Clinical, imaging and histopathological characterization of a series of three cats with cerebellar cortical degeneration.

BACKGROUND: Neurological inherited disorders are rare in domestic animals. Cerebellar cortical degeneration remains amongst the most common of these disorders. The condition is defined as the premature loss of fully differentiated cerebellar components due to genetic or metabolic defects. It has been studied in dogs and cats, and various genetic defects and diagnostic tests (including magnetic resonance imaging (MRI)) have been refined in these species. Cases in cats remain rare and mostly individual, and few diagnostic criteria, other than post-mortem exam, have been evaluated in reports with multiple cases. Here, we report three feline cases of cerebellar cortical degeneration with detailed clinical, diagnostic imaging and post-mortem findings. CASE PRESENTATION: The three cases were directly (siblings, case #1 and #2) or indirectly related (same farm, case #3) and showed early-onset of the disease, with clinical signs including cerebellar ataxia and tremors. Brain MRI was highly suggestive of cerebellar cortical degeneration on all three cases. The relative cerebrospinal fluid (CSF) space, relative cerebellum size, brainstem: cerebellum area ratio, and cerebellum: total brain area ratio, were measured and compared to a control group of cats and reference cut-offs for dogs in the literature. For the relative cerebellum size and cerebellum: total brain area ratio, all affected cases had a lower value than the control group. For the relative CSF space and brainstem: cerebellum area ratio, the more affected cases (#2 and #3) had higher values than the control group, while the least affected case (#3) had values within the ranges of the control group, but a progression was visible over time. Post-mortem examination confirmed the diagnosis of cerebellar cortical degeneration, with marked to complete loss of Purkinje cells and associated granular layer depletion and proliferation of Bergmann glia. One case also had Wallerian-like degeneration in the spinal cord, suggestive of spinocerebellar degeneration. CONCLUSION: Our report further supports a potential genetic component for the disease in cats. For the MRI examination, the relative cerebellum size and cerebellum: total brain area ratio seem promising, but further studies are needed to establish specific feline cut-offs. Post-mortem evaluation of the cerebellum remains the gold standard for the final diagnosis.

Phenotypic clustering of patients hospitalized in intensive cardiac care units: Insights from the ADDICT-ICCU study.

BACKGROUND: Intensive cardiac care units (ICCUs) were created to manage ventricular arrhythmias after acute coronary syndromes, but have diversified to include a more heterogeneous population, the characteristics of which are not well depicted by conventional methods. AIMS: To identify ICCU patient subgroups by phenotypic unsupervised clustering integrating clinical, biological, and echocardiographic data to reveal pathophysiological differences. METHODS: During 7-22 April 2021, we recruited all consecutive patients admitted to ICCUs in 39 centers. The primary outcome was in-hospital major adverse events (MAEs; death, resuscitated cardiac arrest or cardiogenic shock). A cluster analysis was performed using a Kamila algorithm. RESULTS: Of 1499 patients admitted to the ICCU (69.6% male, mean age 63.3±14.9 years), 67 (4.5%) experienced MAEs. Four phenogroups were identified: PG1 (n=535), typically patients with non-ST-segment elevation myocardial infarction; PG2 (n=444), younger smokers with ST-segment elevation myocardial infarction; PG3 (n=273), elderly patients with heart failure with preserved ejection fraction and conduction disturbances; PG4 (n=247), patients with acute heart failure with reduced ejection fraction. Compared to PG1, multivariable analysis revealed a higher risk of MAEs in PG2 (odds ratio [OR] 3.13, 95% confidence interval [CI] 1.16-10.0) and PG3 (OR 3.16, 95% CI 1.02-10.8), with the highest risk in PG4 (OR 20.5, 95% CI 8.7-60.8) (all P<0.05). CONCLUSIONS: Cluster analysis of clinical, biological, and echocardiographic variables identified four phenogroups of patients admitted to the ICCU that were associated with distinct prognostic profiles. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05063097.

Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells.

