Strasbourg University Research Articles

Acute myeloid leukemia with mutated RUNX1 at the university hospitals of Strasbourg

RUNX1 is essential during human hematopoiesis. Numerous RUNX1 deregulations have been described, including translocations and germline or somatic mutations. Recurrent de novo RUNX1 mutations in acute myeloid leukemias (AML) prompted the creation of a provisional entity of AML with mutated RUNX1 in the 2016 WHO. In addition, recent genomic studies underlined rare AML patients with plasmacytoid dendritic cell (pDC) expansion and high RUNX1 mutations frequency. To better characterized AML with RUNX1 mutations, we retrospectively investigated a cohort of 32 patients diagnosed at Strasbourg University Hospital. Detailed clinical and biological features were aggregated. The presence of a pDC contingent was assessed by cytology and flow cytometry. In our cohort, no common features were identified either in term of cytology, stage of leukemia arrest or mutational features. Based on our observations, mutated RUNX1 AMLs do not appear to be a distinct AML entity. The new 2022 WHO classification includes AML with mutated RUNX1 within AML myelodysplasia-related category. We also identified within our cohort a patient whose AML fulfilled AML-pDC criteria, a rare and newly included entity in the last WHO classification.

Underdiagnosis of arbovirus infections in returned travelers in an area with growing circulation of Aedes albopictus in North-Eastern France

BackgroundVector-borne diseases such as malaria and arboviruses are common etiologies of post-travel fever. MethodsAfter excluding malaria, we retrospectively analyzed the diagnosis of dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) infections following recent travel by patients treated at the Strasbourg University Hospital between 2014 and 2023. Available serums (n = 35) sampled in 2023 were retrospectively tested for DENV, CHIKV, and ZIKV infections. ResultsOur results showed that 78% of the 915 malaria-negative patients without changes over the course of ten years had not undergone arbovirus infection testing. Retrospective testing revealed missing arbovirus infections: two DENV infections and one CHIKV infection, representing 8.6% (3/35) of patients for whom no mandatory declaration or vector control could be undertaken. ConclusionOur results highlight the need for early case detection, particularly in the context of the upcoming 2024 Olympic Games.

P-562 Molecular aspects of preimplantation genetic testing (PGT) for Neurofibromatosis type 1 (NF1) in three large European PGT centers: challenges and pitfalls

Abstract Study question What are the technical challenges and pitfalls of PGT for NF1 (n = 296 families) as experienced by three large European PGT centers? Summary answer The high (de novo) mutation rate and presence of germline mosaicism, especially in case of deletions, is challenging in PGT test development for NF1. What is known already NF1 is a neurocutaneous disorder with complete penetrance and extreme clinical variability. It is one of the most frequently requested autosomal dominant indications for PGT. The NF1 gene is large and has a high mutation rate. A high number of variants occur de novo, are mostly unique and more frequently associated with germline mosaicism in the index. These characteristics can pose difficulties in counseling, test development and PGT treatment. Large NF1 deletions are associated with a more severe phenotype and relative frequent mosaicism, but this has not been described in literature for intragenic deletions. Study design, size, duration Retrospective analysis of data on all test development procedures with the indication NF1 completed by August 2022 (n = 296). The data on test development were collected from medical files by the laboratories of the three participating PGT centers. The study was approved by the Medical and Ethical Review Committee of all three centers. The Medical Research Involving Human Subjects Act was not applicable. Participants/materials, setting, methods The three participating PGT centers were Maastricht University Medical Center (the Netherlands), University Hospital Brussels (Belgium) and Strasbourg University Hospital (France). Techniques applied were locus specific PCR-STR with or without the specific causative variant or genome wide haplotyping methods (NGS based OnePGT or karyomapping) or a combination of the above. Main results and the role of chance Test development was completed for 296 cases involving 228 different variants in the NF1 gene (125 truncating, 31 missense, 47 splice and 7 in-frame or synonymous variants, 8 larger deletions, 1 translocation, 9 awaiting further classification). We observed 36 recurring variants for 104 couples, of which 55 were sporadic cases, The majority of the 296 cases were sporadic (60%), signs of mosaicism were observed in 14 of these cases (8%). In our cohort, 6 sporadic cases involved a complete gene deletion (n = 1) or a deletion of ≥ 1 exons in the NF1 gene (n = 5). Mosaicism was detected in 4 of these cases (67%). In one case, the mutation was not detected in sperm cells during test set-up. PGT treatment was started for 10 couples with signs of mosaicism, in 6 no affected embryos were detected in 1-2 cycles and 1 resulted in a misdiagnosis because of phasing based on unaffected offspring. Two cases had NF1 caused by a different variant in the NF1 gene than their affected family members. A successful PGT test was developed in 289 cases (98%), 5 couples opted out during test development and in only 2 cases, development of a test was not possible for technical reasons. Limitations, reasons for caution The observed challenges and pitfalls depend on the techniques used and local procedures, so results may not be applicable to all PGT laboratories. However, due to the large sample size with exhaustive data and the fact that ESHRE guidelines were followed, there is probably little reason for caution. Wider implications of the findings Our findings could improve broader reproductive counseling of NF1 patients. Also, this large cohort contains previously unpublished variants in the NF1 gene, which is relevant for genetic diagnosis in NF1 patients in general. Our findings could possibly aid in test development for other autosomal dominant PGT indications with similar characteristics. Trial registration number Not applicable.

