT01008228).

Perioperative blood glucose variability and autonomic nervous system activity in on-pump cardiac surgery patients: Study protocol of a single-center observational study.

INTRODUCTION: On-pump coronary artery bypass graft (CABG) and surgical valve replacement (SVR) are high-risk procedures. Several studies reported that perioperative blood glucose (BG) variability was independently associated with impaired postoperative outcome. However, the underlying mechanisms contributing to increased perioperative BG variability and to its deleterious impact remain unknown. The hypothesis of the study is that perioperative BG variability could be related to perioperative alteration of the autonomic nervous system (ANS) activity and to preoperative BG variability. METHODS AND ANALYSIS: We designed a prospective observational single-center study. Four groups of 30 patients will be studied: group 1, including insulin-requiring type 2 diabetic patients undergoing on-pump CABG; group 2, including non-insulin-requiring type 2 diabetic patients undergoing on-pump CABG; group 3, including non-diabetic patients undergoing aortic SVR; and group 4, including non-diabetic patient undergoing on-pump CABG. Preoperative (baseline) and postoperative BG variability will be quantified using the Abbott's Freestyle Libre Pro sensor allowing for continuous subcutaneous BG monitoring. Preoperative (baseline) and postoperative ANS activity will be measured using noninvasive continuous heart rate monitoring (Mooky HR memory®). Blood level and urinary concentration of inflammatory and endothelial dysfunction biomarkers will be measured from blood and urinary samples at the end of the surgery and on postoperative day 1 and 2. The primary objective is to describe the relationship between baseline BG variability and postoperative BG variability. The secondary objectives are to describe the relationship: between baseline and postoperative BG variability according to the diabetes phenotype and to the type of surgery; between the ANS activity and the BG variability; and between postoperative BG variability and, urinary and blood biomarkers.

Reporting Criteria for Clinical Trials on Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review and Recommendations.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication caused by anti-resorptive agents and anti-angiogenesis drugs. Since we wanted to write a protocol for a randomized clinical trial (RCT), we reviewed the literature for the essential information needed to estimate the size of the active patient population and measure the effects of therapeutics. At the same time, we designed a questionnaire intended for clinicians to collect detailed information about their practices. Twelve essential criteria and seven additional items were identified and compiled from 43 selected articles. Some of these criteria were incorporated in the questionnaire coupled with data on clinical practices. Our review found extensive missing data and a lack of consensus. For example, the success rate often combined MRONJ stages, diseases, and drug treatments. The occurrence date and evaluation methods were not harmonized or quantitative enough. The primary and secondary endpoints, failure definition, and date coupled to bone measurements were not well established. This information is critical for writing a RCT protocol. With this review article, we aim to encourage authors to contribute all their findings in the field to bridge the current knowledge gap and provide a stronger database for the coming years.

Human amniotic membrane application in oral surgery-An ex vivo pilot study.

Objectives: The purpose of this pilot porcine study was to explore and illustrate the surgical application of human amniotic membrane (hAM) in an ex vivo model of medication-related osteonecrosis of the jaw (MRONJ). Material and methods: Five oral and maxillofacial surgeons participated to this study. MRONJ was simulated on porcine mandible specimens. hAM was applied using four different techniques: implantation with complete coverage, implantation with partial coverage, apposition and covering graft material. At the same time, the surgeons evaluated how well the hAM handled and its physical properties during the surgery. Results: Surgeons found that hAM had suitable mechanical properties, as it was easy to detach from the support, handle, bind to the defect and bury. hAM was also found to be strong and stable. The "implantation with complete coverage" and "implantation with partial coverage" techniques were the preferred choices for the MRONJ indication. Conclusion: This study shows that hAM is a graft material with suitable properties for oral surgery. It is preferable to use it buried under the gingiva with sutures above it, which increases its stability. This technical note aims to educate surgeons and provide them with details about the handling of hAM in oral surgery. Clinical relevance: Two surgical techniques for hAM application in MRONJ were identified and illustrated. hAM handling and physical properties during surgery were reported.

Clinical effectiveness of hypertonic sodium lactate infusion for intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection: A study protocol of a single center double-blind randomized controlled phase II pilot trial.

INTRODUCTION: Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection. METHODS AND ANALYSIS: We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020).

Tips and Tricks and Clinical Outcome of Cryopreserved Human Amniotic Membrane Application for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Pilot Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, antifibrotic, antimicrobial, antiviral, and analgesic effects. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with suitable mechanical properties (permeability, stability, elasticity, flexibility, and resorbability) to prevent the proliferation of fibrous tissue and promote early neovascularization at the surgical site. In oral surgery, hAM stimulates healing and facilitates the proliferation and differentiation of epithelial cells in the oral mucosa and therefore its regeneration. We proposed using cryopreserved hAM to eight patients suffering from cancer (11 lesions) with stage 2-3 MRONJ on a compassionate use basis. A collagen sponge was added in some cases to facilitate hAM grafting. One or three hAMs were applied and one patient had a reapplication. Three patients had complete closure of the surgical site with proper epithelialization at 2 weeks, and two of them maintained it until the last follow-up. At 1 week after surgery, three patients had partial wound dehiscence with partial healing 3 months later and two patients had complete wound dehiscence. hAM reapplication led to complete healing. All patients remained asymptomatic with excellent immediate significant pain relief, no infections, and a truly positive impact on the patients' quality of life. No adverse events occurred. At 6 months of follow-up, 80% of lesions had complete or partial wound healing (30 and 50%, respectively), while 62.5% of patients were in stage 3. Radiological evaluations found that 85.7% of patients had stable bone lesions (n = 5) or new bone formation (n = 1). One patient had a worsening MRONJ but remained asymptomatic. One patient did not attend his follow-up radiological examination. For the first time, this prospective pilot study extensively illustrates both the handling and surgical application of hAM in MRONJ, its possible association with a collagen sponge scaffold, its outcome at the site, the application of multiple hAM patches at the same time, and its reapplication.

