French Multicenter Retrospective Study Research Articles

Increased incidence of diabetes in people living with HIV treated with first-line integrase strand transfer inhibitors: A French multicentre retrospective study.

Prevention of cardiovascular disease is a major issue in the current management of people living with HIV. Concern is growing about the metabolic impact of integrase strand transfer inhibitors (INSTIs), which could lead to an increased risk of diabetes, but the data are conflicting. This is an updated version of our previous analysis, with longer follow-up and new molecules. We retrospectively evaluated the incidence of new-onset diabetes in people living with HIV starting combined antiretroviral therapy with an INSTI compared with non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Data were collected from the Dat'AIDS cohort study, a collaboration of 30 HIV treatment centres in France. We used a propensity score-based inverse probability of treatment weighting approach to adjust for baseline characteristics between the two groups (INSTI and non-INSTI). Between 2009 and 2021, a total of 12 150 people living with HIV were included. The incidence of diabetes was higher in the INSTI group than in the non-INSTI group (hazard ratio 1.38; 95% confidence interval 1.07-1.77; p = 0.012). Regardless of the third drug, but to a greater extent for INSTIs, we observed a peak of new-onset diabetes in the year following initiation of combined antiretroviral therapy. The incidence of diabetes was higher in people treated with integrase inhibitors than in those receiving other third agents. This increased risk occurred both during the first year of treatment and in the longer term.

Epstein-Barr Virus-Associated Smooth Muscle Tumor After Kidney Transplantation: A French Multicenter Retrospective Study.

Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (EBV-SMT). EBV-SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV-SMT (PT-SMT) are scarce in kidney transplant recipients. We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT-SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT-SMT, evolution of graft function, and patient survival. Eight patients were included. The median age at PT-SMT diagnosis was 31 years (range 6.5-40). PT-SMT occurred after a median delay of 37.8 months after transplantation (range 6-175). PT-SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow-up after PT-SMT diagnosis (median 33 months (range 17-132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow-up. PT-SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT-SMT is low in kidney transplant recipients (0.07% in our cohort), PT-SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients.

Outcomes of lung transplantation for pleuroparenchymal fibroelastosis: A French multicentric retrospective study

BackgroundPleuroparenchymal fibroelastosis (PPFE) has no currently available specific treatment. Benefits of lung transplantation (LT) for PPFE are poorly documented. MethodsWe conducted a nation-wide multicentric retrospective study in patients who underwent lung or heart-lung transplantation for chronic end-stage lung disease secondary to PPFE between 2012 and 2022 in France. ResultsThirty-one patients were included. At transplantation, median age was 48 years [IQR 35 – 55]. 64.5% were women. Twenty-one (67.7%) had idiopathic PFFE. Sixteen (52%) had bilateral LT, 10 (32%) had single LT, 4 (13%) had lobar transplantation and one (3%) had heart-lung transplantation. Operative mortality was 3.2%. Early mortality (< 90 days or during the first hospitalization) was 32%. Eleven patients (35.5%) underwent reoperation for hemostasis. Eight (30.8%) experienced bronchial complications. Mechanical ventilation time was 10 days [IQR 2–55]. Length of stay in intensive care unit and hospital were 34 [IQR 18–73] and 64 [IQR 36–103] days, respectively. Median survival was 21 months. Post-transplant survival rates after 1, 2, and 5 years were 57.9%, 42.6% and 38.3% respectively. Low albuminemia (p=0.046), FVC (p=0.021), FEV1 (p=0.009) and high emergency lung transplantation (p=0.04) were associated with increased early mortality. Oversized graft tended to be correlated to a higher mortality (p=0.07). ConclusionLT for PPFE is associated with high post-operative morbi-mortality rates. Patients requiring high emergency lung transplantation with advanced disease, malnutrition, or critical clinical status experienced worse outcomes. ClinicalTrials.gov IdentifierNCT05044390.

