Large Monocentric Cohort Research Articles

Value of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Identifying Osteoarticular Septic Grafts in Suspected Infective Endocarditis: Results from a Large Monocentric Cohort.

Background: 18F-fluorodeoxyglucose positron emission tomography-CT (FDG-PET/CT) is useful for identifying infective endocarditis (IE) but also the detection of other concomitant septic foci. Previously, we found that FDG-PET/CT identified an osteoarthritic septic graft (OASG) in 19.1% of IE patients, frequently asymptomatic. These preliminary results encouraged us to extend our analyses to a larger population, including all patients initially explored for suspected IE, to assess the prevalence, characteristics, and OASG locations brought out by FDG-PET/CT and to identify predictive factors. Methods: From a single-center cohort of patients referred for a clinical and/or biological suspicion of IE, we included all patients who underwent FDG-PET/CT, mainly performed to confirm a prosthesis heart valve or a foreign cardiac device infection. We excluded those who did not meet the 2015 modified Duke Criteria and those for whom another infectious diagnosis was finally retained or for whom all bacterial samples were negative. Demographic, clinical, bacteriological, imaging, and therapeutic data were collected. FDG-PET/CT images were retrospectively analyzed by three blinded nuclear medicine specialists to identify OASGs. Results: We identified 72 distinct OASG locations by FDG-PET/CT in 48 of 174 patients (27.6%), mainly located in the spine (21 OASGs in 20 patients); 14 patients (8.0%) had several OASG locations. In total, 43.8% of OASG locations were asymptomatic. In multivariate analysis, the presence of OASGs was associated with musculoskeletal pain (p < 0.001) and tricuspid valve involvement (p = 0.002). Conclusions: FDG-PET/CT is useful for identifying OASGs in patients with suspected IE, especially those with tricuspid IE or musculoskeletal pain. The identification of OASGs could impact antibiotic therapy and would allow adapted orthopedic management to be proposed.

Antibody profiles in the mosaic of "seronegative" APS syndrome.

Clinical manifestations, as distinct from thrombotic and obstetric morbidity, were recently included in the update of classification criteria of the antiphospholipid syndrome (APS). However, the existence of several patients with clinical manifestations suggestive of APS, but negative for criteria antiphospholipid antibodies (aPLs) [anti-cardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2-GPI) and lupus anticoagulant] may suggest an update of diagnostic criteria. In this study, we analyzed the prevalence of six non-criteria aPLs in a large monocentric cohort of patients with seronegative APS (SN-APS), to investigate their possible diagnostic role. aCL IgA, aβ2-GPI IgA and aβ2-GPI Domain 1 antibodies were detected by chemiluminescence, anti-phosphatidylserine/prothrombin (aPS/PT) IgG, anti-vimentin/cardiolipin (aVim/CL) IgG and anti-carbamylated-β2-glycoprotein I (aCarb-β2-GPI) IgG by ELISA in sera from 144 SN-APS patients. In SN-APS patients, aCL IgA were detected in 4/144 (2.77%), aβ2-GPI IgA in 2/144 (1.39%), aβ2-GPI-Domain 1 in 1/144 (0.69%), aPS/PT in 16/144 (11.11%), aVim/CL in 37/144 (25.69%) and aCarb-β2-GPI in 43/144 patients (29.86%). Patients negative for all non-criteria aPL assays were 77/144 (53.47%). Notably, the Venn diagram showed that aCarb-β2-GPI together with aVim/CL represented the prevalent combination of positive antibodies. In SN-APS patients, aCL IgA were associated with recurrent thrombosis (OR11.48; p=0.03); in obstetric SN-APS patients, aPS/PT were significantly associated with foetal deaths (OR4.84; p=0.01), aVim/CL with spontaneous abortions (OR2.71; p=0.016). This study indicates that aPS/PT, aVim/CL and aCarb-β2-GPI antibodies may represent useful tools to identify "seronegative" APS patients, who are negative for criteria aPLs, supporting the need to make testing for non-criteria aPLs more accessible in patients with SN-APS.

