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International audience; Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1)

Highlights • Brachytherapy boost is a standard of care for locally advanced cervical cancer. • High-dose-rate brachytherapy (HDR-BT) boost procedure is not standardized. • The number of implants, fractions, doses and imaging differ in literature. • Bi-fractionated HDR-BT in 1 implant is feasible with good oncological outcome. • Bi-fractionated HDR-BT dose escalation slightly increases acute toxicity., Purpose Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT. Patients and methods This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported. Results From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45–132] and median EQD210D90CTVHR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81–90], 83% [79–86], 70% [67–73], 61% [57–64] and 75% [69–78] respectively, with no significant difference between the groups. EQD210D90CTVHR

Work-related asthma (WRA) accounts for 10-25% of all adult asthma. It therefore seems important to raise questions regarding an asthmatic's approach to occupational or job training activities. WRA takes on two forms: work-exacerbated asthma (WEA) and occupational asthma (OA), which encompasses different subtypes of heterogeneous mechanisms. It currently represents a major challenge for occupational medicine in terms of detailed diagnosis, social care, the economic repercussions for workers and employers and, last but not least, social insurance. This review aims to sensitize health care practitioners to the peculiarities of WRA management in routine practice. More specifically, prognosis depends on early diagnosis, medical care and work adjustment measures. WEA and OA are explained in detail in view of identifying causative agents and at-risk occupations and defining adapted medical strategy. Relevant lines of questioning and complementary exams are presented. In addition, the key role of the occupational physician, especially as regards recognition and identification of occupational disease, is underlined, the objective being to facilitate optimal professional and social management. In future studies, the key role of counseling and orientation mechanisms should be highlighted as means of preventing WRA occurrence.

Introduction Multikinase inhibitor (MKI) treatments have shown efficacy in progressive radioiodine refractory thyroid cancers (RAIR-TC), but most patients experienced substantial adverse effects. This randomised multicentric study investigated intermittent versus continuous pazopanib administration. Patients and methods The PAZOTHYR study included RAIR-TC patients with progressive disease in the last 12 months, who may have received one prior MKI. RAIR-TC patients received pazopanib for 6 months, and patients with stable disease or tumour response were randomly assigned (1:1) to receive continuous (CP) or intermittent (IP) pazopanib until progression. The primary end-point was time to treatment failure (TTF) defined as the time from randomisation to permanent discontinuation of pazopanib, due to any cause. One hundred randomised patients were needed to demonstrate an increase from 50% (CP) to 70% (IP) (hazard ratio (HR) 0.515, 80% power) in the rate of patients still under treatment 6 months (6m-SuT) post-randomisation. Secondary end-points included the overall response rate (ORR), progression-free survival (PFS) under pazopanib and safety. Results RAIR-TC patients (168) enrolled from June 18, 2013 to January 16, 2018, received 6-month pazopanib treatment and showed 35.6% (95% CI 28.2–43.6) best response rate and 89.4% (83.5–93.7) disease control rate. One hundred patients were randomised (IP:50; CP:50). With a median follow-up of 31.3 months, median TTF was not statistically different between arms (IP:14.7, 95% confidence interval (CI) 9.3–17.4; CP:11.9, 95% CI 7.5–15.6) months (HR 0.79, 0.49–1.27). 6m-SuT rates were similar (IP:80% 66.0–88.7%; CP:78% 63.8–87.2%). Median PFS under pazopanib were not statistically different (IP:5.7 4.8–7.8; CP: 9.2 7.3–11.1) months (HR 1.36, 0.88–2.12). Pazopanib-related adverse events grade 3–4 occurred in 36 (IP: 19, 38%; CP: 17, 34%) randomised patients. Seven pazopanib-related deaths occurred. Conclusions Intermittent administration of pazopanib did not demonstrate significant superiority in efficacy or tolerance compared with continuous treatment. An intermittent administration scheme cannot be recommended outside clinical trials. This study was registered with ClinicalTrial.gov , number NCT01813136 .

The objective of this cohort study was to determine whether hypercalcemia in early COVID-19 was associated with 3-month mortality in frail elderly patients. Circulating calcium and albumin concentrations at hospital admission and 3-month mortality were assessed in geriatric patients hospitalized for COVID-19 with normal-to-high calcium concentrations. Hypercalcemia was defined as corrected calcium >2.5mmol/L. Covariables were age, sex, functional abilities, malignancies, hypertension, cardiomyopathy, number of acute health issues, use antibiotics and respiratory treatments. In total, 94 participants (mean±SD 88.0±5.5years;47.9% women;22.3% hypercalcemia;0% hypocalcemia) were included. Sixty-five participants who survived at 3months exhibited less often hypercalcemia at baseline than the others (13.9% versus 41.4%, P=0.003). Hypercalcemia was associated with 3-month mortality (fully-adjusted HR=3.03, P=0.009) with specificity=0.86 and sensitivity=0.41. Those with hypercalcemia had shorter survival time than those with normocalcemia (log-rank P=0.002). In conclusion, hypercalcemia was associated with poorer survival in hospitalized frail elderly COVID-19 patients. © 2021, Serdi-Editions and Springer-Verlag France.

Background Lyme borreliosis (LB) is the most frequent tick-borne disease in France. In the absence of a vaccine, LB prevention mainly relies on reducing tick bites. In 2016, the French Ministry of Health launched a national plan against tick-borne infections, including a prevention component. To evaluate the impact of this prevention strategy, we assessed knowledge and practices of tick bite prevention using the 2016 and 2019 national surveys on health attitudes and beliefs known as the French Health Barometer. Methods The Health Barometer is a repeated nationwide phone survey conducted annually on a random sample aged 18 to 75 years living in mainland France. In 2016 and 2019, participants were asked, among others, about their exposure to ticks, their behavior and practices regarding tick bites, and their knowledge about LB and its prevention. Results In 2019, 30% of the population reported a lifetime tick bite and 6% in the last year, an increase from 25% and 4%, respectively, in 2016 (p p p p p Conclusions A substantial proportion of French residents are exposed to tick bites and apply protective measures. Our findings indicate a trend toward an increased knowledge and awareness of tick bites and LB between 2016 and 2019 in France. Our results can be used to target future information campaigns to specific age groups or at-risk areas in addition to the general population. However, we need to further study the barriers to the use of preventive measures.