Abstract PS08-02: Efficacy of Sacituzumab-Govitecan (SG) post Trastuzumab-deruxtecan (T-DXd) and vice versa for HER2low advanced or metastatic breast cancer (MBC): a French multicentre retrospective study

Abstract Background: Based on ASCENT, TROPICS-02 and DESTINY-Breast04 trials, SG and T-DXd recently became approved for HER2low MBC. Since the payloads of both SG and T-DXd belong to the same cytotoxic class (topoisomerase-1 inhibitor), cross-resistance is a potential concern. However, no data is available on the efficacy of one antibody drug conjugate (ADC) after another and the best therapeutic sequence has not been evaluated yet. Methods: We conducted a retrospective study in 19 French comprehensive cancer centres. All patients (pts) with HR+ or HR- and HER2low MBC treated with SG followed, immediately or not, by T-DXd (or vice versa) were included. HR expression was defined on the last available tumor sample. The study primary objective was to report the second ADC (ADC2) progression-free survival (PFS) in the whole population. Secondary objectives included first ADC (ADC1) progression-free interval (PFI) and overall survival (OS) in the whole population and subgroup analyses by HR status. Results: The individual data of 126 eligible women were obtained from 19 participating centres. Median age was 54.5 years (range: 30-80y). N=110 (87.3%) pts had invasive carcinoma of not special type, N=12 (9.5%) invasive lobular carcinoma and 4 (3.2%) other histological subtype. N=87 (69%) and 39 (31%) had HR+/HER2low and HR-/HER2low MBC, respectively. N=16 patients were germline mutation carriers (BRCA1 N=7; BRCA2 N=6; other genes on HBOC panel N=3). ADC1 was given as a median of third (range: 1-10) line of chemotherapy and ADC2 as fifth (range: 2-12) line. A large majority (N=94, 74.6%) of pts received SG as ADC1 (N=82 with HR- and N=12 with HR+ MBC) while N=32 (25.4%) received T-DXd as ADC1 (N=27 with HR+ and n=5 with HR- MBC). 53.2% (N=67) received ADC1 immediately followed by ADC2 while 46.8% (N=59) received ADC2 after 1 (N=40) or 2 (N=12) or ≥ 3 (N=6) other lines of chemotherapy. N=19 (15.07%) and N=26 (20.63%) had a meningeal and/or cerebral metastasis at the time of the initiation of ADC1 and ADC2 respectively. After a median follow-up of 3 months, ADC2 was discontinued in 63 pts of which 51 (82.3%) for progression disease and 4 (6.5%) for toxicity due to T-DXd. Importantly, 50% of pts (N=63) were still under ADC2 at the time of this first analysis. The observed median PFS for ADC2 and median PFI for ADC1 are presented in the Table below: Median OS was not reached independently of the sub-populations of pts. Population and sequential regimen Median (mo) PFI ADC1 Median (mo) PFS ADC2 Whole population (N=126) SG → T-DXd (N=94) T-DXd→SG (N=32) 4.5 (95%CI [3.4-5.1]) 2.7 (95%CI [2.1-3.3] HR-/HER2low (N=82) having received SG as ADC1 then T-DXd as ADC2 4.8 (95%CI [3.8-5.1]) 3.3 (95%CI [2.5-3.7]) HR+/HER2low (n=27) having received T-DXd as ADC1 then SG as ADC2 2.7 (95%CI [2.0-3.2]) 2.0 (95%CI [1.6-NR]) Conclusion: To the best of our knowledge, this is the largest cohort evaluating the efficacy of subsequent ADCs administration in HER2low MBC. In these heavily pre-treated pts, subsequent use of ADCs seem to be associated with shortened PFS in both HR+/HR- subgroups, independently of their administration order. Data will be updated and completed for the meeting. Moreover, the number of eligible pts will be increased. Table 1: median TPP and PFS2 in whole population and HR subgroups Citation Format: François Poumeaud, Mathilde Morisseau, Luc Cabel, Anthony Gonçalves, Charlène Rivier, Olivier Trédan, Elsa Volant, Jean Sebastien FRENEL, Sylvain Ladoire, William Jacot, Mathieu Jamelot, Hervé Fokatichoue, Luis Teixeira, Francois-Clement Bidard, Delphine Loirat, Christelle Levy, Bastien Cabarrou, Antoine Deleuze, Elise Deluche, Thomas Grellety, Frédéric Fiteni, Hervé Bischoff, Roman Vion, Stéphanie Becourt, Thibaut Reverdy, Alexandre de Nonneville, Florence Dalenc. Efficacy of Sacituzumab-Govitecan (SG) post Trastuzumab-deruxtecan (T-DXd) and vice versa for HER2low advanced or metastatic breast cancer (MBC): a French multicentre retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-02.