Inflammation-based scores in a large monocentric cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern

Inflammation-based scores in a large monocentric cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern

Uterine adenosarcoma: Clinical significance of histological classification and SNP array analysis

Mullerian adenosarcoma is a rare malignant biphasic tumor. The mesenchymal component may be low or high grade, with or without sarcomatous overgrowth (SO). Little is known about the molecular heterogeneity of these tumors. In this study, we aim to reclassify a large retrospective monocentric cohort of uterine adenosarcomas according to tumor grade and SO, to evaluate the clinical significance of pathological classification and to correlate with copy-number variations inferred from single nucleotide polymorphism array. Of the 67 uterine adenosarcomas, 18 (26.9%) were low grade without SO, 7 (10.4%) low grade with SO, 8 (11.9%) high grade without SO and 34 (50.7%) high grade with SO. SO, necrosis and RMS were more frequent in high grade than low grade adenosarcomas (p < 0.001). Low-rank test showed that recurrence-free survival was significantly shortened in high grade than low grade adenosarcomas (p = 0.035) and SO was associated with shortened overall and recurrence-free survival (p = 0.038 and p = 0.009, respectively). High-grade tumors displayed complex genomic profiles with multiple segmental losses including TP53, ATM and PTEN genes. The median genomic index was significantly higher in high grade than low grade tumors (27 [3–60] vs 5,3 [0–16], p < 0.0001) and was significantly higher in presence of SO in low grade tumors (12,8 [10–16] vs 2,6 [0–10], p = 0.0006). We propose to report sarcomatous overgrowth with the tumor grade for prognostication in adenosarcoma and representative sampling is crucial for evaluation of these histological criteria.

Insights from Real-World Practice: The Dynamics of SARS-CoV-2 Infections and Vaccinations in a Large German Multiple Sclerosis Cohort.

The SARS-CoV-2 pandemic profoundly impacted people with multiple sclerosis (pwMS). Disease-related aspects and demographic factors may influence vaccination rates, infection susceptibility, and severity. Despite prior research, comprehensive real-world data obtained throughout the pandemic remain limited. We investigated SARS-CoV-2 vaccination and infection patterns in a large monocentric real-world cohort. We collected prospective data from medical visits at the MS Center Dresden, Germany, from the pandemic's beginning until 31 May 2022. Logistic regression and rank correlation analyses were used to explore associations between SARS-CoV-2 outcomes and patient characteristics. Of 2115 pwMS assessed (mean age 46.5, SD ± 12.9; median expanded disability status scale 2.5), 77.9% were under disease-modifying treatment (DMT), primarily B-cell depletion (25.4%). A total of 35.5% reported SARS-CoV-2 infections, and 77.4% were fully vaccinated. PwMS with increased disability, older age, and comorbidities were associated with higher vaccination rates, possibly due to the awareness of these populations regarding complications of SARS-CoV-2 infections. Infections were more common in younger females, people with a lower degree of disability, those with relapsing MS, and those who were not vaccinated. PwMS on B-cell depletion reported more infections than untreated pwMS and those receiving other types of disease-modifying therapy, despite higher vaccination rates. Most infections were mild, with no severity differences according to demographic or disease-related factors, except for gender. Notably, all fatal cases occurred in unvaccinated pwMS. Our studies suggest that demographic and disease-related factors, especially age and the use of B-cell depletion, significantly influenced SARS-CoV-2 vaccination and infection rates in our cohort. These factors may be considered in future preventive campaigns in further pandemics.

A Comparison of Presentation, Treatment, and Survival After Hepatocellular Carcinoma of Viral and Non-Viral Etiology in Damietta, Egypt, 2007-2019.

The difference in prognosis between patients diagnosed with viral versus non-viral hepatocellular carcinoma (HCC) in Egypt remains unclear. We used data from patients diagnosed with HCC between 2007 and 2019 from a large monocentric retrospective cohort at the Damietta Oncology referral center (northern Egypt). Presentation and treatment were compared between viral versus non-viral etiology HCC patients. Survival was compared relying on univariate and multivariate Cox regressions. Data from 4714 HCC patients were analyzed. Among them, 204 (4.3%) presented with a non-viral etiology. Patients with non-viral versus viral etiology had a similar presentation overall, especially regarding the BCLC stage at HCC diagnosis. After controlling for various individual characteristics, patients with non-viral versus viral etiology had poorer survival (adjusted Hazard Ratio: 1.244; 95% Confidence Interval: 1.069-1.447). Despite similar features, patients with non-viral- related HCC had poorer survival compared to patients with viral-related HCC.

