A French single-center experience on allogeneic stem cell transplant cryopreservation during severe acute respiratory syndrome coronavirus 2 pandemic.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for chemo-resistant hematological malignancies. Because of transport restriction imposed by the coronavirus disease 2019 pandemic, regulatory bodies and societies recommended graft cryopreservation before recipient conditioning. However, the freezing and thawing processes, including washing steps, might impair CD34+ cell recovery and viability, thereby impacting the recipient engraftment. Over 1 year (between March 2020 and May 2021), we aimed to analyze the results of frozen/thawed peripheral blood stem cell allografts in terms of stem cell quality and clinical outcomes. METHODS: Transplant quality was evaluated by comparing total nucleated cells (TNCs), CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM)/kg numbers as well as TNC and CD34+ cell viabilities before and after thawing. Intrinsic biological parameters such as granulocyte, platelet and CD34+ cell concentrations were analyzed, as they might be responsible for a quality loss. The impact of the CD34+ cell richness of the graft on TNC and CD34 yields was evaluated by designing three groups of transplants based on their CD34 /kg value at collection: >8 × 10 6/kg, between 6 and 8 × 106/kg and <6 × 106/kg. The consequences of cryopreservation were compared in the fresh and thawed group by evaluating the main transplant outcomes. RESULTS: Over 1 year, 76 recipients were included in the study; 57 patients received a thawed and 19 patients a fresh allo-SCT. None received allo-SCT from a severe acute respiratory syndrome coronavirus 2-positive donor. The freezing of 57 transplants led to the storage of 309 bags, for a mean storage time (between freezing and thawing) of 14 days. For the fresh transplant group, only 41 bags were stored for potential future donor lymphocyte infusions. Regarding the graft characteristics at collection, median number of cryopreserved TNC and CD34+ cells/kg were greater than those for fresh infusions. After thawing, median yields were 74.0%, 69.0% and 48.0% for TNC, CD34+ cells and CFU-GM, respectively. The median TNC dose/kg obtained after thawing was 5.8 × 108, with a median viability of 76%. The median CD34+ cells/kg was 5 × 106, with a median viability of 87%. In the fresh transplant group, the median TNC/kg was 5.9 × 108/kg, and the median CD34+ cells/kg and CFU-GM/kg were 6 × 106/kg and 276.5 × 104/kg, respectively. Sixty-one percent of the thawed transplants were out of specifications regarding the CD34+ cells/ kg requested cell dose (6 × 106/kg) and 85% of them would have had this dose if their hematopoietic stem cell transplant had been infused fresh. Regarding fresh grafts, 15.8% contained less than 6 × 106 CD34+ cells /kg and came from peripheral blood stem cells that did not reach 6 × 106 CD34+ cells /kg at collection. Regarding the factor that impaired CD34 and TNC yield after thawing, no significant impact of the granulocyte count, the platelet count or the CD34+ cells concentration/µL was observed. However, grafts containing more than 8 × 10 6/kg at collection showed a significantly lower TNC and CD34 yield. CONCLUSIONS: Transplant outcomes (engraftment, graft-versus-host disease, infections, relapse or death) were not significantly different between the two groups.

Combination of serum and peritoneal 1.3-beta-D-glucan can rule out intra-abdominal candidiasis in surgical critically ill patients: a multicenter prospective study.

BACKGROUND: Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-D-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC. METHODS: This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako® beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell® beta-D-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements. RESULTS: Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54-72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5-1578.0] pg/ml) compared to non-IAC patients (133 [16.0-831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0-9.0] pg/ml) than in non-IAC patients (3 [3.0-3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0-211.0] pg/ml) than in non-IAC patients (50 [23.0-141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%. CONCLUSION: In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).

Intravitreal Injection of Bevacizumab for the Prevention of Postoperative Proliferative Vitreoretinopathy in High-Risk Patients Selected by Laser Flare Photometry.