Theological faculties at the University of Strasbourg and the political role of Alsace in the interwar France

Theological faculties at the University of Strasbourg and the political role of Alsace in the interwar France

Infectious Mediastinitis: A Retrospective Cohort Study.

This study aimed to characterize the demographics, microbiology, management and treatment outcomes of mediastinitis according to the origin of the infection. This retrospective observational study enrolled patients who had mediastinitis diagnosed according to the criteria defined by the Centers for Disease Control and Prevention and were treated in Strasbourg University Hospital, France, between 1 January 2010 and 31 December 2020. We investigated 151 cases, including 63 cases of poststernotomy mediastinitis (PSM), 60 cases of mediastinitis due to esophageal perforation (MEP) and 17 cases of descending necrotizing mediastinitis (DNM). The mean patient age (standard deviation) was 63 (14.5) years, and 109 of 151 patients were male. Microbiological documentation varied according to the origin of the infection. When documented, PSM cases were mostly monomicrobial (36 of 53 cases [67.9%]) and involved staphylococci (36 of 53 [67.9%]), whereas MEP and DNM cases were mostly plurimicrobial (38 of 48 [79.2%] and 8 of 12 [66.7%], respectively) and involved digestive or oral flora microorganisms, respectively. The median duration of anti-infective treatment was 41 days (interquartile range, 21-56 days), and 122 of 151 patients (80.8%) benefited from early surgical management. The overall 1-year survival rate was estimated to be 64.8% (95% confidence interval, 56.6%-74.3%), but varied from 80.1% for DNM to 61.5% for MEP. Mediastinitis represents a rare yet deadly infection. The present cohort study exhibited the different patterns observed according to the origin of the infection. Greater insight and knowledge on these differences may help guide the management of these complex infections, especially with respect to empirical anti-infective treatments.

Knowledge-based, computerized, patient clinical decision support system for perioperative pain, nausea and constipation management: a clinical feasibility study

Opioid administration is particularly challenging in the perioperative period. Computerized-based Clinical Decision Support Systems (CDSS) are a promising innovation that might improve perioperative pain control. We report the development and feasibility validation of a knowledge-based CDSS aiming at optimizing the management of perioperative pain, postoperative nausea and vomiting (PONV), and laxative medications. This novel CDSS uses patient adaptive testing through a smartphone display, literature-based rules, and individual medical prescriptions to produce direct medical advice for the patient user. Our objective was to test the feasibility of the clinical use of our CDSS in the perioperative setting. This was a prospective single arm, single center, cohort study conducted in Strasbourg University Hospital. The primary outcome was the agreement between the recommendation provided by the experimental device and the recommendation provided by study personnel who interpreted the same care algorithm (control). Thirty-seven patients were included in the study of which 30 (81%) used the experimental device. Agreement between these two care recommendations (computer driven vs. clinician driven) was observed in 51 out 54 uses of the device (94.2% [95% CI 85.9–98.4%]). The agreement level had a probability of 86.6% to exceed the 90% clinically relevant agreement threshold. The knowledge-based, patient CDSS we developed was feasible at providing recommendations for the treatment of pain, PONV and constipation in a perioperative clinical setting.Trial registration number & date The study protocol was registered in ClinicalTrial.gov before enrollment began (NCT05707247 on January 26th, 2023).

Visual outcomes after cataract surgery in monocular compared to binocular patients: a case-control study.

We aimed to identify ocular comorbidities and reasons of blindness in monocular patients and to compare visual outcomes of cataract surgery between monocular and binocular patients. A single-center case-control study was conducted between November 2011 and May 2019 to compare consecutive series of patients needing cataract surgery in Strasbourg University Hospitals, France. Cases were patients with permanent monocular vision loss. Controls were binocularly sighted patients. All patients underwent cataract surgery using phacoemulsification technique. Chart analysis included demographic data, medical history, and surgical determinants data. Student's t tests and Fisher's exact tests were the main methods used for statistical analysis. Each group included 80 patients. The mean age at the time of surgery was significantly higher in monocular than binocular patients (77 vs. 71years, p < 0.001). Thirty-two monocular patients (40%) had ocular comorbidities, compared to only 19 (23%) in the control group (p < 0.05). The leading cause of monocular status was amblyopia caused by strabismus (22 patients, 27.5%). Age-related macular degeneration, open-angle glaucoma, and diabetic retinopathy were the three main ocular comorbidities that were observed in the monocular group. Monocular patients had significantly lower visual acuity than the control group (p < 0.01) before and after cataract surgery. Conversely, improvement in visual acuity after surgery was not statistically different between groups (p = 0.054). There was no statistically significant difference in the rate of surgical complications between groups (p = 0.622). This study illustrates that cataract surgery in monocular patients is not more complicated than in binocular patients, but that it is significantly delayed.

Impact of the COVID-19 pandemic on lung transplant patients and on a cohort of patients with rare lung disease: A single-center study

IntroductionDue to the COVID-19 pandemic, France underwent several lockdown periods during 2020. Our aim was to evaluate its clinical and social impact on lung transplant (LT) patients treated at Strasbourg University Hospital, by comparing three periods: first lockdown (T1: March-May 2020), end of the first lockdown (T2: May-October 2020), and second lockdown (T3: November-December 2020) and the incidence of COVID-19 infections. A cohort of patients with rare lung disease (RLD) was also studied during T2. MethodsWe used clinical and paraclinical data collected during routine follow-up. A questionnaire was submitted to each patient at each period to assess their lifestyle, adherence to protective measures against COVID-19, contacts with their family and friends, and contagion risk. The incidence of new COVID-19 cases was also assessed. ResultsOverall, 283 LT and 57 RLD patients were included. We observed only eight COVID-19 cases over the three periods (n = 4 during T1, n = 0 during T2, and n = 4 during T3) in LT patients, with 37.5 % of patients hospitalized, no ICU transfers, and 100 % favorable outcomes. No case of COVID-19 was diagnosed in the RLD cohort. When comparing the three periods in the LT group, fewer patients limited their out-of-home activities during T2 (p < 0.0001). The frequency of these activities increased after the first lockdown, for the purchase of basic necessities (p < 0.0001), and professional activity continued (p = 0.008). We observed a significant increase in unscheduled medical consultations and in the prescription of anti-infective treatments during the end of the lockdown (p = 0.0002 and p = 0.005, respectively). Adherence to lockdown and to protective measures was high in both groups of patients. ConclusionCOVID-19 incidence remained low in both groups and there were significant lifestyle evolutions in LT patients and in those with RLD between first and second lockdown.

The history of the Vienna Protocol on dealing with Holocaust era human remains and its resonance with ethical considerations in African American bioarcheology.