Supplemental Digital Content is available in the text., Background. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in kidney transplant recipients (KTRs) remain rare. We sought to shed further light on this issue by conducting a single-center study in a kidney transplant center located in one of the France’s highest risk zone (Grand Est) for coronavirus disease 2019 (Covid-19) during the initial disease outbreak. Methods. To this aim, we used a survey approach coupled with systematic investigation of SARS-CoV-2 serology in a cohort of 1390 KTRs. Results. SARS-CoV-2 serologies were available for 780 survey respondents, among whom 48 had anti-SARS-CoV-2 antibodies (total seroprevalence: 6.2%). Thirty-five of the 48 seropositive KTRs had previously received a diagnosis of Covid-19, whereas the remaining 13 patients were not known to be infected (8 asymptomatic cases). Specifically, 18.7% of seropositive KTRs and 1.1% of the entire cohort were asymptomatic. Household exposure was found to markedly increase the risk of SARS-CoV-2 transmission. Conclusions. Our findings demonstrate that the overall SARS-CoV-2 seroprevalence in KTRs living in one of the France’s highest risk zone for Covid-19 during the first French lockdown was as low as 6.3%. Rapid and strict implementation of protective measures could have significantly mitigated virus spread even in an area of high virus circulation.

The origin of penile metastases is in 70% of cases from primary pelvic cancers (genitourinary and recto-sigmoid primary tumors). The prognosis is poor and it is often associated with synchronous bone metastases at the time of diagnosis. We present the case of a 61-year-old patient who developed a penile induration 7 years after radical prostatectomy followed by adjuvant external beam radiation therapy for high-risk prostatic adenocarcinoma. Biopsies confirmed the metastatic localization and a detailed assessment failed to find any further remote lesions. Faced with this penile oligometastatic prostate cancer, we proposed an ablative treatment based on interstitial multi-catheter high-dose rate brachytherapy. At the six-month follow-up, clinical examination and 68Ga-PSMA-11-PET confirmed a complete response of the penile tumor without new lesion at a distance.

BACKGROUND: Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC). OBJECTIVE: To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models. DESIGN, SETTING, AND PARTICIPANTS: This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models. RESULTS AND LIMITATIONS: Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p

Introduction Sertoliform cystadenoma is a very rare, benign lesion of the rete‐testis difficult to distinguish from other malignancies of the testicle. Case presentation We present the case of a 42‐year‐old male who presented with a right testicular mass, asymptomatic for 1 year. Clinical examination revealed a palpable, painless, and well‐delimited right testicular superior pole nodule. Testicular ultrasound confirmed the nodule, whereas serum tumoral markers were normal. The patient underwent inguinal partial orchiectomy. Intraoperative excisional biopsy and frozen section pathology were performed, reporting undetermined tumoral origin with negative surgical margins. Ischemia time was 12 minutes. The final pathology report showed a Sertoliform cystadenoma of rete testis, with immunomorphology positive for AE1, CK7, and negative surgical margins. Conclusion To our knowledge, this is the first report of testicular sparing surgery for Sertoliform cystadenoma, a very rare benign tumor of rete testis. All previously reported cases were managed by radical inguinal orchidectomy.

OBJECTIVE Bone biopsy (BB) performed by a surgeon or an interventional radiologist is recommended for suspicion of osteomyelitis underlying diabetic foot ulcer (DFU). To facilitate its practice, we developed a procedure allowing bedside blind bone biopsy (B4) by a diabetologist. RESEARCH DESIGN AND METHODS We conducted a three-step observational study consisting of a feasibility and safety phase (phase 1) to assess the success and side effects of B4, a validity phase (phase 2) to compare DFU outcomes between positive (B4+) and negative (B4−) bone cultures, and a performance phase (phase 3) to compare B4 with the conventional surgical or radiological procedure basic bone biopsy (B3). Primary end points were the presence of bone tissue (phase 1) and complete DFU healing with exclusive medical treatment at 12 months (phases 2 and 3). RESULTS In phase 1, 37 consecutive patients with clinical and/or radiological suspicion of DFU osteomyelitis underwent B4. Bone tissue was collected in all patients with few side effects. In phase 2, a B4+ bone culture was found in 40 of 79 (50.6%) participants. Among B4+ patients, complete wound healing after treatment was 57.5%. No statistical difference was observed with patients with B4− bone culture not treated with antibiotics (71.8%, P = 0.18). In phase 3, the proportion of patients with positive BB was lower in B4 (40 of 79, 50.6%) than in B3 (34 of 44, 77.3%, P < 0.01). However, complete healing was similar (64.6% vs. 54.6%, P = 0.28). No difference in rate of culture contamination was observed. CONCLUSIONS B4 is a simple, safe, and efficient procedure for the diagnosis of DFU osteomyelitis with a similar proportion of healing to conventional BB.

Summary Objective This study aimed to describe reports of psychiatric adverse drug reaction (ADR) in the spectrum of bipolar (manic features) or psychotic disorders that occurred under tumor necrosis factor alpha (TNF-α) inhibitors therapy. Methods We searched the French pharmocovigilance database for reports of psychiatric ADR in the spectrum of bipolar (manic features) or psychotic disorders during treatment with TNF-α inhibitors. Psychiatric symptoms were divided in 2 categories: (i) confirmed diagnosis of manic episode or acute psychosis and (ii) psychiatric symptoms with psychotic or manic features but not meeting sufficient criteria for diagnosis of psychosis or manic disorder. Results Overall, 9942 reports of ADR were registered in the French pharmacovigilance database with TNF-α inhibitors, including 243 reports of psychiatric ADR. Among them, we identified 41 reports of psychotic or manic disorders as define above: 9 characterised manic episodes and 32 psychiatric disorders with psychotic or manic features. TNF-α inhibitors were the only medication suspected in 23 reports (56%). The delay between starting TNF-α inhibitors treatment and onset of symptoms varied from hours to years with a median time of 40 days. Psychiatric symptoms improved in 22/23 patients in whom the TNF-α inhibitor was withdrawn. Conclusion Depressive disorders are well-known ADR of TNF-α inhibitors, but we report, here, 41 reports of psychiatric ADR diagnosed as manic or psychotic disorders or in the spectrum of bipolar or psychotic disorders with these treatments. Epidemiological studies are needed to confirm this signal.

International audience; Purpose: Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015.Methods: This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression.Results: Among the 771 enrolled patients (median age 66 years, IQR [52.0-79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines.Conclusion: We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients.Clinical trial: ClinicalTrial. Gov identification number: NCT01730690.