Recurrent (or episodic) fever of unknown origin (FUO) as a variant subgroup of classical FUO: A French multicentre retrospective study of 170 patients

BackgroundRecurrent FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking. MethodsWe performed a retrospective multicentre study of patients with recurrent FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical and prognostic variables independently associated with final diagnosis and mortality. ResultsOf 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR = 5.2; p < 0.001), contributory history (OR = 10.4; p < 0.001), and abnormal clinical examination (OR = 4.0; p = 0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p = 0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death. ConclusionThis study extends the known yield of recurrent FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow-up. Moreover, their overall prognosis is excellent.

Perinatal outcomes between immediate vs deferred selective termination in dichorionic twin pregnancies with fetal congenital anomalies: a French multicenter study

Because selective termination for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal. To determine whether perinatal outcomes were more favorable following deferred rather than immediate selective termination. A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with selective termination for fetal conditions, which were diagnosed before 24 weeks gestation. Pregnancies with additional risk factors for late miscarriage were excluded. We defined 2 groups according to the intention to perform selective termination within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate selective termination) or to wait until the third trimester (deferred selective termination). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 weeks gestation and preterm delivery. Of 390 pregnancies, 258 were in the immediate selective termination group and 132 in the deferred selective termination group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate selective termination group vs 100% (132/132) in the deferred selective termination group (P<.01). Preterm birth <37 weeks gestation was lower in the immediate than in the deferred selective termination group (66.7% vs 20.2%; P<.01); preterm birth <28 weeks gestation and <32 weeks gestation did not differ significantly (respectively 1.7% vs 0.8%; P=.66 and 8.26% vs 11.4%; P=.36). In the deferred selective termination group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery. Overall survival after selective termination was high regardless of the gestational age at which the procedure was performed. Postponing selective termination until the third trimester seems to improve survival, whereas immediate selective termination reduces the risk of preterm delivery. Furthermore, deferred selective termination requires an expert center capable of performing the selective termination procedure on an emergency basis if required.

Are there reliable criteria for predicting the chances of pregnancy in recipients of egg donation? What makes a “good donor”? French multicentre retrospective study conducted by GEDO (Groupe d’Etudes pour le Don d’Ovocytes)

Are there reliable criteria for predicting the chances of pregnancy in recipients of egg donation? What makes a “good donor”? French multicentre retrospective study conducted by GEDO (Groupe d’Etudes pour le Don d’Ovocytes)

Hypomethylating agent monotherapy in core binding factor acute myeloid leukemia: a French multicentric retrospective study