The Vienna Protocol on How to Deal with Holocaust Era Human Remains describes what to do when possibly Jewish human remains are found. Based on Jewish medical ethics, it responds to the 2014-2017 discoveries of human remains stemming from biomedical contexts of the Nazi period. Among the finding sites were the Dahlem campus of the Free University of Berlin, the Medical University of Strasbourg, and Max Planck Institute archives. The Vienna Protocol is unique among similar recommendations on Nazi era human remains in its representation of the voices of those who suffered violence and were targeted as victims by Nazi persecution. In addition to discussing the ethics of dealing with physical human remains, these recommendations address the use of images (i.e., visual data) from the bodies of victims of Nazi violence. This paper presents the historical background of the Vienna Protocol and its impact. It also offers a first analysis as to why, at the time of the protocol's formulation, its authors were unaware of its resonance with ethical considerations from African American bioarcheology and a new ethical culture in bioanthropology. Potential reasons for this disconnect may include the historic marginalization of the voices of black scholars in anthropology within the wider scientific community. However, more detailed studies are needed to analyze similarities and differences between the histories and continuities of antisemitism and racism in Europe and the U.S.A., and their ties with scientific theories and practices of disciplines that gain knowledge from human remains.

Suppressive antibiotic therapy for infectious endocarditis

ObjectivesSuppressive antibiotic therapy (SAT) is a long-term antibiotic strategy at times applied when an indicated surgical management of infective endocarditis (IE) is not possible. Our aim was to describe the characteristics and outcomes of patients having received SAT for IE. MethodsWe conducted a retrospective, observational study at Strasbourg University Hospital, France between January 2020 and May 2023. We reviewed all medical files taken into consideration at weekly meetings of the local Multidisciplinary Endocarditis Team (MET) during the study period. We included patients having received SAT following the MET evaluation. The primary endpoint was all-cause mortality at most recent follow-up. Secondary endpoints included all-cause mortality at 3 and 6 months, infection relapse, and tolerance issues attributed to SAT. ResultsThe MET considered 251 patients during the study time, among whom 22 (9 %) had received SAT. Mean age was 77.2 ± 12.3 years. Patients were highly comorbid with a mean Charlson index score of 6.6 ± 2.5. Main indication for SAT was surgery indicated but not performed or an infected device not removed (20/22). Fourteen patients had prosthetic valve IE, including 9 TAVIs. Six patients had IE affecting cardiac implantable electronic devices. Staphylococcus aureus and enterococci were the main bacteria involved (6/22 each). Median follow-up time was 249 days (IQR 95–457 days). Mortality at most recent follow-up was 23 % (5/22). Three patients (14 %) presented tolerance issues attributed to SAT, and two patients suffered late infectious relapse. ConclusionMortality at most recent follow-up was low and tolerance issues were rare for patients under SAT, which might be a palliative approach to consider when optimal surgery or device removal is not possible.

Süddeutsche Reichsstädter an der Universität Basel (1460–1802)

This article examines the attendance at the Basel University by students from 42 imperial cities from the Upper Rhine, Swabian, Franconian and Bavarian imperial circles in the period 1460 to 1802. The analysis focuses on the chronology of these students’ university attendance and their educational goals. The author also tries to identify particular urban and regional educational patterns. In the concluding part, results of this research on attendance at the Basel University in the 17th and 18th centuries are compared with the results of this author’s earlier research on attendance at the University of Strasbourg by students from the same imperial cities.

Solution and Solvent-Free Stopper Exchange Reactions for the Preparation of Pillar[5]arene-Containing [2] and [3]Rotaxanes.

Invited for the cover of this issue are the group of Iwona and Jean-François Nierengarten from the University of Strasbourg (LIMA, UMR 7042, CNRS) and collaborators from the University of Carthage and the IPHC (University of Strasbourg and CNRS, UMR 7178). The image illustrates the fast motions of a pillar[5]arene subunit along the axle of a rotaxane, reminiscent of those of a guitarist's hand along the neck allowing him to use random parts of a scale with certain sweet spots when improvising a solo. Read the full text of the article at 10.1002/chem.202304131.

Stepwise Functionalization of a Pillar[5]arene-Containing [2]Rotaxane with Pentafluorophenyl Ester Stoppers.

Invited for the cover of this issue are the group of Iwona and Jean-François Nierengarten from the University of Strasbourg (LIMA, UMR 7042, CNRS) and collaborators from the University of Carthage. The image depicts a sky of umbrellas floating in the air to illustrate the protective effect allowing the efficient mono-acylation of a symmetrical rotaxane building block with two pentafluorophenyl ester stoppers. Read the full text of the article at 10.1002/chem.2023003501.

Fred Vlès – Early Holistic Biophysicist and Pioneer of “Earthing”

The paper reports on the life and works of Fred Vlès (1885-1944) and Paul Reiss (1901-1944), and Charles Laville (1877-1959) who worked in a similar field. Vlès was the founder of the first institute of biophysics in France at the University of Strasbourg, and Reiss was his pupil and associate. They worked in the time of 1910 to 1944 on the acid-alkaline balance and the reduction-oxidation (redox) potentials of the body fluids and tissues and their influence on the proteins and colloids of the “terrain”, along the lines given by the “milieu interne” (internal environment) or homeostasis concept by Claude Bernard. Vlès and Reiss were also electrobiologists and were some of the first scientists to investigate the physiological effects of electrical grounding where also the work of Charles Laville is relevant. In the conclusion we link this historical narrative to contemporary research.

Disseminated intravascular coagulation is strongly associated with severe acute kidney injury in patients with septic shock

BackgroundDisseminated intravascular coagulation (DIC) worsens the prognosis of septic shock and contributes to multiple organ failure. To date, no data linking DIC and acute kidney injury (AKI) occurrence, severity, and evolution in this setting are available. We aimed at analyzing the association between AKI occurrence, severity and evolution in patients with septic shock-induced DIC. In a prospective monocentric cohort study, consecutive patients, 18 years and older, admitted in the ICU of Strasbourg University Hospital in the setting of systemic hypotension requiring vasopressor related to an infection, without history of terminal chronic kidney disease were eligible. AKI was defined according to the KDIGO classification. DIC diagnosis was based on the International Society on Thrombosis and Haemostasis (ISTH) score. Evolution of AKI was evaluated through the composite endpoint of major adverse kidney events. Only patients with DIC that occurred before or at the time of AKI diagnosis were considered. Univariate and multivariate analysis were performed to determine factors associated with renal outcomes.Results350 patients were included, of whom 129 experienced DIC. Patients with DIC were more seriously ill (median SAPS II 64 vs. 56, p < 0.001), and had higher 28-day mortality (43.3% vs. 26.2%, p < 0.001). AKI was more frequent in patients with DIC (86.8% vs. 74.2%, p < 0.005), particularly for the more severe stage of AKI [KDIGO 3 in 58.1% of patients with DIC vs. 30.8% of patients without DIC, p < 0.001, AKI requiring renal replacement therapy (RRT) in 47.3% of patients with DIC vs. 21.3% of patients without DIC, p < 0.001]. After adjustment for confounding factors, DIC occurrence remained associated with the risk of having the more severe stage of AKI with an odds ratio (OR) of 2.74 [IC 95% (1.53–4.91), p < 0.001], and with the risk of requiring RRT during the ICU stay [OR 2.82 (1.53–5.2), p < 0.001].ConclusionDIC appears to be strongly associated with the risk of developing the more severe form of AKI (stage 3 of the KDIGO classification, RRT requirement), even after adjustment for severity and other relevant factors.

University procurement-led innovation: Sources, procedures, and effects. Some field-study evidence

This paper introduces a new perspective about the economic role of research by focusing on the impact of university procurement on firm innovation. We discuss how universities play a leading role in scientific equipment innovation, akin to the one portrayed for US and European government agencies in the context of military equipment and driven by specific missions. The key difference is that missions in university procurement emerge in a bottom-up fashion, and they are driven by the scientific agenda of university researchers. Furthermore, we discuss the basic ingredients of such a “university procurement-led innovation” and we support our claims with field-study evidence about the development of five advanced equipment co-developed by researchers at the University of Strasbourg (France) together with their suppliers.

The Studium – University Library and Student Union Building, a Learning Centre in Strasbourg

Abstract This article presents the Studium, the new learning centre that opened in October 2022 at the University of Strasbourg. Both a library and a student centre, the building is surprisingly curved and open. The Studium offers the university community a wide range of services specifically designed to meet their needs.