Accelerated partial breast irradiation (APBI) represents a validated technique for low-risk breast cancer. Recently, ultra-APBI (uAPBI) using fewer than 5 fractions was described in the literature. We compared clinical outcomes and late toxicity after APBI or uAPBI in older patients.Two cohorts of older patients (aged ≥70 years) with low-risk breast cancer treated with APBI (interstitial brachytherapy) were analyzed retrospectively. A total dose of 34 Gy in10 fractions (APBI) or 16 Gy in 1 fraction (uAPBI) was delivered from 2004 to 2012 and from 2013 to 2018, respectively. Oncologic outcome analyzed the cumulative incidence of local relapse, regional relapse, and distant metastases with disease-free survival, cause-specific survival, and overall survival. Late toxicity and cosmetic results were investigated.One hundred fifty-seven patients (APBI, n = 109 patients; uAPBI, n = 48 patients) underwent APBI according to the same selection criteria. Apart from the median follow-up (97 vs 72 months for APBI and uAPBI; P.002), no significant difference was noted between the 2 groups. Regarding 6-year oncologic outcome, no significant difference was observed between APBI and uAPBI for local recurrence (1.3% vs 0%; P = .4), regional recurrence (2.5% vs 2.3%; P = .9), distant metastases (4.3% vs. 2.4%; P = .6), disease-free survival (85.2% vs. 82.2%; P = .8), cause-specific survival (96.7% vs. 96.2%; P = .9), and overall survival (86.7% vs. 82.2%; P = .7). Regarding late toxicity, no significant difference was observed between APBI and uAPBI (total complication number, 45 vs 33%; P = .173) with only grade 1 (88.4% vs. 95%) and grade 2 (11.6% vs. 5%) late toxicities (P = .677). Similarly, no significant difference was observed for excellent/good cosmetic results between the 2 cohorts (P = .98).We report the first study comparing APBI versus uAPBI in a cohort of older patients with low-risk breast cancer. No significant difference was found between the 2 treatment groups regarding oncologic outcome, late toxicity, and cosmetic result. uAPBI based on a single fraction of brachytherapy represents an attractive option for therapeutic de-escalation in older patients with breast cancer.

Objective: to monitor the current trends and developments in organ donation and transplantation in the Russian Federation based on the 2020 data.Materials and methods. Heads of organ transplant centers were surveyed through questionnaires. Data control was done using the information accounting system of the Russian Ministry of Health. Between separate federal subjects of the Russian Federation and between transplantation centers, comparative analysis of data obtained over years was performed.Results. Based on data retrieved from the 2020 Registry, 44 kidney, 29 liver and 16 heart transplantation programs were functioning in the Russian Federation in 2020. The kidney transplant waitlist in 2020 included about 11.5% of the total 60,000 patients receiving dialysis. Organ donation activity in 2020 was 3.9 per million population, with a 74.6% multi-organ procurement rate and an average of 2.9 organs being procured from one effective donor. In 2020, there were 7.7 kidney transplants per million population, 3.8 liver transplants per million population and 1.7 heart transplants per million population. Same year, the number of transplant surgeries performed in the Russian Federation fell by 19.2% to 13.4 per million population against the background of the outbreak caused by the new coronavirus disease COVID-19. The city of Moscow and the Moscow region in 2020 accounted for 13 out of the 14 functioning organ transplantation centers, performing 66.3% of all kidney transplants and 72.4% of all extrarenal transplants in the country. The number of organ recipients in the Russian Federation have exceeded 130 per million population.Conclusion. In 2020, despite the new coronavirus disease COVID-19 pandemic and accompanying restrictive measures, transplant centers continued to perform organ transplants, run a waiting list and monitor organ recipients. However, the number of effective donors (–22.9%) and organ transplants (–19.2%) decreased, tentatively to the 2017 levels. In 2021, transplant centers with support from health authorities will have to restore the volume of transplant care with consideration to the real needs of the population and the donor resource. The COVID-19 factor, including vaccination of the population, as well as financial support to transplantation programs, will be decisive in shaping the trend of transplantation care and organ donation in the federal subjects of the Russian Federation in the coming 1–2 years.

Resume Introduction La photo-vaporisation selective de la prostate (PVP) par le laser Greenlight XPS®-180 W (AMS, San Jose, USA) est une option dans le traitement chirurgical de l’hyperplasie benigne de la prostate (HBP). L’objectif de notre travail etait d’etudier les effets de la densite d’energie delivree pour la vaporisation prostatique sur les resultats postoperatoires et le taux de PSA total serique. Patients et methodes Une etude retrospective monocentrique a ete conduite dans le service d’urologie des hopitaux civils de Colmar, chez des patients avec une HBP symptomatique, traites par PVP, entre janvier 2016 et janvier 2019. Nous avons reparti les patients en deux groupes selon la densite d’energie delivree rapportee au volume prostatique mesure en preoperatoire : faible densite ( 4 kJ/mL). L’evaluation a porte sur la survenue de complications postoperatoires, l’evolution du taux de PSA total serique et les resultats fonctionnels (score IPSS, score de qualite de vie liee aux symptomes urinaires, debit urinaire maximal et residu post-mictionnel) avec un recul minimal de 6 mois. Resultats Au total, 215 patients ont ete inclus avec un suivi median de 25 mois. Une densite energetique elevee etait associee a un volume glandulaire moins important. La diminution du PSA Total postoperatoire etait superieure dans le groupe de haute energie (41 % vs 28 %, p = 0,03). Il n’existait pas de difference significative selon la densite d’energie delivree concernant les complications per- et postoperatoires et les resultats fonctionnels. Le taux de reintervention etait comparable dans les deux groupes. Conclusion Les complications postoperatoires et les resultats fonctionnels de la PVP avec le laser Greenlight XPS-180 W sont comparables en fonction de la densite d’energie delivree. La diminution plus importante du PSA total postoperatoire pour une densite d’energie elevee pourrait neanmoins evoquer une destruction tissulaire de meilleure qualite. Niveau de preuve 3.

Objective A real-world, randomized study assessing the impact of a new, personalized, pharmacist-led text messaging service for managing type 2 diabetes (T2D). Methods Messages were tailored to patient’s needs based on their disease management habits, propensity for reactance, and physical activity levels at baseline. Treatment adherence (assed using the Morisky Medication Adherence Scale, MMAS-8, questionnaire), clinical factors (body mass index and physical activity) and biological markers for T2D were compared between patients who received a text message daily for 3 months in addition to standard care (SMS group) and those who received standard care alone (control group). Results 114 pharmacies recruited 499 patients. Greater increases in global MMAS-8 scores were observed after 3 months for the SMS group than for the control group, however, this improvement was not sustained after the text messages stopped. Body mass index was found to improve with the text messaging service. Conclusion This study indicated that personalized text messages provided by community pharmacists can have an impact on adherence levels among T2D patients. Practice implications Pharmacy-led innovations, such as text messaging services, could be used to accompany patients in their treatment and to improve patient understanding of their illness between healthcare appointments.

BackgroundEvidence-based international expert consensus regarding the impact of peripheral nerve block (PNB) use in total hip/knee arthroplasty surgery.MethodsA systematic review and meta-analysis: randomized controlled and observational studies investigating the impact of PNB utilization on major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, thromboembolic, neurologic, infectious, and bleeding complications.Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, were queried from 1946 to August 4, 2020.The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess evidence quality and for the development of recommendations.ResultsAnalysis of 122 studies revealed that PNB use (compared with no use) was associated with lower ORs for (OR with 95% CIs) for numerous complications (total hip and knee arthroplasties (THA/TKA), respectively): cognitive dysfunction (OR 0.30, 95% CI 0.17 to 0.53/OR 0.52, 95% CI 0.34 to 0.80), respiratory failure (OR 0.36, 95% CI 0.17 to 0.74/OR 0.37, 95% CI 0.18 to 0.75), cardiac complications (OR 0.84, 95% CI 0.76 to 0.93/OR 0.83, 95% CI 0.79 to 0.86), surgical site infections (OR 0.55 95% CI 0.47 to 0.64/OR 0.86 95% CI 0.80 to 0.91), thromboembolism (OR 0.74, 95% CI 0.58 to 0.96/OR 0.90, 95% CI 0.84 to 0.96) and blood transfusion (OR 0.84, 95% CI 0.83 to 0.86/OR 0.91, 95% CI 0.90 to 0.92).ConclusionsBased on the current body of evidence, the consensus group recommends PNB use in THA/TKA for improved outcomes.Recommendation: PNB use is recommended for patients undergoing THA and TKA except when contraindications preclude their use. Furthermore, the alignment of provider skills and practice location resources needs to be ensured. Evidence level: moderate; recommendation: strong.

Background: Injectable soft-tissue devices are increasingly used for improving skin defects and deficiencies related to ageing. Objectives: To assess the safety and efficacy of KIO015, a new injectable soft-tissue device formulated with carboxymethyl chitosan for the intradermal treatment of skin defects associated with ageing. Materials & Methods: Twenty-two subjects (40–65 years) were randomized to receive injections in the neckline of KIO015 and a non-cross-linked HA-based device, and were followed for up to 10 months. Injection site reactions (ISRs) and adverse events (AEs) were documented. Skin improvement was assessed instrumentally and clinically. Skin biopsies at injection zones in the lower back were taken at Day 28 for histopathology and immunohistochemistry analyses, to further assess product performance. Histomorphometric analyses on rabbits and in vitro assessment of KIO015 antioxidant capacity were also conducted. Results: KIO015 was very well tolerated. Only expected and transient ISRs were observed; mainly erythema and hematoma. No adverse local effects or foreign body granuloma were observed histologically. Both clinical and instrumental evaluations confirmed the performance of KIO015. The skin was firmer and more elastic. Skin hydration showed significant improvement three days after injection. KIO015 exhibited superior overall maintenance of skin hydration after 10 months as compared to HA. These clinical results were supported by in vitro trials and implantation tests in the rabbit. Conclusion: The results from this pilot study support the use of KIO015 as an innovative alternative to HA-based devices for intradermal treatment of skin disorders.

To determine the prevalence of diabetic retinopathy (DR) and its risk factors in adult type 1 diabetes (T1D) patients METHODS: In this cross-sectional study, all T1D patients followed in the University Center for Diabetes and its Complications of Lariboisière Hospital (Paris, France) between January 2017 and February 2019 were included. Ophthalmologic and systemic data were collected from electronic records. The association between DR (and each grade) and associated factors were estimated by univariate and multivariate analyses using logistic regression models.A total of 1464 patients (46.2% of women, mean age: 42.2 ± 15.8 years) were included. The mean hemoglobin A1c (HbA1c) was 7.8 ± 1.7% and the mean diabetes duration was 20.5 ± 13.5 years. DR prevalence was 50.1% (47.4-52.6) and the prevalence of mild, moderate, and severe non-proliferative DR and proliferative DR was 19.1%, 9.4%, 3.9%, and 17.6%, respectively. DR was significantly associated with male gender, an older age, former and current smoking status, a higher BMI, the presence of nephropathy and neuropathy, higher HBA1c, and longer diabetes duration. Patients with HbA1c 10% had an adjusted odds ratio (OR) of 3.25 (1.77-6.01) of having DR compared to patients with HbA1c 6.5%. Patients with a diabetes duration 30 years had an adjusted OR of 24.87 (14.82-42.67) higher of having DR compared to patients with a diabetes duration 10 years.In this study, 50.1% of adult T1D patients had DR and 17.6% had proliferative DR. Diabetes duration and HbA1c were major risk factors.

Kidney injury in heart transplant recipients is of a complex nature and bears the features of all types of cardiorenal interaction impairment. Pre-transplant renal dysfunction, perioperative acute kidney injury, as well as factors associated with graft and immunosuppression, determine the prevalence and severity of kidney pathology in this group of patients. This review examines the pathophysiology of kidney dysfunction in heart failure, the epidemiology, and criteria for acute kidney injury.

International audience; The use of immunomodulatory and/or immunosuppressive therapy (IT) is increasingly common in the management of chronic inflammatory disease. Skin reactions to any drug (IT or not) are not rare in these patients, justifying allergological investigations. The influence of IT on allergological tests for drugs is not clearly described. IT cannot be interrupted due to the underlying disease. The data assessing the benefit and the safety of allergological test for drug allergy in patients under IT are missing.