INTRODUCTION: To evaluate the effect of an intravitreal injection of bevacizumab at the time of rhegmatogenous retinal detachment (RRD) surgery, on postoperative proliferative vitreoretinopathy (PVR) in high-risk patients selected by laser flare photometry. METHODS: This single-center observational retrospective cohort study included 137 consecutive patients who underwent pars plana vitrectomy and gas tamponade for primary RRD with increased aqueous flare between July 2016 and June 2021. From June 2019, an intravitreal injection of bevacizumab was administered as an adjunct to RRD repair. Patients who underwent surgery before this time and who did not receive intravitreal bevacizumab served as controls. The main outcome was the rate of retinal redetachment due to PVR. RESULTS: The median flare value was 22.0 (16.5-36.5) pc/ms in the control group and 28.2 (19.7-41.0) pc/ms in the bevacizumab group (p = 0.063). Eyes treated with bevacizumab were more likely to have macula-off RRD (p = 0.003), grade B PVR (p = 0.038), and worse visual acuity (p = 0.004) than controls. The rate of PVR redetachment was significantly lower in the bevacizumab group (11.1%) than in the control (30.1%) (p = 0.012). This difference was more pronounced after adjusting for potential confounding factors (p = 0.005); the risk of developing PVR was 4.5-fold higher in controls (95% CI, 1.6-12.8). After adjustment, the final median visual acuity was also significantly higher in eyes treated with bevacizumab (p = 0.025). CONCLUSION: This pilot study provides preliminary evidence that bevacizumab may reduce the risk of PVR-related recurrent RRD and improve visual outcomes in high-risk patients selected by laser flare photometry.

A Magnetic Resonance Imaging Index to Predict Crohn's Disease Postoperative Recurrence: The MONITOR Index.

BACKGROUND & AIMS: We developed and validated a magnetic resonance imaging-based index to predict Crohn's disease (CD) postoperative recurrence (POR). METHODS: Patients with CD who underwent a postoperative evaluation for recurrence (with colonoscopy and MRI no longer than 105 days apart) were included between 2006 and 2016 in University Hospital of Nancy, France. MRI items with good levels of intra-rater and inter-rater agreement (Gwet's coefficient ≥0.5) were selected. The MRI in Crohn's Disease to Predict Postoperative Recurrence (MONITOR) index's performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and accuracy, by considering the Rutgeerts score as the gold standard. The MONITOR index was validated with a bootstrap method and an independent cohort. RESULTS: Seventy-three MRI datasets were interpreted by 2 radiologists. Seven items (bowel wall thickness, contrast enhancement, T2 signal increase, diffusion-weighted signal increase, edema, ulcers, and the length of the diseased segment) had a Gwet's coefficient ≥0.5 and were significantly associated with the Rutgeerts score, leading to their inclusion in the MONITOR index. All the items had a weighting of 1, except the "ulcers" item weighting 2.5, reflecting the higher adjusted odds ratio. The AUROC [95% confidence interval] for the prediction of endoscopic POR (Rutgeerts score >i1) was 0.80 [0.70-0.90]. The optimal threshold was a MONITOR index ≥1, giving a sensitivity of 79%, a specificity of 55%, a predictive positive value of 68%, and a predictive negative value of 68%. The bootstrap validation gave an AUROC of 0.85 [0.73-0.97]. In the validation cohort, a MONITOR index ≥1 gave a sensitivity of 87%, a specificity of 75%, a predictive positive value of 84.6%, and a predictive negative value of 75%. CONCLUSIONS: The MONITOR index is an efficient, reliable, easy-to-apply tool that can be used in clinical practice to predict the POR of CD.

Relevance of sensitization to legumes in peanut-allergic children.