Hyperendemicity of cysticercosis in Madagascar: Novel insights from school children population-based antigen prevalence study.

OBJECTIVE: Taenia solium (Ts) cysticercosis is a neglected zoonotic disease particularly prevalent in Madagascar. Few data are available for children, current data mainly rely on antibody prevalence. We sought to determine the Ts-antigen seroprevalence-determining active cysticercosis-amongst school children from various cities in Madagascar (excluding the capital) and evaluated associated risk factors. METHODS: In seven cities in Madagascar, the presence of cysticercosis in school children (n = 1751) was investigated in 2007 using the B158/B60 antigen (Ag)-ELISA. RESULTS: The overall prevalence based on Ag detection was 27.7% [95%CI: 10-37%]. Risk factors associated with Ag positivity were age, biotope, altitude and annual average rainfall. CONCLUSION: These results highlight the high prevalence of active cysticercosis in Madagascar among school children in an urban setting. This high prevalence as well as the risk factors unraveled point to the emergency to implement appropriate Public Health measure son a national scale.

Ustekinumab for Perianal Crohn's Disease: The BioLAP Multicenter Study From the GETAID.

INTRODUCTION: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.

To assess hemodynamic disturbances to the ostia of the renal arteries generated by the implantation of EVAR with a suprarenal fixation.

INTRODUCTION: The treatment of abdominal aortic aneurysm (AAA) is increasingly performed via endovascular aneurysm repair (EVAR). Different types of fixation are possible with EVAR, i.e., below (infrarenal fixation) or above (suprarenal fixation) the renal arteries. Hemodynamic alterations in renal arterial flow with suprarenal (SR) fixation remain to be demonstrated. The IFIXEAR (Impact of Supra-renal Fixation of EVAR on Hemodynamics of Renal Arteries) study is designed to assess the hemodynamic effects at the ostia of at least 1 renal artery, generated immediately post-surgery by the implantation of an aortic stent with SR fixation. METHODS: IFIXEAR is a prospective, 2 center study. Every patient undergoing elective EVAR with SR fixation is eligible for inclusion. Patients with previous hemodynamic disturbances to the ostia of 1 of the renal arteries are not eligible. All patients undergo echocardiography and renal arteries duplex ultrasound within a month before surgery, and at 1 and 12 months after surgery. The primary endpoint is hemodynamic disturbance, defined as a peak systolic velocity greater than 120 cm/second, at the ostia of 1 of the renal arteries in the immediate postoperative period. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee "Comité de Protection des Personnes Ouest V" under the number 18/019-2 on April 20, 2018. All patients provide written informed consent before inclusion. The University Hospital of Besancon is the trial sponsor. Results of the study will be submitted for publication in a peer-reviewed international medical journal. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT03594786, principal investigator: Dr Patricia Costa, Registered on April 24, 2018).

Vedolizumab for perianal Crohn's disease: a multicentre cohort study in 151 patients.

BACKGROUND: The management of Crohn's disease patients with perianal lesions and anti-TNF failure is challenging. AIMS: To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real-life cohort. METHODS: We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. RESULTS: One hundred and fifty-one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. CONCLUSIONS: We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.

Sarcopenia and visceral obesity assessed by computed tomography are associated with adverse outcomes in patients with Crohn's disease.

BACKGROUND: Altered body composition may impact on the clinical course of Crohn's disease (CD) but is not detected by the simple body mass index (BMI) assessment. AIM: To assess the prevalence of sarcopenia and visceral obesity by a single computed tomography (CT) slice, and its association with adverse events in an adult hospitalized CD cohort. METHODS: 88 CD patients who had abdominal CT scans during hospitalization were retrospectively enrolled. The skeletal muscle index (SMI) at the third lumbar vertebra level was used to assess sarcopenia. Sarcopenia was defined as a SMI <38.5 cm2/m2 in women, <52.4 cm2/m2 in men and visceral obesity as a visceral fat area ≥130 cm2. Clinical malnutrition was defined by a BMI <18.5 kg/m2. Univariate analysis was performed, and predictors for surgery in the follow-up were entered in a stepwise logistic regression model for multivariate analysis. RESULTS: The prevalence of sarcopenia was 58%, malnutrition 21.6%, and visceral obesity 19.3%. Among sarcopenic patients, 49% had a normal BMI, 13.7% were overweight, and 1(2%) was obese. Sarcopenic CD patients had significantly more abscesses (51% vs 16.7%, p = 0.001), hospitalizations (61.2% vs 36.1%, p = 0.022) and digestive surgery (63.3% vs 27.8%, p = 0.001) than non-sarcopenic patients during the follow-up, whereas usual malnutrition assessment was not correlated with disease outcomes. In multivariate analysis, both sarcopenia and visceral obesity were associated with further occurrence of digestive surgery. CONCLUSION: Both sarcopenia and visceral obesity were associated with adverse outcomes in severe CD patients whereas usual nutritional assessment was not.