Very few data are available about hypomethylating agent (HMA) efficiency in core binding factor acute myeloid leukemias (CBF-AML). Our main objective was to evaluate the efficacy and safety of HMA in the specific subset of CBF-AML. Here, we report the results of a multicenter retrospective French study about efficacy of HMA monotherapy, used frontline or for R/R CBF-AML. Forty-nine patients were included, and received a median of 5 courses of azacitidine (n = 46) or decitabine (n = 3). ORR was 49% for the whole cohort with a median time to response of 112 days. After a median follow-up of 72.3 months, median OS for the total cohort was 10.6 months. In multivariate analysis, hematological relapse of CBF-AML at HMA initiation was significantly associated with a poorer OS (HR: 2.13; 95%CI: 1.04–4.36; p = 0.038). Responders had a significantly improved OS (1-year OS: 75%) compared to non-responders (1-year OS: 15.3%; p < 0.0001). Hematological improvement occurred for respectively 28%, 33% and 48% for patients who were red blood cell or platelet transfusion-dependent, or who experienced grade 3/4 neutropenia at HMA initiation. Adverse events were consistent with the known safety profile of HMA. Our study highlights that HMA is a well-tolerated therapeutic option with moderate clinical activity for R/R CBF-AML and for patients who cannot handle intensive chemotherapy.

Postnatal outcome of children with antenatal colonic hyperechogenicity.

To evaluate the postnatal outcome of children with antenatal colonic hyperechogenicity, currently considered as a sign of lysinuria-cystinuria, but which may also be a sign of other disorders with a more severe prognosis. We carried out a French multi-centric retrospective study via 15 Multidisciplinary Center for Prenatal Diagnosis from January 2011 to January 2021. We included pregnancies for which fetal colonic hyperechogenicity had been demonstrated. We collected the investigations performed during pregnancy and at birth as well as the main clinical features of the mother and the child. We then established the prevalence of pathologies such as lysinuria-cystinuria (LC), hypotonia-cystinuria syndrome (HC), or lysinuric protein intolerance (LPI). Among the 33 cases of colonic hyperechogenicity collected, and after exclusion of those lost to follow-up, we identified 63% of children with lysinuria-cystinuria, 8% with lysinuric rotein intolerance, and 4% with hypotonia-cystinuria syndrome. Management of prenatal hyperechoic colon should include a specialized consultation with a clinical geneticist to discuss further investigations, which could include invasive amniotic fluid sampling for molecular diagnosis. A better understanding of diagnoses and prognosis should improve medical counseling and guide parental decision making.

Comparison of effective regurgitant orifice area by the PISA method and tricuspid coaptation gap measurement to identify very severe tricuspid regurgitation and stratify mortality risk

Abstract Background Various definitions of very severe (VS) tricuspid regurgitation (TR) have been proposed based on the effective regurgitant orifice area (EROA) or tricuspid coaptation gap (TCG). Because of the inherent limitations associated with the EROA, we hypothesized that the TCG would be more suitable for defining VSTR and predicting outcomes. Purpose To compare EROA and TCG for outcome prediction in patients with severe TR. Methods In this French multicentre retrospective study, we included 606 patients with ≥ moderate-to-severe isolated TR (without structural valve disease or an overt cardiac cause) according to the recommendations of the European Association of Cardiovascular Imaging. Patients were further stratified into VSTR according to the EROA (≥60 mm²) and then according to the TCG (≥10 mm). The primary endpoint was all-cause mortality and the secondary endpoint was cardiovascular mortality. Results The relationship between the EROA and TCG was poor (R²=0.21), especially when the size of the defect was large. Four-year survival was comparable between patients with an EROA &amp;lt;60 mm² vs. ≥ 60 mm² (67±3% vs. 64±4%, p=0.64), even after adjustment, for all-cause (p=0.72) and cardiovascular mortality (p=0.18). A TCG ≥10 mm was associated with lower four-year survival than a TCG &amp;lt;10 mm (53±7% vs. 69±3%, p&amp;lt;0.001). After adjustment for covariates, including age, comorbidity, right heart failure, dose of diuretics, and right ventricular dysfunction, a TCG ≥10 mm remained independently associated with higher all-cause mortality (adjusted HR[95%CI]=1.46[1.15-2.18], p=0.015) and cardiovascular mortality (adjusted HR[95%CI]=1.95[1.22-3.14], p &amp;lt;0.001), whereas an EROA ≥60 mm² was not associated with all-cause or cardiovascular mortality (adjusted HR[95%CI]:1.07[0.75-1.51], p=0.720, and adjusted HR[95%CI]:1.35[0.87-2.09], p=0.176, respectively). Conclusion The correlation between the TCG and EROA is weak and decreases with increasing defect size. A TCG ≥10mm is associated with increased all-cause and cardiovascular mortality and should be used to define VSTR in isolated TR.Correlation between EROA and TCGEvent free survival curves