Renal artery involvement is associated with increased morbidity but not mortality in Takayasu arteritis: a matched cohort study of 215 patients.

We analyzed differences in presentation and survival of Takayasu arteritis (TAK) with or without renal artery involvement (RAI) from a large monocentric cohort of patients with TAK. Clinical and angiographic features were compared between TAK with versus without RAI, with bilateral versus unilateral RAI, and with bilateral RAI versus without RAI using multivariable-adjusted logistic regression. Inter-group differences in survival were analyzed [hazard ratios (HR) with 95% confidence intervals (95%CI)] adjusted for gender, age at disease onset, diagnostic delay, baseline disease activity, and significant clinical/angiographic inter-group differences after multivariable-adjustment/propensity score matching (PSM). Of 215 TAK, 117(54.42%) had RAI [66(56.41%) bilateral]. TAK with RAI or with bilateral RAI had earlier disease onset than without RAI (p < 0.001). Chronic renal failure (CRF) was exclusively seen in TAK with RAI. TAK with RAI (vs without RAI) had more frequent hypertension (p = 0.001), heart failure (p = 0.047), abdominal aorta (p = 0.001) or superior mesenteric artery involvement (p = 0.018). TAK with bilateral RAI (vs unilateral RAI) more often had hypertension (p = 0.011) and blurring of vision (p = 0.049). TAK with bilateral RAI (vs without RAI) more frequently had hypertension (p = 0.002), heart failure (p = 0.036), abdominal aorta (p < 0.001), superior mesenteric artery (p = 0.002), or left subclavian artery involvement (p = 0.041). Despite higher morbidity (hypertension, CRF), mortality risk was not increased with RAI vs without RAI (HR 2.32, 95%CI 0.61-8.78), with bilateral RAI vs unilateral RAI (HR 2.65, 95%CI 0.52-13.42) or without RAI (HR 3.16, 95%CI 0.79-12.70) even after multivariable adjustment or PSM. RAI is associated with increased morbidity (CRF, hypertension, heart failure) but does not adversely affect survival in TAK. Key Points •Renal artery involvement in TAK is associated with chronic renal failure. •TAK with renal artery involvement more often have heart failure and hypertension. •Bilateral renal artery involvement (compared with unilateral) is more often associated with hypertension and visual symptoms. •Renal artery involvement is not associated with an increased risk of mortality in TAK.

Systematic ophthalmologic evaluation in cardio-facio-cutaneous syndrome: A genotype-endophenotype correlation.

Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder belonging to the RASopathies, a group of developmental syndromes caused by upregulated RAS/MAPK signaling. Pathogenic variants affecting four genes, KRAS, BRAF, MAP2K1 and MAP2K2, encoding core signal transducers of the pathway, underlie the condition. Major clinical features include a distinctive facies, ectodermal and cardiac anomalies, reduced postnatal growth, intellectual disability, and musculoskeletal abnormalities. Similar to other RASopathies, reports of visual impairment, high refractive error, optic nerve pallor, and other ocular abnormalities have been anecdotally reported in the literature. The aim of our study is to report the prevalence of ophthalmologic abnormalities in a large monocentric cohort of individuals affected by CFCS and explore the occurrence of genotype-endophenotype correlations in this series of patients. We observed that BRAF mutations are associated to a higher prevalence of anisometropia >3D (11.8% vs. 0%) and high astigmatism (29.4% vs. 0%; both p < 0.001) while patients with mutations in other genes had a significantly higher prevalence of myopia >6 D (60% vs. 5.9%; p = 0.012). Pale optic disc was associated with higher prevalence of inferior oblique muscle (IO) overaction (33.3% vs. 0%) and lower prevalence of ptosis (0% vs. 11.8%; both p < 0.001). Combined exotropia, IO overaction and nystagmus were frequent in patients with pale optic nerve. Our findings might suggest the need for earlier ophthalmologic referral for CFCS patients due to high risk of amblyopia, especially those expressing BRAF mutations.