Pregnancy vulnerability in urban areas: a pragmatic approach combining behavioral, medico-obstetrical, socio-economic and environmental factors.

Multiple risk factors are associated with adverse pregnancy outcomes (APO), but how all these different factors combine and accumulate remains unknown. The objective of this observational retrospective study was to describe the accumulation of multiple vulnerability markers in pregnant women living in an urban area. Women living in Besançon (France) who delivered between 2005 and 2009 were included. Individual data were collected from the obstetrical records while environmental exposures were collected using environmental prediction models. The accumulation of 15 vulnerability markers, grouped into six dimensions (maternal age, smoking, body mass index (BMI), socio-economic, medico-obstetrical and environmental vulnerabilities) was described and analyzed in comparison with four APO. Among the 3686 included women, 20.8% were aged under 20 or over 34 and 21.9% had an extreme pre-pregnancy BMI. 18.8% declared smoking during pregnancy. Women exposed to socio-economic, medico-obstetrical or environmental vulnerability were 14.2%, 31.6% and 42.4% respectively. While 20.6% were not exposed to any marker, 18.8% accumulated three or more dimensions. The risk of APO increased significantly with the cumulative number of vulnerabilities. Define and validate a vulnerability score could be useful to identify vulnerable women, adapt their pregnancy monitoring and help policy makers to implement appropriate education or health promotion programs.

Abdominal compartment syndrome and ruptured aortic aneurysm: Validation of a predictive test (SCA-AAR).

BACKGROUND: The abdominal compartment syndrome (ACS) has been clearly identified as being one of the main causes of mortality after ruptured abdominal aortic aneurysm (rAAA). The ACS is defined as a sustained intra-abdominal pressure > 20 mm Hg associated with a new organ dysfunction or failure. A pilot study was conducted and found that the threshold of 3 among 8 selected criteria, we would predict an ACS occurrence with a 54% positive predictive value and a 92% negative predictive value. But a multicentric prospective study was clearly needed to confirm these results. The outcome of this new study is to assess the qualities of a predictive test on occurrence of the ACS after rAAA surgery. METHODS: This is a 30 months prospective cohort study conducted in 12 centers and 165 patients will be included. All patients with a rAAA will be consecutively included, whatever the surgical treatment. At the end of surgery, all patients have an abdominal closure and a monitoring of intrabladder pressure will be established every 3 to 4 hours. Decompressive laparotomy will be indicated when ACS occurs. Follow-up period is 1 month. Eight pre- and per-operative criteria will be studied: anemia, hypotension, cardiac arrest, obesity, massive fluid resuscitation, transfusion, hypothermia, and acidosis. DISCUSSION: In the literature, there is no recommendation about prophylactic decompression, but early decompressive laparotomy appears to improve survival. This study should make it possible to establish a predictive test, detect the ACS early, and consider a prophylactic decompression in the operating room. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02859662, Registered on 4 August 2016.

High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease.

BACKGROUND & AIMS: The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France. METHODS: We analyzed anal tissue samples collected from 469 consecutive patients (median age 54 years, 52% women), including 112 who received immunosuppressant therapies and 101 with inflammatory bowel disease (70 with Crohn's disease), who underwent colonoscopy examinations from April 1, 2012 to April 30, 2015. HPV was detected and genotyped using the INNO-LiPA assay, and we collected medical and demographic data from all subjects. Risk factors for any HPV, high-risk HPV (HR-HPV) and HPV16 infection were assessed by bivariate and multivariate analysis. The primary outcomes association of HR-HPV or HPV16 with medical and demographic features. RESULTS: We detected HPV DNA in anal tissues from 34% of the subjects and HR-HPV in 18%. HPV16 was the most prevalent genotype (detected in 7%), followed by HPV51, HPV52, and HPV39. HR-HPV was detected in a significantly higher proportion of samples from women (23.1%) than men (12.8%) (P = .0035); HR-HPV and HPV16 were detected in a significantly higher proportion of patients with Crohn's disease (30.0%) than without (18.1%) (P = .005). Female sex, history of sexually transmitted disease, lifetime and past year-number of sexual partners, active smoking, and immunosuppressive therapies were independent risk factors for anal HR-HPV infection in multivariate analysis. CONCLUSION: One third of patients who underwent colonoscopy at a gastroenterology department were found to have anal canal HPV infection. We detected HR-HPV infection in almost 20% of patients and in a significantly higher proportion of patients with Crohn's disease than without. Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening.