Intravesical injections of botulinum neurotoxin A to treat overactive bladder and/or detrusor overactivity related to multiple sclerosis: 5-Year continuation rate and specific risk factors for discontinuation-A study from the neuro-urology committee of the French Association of Urology.

BACKGROUND: While intravesical injections of botulinum neurotoxin A (BoNT-A) are currently recommended for patients experiencing refractory neurogenic overactive bladder and/or detrusor overactivity (OAB/DO), it is unclear how much this therapy is effective and sustainable in the long-term in patients with multiple sclerosis (MS). OBJECTIVES: To assess the mid-term continuation rate of BoNT-A injections to treat neurogenic OAB/DO in MS patients and to investigate MS-specific risk factors for discontinuation. METHODS: This retrospective study involved 11 French university hospital centers. All MS patients who received BoNT-A to treat neurogenic OAB/DO between 2008 and 2013 and were subsequently followed up for at least 5 years were eligible. RESULTS: Of the 196 MS patients included, 159 (81.1%) were still under BoNT-A 5 years after the first injection. The combination of the Expanded Disability Status Scale (EDSS < 6 or ⩾ 6) and of the MS type (relapsing-remitting vs progressive) predicted the risk of discontinuation. This risk was 5.5% for patients with no risk factor, whereas patients presenting with one or two risk factors were 3.3 and 5.7 times more likely to discontinue, respectively. CONCLUSION: BoNT-A is a satisfying mid-term neurogenic OAB/DO therapy for most MS patients. Combining EDSS and MS type could help predict BoNT-A discontinuation.

New-onset inflammatory bowel diseases among IL-17 inhibitor-treated patients: results from the case-control MISSIL study.

OBJECTIVES: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life. METHODS: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease. RESULTS: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD. CONCLUSION: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.

Ibrutinib as a treatment of hematologic autoimmune disorders in patients with indolent B-cell lymphoma.

BACKGROUND: Autoimmune conditions in B-cell lymphomas are frequent. Steroids are standard of care, but many patients require other immunosuppressive agents. Ibrutinib is a Bruton Tyrosine Kinase inhibitor that is approved for B-cell indolent lymphoma treatment. We evaluated the use of ibrutinib in previously treated hematologic immune manifestations associated with B-cell lymphomas. RESULTS: We conducted a retrospective multicentric observational study. Patients presenting with active, relapsed/refractory B-cell lymphoma associated hematological immune manifestation (autoimmune cytopenia, acquired immune-mediated bleeding disorders) were included. Twenty-five patients were identified. Median age at ibrutinib introduction was 69 years (range 44-84) and median number of previous treatment lines before ibrutinib was 2 (1-7). Twenty-two patients (88%) were on concomitant stable treatment at inclusion. Within a median exposure of 8 months (2-35), overall response rate to ibrutinib on immune manifestations was 76% (95% CI, 54.9-90.6); complete response rate 44%. Fourteen patients (63%) were able to be weaned from concomitant treatments. Fourteen patients (56%) presented treatment-related adverse events, mostly Grade 1 or 2. CONCLUSIONS: Ibrutinib in this setting provides good efficacy and safety profile. Clinical trials are needed to define subgroups of patients who will benefit from this strategy and establish its place in the therapeutic arsenal.

Is V-NOTES Hysterectomy as Safe and Feasible as Outpatient Surgery Compared with Vaginal Hysterectomy?

STUDY OBJECTIVE: The vaginal approach is the reference surgical route to perform hysterectomy for benign pathologies. Hysterectomy via transvaginal natural orifice transluminal endoscopic surgery (V-NOTES) is a new technique that would overcome the limitations of vaginal surgery by allowing a complete exploration of the peritoneal cavity and a constant visual control of the adjacent structures. The aim of this study is to assess the V-NOTES technique compared with vaginal hysterectomy (VH). DESIGN: A retrospective cohort study. SETTING: French teaching hospital. PATIENTS: The first 50 V-NOTES hysterectomies were included successively and compared with the last 50 VH performed from March 2019 to November 2020. The study concerned all patients requiring hysterectomy unless it was for endometriosis or cancer (except for grade 1 endometrioid adenocarcinoma). INTERVENTIONS: The baseline characteristics and the surgical outcomes were compared. The main outcome assessed was the performing of outpatient surgery. Secondary end points were uterine weight and intraoperative and postoperative complications. MEASUREMENTS AND MAIN RESULTS: The rate of outpatient surgery did not differ between the 2 surgical techniques (p = .23). The success rate of outpatient management was 77% in the V-NOTES group versus 75% in the VH group (p = .85). There was no difference in surgical outcomes between the 2 groups, except for the rate of salpingectomies or adnexectomies, which was significantly higher in the V-NOTES group, with 100% of patients undergoing one of these procedures, compared with 60% of patients in the vaginal route group (p < .001). There were 2 cases of re-admission in the month following the intervention in the vaginal group and 0 cases in the V-NOTES group. CONCLUSION: Hysterectomy by V-NOTES can be performed as a safe and adequate alternative to VH. This surgical route is a good candidate for outpatient management. However, more studies need to be conducted to confirm these findings.

Predictive factors of urinary incontinence after holmium laser enucleation of the prostate: a multicentric evaluation.

OBJECTIVE: To evaluate predictive factors of urinary incontinence (UI) after holmium laser enucleation of the prostate (HoLEP). METHODS: Patients (n = 2346) were included in a retrospective multicentric study from April 2012 to November 2017. Patients' characteristics (age, BMI, percentage with diabetes), preoperative data (IPSS score, whole gland volume, urinary drainage), operative data (enucleation time, enucleation efficiency, tissue enucleated weight, total delivered energy) and postoperative data were recorded. Absence of UI was defined as no pads at 3 and 6 months. Surgeon experience was stratified in three categories: beginners (< 21 cases), intermediate (21-40 cases) and experienced (> 40 cases). Multivariate logistic regression analysis was performed. RESULTS: UI was observed in 14.5% of patients (340/2346) at 3 months (95%CI 13-16%) and in 4.2% (98/2346) at 6 months (95%CI 3-5%). On multivariate analysis at 3 months, increasing age (OR per SD = 1.3 [1.14-1.48]), elevated BMI (OR per SD = 1.23 [1.09-1.38]), preoperative urinary drainage (OR = 0.62 [0.45-0.85]), increasing enucleated tissue weight (OR per SD = 1.29 [1.16-1.45]) and experienced surgeon with at least 40 cases (OR = 0.56 [0.42-0.75]) were significantly associated with UI. At 6 months, increasing age (OR per SD = 1.25 [1.01-1.53]), elevated BMI (OR per SD = 1.25 [1.03-1.5]), increasing whole gland volume (OR per one SD log = 1.24 [1.01-1.53]) and diabetes disorder (OR = 1.7 [1.03-2.78]) were significantly associated with UI. CONCLUSION: UI after HoLEP was observed in 14.5% of patients at 3 months and 4.2% at 6 months, with stress UI in half of the cases. Surgeon experience with at least 40 cases was the main predictive factor of 3 months UI after HoLEP and diabetes disorder of persistent UI at 6 months.

Influence of nocturnal hypoxemia on follow-up course after type B acute aortic syndrome.

INTRODUCTION: Association between sleep nocturnal breathing disorders and acute aortic syndrome (AAS) has been described but mid-term data are scarce. OBJECTIVES: We assessed the prognostic value of sleep apnea parameters and their relationship with aortic morphology after the onset of a type B AAS. METHODS: Between January 2010 and January 2018, sleep apnea screening in post type B AAS was prospectively performed. The association of sleep apnea parameters with aortic morphology and aortic expansion during follow-up was studied. RESULTS: Over the 8-year-study period, 103 patients were included, with a mean age of 57.8 ± 12.1 years old. Median follow-up was 25.0 months (11.0-51.0). Thirty-two patients (31%) required aortic stenting during the acute phase. In patients treated by aortic stenting, the descending thoracic aortic diameter was positively associated with a higher percentage of nocturnal time of saturation ≤ 90% after adjustment (p = 0.016). During follow-up, the nocturnal time of saturation ≤ 90% in patients treated by medical therapy was the only parameter associated with significant aortic expansion rate (r = 0.26, p = 0.04). Thirty-eight patients started and sustained nocturnal ventilation during follow-up. The association between aortic expansion rate and nocturnal time of saturation ≤ 90% did not persist during follow-up after adjustment on nocturnal ventilation initiation (r = 0.25, p = 0.056). CONCLUSIONS: Nocturnal hypoxemia parameters are positively associated with the max onset aortic diameter and significant aortic growth after type B AAS. Nocturnal ventilation seems to mitigate aortic expansion during follow-up.