Reshaping the diagnostic borders: Historical analysis of the diagnostic changes following the introduction of the schizophrenia concept

BackgroundAlthough the concept of schizophrenia is still widely presented as having replaced that of dementia praecox, studies have shown that the former was broader than the latter, resulting in a more complex diagnostic redistribution. However, this is poorly documented by quantitative approaches. AimsWe sought to test the hypothesis that the use of the concept of schizophrenia had caused a diagnostic redistribution and to quantify it. MethodA retrospective study, based on admission register archives of the Strasbourg University Clinic of Psychiatry was conducted. The frequency of diagnoses given to patients were examined at two key time periods: one before (TP1) and one after (TP2) the introduction of the schizophrenia concept (established between 1926 and 1928). Eight main diagnoses related to schizophrenia were considered. ResultsPatients diagnosed with schizophrenia at TP2 mainly received the diagnoses of dementia praecox but also depression, hebephrenia, manic depressive illness, hysteria, paraphrenia, catatonia and mania at TP1. Dementia praecox and hebephrenia were the most relayed by schizophrenia. Bayesian sensitivity analyses confirmed the robustness of our data against distinct scenarios challenging our hypothesis. ConclusionsOur results confirm the broadening of the concept of schizophrenia compared to that of dementia praecox but also qualify the different concepts supposed to have been impacted. They provide unique quantitative data that define the contours of the diagnostic redistribution thus provoked. They also give relevant input in the current context where the need to rethink the DSM/ICD concept of schizophrenia is still debated.

Micro-costing analysis of suspected lower respiratory tract infection care in a French emergency department.

In the context of budgetary constraints faced by healthcare systems, the medical-economic evaluation of care strategies becomes essential. In particular, valuing consumed resources in the overcrowded emergency departments (EDs) has become a priority to adopt more efficient approaches in treating the growing number of patients. However, precisely measuring the cost of care is challenging. While bottom-up micro-costing is considered the gold standard, its practical application remains limited. The objective was to accurately estimate the ED care cost for patients consulting in a French ED for suspected lower respiratory tract infection. The authors conducted a cost analysis using a bottom-up micro-costing method. Patients were prospectively included between January 1, and March 31, 2023. The primary endpoint was the mean cost of ED care. Resources consumed were collected using direct observation method and cost data were obtained from information available at Strasbourg University Hospital. The mean cost of ED care was €411.68 (SD = 174.49). The cost elements that made the greatest contribution to the total cost were laboratory tests, labor, latency time, imaging and consumables. Considering this cost and the current epidemiological data on respiratory infections in France, the absence of valuation for outpatient care represents an annual loss of over 17 million euros for healthcare facilities. Micro-costing is a key element in valuing healthcare costs. The importance of accurately measuring costs, along with measuring the health outcomes of a defined care pathway, is to enhance the relevance of health economic evaluations and thus ensure efficient care.

Long-Term Survival Outcomes After Transcatheter Aortic Valve Replacement: A Real-World Experience of a Large Tertiary Center

Transcatheter aortic valve replacement (TAVR) becomes the leading therapeutic choice for severe aortic stenosis. There is a growing body of knowledge on long-term survival outcomes, but available data from real-world observational studies are scarce. An observational cohort study was conducted on 705 consecutive patients who underwent TAVR at Strasbourg University Hospital between February 2010 and June 2017. We observed the living status (dead or alive) for each study participants by March 2023. The primary end point was to evaluate the all-cause mortality rate beyond 5years after TAVR, compare the survival outcomes according to valve type, and identify predictors of mortality. Of the 705 study participants, 91.8% of the TAVR procedures were performed through the common femoral artery and 60.6% were treated with a balloon-expandable valve. Over a mean study period of 5.4 ± 3years, the all-cause mortality rate was 45.8%. No difference in survival outcomes according to valve type was observed (p=0.449). All-cause mortality rate was associated with age ≥90years (hazard ratio [HR] 1.625, 1.109 to 2.380, p=0.013), female gender (HR 0.228, 0.176 to 0.294, p <0.001), diabetes mellitus (HR 1.356, 1.070 to 1.719, p=0.012), post-TAVR stroke (HR=2.867, 1.690 to 4.865, p <0.001), and post-TAVR acute kidney injury (HR 1.977, 1.445 to 2.703, p <0.001). In conclusion, the present real-world large tertiary center experience showed that more than half of patients who underwent TAVR are alive beyond 5years from procedure's date. All-cause mortality is mainly determined by advanced age and co-morbid conditions, and valve type has no advantage on the survival outcomes.