483P Prognostic value of androgen receptor expression in patients with advanced triple-negative metastatic breast cancer treated with sacituzumab govitecan: A French multicentre retrospective study

483P Prognostic value of androgen receptor expression in patients with advanced triple-negative metastatic breast cancer treated with sacituzumab govitecan: A French multicentre retrospective study

Rituximab resistance at 3 months of induction therapy in newly diagnosed or relapsing ANCA associated vasculitis: a French multicentre study.

To evaluate rituximab (RTX) resistance at 3 months (M3) of induction therapy in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). Multicentre French retrospective study conducted between 2010 and 2020 including patients with newly diagnosed or relapsing AAV (granulomatosis with polyangiitis or microscopic polyangiitis) having received induction therapy with RTX. Primary endpoint was the presence of RTX resistance at 3 months (M3) defined as uncontrolled disease (worsening feature on the BVAS/WG 1 month after RTX induction) or disease flare (increase in BVAS/WG of ≥1 point before M3). Out of 121 patients included, we analysed 116 patients. Fourteen patients (12%) had RTX resistance at M3 with no difference in baseline demographics, vasculitis type, ANCA type, disease status or organ involvement. Patients with RTX resistance at M3 had a greater proportion of localized disease (43% vs 18%, P<0.05) and were less often treated by initial methylprednisolone (MP) pulse (21% vs 58%, P<0.01). Out of the 14 patients with RTX resistance, seven received additional immunosuppressive therapy. All patients were in remission at 6 months. Compared to responders, patients with RTX resistance at M3 were less often treated with prophylactic trimethoprim-sulfamethoxazole (57% vs 85%, P<0.05). Twenty-four patients died during follow-up, one-third of them from infections and half of them from SARS-CoV-2. 12% of patients had RTX resistance at M3. These patients more often had localized form of the disease and were less treated by initial MP pulse and by prophylactic trimethoprim-sulfamethoxazole.

Chronic Myelomonocytic Leukemia Patients With Lysozyme Nephropathy and Renal Infiltration Display Markers of Severe Disease

Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes. We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Sixteen patients (males, n= 14; median age 76.5 years [71.9-83]) developed a kidney disease 6 months [1.6-25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25-3.4], and median serum creatinine was 2.26 mg/dl [1.46-2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9-34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P< 0.001), had more CMML-1 (P= 0.005), were more susceptible to develop an AML (P= 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P< 0.001), but no survival difference was seen between the 2 groups (P= 0.6978). In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.

Combined Nivolumab and Ipilimumab in Octogenarian and Nonagenarian Melanoma Patients.

Data regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3-93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade ≥ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question.

Epidemiology and Clinical Patterns of Lung Abscesses in ICU: A French Multicenter Retrospective Study

Data are scarce regarding epidemiology and management of critically ill patients with lung abscesses. What are the clinical and microbiological characteristics of critically ill patients with lung abscesses, how are they managed in the ICU, and what are the risk factors of in-ICU mortality? This was a retrospective observational multicenter study, based on International Classification of Diseases, 10th Revision, codes, between 2015 and 2022 in France. In-ICU mortality-associated factors were determined by multivariate logistic regression. We analyzed 171 ICU patients with pulmonary abscesses. Seventy-eight percent were male, with a mean age of 56.5 ± 16.4 years; 20.4%misused alcohol, 25.2%had a chronic lung disease (14%COPD), and 20.5%had a history of cancer. Overall, 40.9%were immunocompromised and 38%qualified for nosocomial infection. Presenting symptoms included fatigue or weight loss in 62%, fever (50.3%), and dyspnea (47.4%). Hemoptysis was reported in 21.7%. A polymicrobial infection was present in 35.6%. The most frequent pathogens were Enterobacteriaceae in 31%, Staphylococcus aureus in 22%, and Pseudomonas aeruginosa in 19.3%. Fungal infections were found in 10.5%. Several clusters of clinicoradiologic patterns were associated with specific microbiological documentation and could guide empiric antibiotic regimen. Percutaneous abscess drainage was performed in 11.7%; surgery was performed in 12.7%, and 12%required bronchial artery embolization for hemoptysis. In-ICU mortality was 21.5%, and age (OR: 1.05 [1.02-1.91], P= .007], renal replacement therapy during ICU stay (OR, 3.56 [1.24-10.57], P= .019), and fungal infection (OR, 9.12 [2.69-34.5], P= .0006) were independent predictors of mortality after multivariate logistic regression, and drainage or surgery were not. Pulmonary abscesses in the ICU are a rare but severe disease often resulting from a polymicrobial infection, with a high proportion of Enterobacteriaceae, S aureus, and P aeruginosa. Percutaneous drainage, surgery, or arterial embolization was required in more than one-third of cases. Further prospective studies focusing on first-line antimicrobial therapy and source control procedure are warranted to improve and standardize patient management.

Extracranial anticoagulant related bleedings admitted to intensive care units: a French multicenter retrospective study

BackgroundAnticoagulants are widely used but can lead to iatrogenic events such as bleeding. Limited data exists regarding the characteristics and management of patients admitted to intensive care units (ICU) for severe anticoagulant-related extracranial bleeding.MethodsA retrospective observational study was conducted in five French ICUs. From January 2007 to December 2018, all patients aged over 18 years admitted to ICU for extracranial bleeding while receiving therapeutic anticoagulation were included.Results486 patients were included, mainly male (61%) with an average age of 73 ± 13 years. Most patients had comorbidities, including hypertension (68%), heart disease (49%) and diabetes (33%). Patients were treated by vitamin K antagonists (VKA, 54%), heparins (25%) and direct oral anticoagulants (DOAC, 7%). The incidence of patients admitted to ICU for anticoagulant-related bleeding increased from 3.2/1000 admissions in 2007 to 5.8/1000 in 2018. This increase was particularly high for DOAC class. Upon admission, patients exhibited severe organ failure, as evidenced by a high SOFA score (7 ± 4) and requirement for organ support therapies such as vasopressors (31.5%) and invasive mechanical ventilation (34%). Adherence to guidelines for the specific treatment of anticoagulant-related bleeding was generally low. ICU mortality was 27%. In multivariate analysis, five factors were independently associated with mortality: chronic hypertension, need for vasopressors, impaired consciousness, hyperlactatemia and prolonged aPTT > 1.2.ConclusionAnticoagulant-related extracranial bleeding requiring ICU admission is a serious complication responsible for organ failure and significant mortality. Its incidence is rising. The therapeutic management is suboptimal and could be improved by educational programs.

Intramuscular capillary-type hemangioma: Diagnosis, treatment, and outcomes. A French multicentric retrospective study of 66 cases