Recent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog kinases 1 and 2 (Lats1 and Lats2) in developing mouse Sertoli cells. Conditional inactivation of Lats1/2 in Sertoli cells resulted in the disorganization and overgrowth of the testis cords, the induction of a testicular inflammatory response and germ cell apoptosis. Stimulated by retinoic acid 8 (STRA8) expression in germ cells additionally suggested that germ cells may have been preparing to enter meiosis prior to their loss. Gene expression analyses of the developing testes of conditional knockout animals further suggested impaired Sertoli cell differentiation, epithelial-to-mesenchymal transition, and the induction of a specific set of genes associated with Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ)-mediated integrin signaling. Finally, the involvement of YAP/TAZ in Sertoli cell differentiation was confirmed by concomitantly inactivating Yap/Taz in Lats1/2 conditional knockout model, which resulted in a partial rescue of the testicular phenotypic changes. Taken together, these results identify Hippo signaling as a crucial pathway for Sertoli cell development and provide novel insight into Sertoli cell fate maintenance.

Rationale and design of the FRENch CoHort of myocardial Infarction Evaluation (FRENCHIE) study.

BACKGROUND: Despite major advances in prevention and treatment, cardiovascular diseases - particularly acute myocardial infarction - remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important. AIMS: The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period. METHODS: FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is an ongoing prospective multicentre observational study (ClinicalTrials.gov Identifier: NCT04050956) enrolling more than 19,000 patients hospitalized for acute myocardial infarction with onset of symptoms within 48hours in 35 participating centres in France since March 2019. Main exclusion criteria are age<18 years, lack of health coverage and procedure-related myocardial infarction (types 4a and 5). Detailed information was collected prospectively, starting at admission, including demographic data, risk factors, medical history and treatments, initial management, with prehospital care pathways and medication doses, and outcomes until hospital discharge. The follow-up period (up to 20 years for each patient) is ensured by linking with the French national health database (Système national des données de santé), and includes information on death, hospital admissions, major clinical events, healthcare consumption (including drug reimbursement) and total healthcare costs. FRENCHIE is also used as a platform for cohort-nested studies - currently three randomized trials and two observational studies. CONCLUSIONS: This nationwide large contemporary cohort with very long-term follow-up will improve knowledge about acute myocardial infarction management and outcomes in France, and provide a useful platform for nested studies and trials.

Three-Year Outcomes With Fractional Flow Reserve-Guided or Angiography-Guided Multivessel Percutaneous Coronary Intervention for Myocardial Infarction.

BACKGROUND: In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up. METHODS: In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577). RESULTS: After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P=0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively. CONCLUSIONS: Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954.

Systemic Scleroderma Induced by Nivolumab in Malignant Melanoma.

BACKGROUND: Immunotherapy using immune checkpoint inhibitors is not devoid of immune-related adverse events (irAEs) including rheumatological conditions. CASE REPORT: We report a rare case of a 47-year-old woman with metastatic melanoma who developed systemic scleroderma after initiating nivolumab. The patient displayed inflammatory arthralgias, morning stiffness, and classical cutaneous manifestations of the disease. Clinical evaluations also revealed carpal tunnel syndrome, cardiac involvement, and dyspnea. RNA-Polymerase III antibodies were positive. Nivolumab, an anti-PD-1 antibody, was considered as a potential trigger for this condition. CONCLUSION: To our knowledge, this is the first case of nivolumab-induced systemic scleroderma in the context of melanoma described in the literature that fulfills the classification criteria of the disease. This case underscores the need for increased awareness of immune-related adverse events in patients receiving immune checkpoint inhibitors, emphasizing timely intervention and further research.

TAPSE/sPAP prognostic value for In-Hospital Adverse Events in Patients Hospitalized for Acute Coronary Syndrome.

AIMS: Although several studies have shown that the right ventricular to pulmonary artery (RV-PA) coupling, assessed by the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) using echocardiography, is strongly associated with cardiovascular events, its prognostic value is not established in acute coronary syndrome (ACS). We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for ACS in a retrospective analysis from the prospective ADDICT-ICCU study. METHODS AND RESULTS: 481 consecutive patients hospitalized in intensive cardiac care unit (mean age 65±13 years, 73% of male, 46% STEMI) for ACS (either ST-elevation [STEMI] or non-ST-elevation [NSTEMI] myocardial infarction) with TAPSE/sPAP available were included in this prospective French multicentric study (39 centers). The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 33 (7%) patients. ROC-curve analysis identified 0.55 mm/mmHg as the best TAPSE/sPAP cut-off to predict in-hospital MACEs. TAPSE/sPAP <0.55 was associated with in-hospital MACEs, even after adjustment with comorbidities (OR:19.1, 95%CI[7.78-54.8]), clinical severity including left ventricular ejection fraction (OR:14.4, 95%CI[5.70-41.7]) and propensity-matched population analysis (OR:22.8, 95%CI[7.83-97.2], all p<0.001). After adjustment, TAPSE/sPAP <0.55 showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.16; global chi-square improvement: 52.8; LR-test p<0.001) with similar results for both STEMI and NSTEMI subgroups. CONCLUSION: A low RV-PA coupling defined as TAPSE/sPAP ratio <0.55 was independently associated with in-hospital MACEs and provided incremental prognostic value over traditional prognosticators in patients hospitalized for ACS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

Standardized reporting for systematic global evaluation of axial spondyloarthritis: An evidence-based and consensus-driven initiative.

INTRODUCTION: National and international scientific societies advocate for a regular, systematic, and standardized global evaluation of axial spondyloarthritis (axSpA) patients. However, there are no recommendations specifying the content of this global evaluation. This initiative aimed to propose a standardized reporting framework, using evidence-based and consensus approaches, to collect data on all domains of axSpA. METHODS: A literature review and consensus process involved a steering committee and an expert panel of 37 rheumatologists and health professionals. The first steering committee took place in March 2022 and identified the main domains for inclusion in the standardized report. A hierarchical literature review was conducted to identify items within these domains and tools for assessment. The items and tools for assessment were discussed and consensus was reached through a vote session during an expert meeting that took place in March 2023. RESULTS: The steering committee identified four main domains to include in the standardized reporting framework: disease assessment, comorbidities, lifestyle, and quality of life. Items and tools for assessment were adopted after the expert meeting. Additionally, recommendations regarding digital tools (websites, apps, social media) were provided. CONCLUSION: This initiative led to a consensus, based on evidence and expertise, on a reporting framework for use during periodic systematic global evaluations of axSpa in daily practice.

Early hybrid cardiac rehabilitation in congenital heart disease: the QUALIREHAB trial.

BACKGROUND AND AIMS: Cardiopulmonary fitness in congenital heart disease (CHD) decreases faster than in the general population resulting in impaired health-related quality of life (HRQoL). As the standard of care seems insufficient to encourage and maintain fitness, an early hybrid cardiac rehabilitation programme could improve HRQoL in CHD. METHODS: The QUALIREHAB multicentre, randomized, controlled trial evaluated and implemented a 12-week centre- and home-based hybrid cardiac rehabilitation programme, including multidisciplinary care and physical activity sessions. Adolescent and young adult CHD patients with impaired cardiopulmonary fitness were randomly assigned to either the intervention (i.e. cardiac rehabilitation) or the standard of care. The primary outcome was the change in HRQoL from baseline to 12-month follow-up in an intention-to-treat analysis. The secondary outcomes were the change in cardiovascular parameters, cardiopulmonary fitness, and mental health. RESULTS: The expected number of 142 patients was enroled in the study (mean age 17.4 ± 3.4 years, 52% female). Patients assigned to the intervention had a significant positive change in HRQoL total score [mean difference 3.8; 95% confidence interval (CI) 0.2; 7.3; P = .038; effect size 0.34], body mass index [mean difference -0.7 kg/m2 (95% CI -1.3; -0.1); P = .022; effect size 0.41], level of physical activity [mean difference 2.5 (95% CI 0.1; 5); P = .044; effect size 0.39], and disease knowledge [mean difference 2.7 (95% CI 0.8; 4.6); P = .007; effect size 0.51]. The per-protocol analysis confirmed these results with a higher magnitude of differences. Acceptability, safety, and short-time effect of the intervention were good to excellent. CONCLUSIONS: This early hybrid cardiac rehabilitation programme improved HRQoL, body mass index, physical activity, and disease knowledge, in youth with CHD, opening up the possibility for the QUALIREHAB programme to be rolled out to the adult population of CHD and non-congenital cardiac disease.