Usefulness of 18F-Fluorodeoxyglucose Positron Emission Tomography in Diagnosing Polymyalgia Rheumatica and Large-Vessel Vasculitis: A Case-Control Study.

INTRODUCTION: We aimed to evaluate the utility of FDG-PET/CT in diagnosing polymyalgia rheumatica (PMR) and associated large-vessel vasculitis (LVV). METHODS: We analyzed FDG-PET/CT completed between 2015 and 2019 on patients diagnosed with PMR. For comparisons, patients with PMR were matched 1:1 to controls based on age and gender. FDG-PET/CT had been completed on the controls over the same period. The FDG uptake was scored visually for 17 articular or periarticular sites and 13 vascular sites using a semi-quantitative scoring system (score of 0-3). RESULTS: Eighty-one patients with PMR and eighty-one controls were included (mean age 70.7 (9.8) years; 44.4% women). Significant differences between the PMR and control groups were found at all articular and periarticular sites for the following: (i) the FDG uptake score (p < 0.001 for all locations); (ii) the number of patients per site with significant FDG uptake (score ≥ 2); (iii) the global FDG articular uptake scores (31 [IQR, 21 to 37] versus 6 [IQR, 3 to 10], p < 0.001); and (iv) the number of sites with significant FDG uptake (score ≥ 2) (scores of 0-17) (11 [IQR, 7 to 13] versus 1 [IQR, 0 to 2], p < 0.001). No significant differences in the global FDG vascular uptake scores were found between the patients who were considered isolated PMR and the control groups. CONCLUSIONS: The FDG uptake score and the number of sites with significant FDG uptake could be pertinent criteria for the diagnosis of PMR. Unlike others, we did not confirm the presence of vascular involvement in patients with isolated PMR.

Impact of Cardiovascular and Metabolic Comorbidities on Long-term Outcomes of Home-based Pulmonary Rehabilitation in COPD.

Background: Cardiovascular and metabolic comorbidities in chronic obstructive pulmonary disease (COPD) are associated with higher symptoms burden. Few center-based studies have evaluated the impact of these comorbidities on short-term pulmonary rehabilitation outcomes with contrasting results. Research Question: This study aimed to determine whether cardiovascular diseases and metabolic comorbidities impacted long-term outcomes of a home-based PR program in COPD patients. Study Design and methods: Data of 419 consecutive COPD patients addressed to our pulmonary rehabilitation program between January 2010 and June 2016 were retrospectively analyzed. Our program consisted of once-weekly supervised home sessions, including therapeutic education and self-management support, with unsupervised retraining exercises and physical activities the other days for 8 weeks. Exercise capacity (6-min stepper test [6MST]), quality of life (visual simplified respiratory questionnaire), and anxiety and depression (hospital anxiety and depression scale) were assessed respectively, before (M0) and at the end (M2) of the pulmonary rehabilitation program, and at 6 (M8) and 12 months (M14) after its achievement. Results: Patients (mean age 64.1±11.2 years, 67% males, mean forced expiratory volume in one second (FEV1) 39.2±17.0% predicted) were classified as having cardiovascular comorbidities (n=195), only metabolic disorders (n=122) or none of these comorbidities (n=102). After adjustment, all outcomes appeared similar between groups at baseline and improved after pulmonary rehabilitation with a greater effect at M14 for patients with only metabolic disorders on anxiety and depression score (-5.0±0.7 vs -2.9±0.8 and -2.6±0.6, p=0.021). Quality of life and exercise capacity improvements were not significantly different between the three groups at M2 and M14. Conclusion: Cardiovascular and metabolic comorbidities do not preclude COPD patients from obtaining clinically meaningful improvements in exercise capacity, quality of life and anxiety-depression up to 1 year after a home-based pulmonary rehabilitation.

Predictors of anastomotic strictures following œsophageal atresia repair.

OBJECTIVES: To identify the risk factors for anastomotic, refractory and recurrent strictures and to establish whether anastomotic stricture is associated with antireflux surgery. DESIGN: This prospective national multicentre study included all infants born with oesophageal atresia (OA) over an 8-year period. Data on OA and complications were collected at birth and at 1 year old. Univariate and multivariate analyses were conducted. RESULTS: 1082 patients from 37 centres were included in the study. The prevalence of anastomotic stricture at 1 year old was 23.2%. Anastomosis under tension (defined by the surgeon at the time of repair) and delayed anastomosis (defined as anastomosis performed more than 15 days after birth, excluding delays due to prematurity or severe cardiac diseases) were found to be independent risk factors for anastomotic stricture (2.3 (1.42-3.74) and 4.02 (2.12-7.63), respectively). Patients with anastomotic stricture had a 2.3-fold higher rate of fundoplication compared with others (p=0.001). Anastomosis under tension and delayed anastomosis were found to be independent risk factors for recurrent stricture (1.92 (1.10-3.34) and 5.73 (2.71-12.14), respectively), while delayed anastomosis was the only risk factor for refractory stricture (8.30 (3.34-20.64)). There was a 2.39-fold (1.42-4.04) higher rate of fundoplication in the anastomotic stricture group than in the group without anastomotic stricture (p=0.001). CONCLUSIONS: Patient-related anatomical factors leading to anastomosis under tension and delayed anastomosis increase the risk of anastomotic stricture.

Changes in bone mineral density after allogenic stem cell transplantation.

OBJECTIVE: Osteoporosis is a complication after allogenic stem cell transplantation (alloSCT). The purpose of this study was to assess changes in bone mineral density (BMD) 6 months and 3 years after alloSCT, as well as predictors of bone loss. METHODS: A longitudinal, prospective, single-center study was conducted at Lille University Hospital between 2005 and 2016. Clinical, biological, radiologic (thoracic and lumbar spine) and densitometric (DXA) assessments were carried out at baseline (pre-transplant), 6 months and 3 years. Patients with myeloma were not included. RESULTS: Two hundred and fifty-eight patients were included (144 men). Among them, 60.1% had leukemia and 65.8% of them, acute myeloid leukemia. At baseline, 6 months and 3 years, DXA-confirmed that osteoporosis was observed in 17%, 22.8% and 17.5% of the patients, respectively, mainly at the femoral neck. At baseline, 6 months and 3 years, 9 (8.5%), 53 (21.5%) and 38 (16.7%) patients, respectively, were receiving anti-osteoporotic treatment. From baseline to 6-month follow-up, BMD decreased significantly (p<0.001) at the lumbar spine (-36 [95%CI; -51 to -20] mg/cm2 of hydroxyapatite), femoral neck (-43 [95%CI; -57 to -29] mg/cm2 of hydroxyapatite) and total hip (-53 [95%CI; -68 to -39] mg/cm2 of hydroxyapatite). From 6-month to 3-year follow-up, a significant increase in BMD was observed at the lumbar spine only (+31 [95%CI; 20 to 42] mg/cm2 of hydroxyapatite, p<0.001). At all 3 sites, changes in BMD did not differ between patients treated or untreated by anti-osteoporotic treatment from 6-month to 3 year follow-up. Incident fractures were found in 4.1% and 5.7% of the patients at 6 months and 3 years, respectively. Between baseline and 6 months, bone loss at all 3 sites was associated with corticosteroid intake. At the total hip, 23.3% of the decrease in BMD from baseline to 6 months was due to an active hematological disease (p<0.05), a bone marrow stem cells (p<0.01) and a corticosteroid intake (p<0.01). CONCLUSION: Our study found evidence of bone fragility in alloSCT patients. Low BMD persisted at the hip 3 years after transplantation due to slower improvement at this site.

Thrombus formation during ECMO: Insights from a detailed histological analysis of thrombus composition.

OBJECTIVES: Intra-device thrombosis remains one of the most common complications during extracorporeal membrane oxygenation (ECMO). Despite anticoagulation, approximately 35% of patients develop thrombi in the membrane oxygenator, pump heads, or tubing. The aim of this study was to describe the molecular and cellular features of ECMO thrombi and to study the main drivers of thrombus formation at different sites in the ECMO circuits. APPROACH AND RESULTS: Thrombi (n = 85) were collected immediately after veno-arterial-(VA)-ECMO circuit removal from 25 patients: 23 thrombi from the pump, 25 from the oxygenator, and 37 from the tubing. Quantitative histological analysis was performed for the amount of red blood cells (RBCs), platelets, fibrin, von Willebrand factor (VWF), leukocytes, and citrullinated histone H3 (H3Cit). ECMO thrombi consist of a heterogenous composition with fibrin and VWF being the major thrombus components. A clustering analysis of the four major histological parameters identified two typical thrombus types: RBC-rich and RBC-poor/fibrin-rich thrombi with no significant differences in VWF and platelet content. Thrombus composition was not associated with the thrombus location, except for higher amounts of H3Cit that were found in pump and oxygenator thrombi compared to tubing samples. We observed higher blood leukocyte count and lactate dehydrogenase levels in patients with fibrin-rich thrombi. CONCLUSION: We found that thrombus composition is heterogenous, independent of their location, consisting of two types: RBC-rich and a fibrin-rich types. We also found that NETs play a minor role. These findings are important to improve current anticoagulation strategies in ECMO.

Which determinants should be considered to reduce social inequalities in paediatric dental care access? A cross-sectional study in France.

Better access to dental care through systemic and educational strategies is needed to lessen the burden of disease due to severe early caries. Our study aims to describe family characteristics associated with severe early caries: parental knowledge, attitudes, practices in oral health and socio-demographic factors. For this cross-sectional study, 102 parents of children aged under 6 years with severe early caries and attending paediatric dentistry service in France completed a questionnaire during face-to-face interviews. Caries were diagnosed clinically by calibrated investigators, using the American Academy of Paediatric Dentistry criteria, and dental status was recorded using the decayed, missing, and filled teeth index. The majority of children were from underprivileged backgrounds and had poor oral health status, with a median dmft index of 10. Parents highlighted the difficulty of finding suitable dental care in private practices. Parents appeared to have good oral health knowledge and engaged in adapted behaviours but showed a low sense of self-efficacy. They perceived the severity of early caries as important but the susceptibility of their child as moderate. The study affirmed the importance of improving the accessibility of paediatric dental care and developing educational strategies to enhance the knowledge, skills, and oral health practices of families.

Is vaginal delivery of a fetus in breech presentation at an extremely preterm gestational age associated with an increased risk of neonatal death? A comparative study.

BACKGROUND: The effect on neonatal mortality of mode of delivery of a fetus in breech presentation at an extremely preterm gestational age remains controversial. OBJECTIVE: To compare mortality associated with planned vaginal delivery (PVD) of fetuses in breech presentation with that of fetuses in breech presentation with a planned cesarean delivery (PCD). MATERIAL AND METHODS: Retrospective study reviewing records over a 19-year period in a level 3 university referral center of singleton infants born between 25+0 and 27+6 weeks of gestation, alive on arrival in the delivery room, and weighing at least 500 grams at birth. Infants in the first group were in breech presentation with PVD and the second in breech presentation with PCD. The principal endpoint was neonatal death. RESULTS: During the study period, we observed 113 breech presentations with PVD, and 80 breech presentations with PCD. Although not significant after adjustment, neonatal mortality in the breech PVD group was more than twice that of the breech PCD group (19.5 vs 7.8%, P = 0.031, ORa = 2.6, 95% CI 0.8-9.3, NNT = 8). This higher neonatal mortality in the breech PVD group was exclusively associated with a higher risk of death in the delivery room (12.4 vs 0.0% P = 0.001, OR not calculable, NNT = 8). In these extremely preterm breech presentations with PVD, neonatal mortality in the delivery room was associated with entrapment of the aftercoming head, cord prolapse, and a short duration of labor. CONCLUSION: For deliveries between 25+0 and 27+6 weeks' gestation, vaginal delivery in breech presentation is associated with a higher risk of death in the delivery room.

Feasibility and safety of transfemoral transcatheter aortic valve implantation performed with a percutaneous coronary intervention-like approach.

BACKGROUND: Transfemoral percutaneous transcatheter aortic valve implantation (TF-TAVI) is a safe, reproducible and established procedure, mainly performed under local anaesthesia, which is mostly administered and monitored by a dedicated anaesthesia team (regular approach). Our centre has developed a standardized pathway of care, and eligible patients are selected for a minimalist TF-TAVI, entirely managed by operators without the presence of the anaesthesia team in the operating room, like most interventional coronary procedures ("percutaneous coronary intervention-like" approach [PCI approach]). AIM: To compare the safety and efficacy of TF-TAVI performed with the PCI approach versus the regular approach. METHODS: The analysis population comprised all patients who underwent TF-TAVI with the PCI or regular approach in our institution from November 2016 to July 2019. The two co-primary endpoints were early safety composite and early efficacy composite at 30days as defined by the Valve Academic Research Consortium-2. The PCI (n=137) and Regular (n=221) approaches were compared using the propensity score based method of inverse probability of treatment weighting. RESULTS: No differences were observed after comparison of TAVI performed with the PCI or regular approach regarding the composite safety endpoint (7.3% vs. 11.3%; odds ratio 0.63, 95% confidence interval 0.37 to 1.07; P=0.086) or the composite efficacy endpoint (4.4% vs. 6.3%; odds ratio 0.78, 95% confidence interval 0.41 to 1.49; P=0.45). CONCLUSIONS: This study suggests that the efficacy and safety of TF-TAVI entirely managed by a PCI approach for selected patients are not different to those when TF-TAVI is performed with the attendance of a full anaesthesia care team. The PCI approach appears to be a safe and efficient clinical pathway, providing an appropriate and rational utilization of anaesthesiology resources, and could be used for the majority of TF-TAVI procedures.

Myocardial Infarction incidence during national lockdown in two French provinces unevenly affected by COVID-19 outbreak: An observational study.

BACKGROUND: A reduction of admission for MI has been reported in most countries affected by COVID-19. No clear explanation has been provided. METHODS: To report the incidence of myocardial infarction (MI) admission during COVID-19 pandemic and in particular during national lockdown in two unequally affected French provinces (10-million inhabitants) with a different media strategy, and to describe the magnitude of MI incidence changes relative to the incidence of COVID-19-related deaths. A longitudinal study to collect all MIs from January 1 until May 17, 2020 (study period) and from the identical time period in 2019 (control period) was conducted in all centers with PCI-facilities in northern "Hauts-de-France" province and western "Pays-de-la-Loire" Province. The incidence of COVID-19 fatalities was also collected. FINDINGS: In "Hauts-de-France", during lockdown (March 18-May 10), 1500 COVID-19-related deaths were observed. A 23% decrease in MI-IR (IRR=0.77;95%CI:0.71-0.84, p<0.001) was observed for a loss of 272 MIs (95%CI:-363,-181), representing 18% of COVID-19-related deaths. In "Pays-de-la-Loire", 382 COVID-19-related deaths were observed. A 19% decrease in MI-IR (IRR=0.81; 95%CI=0.73-0.90, p<0.001) was observed for a loss of 138 MIs (95%CI:-210,-66), representing 36% of COVID-19-related deaths. While in "Hauts-de-France" the MI decline started before lockdown and recovered 3 weeks before its end, in "Pays-de-la-Loire", it started after lockdown and recovered only by its end. In-hospital mortality of MI patients was increased during lockdown in both provinces (5.0% vs 3.4%, p=0.02). INTERPRETATION: It highlights one of the potential collateral damages of COVID-19 outbreak on cardiovascular health with a dramatic reduction of MI incidence. It advocates for a careful and weighted communication strategy in pandemic crises. FUNDING: The study was conducted without external funding.

Bone and joint complications in patients with hereditary hemochromatosis: a cross-sectional study of 93 patients.

BACKGROUND: The aim of this study was to determine the frequency and characteristics of bone and joint complications, specifically bone fragility, joint replacement surgery, and arthropathy, in hereditary hemochromatosis (HH) and related factors. METHODS: This study was a cross-sectional observational study of 93 patients with HH. Radiographs of the hands, wrists, knees, and ankles were scored for joint space narrowing, erosions and cysts, osteophytes, and chondrocalcinosis. Prevalent (vertebral and non-vertebral) fragility fractures were recorded and bone mineral density (BMD) was systematically evaluated by dual energy X-ray absorptiometry. Bone fragility was defined as (i) a T-score ⩽ -2.5 at any site with or without a prevalent fragility fracture, or (ii) a T-score between -1.0 and -2.5 at any site and a prevalent fragility fracture. RESULTS: The mean age of the patients was 60.0 (11.2) years, and 58.0% of them were men. The frequency of radiographic MCP2-3 arthropathy was 37.6% (95% CI 0.28-0.48). Radiographic MCP2-3 arthropathy was independently associated with older age [OR 1.17 (1.09-1.26) per year, p < 0.0001], male sex [OR 3.89 (1.17-12.97), p = 0.027] and C282Y+/+ genotype [OR 4.78 (1.46-15.68), p = 0.010]. The frequency of joint replacement surgery was 12.9% (95% CI 0.07-0.21). The frequency of bone fragility was 20.4% (95% CI 0.13-0.30). Bone fragility was independently associated with hepatic cirrhosis [OR 8.20 (1.74-38.68), p = 0.008]. DISCUSSION: Radiographic MCP2-3 arthropathy was found to occur in 37.6% of patients with HH. The association observed between this form of arthropathy and C282Y homozygosity, male sex, and older age suggests that demographic characteristics and genetic background are likely to be major determinants of this joint disorder and play a more important role than severity of iron overload. Bone fragility was observed in a fifth of the patients with HH, independently of genetic background and severity of iron overload, and was strongly associated with hepatic cirrhosis. CONCLUSION: Future investigations should focus on pathogenesis and early identification of patients at risk of developing bone and joint complications secondary to HH.

Identification of prognostic markers in diffuse midline gliomas H3K27M-mutant.

Pediatric diffuse midline gliomas are devastating diseases. Among them, diffuse midline gliomas H3K27M-mutant are associated with worse prognosis. However, recent studies have highlighted significant differences in clinical behavior and biological alterations within this specific subgroup. In this context, simple markers are needed to refine the prognosis of diffuse midline gliomas H3K27M-mutant and guide the clinical management of patients. The aims of this study were (i) to describe the molecular, immunohistochemical and, especially, chromosomal features of a cohort of diffuse midline gliomas and (ii) to focus on H3K27M-mutant tumors to identify new prognostic markers. Patients were retrospectively selected from 2001 to 2017. Tumor samples were analyzed by immunohistochemistry (including H3K27me3, EGFR, c-MET and p53), next-generation sequencing and comparative genomic hybridization array. Forty-nine patients were included in the study. The median age at diagnosis was 9 years, and the median overall survival (OS) was 9.4 months. H3F3A or HIST1H3B mutations were identified in 80% of the samples. Within the H3K27M-mutant tumors, PDGFRA amplification, loss of 17p and a complex chromosomal profile were significantly associated with worse survival. Three prognostic markers were identified in diffuse midline gliomas H3K27M-mutant: PDGFRA amplification, loss of 17p and a complex chromosomal profile. These markers are easy to detect in daily practice and should be considered to refine the prognosis of this entity.