PurposeIntramuscular capillary-type hemangiomas (ICTHs) are rare entities, belonging to the group of intramuscular “hemangiomas.” The diagnosis remains challenging. We aimed to assess the diagnostic criteria, treatments and outcomes of ICTHs. MethodsThis retrospective study collected all cases of ICTH followed up in 9 French hospital centers, reviewed by an adjudication expert group. ResultsAmong 133 patients screened, 66 with ICTH were included. The median age of patients at diagnosis was 28.0 years, interquartile range (21.0–––36.0). The lesion, mainly presenting as a gradually increasing mass (83.9%), was painless (88.9%) and was located in the head and neck (42.4%). MRI (available in all cases) mainly revealed a well-delineated lesion, isointense to the muscle on T1-weighted images, with enhancement after contrast injection; hyperintense on T2-weighted images; and containing flow voids. Among the 66 cases, 59 exhibited typical ICTH features and 7 shared some imaging features with arteriovenous malformations. These latter were larger than typical ICTHs and more painful and appeared on imaging as less well delimited and more heterogeneous tissue masses, with larger tortuous afferent arteries, earlier draining vein opacification and mild arteriovenous shunting. We propose to name these lesions arteriovenous malformation (AVM)-like ICTH. Pathological reports were similar in typical and AVM-like ICTH, showing capillary proliferation with mainly small-size vessels, negative for GLUT-1 and positive for ERG, AML, CD31 and CD34, with low Ki67 proliferation index (<10%), and adipose tissue. The most frequent treatment for ICTH was complete surgical resection (17/47, 36.2%), preceded in some cases by embolization, which led to complete remission. ConclusionsICTH can be diagnosed on MRI when it is typical. Biopsy or angiography are required for atypical forms.

Comparison of effective regurgitant orifice area by the PISA method and tricuspid coaptation gap measurement to identify very severe tricuspid regurgitation and stratify mortality risk

Abstract Funding Acknowledgements Type of funding sources: None. Background Various definitions of very severe (VS) tricuspid regurgitation (TR) have been proposed based on the effective regurgitant orifice area (EROA) or tricuspid coaptation gap (TCG). Because of the inherent limitations associated with the EROA, we hypothesized that the TCG would be more suitable for defining VSTR and predicting outcomes. Purpose To compare EROA and TCG for outcome prediction in patients with severe TR Methods In this French multicentre retrospective study, we included 606 patients with ≥ moderate-to-severe isolated TR (without structural valve disease or an overt cardiac cause) according to the recommendations of the European Association of Cardiovascular Imaging. Patients were further stratified into VSTR according to the EROA (≥60 mm²) and then according to the TCG (≥10 mm). The primary endpoint was all-cause mortality and the secondary endpoint was cardiovascular mortality. Results The relationship between the EROA and TCG was poor (R²=0.21), especially when the size of the defect was large. Four-year survival was comparable between patients with an EROA &amp;lt;60 mm² vs. ≥ 60 mm² (67±3% vs. 64±4%, p = 0.64), even after adjustment, for all-cause (p = 0.72) and cardiovascular mortality (p = 0.18). A TCG ≥10 mm was associated with lower four-year survival than a TCG &amp;lt;10 mm (53±7% vs. 69±3%, p&amp;lt;0.001). After adjustment for covariates, including age, comorbidity, right heart failure, dose of diuretics, and right ventricular dysfunction, a TCG ≥10 mm remained independently associated with higher all-cause mortality (adjusted HR[95%CI]=1.46[1.15–2.18], p = 0.015) and cardiovascular mortality (adjusted HR[95%CI]=1.95[1.22–3.14], p &amp;lt;0.001), whereas an EROA ≥60 mm² was not associated with all-cause or cardiovascular mortality (adjusted HR[95%CI]:1.07[0.75–1.51], p = 0.720, and adjusted HR[95%CI]:1.35[0.87–2.09], p = 0.176, respectively) Conclusion The correlation between the TCG and EROA is weak and decreases with increasing defect size. A TCG ≥10mm is associated with increased all-cause and cardiovascular mortality and should be used to define VSTR in isolated TR.