In-hospital Prognostic Value of TAPSE/sPAP in Patients Hospitalized for Acute Heart Failure.

AIMS: TAPSE/sPAP (tricuspid annular plane systolic excursion over systolic pulmonary artery pressure) assessed by echocardiography appears to be a good noninvasive approach for right ventricular to pulmonary artery coupling assessment. We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for acute heart failure (AHF). METHODS AND RESULTS: 333 consecutive patients (mean age 68 ± 14 years, 70% of male, mean LVEF 44 ± 16%) hospitalized for AHF across 39 French cardiology department, with TAPSE/sPAP measured by echocardiography within the 24 first hours of hospitalization were included in this prospective study. The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 50 (15%) patients. Using receiver operating characteristics curves analysis, the best TAPSE/sPAP threshold for in-hospital MACEs was 0.40 mm/mmHg. TAPSE/sPAP <0.40 mm/mmHg was independently associated with in-hospital MACEs, even after adjustment with comorbidities (OR:3.75, 95%CI[1.87-7.93], p < 0.001), clinical severity (OR:2.80, 95%CI[1.36-5.95], p = 0.006). Using a 1:1 propensity-matched population, TAPSE/sPAP ratio <0.40 was associated with a higher rate of in-hospital MACEs (OR:2.98, 95%CI[1.53-6.12], p = 0.002). After adjustment, TAPSE/sPAP <0.40 showed the best improvement in model discrimination and reclassification above traditional prognostic factors (C-statistic improvement: 0.05; Chi-2 improvement: 14.4; LR-test p < 0.001). These results were consistent in an external validation cohort of 133 patients. CONCLUSION: TAPSE/sPAP < 0.40 mm/mmHg assessed by an early echocardiography during an AHF episode is independently associated with in-hospital MACEs suggesting enhanced close monitoring and strengthened HF-specific care in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

In-hospital prognosis of acute ST-elevation myocardial infarction in patients with recent recreational drug use.

AIMS: Although recreational drug use may induce ST-elevated myocardial infarction (STEMI), its prevalence in patients hospitalized in intensive cardiac care units (ICCUs), as well as its short-term cardiovascular consequences, remains unknown. We aimed to assess the in-hospital prognosis of STEMI in patients with recreational drug use from the ADDICT-ICCU study. METHODS AND RESULTS: From 7-22 April 2021, recreational drug use was detected prospectively by a systematic urine multidrug test in all consecutive patients admitted for STEMI in 39 ICCUs across France. The primary endpoint was major adverse cardiac events (MACEs) defined by death, resuscitated cardiac arrest, or cardiogenic shock. Among the 325 patients (age 62 ± 13 years, 79% men), 41 (12.6%) had a positive multidrug test (cannabis: 11.1%, opioids: 4.6%, cocaine: 1.2%, 3,4-methylenedioxymethamphetamine: 0.6%). The prevalence increased to 34.0% in patients under 50 years of age. Recreational drug users were more frequently men (93% vs. 77%, p = 0.02), younger (50 ± 12 years vs. 63 ± 13 years, P < 0.001), and more active smokers (78% vs. 34%, P < 0.001). During hospitalization, 17 MACEs occurred (5.2%), including 6 deaths (1.8%), 10 cardiogenic shocks (3.1%), and 7 resuscitated cardiac arrests (2.2%). Major adverse cardiac events (17.1% vs. 3.5%, P < 0.001) and ventricular arrhythmia (9.8% vs. 1.4%, P = 0.01) were more frequent in recreational drug users. Use of recreational drugs was associated with more MACEs after adjustment for comorbidities (odds ratio = 13.1; 95% confidence interval: 3.4-54.6). CONCLUSION: In patients with STEMI, recreational drug use is prevalent, especially in patients under 50 years of age, and is independently associated with an increase of MACEs with more ventricular arrhythmia. TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT05063097.