Clinical scales in autoimmune encephalitis-A retrospective monocentric cohort study.

Assessing severity of antibody-mediated encephalitis (AE) or paraneoplastic encephalitis (PE) requires valid and reliable scores to guide treatment decisions and predict outcome both in clinical routine and studies. We aimed to validate the prognostic value of the clinical assessment scale in autoimmune encephalitis (CASE) and the anti-NMDAR-encephalitis one-year functional status (NEOS) score in patients suffering from AE and PE in a large monocentric cohort. We retrospectively applied the CASE and NEOS score to patients with definite AE and PE treated at a tertiary hospital. Correlations were established between the CASE and NEOS score and the modified Rankin scale (mRs). Multivariable analyses were calculated to identify predictors of outcome. Thirty-four patients (27 AE, 7 PE) were included. Correlations between mRS and CASE score were strongest in patients with AE compared to PE at all intervals, but in the subgroups (LGI1, NMDAR, GAD, miscellaneous surface antibodies, PE) the correlation was strongest in the interval after baseline. Patients with AE seemed to display better outcomes compared to PE, which was underlined by multivariable analysis. Improvement was mostly observed within 6-12 months after disease onset, after which little or no further improvement was noted with some exception for two patients with anti-NMDARE who recovered substantially even after 12 months of treatment. The NEOS score significantly predicted the outcome at last follow-up in patients with AE with a sensitivity of 79% at a cut-off value of 2 points (AUC 0.79, 95% CI 0.58-0.99, p = 0.04). The CASE and NEOS score are suitable supplementary tools in addition to the mRS for capturing diverse symptoms, for grading and monitoring symptom severity.

Safety profile of subdural and depth electrode implantations in invasive EEG exploration of drug-resistant focal epilepsy

PurposeTo analyze the safety profile of subdural and depth electrode implantation in a large monocentric cohort of patients of all ages undergoing intracranial EEG exploration because of drug resistant focal epilepsy diagnosed and implanted by a constant team of epileptologists and neurosurgeons. MethodsWe retrospectively analyzed data from 452 implantations in 420 patients undergoing invasive presurgical evaluation at the Freiburg Epilepsy Center from 1999 to 2019 (n = 160 subdural electrodes, n = 156 depth electrodes and n = 136 combination of both approaches). Complications were classified as hemorrhage with or without clinical manifestations, infection-associated and other complications. Furthermore, possible risk factors (age, duration of invasive monitoring, number of electrode contacts used) and changes in complication rates during the study period were analyzed. ResultsThe most frequent complications in both implantation groups were hemorrhages. Subdural electrode explorations caused significantly more symptomatic hemorrhages and required more operative interventions (SDE 9.9%, DE 0.3%, p < 0.05). Hemorrhage risk was higher for grids with 64 contacts than for smaller grids (p < 0.05). The infection rate was very low (0,2%). A transient neurological deficit occurred in 8.8% of all implantations and persisted for at least 3 months in 1.3%. Transient, but not persistent neurological deficits were more common in patients with implanted subdural electrodes than in the depth electrode group. ConclusionThe use of subdural electrodes was associated with a higher risk of hemorrhage and transient neurological symptoms. However persistent deficits were rare with either approach, demonstrating that intracranial investigations using either subdural electrodes or depth electrodes carry acceptable risks in patients with drug-resistant focal epilepsy.

Atypical clinical and novel radiological findings in Susac syndrome: Experience from a large monocentric cohort

Susac syndrome (SuS) is a rare immune-mediated endotheliopathy that affects the brain, retina and inner ear and is characterised by the variable clinical triad of encephalopathy, visual and vestibulocochlear dysfunction. Here, we present clinical and paraclinical data of 19 SuS patients followed at Ghent University Hospital and highlight some atypical clinical and novel radiological findings. Our findings suggest that spinal involvement expands the clinical phenotype of SuS. We further introduce dark blood sequences as a more sensitive technique to detect radiological disease activity in SuS. Our data add to the current understanding of the diagnosis, monitoring and treatment of SuS.

Intracranial hemorrhages in full-term newborns: nosological and etiological insights in a large monocentric cohort (Winner of the SIMP EUBRAIN Award, in memory of Sir John William Little for his fundamental study of 1862)

Intracranial hemorrhages in full-term newborns: nosological and etiological insights in a large monocentric cohort (Winner of the SIMP EUBRAIN Award, in memory of Sir John William Little for his fundamental study of 1862)

Association of Lipoprotein(a) Levels With Incidence of Major Adverse Limb Events

High lipoprotein(a) (Lp[a]) levels are involved in the development of cardiovascular events, particularly in myocardial infarction, stroke, and peripheral artery disease. Studies assessing the Lp(a) levels associated with adverse lower-limb events are lacking. To assess the association between Lp(a) levels and incidence of major adverse limb events in unselected hospitalized patients. This large retrospective monocentric cohort study was conducted from January 1, 2000, to December 31, 2020. Data were derived from the clinical information system of the Hôpital Européen Georges-Pompidou, a Paris-based university hospital. Patients who underwent at least 1 Lp(a) measurement at the center during the study period were included. Patients who had no follow-up data or who had the first Lp(a) measurement after the study outcome had occurred were excluded. Data analyses were performed from May 2021 to January 2022. The primary outcome was the first inpatient major adverse limb event, defined as a major amputation, peripheral endovascular revascularization, or peripheral surgical revascularization, during follow-up. Secondary outcomes included individual components of the primary outcome. Lipoprotein(a) levels were categorized as follows: normal (<50 mg/dL), high (50 to <134 mg/dL), and very high (≥134 mg/dL); to convert Lp(a) values to milligrams per liter, multiply by 0.1. A total of 16 513 patients (median [IQR] age, 58.2 [49.0-66.7] years; 9774 men [59.2%]) were included in the cohort. The median (IQR) Lp(a) level was 24 (10.0-60.0) mg/dL. The 1-year incidence of major adverse limb event was 2.44% in the overall population and 4.54% among patients with very high Lp(a) levels. High (adjusted accelerated failure time [AFT] exponential estimate: 0.43; 95% CI, 0.24-0.78; Benjamini-Hochberg-corrected P = .01) and very high (adjusted AFT exponential estimate: 0.17; 95% CI, 0.07-0.40; Benjamini-Hochberg-corrected P < .001) Lp(a) levels were independently associated with an increased risk of major adverse limb event. Results of this study showed that higher Lp(a) levels were independently associated with an increased risk of a major adverse limb event in hospitalized patients. The Lp(a) measurement needs to be taken into account to improve lower-limb vascular risk assessment.

Insights into the clinical presentation of juvenile systemic lupus erythematosus: the PRAGMA monocentric cohort of 177 patients.

The aim of this work is to describe the clinical manifestations at onset and during follow-up in a monocentric cohort of patients with juvenile systemic lupus erythematosus (jSLE) from the Paediatric Rheumatology group of the Milan area (PRAGMA). Patients were retrospectively included in case of i) SLE diagnosis according to the 1997 American College of Rheumatology or the 2012 SLICC classification criteria and ii) disease onset before 18 years. Among the 177 recruited patients (155 females), haematologic involvement was the most common disease manifestation (75%), followed by joint and cutaneous involvements (70% and 57%, respectively). Renal disease was observed in 58 patients (32.8%), neurological complications in 26 cases (14.7%). Patients presented most commonly 3 clinical manifestations (32.8%), while 2 organ involvements were identified in 54 patients (30.5%) and 4 in 25 subjects (14.1%). The 49 patients with disease onset <10 years had less commonly articular involvement (p=0.02), while patients aged >14.8 years displayed less neurological manifestations (p=0.02). At a median follow-up of 118 month, the disease progressed in 93 patients, with a median of 2 new manifestations per patient. Low complement at diagnosis predicted new clinical manifestations (p=0.013 for C3 and p=0.0004 for C4). The median SLEDAI at diagnosis was 13; SLEDAI was substantially similar at 6 months, decreased at 12 months to remain stable at 18 months and further reduce at 24 months (p<0.0001). These data from a large jSLE monocentric cohort allow gaining further insights into a rare disease with a still high morbidity burden.

Pulmonary arteries growth after bidirectional cavopulmonary connection in functionally univentricular heart program

The optimization of the pulmonary arteries (PA) size is an important concern after the bidirectional cavopulmonary connection (BDCPC) in patients with functionally univentricular heart as it precedes the completion of the Fontan program. We analyzed the PA growth between the time of the BDCPC and the time of the total cavopulmonary connection (TCPC) in a large monocentric cohort of children, and we explored the factors associated with differential growth profiles. In total, 118 patients (median age at the BDCPC 8 months (IQR 5–18)) were included. Diameters of the right and the left PA were measured proximally to the first lobar bifurcation on the pulmonary artery angiography obtained before BDCPC and compared to angiographies obtained before TCPC. Nakata index was also calculated using these two measurements. Associations of pertinent covariables with the PA growth were explored. Both pulmonary artery branches grew between BDCPC and TCPC (9.1 mm of diameter (IQR 7.2–12.2) to 12.2 mm (IQR 9.9–14.4) for right PA; P < 0.0001, 8.5 mm of diameter [db1] (IQR 6.5–7.3) to 9.6 mm (IQR 8.0–12.4) for left PA; P = 0.0001). However, PA branches growth was not proportional to child's growth as we noted a decrease of the Nakata index over this period. The main factor associated with a better PA branch growth was the presence of an additional pulmonary blood flow through a pulsatile antegrade flow (+28.2 mm 2 of section area for right PA; P = 0.020, +16.8 mm 2 for left PA; P = 0.043). No other factor preceding BDCPC or associated procedure performed simultaneously had an impact on PA branch growth. PA branches growth is reduced after BDCPC and this may hamper the functioning of the future TCPC. Maintaining a pulsatile antegrade blood flow whenever possible could optimize PA growth and prevent deleterious early remodeling of the pulmonary vascular bed.

Sacroiliitis at diagnosis as a protective predictor against disease flare after stopping medication: outcomes of a Southeast Asian enthesitis-related arthritis (ERA) longitudinal cohort.

To assess short- and long-term outcomes of ERA in a large monocentric cohort in Singapore. Children diagnosed with ERA according to ILAR criteria from 2002 to 2021 were recruited. Nonparametric statistics were used to describe the data. Outcomes were defined according to modified Wallace criteria, and probabilities and predictors were determined using Kaplan-Meier survival and logistic regression analyses. One hundred fifty-one ERA patients (male 86%; Chinese 81%) were included. The median age at onset was 11.9years (IQR: 9.4-13.9), and disease duration was 5.3years (IQR: 2.9-8.4). At diagnosis, 39% of the patients had sacroiliitis. HLA-B27 was positive in 83%, and biologics were used in 72% of the patients. Clinical inactive disease (CID) was achieved in 92% of the patients, of which 27% achieved within 6months. Sacroiliitis at diagnosis is an unfavorable predictor of early CID at 6months. Medication was discontinued in one-third of the patients. Favorable predictor of medication withdrawal includes male gender, while unfavorable predictors include positive HLA-B27 and ANA. Two-thirds of the patients with CID had at least one disease flare. Sacroiliitis at diagnosis is a protective predictor of flare after stopping medication. Despite a high proportion of ERA patients achieving CID, only one-third could stop medication with high rates of disease flare. Unfavorable predictors include older age at onset, HLA-B27, and ANA positivity. While sacroiliitis at diagnosis is a negative predictor of CID at 6months, it is associated with less disease flare after discontinuing medication.

Revisiting the spectrum of IgM-related neuropathies in a large cohort of IgM monoclonal gammopathy.