Aims Our retrospective analysis reports the outcome of patients operated for slipped capital femoral epiphysis using the modified Dunn procedure. Results, complications, and the need for revision surgery are compared with the recent literature. Methods We retrospectively evaluated 17 patients (18 hips) who underwent the modified Dunn procedure for the treatment of slipped capital femoral epiphysis. Outcome measurement included standardized scores. Clinical assessment included ambulation, leg length discrepancy, and hip mobility. Radiographically, the quality of epiphyseal reduction was evaluated using the Southwick and Alpha-angles. Avascular necrosis, heterotopic ossifications, and osteoarthritis were documented at follow-up. Results At a mean follow-up of more than nine years, the mean modified Harris Hip score was 88.7 points, the Hip Disability and Osteoarthritis Outcome Score (HOOS) 87.4 , the Merle d’Aubigné Score 16.5 points, and the UCLA Activity Score 8.4. One patient developed a partial avascular necrosis of the femoral head, and one patient already had an avascular necrosis at the time of delayed diagnosis. Two hips developed osteoarthritic signs at 14 and 16 years after the index operation. Six patients needed a total of nine revision surgeries. One operation was needed for postoperative hip subluxation, one for secondary displacement and implant failure, two for late femoroacetabular impingement, one for femoroacetabular impingement of the opposite hip, and four for implant removal. Conclusion Our series shows good results and is comparable to previous published studies. The modified Dunn procedure allows the anatomic repositioning of the slipped epiphysis. Long-term results with subjective and objective hip function are superior, avascular necrosis and development of osteoarthritis inferior to other reported treatment modalities. Nevertheless, the procedure is technically demanding and revision surgery for secondary femoroacetabular impingement and implant removal are frequent. Cite this article: 2020;1-4:80–87.

The management of complicated distal femur fractures (DFF) of the elderly continues to pose a challenge. Knee mega-prosthesis are mostly used for Total knee arthroplasty revision and tumor resection surgery but they can be used for the treatment of complex knee fractures. The purpose of the present study is to examine the short- to mid- term outcomes of their use for complex DFF of the elderly. We retrospectively identified 4 patients with DFF AO33C3 on osteoporotic bone treated by total knee arthroplasty from September 2015 to October 2019. The average age at the time of the surgery was 79,5 years (range, 69 to 95 years). All patients were females and underwent a total knee replacement by one senior surgeon, with the OSS TM Orthopaedic Salvage System (Zimmer Biomet, Warsaw, Indiana, USA). Outcome measures included clinical outcome scores, radiological analyses, reoperation rate and complications. At an average follow-up of 2,3 years (range, 0,6 to 4,2 years), the average Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) was 17,25 (range, 7 to 37), the average Oxford knee score was 35,25 (range, 25 to 41) and the average pain Numerical Rating Scale (NRS) was 0,5 (range, 0 to 1). 3 Patients had postoperative anemia but no implant related complications has been reported. Complex DFF of the elderly treated with mega knee arthroplasty exhibit good clinical outcomes scores. The patients should be selected carefully as the complication rate found in the literature remains high.

Tuberculosis (TB) is a major cause of morbidity and mortality in children, and early diagnosis and treatment are crucial to reduce long-term morbidity and mortality. In this study, we explore whether urine nuclear magnetic resonance (NMR)-based metabolomics could be used to identify differences in the metabolic response of children with different diagnostic certainty of TB. We included 62 children with signs and symptoms of TB and 55 apparently healthy children. Six of the children with presumptive TB had bacteriologically confirmed TB, 52 children with unconfirmed TB, and 4 children with unlikely TB. Urine metabolic fingerprints were identified using high- and low-field proton NMR platforms and assessed with pattern recognition techniques such as principal components analysis and partial least squares discriminant analysis. We observed differences in the metabolic fingerprint of children with bacteriologically confirmed and unconfirmed TB compared to children with unlikely TB (p = 0.041 and p = 0.013, respectively). Moreover, children with unconfirmed TB with X-rays compatible with TB showed differences in the metabolic fingerprint compared to children with non-pathological X-rays (p = 0.009). Differences in the metabolic fingerprint in children with different diagnostic certainty of TB could contribute to a more accurate characterisation of TB in the paediatric population. The use of metabolomics could be useful to improve the prediction of TB progression and diagnosis in children.

Context Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear. Objective To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. Design Setting and Participants We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020. Main Outcome Measure(s) The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. Results Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those 80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in Conclusions Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.

Objective. To evaluate the efficacy and safety of an endoscopic bag during laparoscopic morcellation of leiomyoma or myomatous uterus. Materials and Methods. A total of 48 patients with symptomatic leiomyoma were randomized for laparoscopic morcellation in two groups: group A with a specific endoscopic bag or group B without any bag. The primary outcome measure was the detection of smooth muscle cells from washing after power morcellation determined by peritoneal cytology and immunohistochemistry (IHC). Results. Cytology and IHC from group A did not revealed any smooth muscle cells, while 29% of cases (7/24) from group B were positive ( p = .009 ). The duration of the surgical procedure was the same in both groups. The duration of positioning the bag did not change significantly during the study. Only in one case the use of the bag was difficult due to a low pneumoperitoneum. Conclusions. The use of a morcellation bag is efficient to prevent the spread of smooth muscle cells during the morcellation of leiomyoma or myomatous uterus. This study confirms the feasibility and the safety of the laparoscopic inbag morcellation versus open morcellation.

Background A high prevalence of pulmonary embolism (PE) has been described during COVID‐19. Our aim was to identify predictive factors of PE in non‐ICU hospitalized COVID‐19 patients. Methods Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID‐19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. Results A total of 88 patients (median [IQR] age of 68 years [60‐78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D‐dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3‐74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3‐1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7‐553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D‐dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0‐397.9], P = .004). Conclusion The white blood count, the D‐dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non‐ICU COVID‐19 patients.

To evaluate the diagnostic performance and interobserver agreement of a magnetic resonance imaging (MRI) protocol that only includes sagittal T2-weighted Dixon fat and water images as an alternative to a standard protocol that includes both sagittal T1-weighted sequence and T2-weighted Dixon water images as reference standard in lumbar degenerative disc disease with Modic changes. From February 2017 to March 2019, 114 patients who underwent lumbar spine MRI for low back pain were included in this retrospective study. All MRI showed Modic changes at least at one vertebral level. Two radiologists read the standard protocol and 1 month later the alternative protocol. All MRI were assessed for Modic changes (types, location, extension) as well as structural changes (endplate defects, facet arthropathy, spinal stenosis, foraminal stenosis, Schmorl nodes, spondylolisthesis, disc bulges, and degeneration). Interobserver agreement was assessed, as well as diagnostic performance using the standard protocol as reference standard. Interobserver agreement was moderate to excellent (kappa ranging from 0.51 to 0.92). Diagnostic performance of the alternative protocol was good for detection of any Modic change (sensitivity = 100.00% [95% CI, 99.03–100.00]; specificity = 98.89% [95% CI, 98.02–99.44]), as well as for detection of each Modic subtype and structural variables (sensitivity respectively 100% and ranging from 88.43 to 99.75% ; specificity ranging respectively from 97.62 to 100% and 99.58 to 99.91% ). Combined with T2-weighted Dixon water images, T2-weighted Dixon fat images provide good diagnostic performance compared to T1-weighted images in lumbar degenerative disc disease with Modic changes, and could therefore allow for a shortened protocol. • Combined with T2-weighted Dixon water images, T2-weighted Dixon fat images (in comparison to T1-weighted sequence) can provide good diagnostic performance in lumbar degenerative disc disease with Modic changes. • Interobserver agreement of the alternative protocol including sagittal T2-weighted Dixon fat and water images was substantial to excellent for every studied variable except for facet arthropathy. • A shortened MRI protocol including T2-weighted Dixon sequence without T1-weighted sequence could be proposed in this clinical setting.

The public French Cord Blood Banks Network was established in 1999 with the objective of standardizing the practices governing umbilical cord blood (UCB) banking in France. The Network adopted a strategy to optimize its inventory and improve the quality of its banked units based on a quality improvement process using outcome data regularly provided by Eurocord. This study aimed to describe the results, over 10 years, of UCBT facilitated by a national network that used the same criteria of UCB collection and banking and to assess how modifications of banking criteria and unit selection might influence transplant outcomes. Nine hundred and ninety-nine units (593 single-unit and 203 double-unit grafts) were released by the Network to transplant 796 patients with malignant (83%) and non-malignant (17%) diseases. Median cell dose exceeded 3.5 × 107 TNC/kg in 86%. There was a trend to select units more recently collected and with higher cell dose. Neutrophil engraftment was 88.2% (85.7–90.7) and 79.3% (72.6–86.5) respectively for malignant and non-malignant diseases with a trend to faster recovery with higher cell doses. The respective 3-year transplant-related mortality were 31.1% (27.5–35.1) and 34.3% (27.0–43.5). OS was 49% ± 4 in malignant and 62% ± 4 in non-malignant disorders. In multivariate analysis, cell dose was the only unit-related factor associated with outcomes. Our results reflect the benefit on clinical outcomes of the strategy adopted by the Network to bank units with higher cell counts.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis. Only limited data are available on the characteristics and outcomes of patients hospitalized for COVID-19 in France. Aims: To investigate the characteristics, cardiovascular complications and outcomes of patients hospitalized for COVID-19 in France. Methods: The Critical COVID-19 France (CCF) study is a French nationwide study including all consecutive adults with a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection hospitalized in 24 centres between 26 February and 20 April 2020. Patients admitted directly to intensive care were excluded. Clinical, biological and imaging parameters were systematically collected at hospital admission. The primary outcome was in-hospital death. Results: Of 2878 patients included (mean ± SD age 66.6 ± 17.0 years, 57.8% men), 360 (12.5%) died in the hospital setting, of which 7 (20.7%) were transferred to intensive care before death. The majority of patients had at least one (72.6%) or two (41.6%) cardiovascular risk factors, mostly hypertension (50.8%), obesity (30.3%), dyslipidaemia (28.0%) and diabetes (23.7%). In multivariable analysis, older age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03−1.06; P < 0.001), male sex (HR 1.69, 95% CI 1.11−2.57; P = 0.01), diabetes (HR 1.72, 95% CI 1.12−2.63; P = 0.01), chronic kidney failure (HR 1.57, 95% CI 1.02−2.41; P = 0.04), elevated troponin (HR 1.66, 95% CI 1.11−2.49; P = 0.01), elevated B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide (HR 1.69, 95% CI 1.0004−2.86; P = 0.049) and quick Sequential Organ Failure Assessment score ≥ 2 (HR 1.71, 95% CI 1.12−2.60; P = 0.01) were independently associated with in-hospital death. Conclusions: In this large nationwide cohort of patients hospitalized for COVID-19 in France, cardiovascular comorbidities and risk factors were associated with a substantial morbi-mortality burden.

COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19.Trial registration: NCT04435223.

BackgroundAll prevention efforts currently being implemented for COVID-19 are aimed at reducing the burden on strained health systems and human resources. There has been little research conducted to understand how SARS-CoV-2 has affected health care systems and professionals in terms of their work. Finding effective ways to share the knowledge and insight between countries, including lessons learned, is paramount to the international containment and management of the COVID-19 pandemic. The aim of this project is to compare the pandemic response to COVID-19 in Brazil, Canada, China, France, Japan, and Mali. This comparison will be used to identify strengths and weaknesses in the response, including challenges for health professionals and health systems.MethodsWe will use a multiple case study approach with multiple levels of nested analysis. We have chosen these countries as they represent different continents and different stages of the pandemic. We will focus on several major hospitals and two public health interventions (contact tracing and testing). It will employ a multidisciplinary research approach that will use qualitative data through observations, document analysis, and interviews, as well as quantitative data based on disease surveillance data and other publicly available data. Given that the methodological approaches of the project will be largely qualitative, the ethical risks are minimal. For the quantitative component, the data being used will be made publicly available.DiscussionWe will deliver lessons learned based on a rigorous process and on strong evidence to enable operational-level insight for national and international stakeholders.

Bariatric surgery may be associated with severe postoperative complications (SPC). Factors associated with the risk of SPC have not been fully investigated. This study aimed to identify preoperative risk factors of SPC within 90 days and to develop a risk prediction model based on these factors. We conducted a retrospective single-center cohort study based on a prospectively maintained database of obese patients undergoing laparoscopic bariatric surgery from October 2005 to May 2019. All SPC occurring up to the 90th postoperative day were recorded according to the Dindo-Clavien classification. Associations between potential risk factors and SPC were analyzed using a logistic regression model, and the risk prediction (“OS-SEV90 score”) was computed. Based on the OS-SEV90 score, the patients were grouped into 3 categories of risk: low, intermediate, and high. Among 1963 consecutive patients, no patient died and 82 (4.2%) experienced SPC within 90 days. History of gastric or esophageal surgery (adjusted odds ratio (aOR) 3.040, 95% confidence interval; CI 1.78–5.20, p< 0.0001), past of thromboembolic event aOR 2.26, 95%; CI 1.12–4.55, p = 0.0225), and surgery performed by a junior surgeon (aOR 1.99, 95%; CI 1.26–3.13, p = 0.003) were all independently associated with risk for SPC, adjusting for ASA physical status system (ASA) score ≥ 3, severe OSA, psychiatric disease, asthma, a history of abdominal surgery, alcohol, cardiac disease, and dyslipidemia. “the OS-SEV90 score” based on these factors was constructed to classify patients into 3 risk groups: low (≤2), intermediate (3–4), and high (≥5). According to “the OS-SEV90 score,” SPC increased significantly from 2.9% in the low-risk group, 7.7% in the intermediate-risk group, and 23.3% in the high-risk group. A predictive model of SPC within 90 days “the OS-SEV90 score” has been developed using 9 baseline risk factors. The use of the OS-SEV90 score may help the multidisciplinary team to identify the specific risk of each patient and inform them about and optimize the comorbidities before the surgery. Further studies are warranted to validate this score in a new independent cohort before using it in clinical practice.