Delayed Life-Threatening Hemorrhage Caused by Cranial Tibial Artery Pseudoaneurysm in Two Dogs.

Two adult dogs were presented at 25 and 30 days following tibial external skeletal fixator placement (case 1) and tibial plateau leveling osteotomy (case 2), respectively. Clinical signs at presentation for each of them included acute onset lethargy, non-weight-bearing lameness, and hemorrhage at the surgical site with large hematoma formation. On admission, emergency whole blood transfusion was required in case 2 with a preoperative packed cell volume of 13%. Both dogs were diagnosed with pseudoaneurysm of the cranial tibial artery based on color Doppler ultrasonography. Additionally, computed tomography angiography was performed in one dog. Surgical treatment of the dogs included ligation of the cranial tibial artery supplying the pseudoaneurysm and curettage of hematoma. The surgery was completed without complications in case 1, but case 2 experienced inadvertent rupture of pseudoaneurysm with significant blood loss, which required another whole blood transfusion during the procedure. Both dogs had excellent functional recovery with no recurrence of clinical signs. We hypothesized that pseudoaneurysms were primarily caused by trauma secondary to placement of surgical implants or osteotomy. For orthopedic surgeons, it is important to recognize clinical signs of a potential tibial arterial pseudoaneurysm, as early surgical intervention may prevent loss of limb or life.

Profile of patients hospitalized in intensive cardiac care units in France: ADDICT-ICCU registry.

BACKGROUND: Intensive cardiac care units (ICCU) were initially developed to monitor ventricular arrhythmias after myocardial infarction. In recent decades, ICCU have diversified their activities. AIM: To determine the type of patients hospitalized in ICCU in France. METHODS: We analysed the characteristics of patients enrolled in the ADDICT-ICCU registry (NCT05063097), a prospective study of consecutive patients admitted to ICCU in 39 centres throughout France from 7th-22nd April 2021. In-hospital major adverse events (MAE) (death, resuscitated cardiac arrest and cardiogenic shock) were recorded. RESULTS: Among 1499 patients (median age 65 [interquartile range 54-74] years, 69.6% male, 21.7% diabetes mellitus, 64.7% current or previous smokers), 34.9% had a history of coronary artery disease, 11.7% atrial fibrillation and 5.2% cardiomyopathy. The most frequent reason for admission to ICCU was acute coronary syndromes (ACS; 51.5%), acute heart failure (AHF; 14.1%) and unexplained chest pain (6.8%). An invasive procedure was performed in 36.2%. "Advanced" ICCU therapies were required for 19.9% of patients (intravenous diuretics 18.4%, non-invasive ventilation 6.1%, inotropic drugs 2.3%). No invasive procedures or advanced therapies were required in 44.1%. Cardiac computed tomography or magnetic resonance imaging was carried out in 12.3% of patients. The median length of ICCU hospitalization was 2.0 (interquartile range 1.0-4.0) days. The mean rate of MAE was 4.5%, and was highest in patients with AHF (10.4%). CONCLUSIONS: ACS remains the main cause of admissions to ICCU, with most having a low rate of in-hospital MAE. Most patients experience a brief stay in ICCU before being discharged home. AHF is associated with highest death rate and with higher resource consumption.

Cancer Spheroids Embedded in Tissue-Engineered Skin Substitutes: A New Method to Study Tumorigenicity In Vivo.