BACKGROUND: Legume consumption has increased during the two past decades. In France, legumes are responsible for 14.6% of food-related anaphylaxis in children, with peanut as the main allergen (77.5%). Few studies have demonstrated cross-reactivities between peanut and other legumes. The aim of this study was to determine prevalence and relevance of sensitization to legumes in peanut-allergic children. METHODS: All children, aged of 1-17 years, admitted to the Pediatric Allergy Department of the University Hospital of Nancy between January 1, 2017 and February 29, 2020 with a confirmed peanut allergy (PA) and a documented consumption or sensitization to at least one other legume were included. Data were retrospectively collected regarding history of consumption, skin prick tests, specific immunoglobulin E (IgE), prior allergic reactions, and oral food challenges for each legume. RESULTS: Among the 195 included children with PA, 122 were sensitized to at least one other legume (63.9%). Main sensitizations were for fenugreek (N = 61, 66.3%), lentil (N = 38, 42.2%), soy (N = 61, 39.9%), and lupine (N = 63, 34.2%). Among the 122 sensitized children, allergy to at least one legume was confirmed for 34 children (27.9%), including six children who had multiple legume allergies (4.9%). Lentil, lupine, and pea were the main responsible allergens. Half of allergic reactions to legumes other than peanut were severe. CONCLUSION: The high prevalence of legume sensitization and the frequent severe reactions reported in children with PA highlight that tolerated legume consumption should be explored for each legume in the case of PA, and sensitization should be investigated if not.

Continuous wound infusion combined with intrathecal morphine for analgesia after Cesarean delivery compared with intrathecal morphine or continuous wound infusion alone.

STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT02279628); registered 31 October 2014.

Incidence of and Risk Factors for Colorectal Strictures in Ulcerative Colitis: A Multicenter Study.

BACKGROUND & AIMS: Ulcerative colitis (UC) is increasingly recognized as a progressive disease and patients with long-standing disease can develop colorectal stricture. Few data about its incidence in UC are available, while risk factors for colorectal strictures in UC remain to be determined. We assessed the incidence of and risk factors for developing colorectal strictures in a large UC population. METHODS: All adult patients followed at Nancy University hospital and at the centre hospitalier de Luxembourg for UC, between January 2004 and July 2019, were eligible for inclusion in this multicenter retrospective cohort study. RESULTS: A total of 439 patients with UC were included. Median follow-up duration was 9.6 years. Incidence of colorectal stricture was 3.6%. The cumulative probability of developing this complication was 1% at 5 years and 2.3% at 10 years. Median age at stricture diagnosis was 47.9 years (41.0; 63.0), and median time from UC diagnosis to onset of stricture was 11.5 years (5; 15.3). Montreal A3 classification (age > 40 years) (P = .008) and steroids use (HR = 4.1; 95% CI, 1.1-16.1) were independent risk factors for stricture, whereas mesalamine-treated patients carried a lower risk (HR = 0.3; 95% CI, 0.1-0.9). Dysplasia was found in 6 patients with strictures (42.9%) and among them 5 developed a colorectal cancer (33.3%). CONCLUSIONS: Patients with Montreal A3 classification and those exposed to steroids have a higher risk for strictures, while use of mesalamine lowers this risk. These factors should be assessed in daily clinical practice to prevent stricture occurrence in these patients.

Serum and peritoneal exudate concentrations after high doses of ß-lactams in critically ill patients with severe intra-abdominal infections: an observational prospective study.

BACKGROUND: Critically ill patients with severe intra-abdominal infections (IAIs) requiring surgery may undergo several pharmacokinetic (PK) alterations that can lead to ß-lactam underdosage. OBJECTIVES: To measure serum and peritoneal exudate concentrations of ß-lactams after high doses and optimal administration schemes. METHODS: This observational prospective study included critically ill patients with suspicion of IAI who required surgery and a ß-lactam antibiotic as empirical therapy. Serum and peritoneal exudate concentrations were measured during surgery and after a 24 h steady-state period. The PK/pharmacodynamic (PD) target was to obtain serum ß-lactam concentrations of 100% fT>4×MIC based on a worst-case scenario (based on the EUCAST highest epidemiological cut-off values) before bacterial documentation (a priori) and redefined following determination of the MIC for the isolated bacteria (a posteriori). Registered with ClinicalTrials.gov (NCT03310606). RESULTS: Forty-eight patients were included with a median (IQR) age of 64 (53-74) years and a SAPS II of 40 (32-65). The main diagnosis was secondary nosocomial peritonitis. Piperacillin/tazobactam was the most administered ß-lactam antibiotic (75%). The serum/peritoneal piperacillin/tazobactam ratio was 0.88 (0.64-0.97) after a 24 h steady-state period. Prior to bacterial documentation, 16 patients (33.3%) achieved the a priori PK/PD target. The identification of microorganisms was available for 34 patients (71%). Based on the MIC for isolated bacteria, 78% of the patients achieved the serum PK/PD target. CONCLUSIONS: In severe IAIs, high doses of ß-lactams ensured 100% fT>4×MIC in the serum for 78% of critically ill patients with severe IAIs within the first 24 h. In order to define optimal ß-lactam dosing, the PK/PD target should take into account the tissue penetration and local ecology.

[Parental representations of children's acute appendicitis and impact on its surgical management in three departments]. / Représentations parentales de l'appendicite de l'enfant et leurs conséquences sur le traitement chirurgical.

INTRODUCTION: Appendicitis is well known by the general and medical population. Yet, the number of appendectomies varies by a factor of one to four depending on French departments.Purpose of research: This study aimed to compare, according to French schooling departments, the representations and attitudes of parents facing abdominal pain of their children, and their use of health care system. We selected three departments which have different proportions of use of appendectomy according to the DRESS's rapport of 2014. Meurthe-et-Moselle's rank is between 15.65 and 23.48/10 000 people, Seine-et-Marne's rank is between 23.48 and 31.30/10 000, and Jura's rank is superior to 31/10 000. RESULTS: 797 questionnaires were analyzed (45.2%). Significant differences exist in the answers of the three departments. Residents of the Jura region and, in a lesser measure, Seine-et-Marnaises answered differently than Meurthe-et-Mosellanses. The first two were the populations who experienced the most appendectomies and the Meurthe-et-Mosellanses the least. Parents who lived in departments of high rank of appendectomy thought more of acute appendicitis when confronted with their children's abdominal pain, and feared less of appendectomy. They were also more in favor of surgical treatment than parents from Meurthe-et-Moselle. CONCLUSION: Knowledge, attitude and use of health care system seem to influence management of acute appendicitis in children's population and can explain, at least partially, the variations of the appendectomy rate in France. Targeted information for physicians may improve the understanding of patients and reassure them if needed in the purpose of reducing this factor of influence of practices.

Are infection specialists recommending short antibiotic treatment durations? An ESCMID international cross-sectional survey.

Objectives: To evaluate the current practice and the willingness to shorten the duration of antibiotic therapy among infection specialists. Methods: Infection specialists giving at least weekly advice on antibiotic prescriptions were invited to participate in an online cross-sectional survey between September and December 2016. The questionnaire included 15 clinical vignettes corresponding to common clinical cases with favourable outcomes; part A asked about the antibiotic treatment duration they would usually advise to prescribers and part B asked about the shortest duration they were willing to recommend. Results: We included 866 participants, mostly clinical microbiologists (22.8%, 197/863) or infectious diseases specialists (58.7%, 507/863), members of an antibiotic stewardship team in 73% (624/854) of the cases, coming from 58 countries on all continents. Thirty-six percent of participants (271/749) already advised short durations of antibiotic therapy (compared with the literature) to prescribers for more than half of the vignettes and 47% (312/662) chose shorter durations in part B compared with part A for more than half of the vignettes. Twenty-two percent (192/861) of the participants declared that their regional/national guidelines expressed durations of antibiotic therapy for a specific clinical situation as a fixed duration as opposed to a range and in the multivariable analysis this was associated with respondents advising short durations for more than half of the vignettes (adjusted OR 1.5, P = 0.02). Conclusions: The majority of infection specialists currently do not advise the shortest possible duration of antibiotic therapy to prescribers. Promoting short durations among these experts is urgently needed.

Survival Impact of Stations of Pathological Lymph Nodes in N2 Non-small Cell Lung Cancer in a French Hospital.

BACKGROUND: The prognosis of lung cancer remains poor; only 20% of patients can undergo surgery. N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease. We conducted a retrospective study to analyze the impact of N2 location on survival. METHODS: This study included 342 NSCLC with N2 involvement between 1988 and 2014. Patient-related data were collected through the CRB biobank and included demographic, therapeutic, and survival data. Survival was analyzed according to Kaplan-Maier method. Cox's regression analysis and analysis of variance (ANOVA) were used to determine factors significantly associated with survival. RESULTS: The population average age was 61.6 years; 82.2% were men, a majority were former smokers (87.1%), and 45.3% had adenocarcinoma. The main prognostic factors were male gender (p = 0.01), number of nodes (p < 0.0001), and tumor size (p < 0.0001). N2 disease had a poor survival (16 months) compared with N0 (32 months) and N1 (21.1 months) disease (p < 0.0001). The patients with involvement of station 4 (survival = 17.8 months) seemed to have a prognosis between those with station 7 (survival = 10.5 months) and N1 (survival = 22.6 months), p = 0.0005. CONCLUSIONS: N2 location has a prognostic impact in surgically NSCLC, and station 4 involvement has a better prognostic than station 7.

Management of bloodstream infections by infection specialists in France and Germany: a cross-sectional survey.

INTRODUCTION: Bloodstream infections (BSI) are frequent infections worldwide. Our objective was to explore variation in the management of patients with BSI by infection specialists in France and Germany. METHODS: This work is part of an international ESCMID cross-sectional internet-based questionnaire survey that was opened from December 2016 to February 2017. All hospital-based infection specialists, senior or trainees, giving at least weekly advice on positive blood cultures could participate. Their practices were evaluated using six clinical vignettes presenting an uncomplicated BSI due to different pathogens. RESULTS: A hundred and ninety-six professionals (125 from Germany and 71 from France) participated. Systematic expert advice for positive blood cultures was more often available in Germany as compared with France (73 vs. 56%, p = 0.004). In Germany, the professional providing the expert advice was more often a microbiologist or a pharmacist as compared with France (p = 0.001 and p = 0.037, respectively) where it was more often an infectious diseases specialist. Fewer German respondents reported to advise systematic IV-oral switch of antibiotic therapy. German respondents also recommended less often combination therapy: for example for Enterococcus faecalis (64 vs. 43%, p = 0.015), ESBL E. coli (94 vs. 67%, p < 0.001) and Pseudomonas aeruginosa (76 vs. 37%, p < 0.001). Overall, management of candidaemia was more often compliant with the IDSA guidelines in France as compared with Germany, but no difference was noted for MRSA bacteraemia. CONCLUSION: Our survey shows that wide variations exist between two neighboring countries in the recommendations by infection specialists for the management of BSI. International guidelines are needed.

Anxious and depressive symptoms in the French Asbestos-Related Diseases Cohort: risk factors and self-perception of risk.

Background: Asbestos is known to be an independent risk factor for lung and pleural cancers. However, to date, little attention has been paid to the psychological effects of asbestos exposure among exposed subjects. The objectives of this study were to estimate the prevalence of anxious and depressive symptoms among >2000 French participants of the Asbestos-Related Diseases Cohort (ARDCO), 6 years after their inclusion, to identify the risk factors associated with those anxious and depressive symptoms and to evaluate the impact of the asbestos-risk perception. Methods: The ARDCO was constituted in four regions of France between October 2003 and December 2005, by including former asbestos workers. Between 2011 and 2012, participants of the ARDCO program were invited to undergo another chest CT scan 6 years after the previous scan. Participants were asked to complete questionnaires including asbestos exposure assessment, Hospital Anxiety and Depression Scale (HADS), asbestos-risk perception and self-perception of asbestos-related diseases. Results: Among the 2225 participants, 2210 fully completed questionnaires were collected and analyzed. The prevalence of symptoms of probable anxiety and probable depression was 19.7% and 9.9%, respectively. The risk of anxious and depressive symptoms was independently associated with self-perception of the intensity of asbestos exposure, asbestos-risk perception and self-perception of asbestos-related diseases. Conclusion: The results obtained in this large study confirm that previously asbestos-exposed subjects are likely to develop anxious and depressive symptoms. Finally, implications related to the prevention of anxiety and depression among asbestos-exposed workers is discussed.

Cancer of the esophagus and asbestos exposure.

BACKGROUND: Our study aimed at analyzing incidence and mortality from esophageal cancer within a cohort of workers with previous occupational asbestos exposure (ARDCo Program). METHODS: A 10-year follow-up study was conducted in the 14 515 male subjects included in this program between October 2003 and December 2005. Follow-up began when exposure stopped. Asbestos exposure was analyzed by industrial hygienists using data from a standardized questionnaire. The Cox model was used, with age as the time axis variable adjusted for smoking, time since first exposure (TSFE) and cumulative exposure index (CEI) of exposure to asbestos. RESULTS: We reported a significant dose-response relationship between CEI of exposure to asbestos and esophageal cancer, in both incidence (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.00-1.58), and mortality (HR 1.40, [95%CI 1.12-1.75]). CONCLUSIONS: This large-scale study suggests the existence of a relationship between asbestos exposure and cancer of the esophagus.

Asbestos exposure, pleural plaques, and the risk of death from lung cancer.

RATIONALE: Although asbestos is a well-known lung carcinogen, the pleural plaque-lung cancer link remains controversial. OBJECTIVES: This study was designed to examine this link in asbestos-exposed workers. METHODS: A 6-year follow-up was conducted to study lung cancer mortality in the 5,402 male subjects participating in an asbestos-related disease screening program conducted from October 2003 to December 2005 in four French regions. Chest computed tomography (CT) scan was performed in all subjects with randomized, independent, double reading of CT scans focusing on benign asbestos-related abnormalities. Cox model survival regression analysis was used to model lung cancer mortality according to the presence of pleural plaques, with age as the main time variable, adjusting for smoking and asbestos cumulative exposure index. All statistical tests were two-sided. MEASUREMENTS AND MAIN RESULTS: Thirty-six deaths from lung cancer were recorded. Lung cancer mortality was significantly associated with pleural plaques in the follow-up study in terms of both the unadjusted hazard ratio of 2.91 (95% confidence interval = 1.49-5.70) and the adjusted hazard ratio of 2.41 (95% confidence interval = 1.21-4.85) after adjustment for smoking and asbestos cumulative exposure index. CONCLUSIONS: Pleural plaques may be an independent risk factor for lung cancer death in asbestos-exposed workers and could be used as an additional criterion in the definition of high-risk populations eligible for CT screening.

Inter-reader agreement in HRCT detection of pleural plaques and asbestosis in participants with previous occupational exposure to asbestos.

OBJECTIVES: To investigate inter-reader agreement for the detection of pleural and parenchymal abnormalities using CT in a large cross-sectional study comprising information on individual cumulative exposure to asbestos. METHODS: The project was approved by the hospital ethics committee, and all patients received information on the study and gave their written informed consent. In 5511 CT scans performed in a cohort of retired workers previously exposed to asbestos and volunteering to participate in a multiregional survey programme (Asbestos Related Diseases Cohort, ARDCO), double randomised standardised readings, triple in case of disagreement, were performed by seven trained expert radiologists specialised in thoracic imaging and blind to the initial interpretation. Inter-reader agreement was evaluated by calculating the κ-weighted coefficient between pairs of expert readers and results of routine practice and final diagnosis after expert reading. RESULTS: κ-Weighted coefficients between trained experts ranged from 0.28 to 0.52 (fair to good), 0.59 to 0.86 (good to excellent) and 0.11 to 0.66 (poor to good) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. κ-Weighted coefficients between results of routine practice and final diagnosis after expert reading were 0.13 (poor), 0.53 (moderate) and 0.11 (poor) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. CONCLUSIONS: Interpretation of benign asbestos-related thoracic abnormalities requires standardisation of the reading and trained readers, particularly for participants asking for compensation, and with a view to the longitudinal survey of asbestos-exposed workers.