#2664 CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) PATIENTS WITH LYSOZYME NEPHROPATHY AND CMML RENAL INFILTRATION DISPLAY MARKERS OF SEVERE DISEASE

Abstract Background and Aims Chronic myelomonocytic leukemia (CMML) is a hematologic disorder which is an overlap syndrome between myelodysplastic syndromes, and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. The objective of this study was to describe kidney involvement in CMML patients, their treatments, and outcomes. Method We conducted a French and American multicenter retrospective observational study in fifteen centers, identifying CMML patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results Sixteen patients (males, n = 14, median age 76.5 [71.9-83]) developed a kidney disease 6 months [1.6-25.6] after the diagnosis of CMML. Median urinary protein to creatinine ratio was 2 g/g [1.3-3.4], and median serum creatinine was 2.26 mg/dL [1.46-2.68]. Fourteen patients (87.5%) underwent a kidney biopsy. The two main renal diagnoses were either a lysozyme nephropathy (n = 9, 56%), or a renal infiltration by the CMML (n = 6, 37.5%). Histological findings showed lesions of acute tubular injury with focal tubular epithelial necrosis (n = 4), a vacuolization of the epithelial cells of the proximal tubules (n = 7), and an inflammatory infiltrate with mostly mononuclear myeloid cells (n = 9). Ten patients received a new treatment following the CMML-associated kidney injury. The effect of CMML treatment on kidney injury could be assessed in 10 patients, and renal function evolution was heterogenous. After a median follow-up of 15 months [9.9-34.9], 4 patients had CKD stage 3, 4 CKD stage 4, 1 an end-stage kidney disease. Two patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocytes count (p&amp;lt;0.001), had more CMML-1 (p = 0.005), were more susceptible to develop an AML (p = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (p&amp;lt;0.001), but no survival difference was seen between the two groups (p = 0.6978). Conclusion In this largest published cohort of CMML patients with a kidney injury, the two most frequent renal complications were lysozyme-induced nephropathy, and renal infiltration by the CMML. The development of a kidney injury during CMML appears to worsen the patient prognosis.

#2663 KIDNEY INVOLVEMENT IN MYELODYSPLASTIC SYNDROMES

Abstract Background and Aims Myelodysplastic syndromes (MDS) are hematologic disorders characterized by ineffective and dysplastic hematopoiesis that can be associated with systemic inflammatory and autoimmune diseases. The objective of this study was to describe kidney involvement in MDS patients, their treatments, and outcomes. Method We conducted a French and American multicenter retrospective observational study in nine centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results Seventeen patients (males n = 11, median age 76 [70-79]) developed a kidney disease 6 months [0-31] after the diagnosis of MDS. Median urinary protein to creatinine ratio was 1.9g/g [0.8-3.3], and median serum creatinine was 3.5mg/dL [1.5-4.7]. Twelve patients (70%) had AKI at presentation, and 14 (82%) extra-renal symptoms, which consisted mostly in cutaneous and pneumological manifestations. The renal diagnoses included antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) (n = 8, 47%), ANCA negative vasculitis (n = 4, 24%), C3 glomerulonephritis (n = 2), immune complex-mediated glomerulonephritis (n = 1), polyarteritis nodosa (n = 1), and IgA vasculitis (n = 1). Kidney biopsies were performed in 10 of the cases. All patients, except one, received a treatment following the MDS-associated kidney injury (n = 16, 94% with steroids). The effect of MDS treatment on kidney injury could be assessed in 8 patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 9 months [4.1-14.2], 4 patients had CKD stage 3, 4 CKD stage 4, 5 an end stage kidney disease. Three patients evolved to an acute myeloid leukemia (AML), and 3 died. Compared to 84 MDS controls, patients who had a kidney involvement were younger (p = 0.03), had a higher number of dysplasia lineages (3 lineages, p = 0.001), and were more eligible to receive hypomethylating agents (p = 0.031), but no survival difference was seen between the two groups (p = 0.5227). Compared to 265 AAV without MDS, MDS-associated AAV were older (p = 0.019), ANCA serology was more frequently negative (p = 0.014), and more cutaneous lesions were seen (p = 0.003). Conclusion The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis, and especially AAV. A diagnosis of ANCA vasculitis in an elderly patient, or with a cutaneous manifestation, or without ANCA positivity, should lead to the search for a possible MDS.