Tumorigenic assays are used during a clinical translation to detect the transformation potential of cell-based therapies. One of these in vivo assays is based on the separate injection of each cell type to be used in the clinical trial. However, the injection method requires many animals and several months to obtain useful results. In previous studies, we showed the potential of tissue-engineered skin substitutes (TESs) as a model for normal skin in which cancer cells can be included in vitro. Herein, we showed a new method to study tumorigenicity, using cancer spheroids that were embedded in TESs (cTES) and grafted onto athymic mice, and compared it with the commonly used cell injection assay. Tumors developed in both models, cancer cell injection and cTES grafting, but metastases were not detected at the time of sacrifice. Interestingly, the rate of tumor development was faster in cTESs than with the injection method. In conclusion, grafting TESs is a sensitive method to detect tumor cell growth with and could be developed as an alternative test for tumorigenicity.

Carbon monoxide and prognosis in smokers hospitalised with acute cardiac events: a multicentre, prospective cohort study.

Background: Smoking cigarettes produces carbon monoxide (CO), which can reduce the oxygen-carrying capacity of the blood. We aimed to determine whether elevated expiratory CO levels would be associated with a worse prognosis in smokers presenting with acute cardiac events. Methods: From 7 to 22 April 2021, expiratory CO levels were measured in a prospective registry including all consecutive patients admitted for acute cardiac event in 39 centres throughout France. The primary outcome was 1-year all-cause death. Initial in-hospital major adverse cardiac events (MAE; death, resuscitated cardiac arrest and cardiogenic shock) were also analysed. The study was registered at ClinicalTrials.gov (NCT05063097). Findings: Among 1379 patients (63 ± 15 years, 70% men), 368 (27%) were active smokers. Expiratory CO levels were significantly raised in active smokers compared to non-smokers. A CO level >11 parts per million (ppm) found in 94 (25.5%) smokers was associated with a significant increase in death (14.9% for CO > 11 ppm vs. 2.9% for CO ≤ 11 ppm; p < 0.001). Similar results were found after adjustment for comorbidities (hazard ratio [HR] [95% confidence interval (CI)]): 5.92 [2.43-14.38]) or parameters of in-hospital severity (HR 6.09, 95% CI [2.51-14.80]) and propensity score matching (HR 7.46, 95% CI [1.70-32.8]). CO > 11 ppm was associated with a significant increase in MAE in smokers during initial hospitalisation after adjustment for comorbidities (odds ratio [OR] 15.75, 95% CI [5.56-44.60]) or parameters of in-hospital severity (OR 10.67, 95% CI [4.06-28.04]). In the overall population, CO > 11 ppm but not smoking was associated with an increased rate of all-cause death (HR 4.03, 95% CI [2.33-6.98] and 1.66 [0.96-2.85] respectively). Interpretation: Elevated CO level is independently associated with a 6-fold increase in 1-year death and 10-fold in-hospital MAE in smokers hospitalized for acute cardiac events. Funding: Grant from Fondation Coeur & Recherche.

Rethinking surgical revisions: impact of the MonarchE trial on axillary dissection in hormone-positive HER2-negative early breast cancer patients potentially eligible for abemaciclib.

INTRODUCTION: The MonarchE trial explored the use of abemaciclib, a CDK4/6 inhibitor, as an adjuvant treatment in high-risk early-stage luminal-like breast cancer. The study's inclusion criteria, especially the N2 status, may require revisiting surgical interventions, including invasive axillary lymph node dissection (ALND)-a procedure that current guidelines generally do not recommend. METHODS: We conducted a single-centre, retrospective, observational cohort study on non-metastatic breast cancer patients managed from 2002 to 2011, at the Institut Curie. Data collection involved clinical and histological characteristics plus treatment follow-up. RESULTS: Out of 8715 treated patients, 721 met the inclusion criteria. Overall, 12% (87) were classified as N2 ( ≥ 4 positive lymph nodes), thus eligible for abemaciclib per "node criterion." Tumour size, positive sentinel lymph nodes, and lobular histology showed a significant correlation with N2 status. Approximately 1000 ALNDs would be required to identify 120 N2 cases and prevent four recurrences. CONCLUSION: The MonarchE trial may significantly affect surgical practices due to the need for invasive procedures to identify high-risk patients for adjuvant abemaciclib treatment. The prospect of unnecessary morbidity demands less invasive N2 status determination methods. Surgical decisions must consider patient health and potential treatment benefits.