One reaction - double stereoinduction: C-H activation as a privileged route towards complex atropisomeric molecules.

Expanding the importance of chirality and implementation of stereogenic information within complex molecular design has recently reached a new level: design of innovative enantiopure scaffolds bearing multiple chiral elements. In particular, regarding sustainability aspects and straightforward use of relatively simple substrates, the C-H activation strategy offers unique opportunities to assemble complex chiral molecules with unique topologies while controlling two stereoselective events in a single transformation. Herein, the emerging field of asymmetric C-H activation allowing rapid construction of atropisomeric molecules bearing a second chirality element, such as a stereogenic center, vicinal chiral axis or planar chirality, is described. Aiming at in-depth comprehension of such innovative systems, the emphasis is put on the nature of stereodiscriminant steps, allowing the simultaneous control of both chiral elements.

Congenital hypothyroidism in children with eutopic gland or thyroid hemiagenesis: prognostic factors for transient vs. permanent hypothyroidism.

OBJECTIVES: More than one third of children with congenital hypothyroidism (CH) and thyroid gland in situ (or eutopic gland) have transient hypothyroidism. It remains difficult to determine early on whether hypothyroidism will be transient which may cause overtreatment and its complications in these children. Our primary aim was to determine prognostic factors for transient hypothyroidism in children with congenital hypothyroidism and eutopic gland or thyroid hemiagenesis. METHODS: We retrospectively reviewed medical records of 111 children, born between 1996 and 2017, diagnosed with congenital hypothyroidism and eutopic gland or hemiagenesis and treated at the Nancy Regional and University Hospital. RESULTS: Fifty four infants (48.6%) had permanent congenital hypothyroidism (PCH) and 57 (51.4%) transient congenital hypothyroidism (TCH). Prognostic factors for TCH included prematurity, twin pregnancy, low birth weight and Apgar score <7, while low FT3 at diagnosis, maternal levothyroxine treatment, a family history of thyroid dysfunction and TSH ≥10 mUI/L while receiving treatment were associated with PCH. Knee epiphyses on X-ray at diagnosis were absent only in children with PCH. The median levothyroxine dose during follow-up was significantly lower in the TCH group compared to the PCH group. A levothyroxine dose of ≤3.95, ≤2.56, ≤2.19 and ≤2.12 µg/kg/day at 6 months, 1, 2 and 3 years of follow-up, respectively, had the best sensitivity-to-specificity ratio for predicting TCH. CONCLUSIONS: Even though it remains difficult to predict the course of hypothyroidism at diagnosis, we were able to identify several prognostic factors for TCH including perinatal problems and lower levothyroxine requirements that can guide the physician on the evolution of hypothyroidism. Clinical Trial Registration Number: NCT04712760.

Dissociated Optic Nerve Fiber Layer Appearance after Macular Hole Surgery: A Randomized Controlled Trial Comparing the Temporal Inverted Internal Limiting Membrane Flap Technique with Conventional Peeling.