A significant number of patients with a peripheral neuropathy have IgM monoclonal gammopathy (IgM-MG). In this work, we encompassed the spectrum and outcome of IgM-related neuropathies (IgM-NP) in a large monocentric cohort of patients with IgM-MG. We retrospectively reviewed the neurological and hematological findings and the course of neuropathy in all patients with IgM-MG over a five-year period in our center (Henri Mondor hospital, Assistance Publique Hôpitaux de Paris (APHP), France). Among 550 patients with IgM-MG, 83 patients (15%) had IgM-NP (55 males, mean age 67 y.o.). The median serum level of IgM-MG was 3.4g/L, mostly kappa light chain component. The hematological diagnosis was Monoclonal Gammopathy of Undetermined Significance (MGUS) in 62 patients. Anti-MAG antibodies were detected in 38 patients with heterogeneous clinical and neurophysiological features. Four patients had neurolymphomatosis presenting as a non-length dependent predominantly motor neuropathy, which occurred long after the finding of IgM-MG and was responsive to hematological treatment. Five patients had an AL amyloid neuropathy revealed by a small fiber neuropathy. Finally, 30 patients were classified as "Neuropathy of Uncertain Relationship with the IgM" (NURIM) with characteristics close to those of an anti-MAG-NP at the time of diagnosis, except for the neurophysiological features with a predominant axonal pattern. This study emphasizes the wide spectrum of IgM-NP associated with a variety of hematological diagnoses. In particular, the course and prognosis vary considerably. In this setting, further studies are needed to unravel the group of patients classified as NURIM.

Diagnostic yield of bone fragility gene panel sequencing in children and young adults referred for idiopathic primary osteoporosis at a single regional reference centre

AimTo describe the presenting features, bone characteristics and molecular genetics in a large monocentric cohort of children and young adults with idiopathic primary osteoporosis. MethodsSixty-six patients (19 children, 47 adults; 28 males, 38 females; age at referral: 3.8 to 65 years) diagnosed with primary osteoporosis were included in this study; patients with features of osteogenesis imperfecta or other known syndromes associated with osteoporosis were excluded. For each patient, the following data were collected by retrospective chart review: family and personal history of fracture and osteoporosis, mineral homeostasis parameters and markers of bone formation and resorption, bone mineral density (BMD) of the lumbar spine (LS-BMD), the total body less head (TB-BMD), and total hip levels (TH-BMD) measured by DXA. As part of the initial assessment process, a bone fragility gene panel sequencing was performed in all of these patients. ResultsThere was a higher predominance of males in the children (63%) and of females in the adults (66%) (p = 0.030). Compared to the adults, the children had a significantly lower frequency of vertebral fractures (26 vs 57%, p = 0.022) and a higher frequency of peripheral fractures (84 vs 53%; p = 0.019). Bone fragility gene panel sequencing allowed the identification of the heterozygous pathogenic variant in 27% of patients (most frequently in LRP5, WNT1 and COL1A1 or 2 genes) and the heterozygous p.(Val667Met) LRP5 variant in 11% of them. The frequency of pathogenic variants tended to be higher in the children compared to the adults without reaching statistical significance (42 vs 19%; p = 0.053). The frequency of the p.(Val667Met) LRP5 variant was similar in children and adults. No significant differences were found regarding the various clinical, biological and radiological characteristics of the patients according to genotype. ConclusionIn this study, we reported the presenting features and bone characteristics in a large cohort of children and young adults with idiopathic primary osteoporosis. Bone fragility gene panel sequencing allowed the identification of genetic variants in a significant proportion of these patients. Molecular diagnosis in these patients is important in order to be able to offer genetic counselling and organise patient management.

Survey of Long-Term Experiences of Sperm Cryopreservation in Oncological and Non-Oncological Patients: Usage and Reproductive Outcomes of a Large Monocentric Cohort.