Complications and Long-Term Outcomes after Combined Tibial Plateau Leveling Osteotomy and Tibial Tuberosity Transposition for Treatment of Concurrent Cranial Cruciate Ligament Rupture and Grade III or IV Medial Patellar Luxation.

OBJECTIVES: This study aims to report complications and long-term outcomes of combined tibial plateau leveling osteotomy and tibial tuberosity transposition (TPLO-TTT) for treatment of concurrent cranial cruciate ligament rupture and medial patellar luxation (MPL). STUDY DESIGN: This is a retrospective study. Dogs that underwent TPLO-TTT for treatment of combined cranial cruciate ligament rupture and grade III or IV MPL were included. Signalment, fixation method, and complications were recorded. Long-term outcome assessment (minimum 1 year postoperatively) was performed through clinical and radiographic reexamination at the authors' institution. RESULTS: Twenty-four stifles (22 dogs) were included. Twenty-one stifles had a grade III MPL, and 3 stifles had grade IV MPL. Four major complications consisting of surgical site infection (n = 3) and recurrent grade II MPL (n = 1) were observed. Dogs with surgical site infections were successfully treated with implant removal and oral antibiotics. No additional surgery was performed for the patient with recurrent MPL as no signs of lameness were observed. Minor complications occurred in five cases. At long-term evaluation (median: 27 months; range: 12-67 months), 21/22 dogs were clinically sound and 23/24 stifles had a complete resolution of MPL. CONCLUSION: TPLO-TTT can be considered as an effective surgical option to treat patients with concurrent cranial cruciate ligament rupture and MPL with a relatively low major complication rate. Owners should be warned of the potential need for implant removal.

Characteristics of difficult-to-treat axial spondyloarthritis: Results of a real-world multicentric study.

OBJECTIVE: The EULAR task force recently published the difficult-to-treat RA (D2T RA) definition, however, a definition of D2T axSpA is still lacking and limitations in this definition exist. The objectives were to study the characteristics of D2T axSpA patients using the EULAR definition and to study a subgroup of patients with a predefined more stringent definition including a temporal criterion. METHODS: A multicentric retrospective study was performed. D2T axSpA was defined as failure of≥2 b/tsDMARDs with different mechanism of action. Very D2T axSpA was defined as failure of≥2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T axSpA patients were compared to non-D2T (nD2T) axSpA patients. RESULTS: Three hundred and eleven axSpA patients were included: 88 D2T axSpA (28.3%) and 223 non-D2T (nD2T) axSpA (71.7%). Peripheral involvement was more prevalent in the D2T group (34.9 vs. 21.4%; P=0.015). BASDAI level at baseline was higher in the D2T group (63.7±16.5 vs. 58.8±14.7; P=0.015). Fibromyalgia was found to be more frequent in the D2T group vs nD2T group (P<0.001). Twelve patients (3.8%) were categorized as very D2T axSpA. Compared to nD2T, Very D2T patients had a higher CRP level at baseline (42.0±31.3 vs. 17.8±23.1; P=0.010). IBD prevalence at baseline was higher in the very D2T group (41.7 vs. 3.1%; P<0.001). None of the very D2T patients presented a fibromyalgia. CONCLUSION: D2T axSpA was associated with higher disease activity, peripheral involvement, extra-musculoskeletal manifestations and fibromyalgia. Very D2T patients represented a minim proportion of patients after applying a more stringent definition including a temporal criterion of 2 years and might be independent from fibromyalgia.