PURPOSE: To evaluate the effect of the temporal inverted internal limiting membrane (ILM) flap technique compared with that of conventional ILM peeling on the extent of the dissociated optic nerve fiber layer (DONFL) and retinal sensitivity in patients undergoing macular hole (MH) surgery. DESIGN: Single-center, prospective, open-label, randomized controlled clinical trial. PARTICIPANTS: Patients requiring vitrectomy for MHs sized > 250 µm. METHODS: Patients were randomly assigned (1:1) to 1 of the following 2 groups: (1) the control group undergoing standard ILM peeling and (2) the experimental group (flap group) undergoing the temporal inverted ILM flap technique. MAIN OUTCOME MEASURES: The primary outcome measure was the total DONFL score at 3 months after surgery. Important secondary outcomes were microperimetry results, primary MH closure rate, external limiting membrane (ELM) and ellipsoid zone (EZ) recovery rates, and best-corrected visual acuity (BCVA). RESULTS: Sixty-five patients were recruited between February 2018 and July 2020; primary outcome data were available for 60 patients. The median DONFL score was 7.0 (3.0-12.5) in the control group and 5.0 (1.5-8.5) in the flap group at 3 months after surgery (P = 0.145). The focal depressions characteristic of the DONFL were limited to the temporal side of the fovea in the flap group, whereas they were found all around the fovea in the control group on spectral-domain OCT images. The MH closure rate (P = 1), EZ and ELM recovery rates (P = 0.252), and BCVA (P = 0.450) were similar between the 2 groups. The 3-month overall median retinal sensitivity (MRS) (P = 0.142) and MRS improvement (P = 0.916) in the control group were comparable with those observed in the flap group. In addition, there was no significant difference between the 2 techniques when considering the temporal area (P = 0.105) or the nasal area (P = 0.468). CONCLUSIONS: The temporal inverted ILM flap technique reduced the extent of the DONFL by preserving the nasal part of the fovea. However, the overall DONFL score was similar between the 2 techniques. In addition, the MRS and BCVA did not differ from those obtained after complete ILM peeling. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Soluble TREM-1 plasma concentration predicts poor outcome in COVID-19 patients.

BACKGROUND: The immuno-receptor Triggering Expressed on Myeloid cells-1 (TREM-1) is activated during bacterial infectious diseases, where it amplifies the inflammatory response. Small studies suggest that TREM-1 could be involved in viral infections, including COVID-19. We here aim to decipher whether plasma concentration of the soluble form of TREM-1 (sTREM-1) could predict the outcome of hospitalized COVID-19 patients. METHODS: We conducted a multicentre prospective observational study in 3 university hospitals in France. Consecutive hospitalized patients with confirmed infection with SARS-CoV-2 were enrolled. Plasma concentration of sTREM-1 was measured on admission and then at days 4, 6, 8, 14, 21, and 28 in patients admitted into an ICU (ICU cohort: ICUC) or 3 times a week for patients hospitalized in a medical ward (Conventional Cohort: ConvC). Clinical and biological data were prospectively recorded and patients were followed-up for 90 days. For medical ward patients, the outcome was deemed complicated in case of requirement of increased oxygen supply > 5 L/min, transfer to an ICU, or death. For Intensive Care Unit (ICU) patients, complicated outcome was defined by death in the ICU. RESULTS: Plasma concentration of sTREM-1 at inclusion was higher in ICU patients (n = 269) than in medical ward patients (n = 562) (224 pg/mL (IQR 144-320) vs 147 pg/mL (76-249), p < 0.0001), and higher in patients with a complicated outcome in both cohorts: 178 (94-300) vs 135 pg/mL (70-220), p < 0.0001 in the ward patients, and 342 (288-532) vs 206 pg/mL (134-291), p < 0.0001 in the ICU patients. Elevated sTREM-1 baseline concentration was an independent predictor of complicated outcomes (Hazard Ratio (HR) = 1.5 (1.1-2.1), p = 0.02 in ward patients; HR = 3.8 (1.8-8.0), p = 0.0003 in ICU patients). An sTREM-1 plasma concentration of 224 pg/mL had a sensitivity of 42%, and a specificity of 76% in the ConvC for complicated outcome. In the ICUC, a 287 pg/mL cutoff had a sensitivity of 78%, and a specificity of 74% for death. The sTREM-1 concentrations increased over time in the ConvC patients with a complicated outcome (p = 0.017), but not in the ICUC patients. CONCLUSIONS: In COVID-19 patients, plasma concentration of sTREM-1 is an independent predictor of the outcome, although its positive and negative likelihood ratio are not good enough to guide clinical decision as a standalone marker.