Progress in oncological treatment has led to an improved long-term survival of young male cancer patients over the last decades. However, standard cancer treatments frequently implicate fertility-damaging potential. Cryopreservation of sperm is the current standard option to preserve patient’s fertility after treatment, yet long-term data on usage and reproductive experiences is still limited. Natural fertility after treatment and especially in relation to the type of treatment has been poorly analyzed so far. Therefore, we performed a retrospective survey including male patients with an indication for gonadotoxic treatment who cryopreserved reproductive material at our institution between 1994 and 2017. Study questionnaires regarding treatment, material usage, and reproductive outcomes were sent to eligible patients. Additionally, semen analyses of study participants from the time of cryopreservation were evaluated. A total of 99 patients were included in the study. Respondents’ median age was 38.0 years. Most frequent diagnoses were testicular cancer (29.3%) and lymphoma (26.3%). A further 8.1% suffered from autoimmune diseases. Testicular cancer patients had a significantly lower pre-treatment median sperm concentration (18.0 million/ml) compared to non-testicular cancer patients (54.2 million/ml). Until November 2020, the determined sperm usage and cumulative live-birth rate per couple were 17.2% and 58.8%, respectively. Most sperm users received treatments with high (40.0%) or intermediate (33.3%) gonadotoxic potential. 20.7% of all patients reported to had fathered at least one naturally conceived child after treatment, this being the case especially if they had been treated with less or potentially gonadotoxic therapies. In conclusion, our findings emphasize the importance of sperm cryopreservation in the context of male fertility preservation. Furthermore, they indicate that the gonadotoxic potential of patients’ treatments could represent a predictive factor for sperm usage.

Impact of gender on long-term prognosis after transcatheter edge-to-edge repair for mitral regurgitation

Abstract Background A symptomatic and prognostic benefit by Transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR) has been proven. A variety of individual factors including female sex has been suggested to be associated with adverse outcome in cardio-surgical procedures. Purpose While gender is factored in common risk factor models for adverse outcome, evidence on sex-specific differences in long-term outcome after TEER for MR is limited. We aimed to investigate the impact of gender on prognosis in a large monocentric cohort with long-term follow-up. Methods We analyzed survival stratified for gender after successful isolated edge-to-edge repair of MR in the period between 06/2010 and 03/2018 (exclusion of combined forms of TMVR) in a monocentric retrospective cohort by performing survival analyses and cox regression analyses. Results Consecutively, 627 patients (47.0% females, 57.4% functional MR; survival status was available in 96.7%) entered the study and were followed for a median follow-up period of 462 days [IQR 142–945 days]. Survival rates were 97.6% at discharge, 75.7% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7 years. Risk score as calculated by the Logistic Euroscore I did not differ significantly between females and males (at baseline: 25.0 [IQR 18.0/34.8] vs. 27.0 [18.4/40.1]%, p=0.093) and no relevant differences were found for in-hospital (2.0 vs. 2.7%, p=0.613), 30 days (4.8 vs. 6.5%, p=0.473) and 1-year mortality (27.0 vs. 25.3%, p=0.675). At the time of procedure, women were older (79.9 [IQR 75.6/84.4] vs. 78.3 [72.9/83.4] years, p&amp;lt;0.001), were less often affected by coronary artery disease (53.1% vs. 75.0% p&amp;lt;0.001), diabetes mellitus (23.7% vs. 31.3%, p=0.040) and impaired left ventricular function (44.5±12.9% vs. 38.9±13.4%, p&amp;lt;0.001). Regarding long-term survival, women had a better prognosis after MR-therapy, especially in functional etiology: e.g., 4-year survival in FMR 65.7 vs. 35.7%, p=0.006 (Figure 1). Remarkably, female sex was associated with a lower risk for long-term mortality in the Cox-regression models, especially in the FMR subgroup (total cohort: univariate HR 0.81 [0.62–1.04], p=0.101; FMR: univariate HR 0.68 [0.49–0.96], p=0.028). Conclusion In our cohort of patients undergoing TEER for MR, we found no evidence for an impaired short- and mid-term prognosis for female patients. In contrary and not as indicated by Logistic Euroscore, female sex was associated with better long-term survival in comparison to men despite higher median age, which might be partly explained by a slightly more favorable cardiovascular risk profile. Funding Acknowledgement Type of funding sources: None. Figure 1