Efficacy of chemotherapy after progression during or following PARPi exposure in ovarian cancer.

BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPis) improved advanced ovarian cancer treatment. Most patients progress during or following PARPi exposure, however, with concerns about sensitivity of subsequent chemotherapy. PATIENTS AND METHODS: In this international cohort study, we evaluated the efficacy of a subsequent chemotherapy following PARPi exposure in high-grade ovarian carcinoma patients. Endpoints included progression-free survival (PFS), overall survival and a multivariable Cox model was built to identify factors influencing PFS. RESULTS: We included 291 patients from four international centers treated between January 2002 and December 2021. The median number of previous chemotherapy was 1 (1.0-7.0), the median duration of PARPi exposure was 6.5 months (0.2-54.3 months). PARPi was used in first line in 14.1% patients. Most progressions occurred under PARPi exposure (89.1%). A BRCA pathogenic variant was identified in 130 patients (44.7%), absent in 157 patients (54.0%), and undocumented in 4 patients (1.4%). Platinum-based CT (PBC) and non-PBC were administered as subsequent treatments in, respectively, 182 patients (62.5%) and 109 patients (37.5%). Multivariable analyses showed that platinum-free interval (PFI) >6 months [adjusted hazards ratio (HR), 0.52; 95% confidence interval (CI) 0.39-0.70] and type of initial surgery (adjusted HR, 1.41; 95% CI 1.07-1.87; interval or closing surgery versus primary surgery) were associated with PFS, independent of BRCA status or line of therapy (≥2 versus 1). In patients with a PFI >6 months, PBC was numerically associated with the best PFS (adjusted HR, 0.68; 95% CI 0.46-1.01). CONCLUSION: This is the largest real-world study assessing the efficacy of subsequent chemotherapy in patients progressing during PARPi exposure. The patients have poor outcomes. PBC is the best option in patients progressing on PARPi and eligible for PBC rechallenge (PFI >6 months).

Feasibility of EXIME® temporary prosthesis placement and removal in men with acute or chronic urinary retention after failure or inability to selfcatheterize.

INTRODUCTION: Urological emergencies represent 7% of admissions, 29% of which are acute urine retention. We report the first results of a protocol evaluating a new device in case of failure of self-catheterization, replacing a permanent catheter: the urethral device EXIME®. METHOD: Intention-to-treat study on the feasibility of inserting the EXIME® prosthesis in a day hospital after simple urethral gel instillation in men with urine retention. EXIME® was proposed to all patients after failure of Foley catheter removal and refusal or inability to learn self-catheterization. The protocol was referenced (NCT04218942) after obtaining the agreement of the committee for the protection of individuals. RESULTS: Among 278 patients admitted for a trial of Foley catheter removal, 15 patients with failed voiding resumption and refusal or failure of self-catheterization were offered the prosthesis. The median age was 73 years with a median retention volume of 700mL. The median prostatic volume was 60g. Fourteen patients had their prosthesis inserted in good conditions of comfort for the practitioner and the patient. One failed placement was noted. The difficulty of insertion was estimated by the practitioner at 0 on median (VAS from 0 to 10), and for its removal at 0. The pain during the insertion of the device was evaluated by the patients at 2.00 and for the removal at 0 (VAS from 0 to 10). 6 patients had satisfactory voiding recovery at D0. DISCUSSION: We proposed the placement of EXIME to patients who had failed the trial of Foley removal and were unable and/or unwilling to self-catheterize. These were patients with poor bladder contractility and a high risk of retention recurrence. Despite this mixed result, the simplicity of the device and the comfortable expectation of an endoscopic procedure seem promising. CONCLUSION: Insertion and retrieval of EXIME®prostatic prosthesis were easy and well tolerated in our population. Insertion failed in one patient. A comparative prospective study with self catheterization is necessary to determine its effectiveness.

[Comparison of systematic, targeted and combined prostate biopsies for the diagnosis of prostate cancer with MRI lesion]. / Comparaison des biopsies de prostate systématiques, ciblées et combinées pour le diagnostic de cancer de prostate en cas de lésion à l'IRM.

OBJECTIVE: The objective of our study is to compare the performance of systematic, targeted and combined biopsies in the same cohort for the detection of clinically significant prostate cancer (csCaP). MATERIAL AND METHOD: We included patients coming for first series of prostate biopsies, from January 2016 to May 2020, with at least one PI-RADS lesion ≥3 on MRI. All patients underwent 12 systematic biopsies, combined with at least 2 biopsies per target lesion, using the MRI/3D ultrasound fusion system Urostation® (Koelis). RESULTS: We included 234 patients. Combined biopsies allowed a better detection rate of csCaP (59.4%) compared to systematic biopsies (55.6%, P=0.01) and targeted biopsies alone (44.4%, P<0.001). The same is true for the overall prostate cancer (CaP) rate: 65.4% for the combined biopsies versus 61.1% for the systematic biopsies (P=0.002) and 49.1% for the targeted biopsies (P<0.001). The detection rates of clinically non-significant prostate cancer (ncsCaP) were similar (6% vs. 5.6% vs. 4.7% for combined, systematic and targeted biopsies respectively). Targeted biopsies found 10 (4.3%) CaP undiagnosed by systematic biopsies including 6 (2.6%) csCaP, and an upgraded ISUP score for 17 (7.3%) patients. Systematic biopsies found 38 (16.2%) CaP undiagnosed by targeted biopsies including 33 (14.1%) csCaP, and allowed an upgraded ISUP score for 19 (8.1%) patients. CONCLUSION: Combined biopsies provide the best detection rate for csCaP in our study.