Bronchial complications are among the main causes of impairing postoperative period and thansplant failure. Severe bronchial complications are very rare but have a high mortality rate. Light forms decrease transplant function and while progressing can leads to life-threatening conditions without required treatment. Nowadays there is a huge necessity in classification of diagnostic and bronchial complications treatment on different terms after lung transplantation. Methods of observation bronchoscopy and interventional bronchology are allowing us to realize prevention, diagnostic and treatment bronchial complications.

Introduction Better understanding how hospital staff members (HSMs), including HCWs, were contaminated by SARS-CoV-2 during the first wave can help refining the control measures, in the context of the current second wave in Europe. Methods From March 5th to May 10th 2020, the infectious diseases unit at Raymond-Poincare teaching Hospital opened a weekday consultation dedicated to HSMs for a PCR testing. While in the waiting room, HSMs were offered to complete a questionnaire on their potential risk exposure to SARS-CoV-2. Results Of the 200 HSMs screened, 70 were positive. Ninety-nine HSMs (including 86 HCWs) completed the questionnaire of whom 28 cases positive. In the multivariable analysis among healthcare workers, age ≥ 44 years-old (aOR = 5.2, 95%CI [1.4-22.5]), not using a facemask systematically when caring for a patient (aOR = 13.9, 95%CI [1.8-293.0]), were significantly associated with SARS-CoV-2 infection. Conversely, working in a ward dedicated to COVID-19 patients (aOR = 0.7, 95%CI [0.2-3.2]) was not significantly associated with SARS-CoV-2 infection. Regarding community related exposures occurring in and outside the hospital among the HSMs, participation to meetings inside the hospital without wearing a facemask (aOR = 21.3, 95%CI [4.5-143.9]) and participation to private gathering (aOR = 10, 95%CI [1.3-91.0]) were significantly associated with SARS-CoV-2 infection. Conclusions Our results support the effectiveness of barrier precautions, underline that in-hospital contaminations not related to patient care may occur, and that part of the contaminations may be related to exposures in the community. Better protecting HCWs against COVID-19 and thereby ensuring workforces is crucial to fight the current second wave of the epidemic.

A significant number of studies invoked diabetes as a risk factor for virus infections, but the issue remains controversial. We aimed to examine whether non-autoimmune diabetes mellitus enhances the risk of virus infections compared with the risk in healthy individuals without non-autoimmune diabetes mellitus. In this systematic review and meta-analysis, we assessed case-control and cohort studies on the association between non-autoimmune diabetes and viruses. We searched PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science with no language restriction, to identify articles published until February 15, 2021. The main outcome assessment was the risk of virus infection in individuals with non-autoimmune diabetes. We used a random-effects model to pool individual studies and assessed heterogeneity (I2) using the χ2 test on Cochrane’s Q statistic. This study is registered with PROSPERO, number CRD42019134142. Out of 3136 articles identified, we included 68 articles (90 studies, as the number of virus and or diabetes phenotype varied between included articles). The summary OR between non-autoimmune diabetes and virus infections risk were, 10.8(95% CI: 10.3–11.4; 1-study) for SARS-CoV-2; 3.6(95%CI: 2.7–4.9, I2 = 91.7%; 43-studies) for HCV; 2.7(95% CI: 1.3–5.4, I2 = 89.9%, 8-studies;) for HHV8; 2.1(95% CI: 1.7–2.5; 1-study) for H1N1 virus; 1.6(95% CI: 1.2–2.13, I2 = 98.3%, 27-studies) for HBV; 1.5(95% CI: 1.1–2.0; 1-study) for HSV1; 3.5(95% CI: 0.6–18.3 , I2 = 83.9%, 5-studies) for CMV; 2.9(95% CI: 1–8.7, 1-study) for TTV; 2.6(95% CI: 0.7–9.1, 1-study) for Parvovirus B19; 0.7(95% CI: 0.3–1.5 , 1-study) for coxsackie B virus; and 0.2(95% CI: 0–6.2; 1-study) for HGV. Our findings suggest that, non-autoimmune diabetes is associated with increased susceptibility to viruses especially SARS-CoV-2, HCV, HHV8, H1N1 virus, HBV and HSV1. Thus, these viruses deserve more attention from diabetes health-care providers, researchers, policy makers, and stakeholders for improved detection, overall proper management, and efficient control of viruses in people with non-autoimmune diabetes.

Background Evidence continues to demonstrate that certain marginalised populations are disproportionately affected by COVID-19. While many studies document the impacts of COVID-19 on social inequalities in health, none has examined how public health responses to the pandemic have unfolded to address these inequities in Canada. The purpose of our study was to assess how social inequalities in health were considered in the design and planning of large-scale COVID-19 testing programs in Montréal (Québec, Canada). Methods Part of the multicountry study HoSPiCOVID, this article reports on a qualitative case study of large-scale testing for COVID-19 in Montréal. We conducted semi-structured interviews with 19 stakeholders involved in planning large-scale testing or working with vulnerable populations during the pandemic. We developed interview guides and a codebook using existing literature on policy design and planning, and analysed data deductively and inductively using thematic analysis in NVivo. Results Our findings suggest that large-scale COVID-19 testing in Montréal did not initially consider social inequalities in health in its design and planning phases. Considering the sense of urgency brought by the pandemic, participants noted the challenges linked to the uptake of an intersectoral approach and of a unified vision of social inequalities in health. However, adaptations were gradually made to large-scale testing to improve its accessibility, acceptability, and availability. Actors from the community sector, among others, played an important role in supporting the health sector to address the needs of specific subgroups of the population. Conclusions These findings contribute to the reflections on the lessons learned from COVID-19, highlighting that public health programs must tackle structural barriers to accessing healthcare services during health crises. This will be necessary to ensure that pandemic preparedness and response, including large-scale testing, do not further increase social inequalities in health.

We assessed 3-year anatomic and functional results using synthetic glue to fix mesh in laparoscopic sacrocolpopexy. Prospective multicenter cohort study in three academic urogynecology departments. Seventy consecutive patients with stage ≥ 3 POP-Q (Pelvic Organ Prolapse Quantification) anterior and/or apical prolapse underwent laparoscopic sacrocolpopexy using synthetic surgical glue to fix anterior and posterior meshes to the vagina. Patients were followed up at 1, 2 and 3 years. Primary outcome was anterior and apical anatomic success (POP-Q stage ≤ 1) at 3 years. Secondary outcomes comprised functional results (international quality of life and sexuality scales), mesh-related morbidity and urinary incontinence at 3 years. Mean age was 56.7 ± 1.2 years. Mean follow-up was 43 months. Anterior compartment anatomic success rate was 87% at 2 years (Ba, −2.4 cm; p

International audience; The purpose of this study was to analyze the influence of grade of obesity on the probability of achieving a VO2 plateau and threshold secondary criteria for verifying VO2max during a treadmill walk test in youths with obesity. Therefore, 72 youths with obesity (aged 8-16) performed an incremental treadmill walk test to exhaustion during which oxygen uptake (VO2), minute ventilation (VE), heart rate (HR) and rating of perceived exertion were continuously measured. HR corresponding to a “hard” level of perceived exertion was reported and expressed as a percentage of the predicted HRmax. The rate of achievement of criteria for validation VO2max (VO2 plateau; HR>95% theoretical HRmax; RER>1.0; rating of perceived exertion ≥ “hard”) was compared between participants with grade I and grade II obesity. 37% of the participants achieved a VO2 plateau and 23% achieved both an HR>95% and RER >1.0. Youths with grade II obesity had lower minute ventilation (p95% (OR = 0.33; P=0.06) and a “hard” rating of perceived exertion than grade I (OR = 4.5; P=0.07). However, there was no influence of grade of obesity on the achievement of VO2 plateau, and RER>1.0.

Objective: To evaluate the role of incomplete metastasectomy (IM) for patients with metastatic renal cell carcinoma (mRCC) on overall survival (OS) and time to introduction of first-line systemic therapy. Methodology: Patients diagnosed with mRCC between Jan 2011 and Apr 2019 in 16 centers were selected from the Canadian Kidney Cancer information system database. We included mRCC patients who had prior nephrectomy and had received an IM (resection of at least 1 metastasis) or no metastasectomy (NM). A propensity score matching was performed to minimize selection bias. Cox proportional hazards analysis was used to assess the impact of the metastasectomy while adjusting for potential confounders. OS was assessed by Kaplan-Meier analysis. Results: A total of 138 patients with mRCC underwent IM, while 1221 patients did not. On multivariate analysis, IM did not improve OS (hazard ratio [HR] 0.96, 95% CI 0.63 to 1.45, P = 0.836) However, subgroup analyses revealed IM improved OS compared with NM when lungs were the only site involved (median time to OS not reached versus 66 months, respectively; P = 0.014). Additionally, lung metastasectomy delayed the systemic therapy compared with NM (median 41 and 13 months, respectively, P = 0.014). IM of endocrine organs (thyroid, pancreas, adrenals) or bone metastases did not impact OS. Conclusion: The role of IM for mRCC is limited. Incomplete resection of lung metastases was associated with improved OS and delayed time to introduction of systemic therapy when lungs were the sole location of metastatic disease. Despite case-matching, unknown unadjusted confounders may explain the relationship between IM and survival in this analysis.

Patients with rheumatoid arthritis (RA) are eligible for treatment with therapeutic monoclonal antibodies (mAbs) that target tumor necrosis factor α (TNFα), as well as others, such as rituximab (RTX) and tocilizumab (TCZ). Although pharmacokinetic variability and the link between concentration-clinical response of anti-TNFα mAbs have been well-described, little is known about RTX and TCZ. We aimed to evaluate the variability of RTX and TCZ serum concentrations in RA patients treated in second-line and the relationship between RTX/TCZ concentrations and the clinical response. Serum mAb trough concentrations of RA patients treated with RTX (n = 35) or TCZ (n = 46) were determined at week 24 by liquid chromatography-tandem mass spectrometry. The clinical response was assessed at week 24 by the change in the disease activity score in the 28 joints-erythrocyte sedimentation rate from baseline (ΔDAS28-Erythrocyte Sedimentation Rate) and according to the European League Against Rheumatism (EULAR) recommendations. RTX and TCZ trough concentrations were highly variable, with a coefficient of variation of 171.3% for RTX (median [10th-90th percentiles]

BACKGROUND AND PURPOSES Cerebral microhaemorrhages (CMHs) are associated with cognitive decline in humans. In rodents, CMHs induces cognitive impairment in male mice along with sex-specific cortical and hippocampal changes affecting neural, glial and vascular functions. Statins, have been proposed to prevent cognitive decline. We tested here the action of atorvastatin on CMH-induced cognitive impairment in a murine model of CMH. EXPERIMENTAL APPROACH Using a multimodal approach combining behavioural tests, in vivo imaging, biochemistry and molecular biology, the effects of oral administration of atorvastatin on the sex-specific changes induced by a cortical CMH were studied in male and female mice (C57BL/6J) at 6-week post-induction using a collagenase-induced model. KEY RESULTS Atorvastatin caused specific effects according to the sex-specific CMH-induced changes. In males, atorvastatin improved the visuospatial memory, induced a local modulation of microglial response and enhanced brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (trkB) and vascular endothelial growth factor (VEGF) expression in the cortex. In the hippocampus, atorvastatin increased glucose metabolism and modulated astrocytes morphology. In females, atorvastatin did not modulate visuospatial memory despite the increased expression of cortical BDNF and the decrease in the number of hippocampal astrocytes. Atorvastatin also induced a decrease in the expression of cortical oestrogen receptors but did not modify body weight nor serum cholesterol levels in both sexes. CONCLUSION AND IMPLICATIONS Atorvastatin modulated the sex-specific cognitive impairment induced by the CMH with a pathophysiological impact mainly within the cortical area. It could represent a promising candidate for future sex-stratified clinical trials in patients with CMH.

Summary Background Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of β-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. Methods We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with β-lactam therapy were randomly assigned (1:1) to receive β-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. Findings Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of β-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or β-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the β-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0–84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the β-lactam group (between-group difference of 9·42%, 95% CI −0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the β-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI −0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the β-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the β-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the β-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). Interpretation Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing β-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. Funding French Ministry of Health.