[Role of echocardiography in the detection and the monitoring of left ventricular systolic dysfunction in patients undergoing cancer therapy]. / Rôle de l'échocardiographie dans le dépistage et le suivi de la dysfonction ventriculaire gauche chez des patients sous traitement anticancéreux.

Cardio-oncology has recently been developed to prevent, identify and manage cardiovascular events in patients with cancer receiving cardiotoxic chemotherapy. Among cardiovascular complications of cancer therapy, myocardial dysfunction and heart failure are one of the most concerning issue. Since cardiotoxicity adversely affect quality of life and prognosis in cancer patients, its prevention, detection and treatment are crucial. This review aimed to describe the main chemotherapies able to induce myocardial dysfunction and to emphazise the pivotal role of echocardiography in the follow up. We also intent to provide to the lector a better understanding of what to do in case of cardiotoxicity.

[Coronary artery spasm revealed by an out-of-hospital cardiac arrest associated with a moyamoya disease. A case report of multimodality imaging]. / Arrêt cardiaque par spasme coronaire associé à une maladie de Moyamoya. Apport de l'imagerie cardiaque multimodale.

Moyamoya disease is a rare angiopathy characterized by a progressive distal occlusion of the internal carotid arteries and their branches. Extracerebral involvement, including coronary arteries, has been described. We report the case of a patient with moyamoya disease who suffered an out-of-hospital cardiac arrest associated with coronary spasm. We discussed the possible links between coronary spasm and moyamoya, as well as the contribution of multimodal cardiac imaging, combining conventional and intracoronary imaging, cardiac MRI, provocative tests for spasm, in the exploration of out-of-hospital cardiac arrest without obvious electrocardiographic and angiographic cause.

[Isolated right ventricular acute myocardial infarction mimicking anterior infarction]. / Infarctus isolé du ventricule droit mimant un infarctus antérieur.

Isolated right ventricular acute myocardial infarction is rare and its presentation can sometimes mimic an anterior ST-segment elevation myocardial infarction. We reported two cases of isolated right ventricular acute myocardial infarction presenting with a ST-elevation in anterior leads. The first case was admitted for an out-of-hospital cardiac arrest due to ventricular fibrillation. The patient died from neurologic consequences of the cardiac arrest, despite a successful prehospital thrombolysis, followed by a percutaneous angioplasty of the right coronary artery. The second case occurred after a complex percutaneous angioplasty of the right coronary artery, complicated by a total occlusion of a right marginal branch. These two cases illustrate the limits of the ECG for the diagnosis of isolated right ventricular acute infarction, and the difficulties of the differential diagnosis with anterior infarction, which may determine the treatment and the prognosis.

Immediate coronary angiography in survivors of out-of-hospital cardiac arrest without obvious extracardiac cause: Who benefits?

BACKGROUND: Immediate coronary angiography (iCA) and primary percutaneous coronary angioplasty (pPCI) in patients successfully resuscitated after out-of-hospital cardiac arrest (OHCA) of suspected cardiac cause is controversial. Our aims were to assess the results of iCA, the prognostic impact of pPCI after OHCA, and to identify subgroups most likely to benefit from this strategy. METHODS: In this single-centre retrospective study, patients aged ≥18 years with sustained return of spontaneous circulation after OHCA and no evidence of a non-cardiac cause underwent routine iCA at admission, with pPCI if indicated. Results of iCA, and factors associated with in-hospital survival were analysed. RESULTS: Between 2006 and 2013, 160 survivors from OHCA presumed of cardiac origin were included (median age, 60 years; 85% males). iCA showed significant coronary-artery lesions in 75% of patients, and acute occlusion or unstable lesion in only 41%. pPCI was performed in 34% of patients and was not associated with survival by univariate or multivariate analysis (P=0.67). ST-segment elevation predicted acute coronary occlusion in 40%. An initial shockable rhythm was associated with higher in-hospital survival (52% vs. 19%; P<0.001). After initial defibrillation, the first rhythm recorded by 12-lead electrocardiography was highly associated with prognosis: secondary asystole had a very low survival rate (5%, 1/21) despite PCI in 43% of patients, compared to sustained ventricular tachycardia/fibrillation (42%, 15/36) and supraventricular rhythm (71%, 50/70) (P<0.001). CONCLUSIONS: In our experience, the prevalence of acute coronary occlusion or unstable lesion immediately after OHCA of likely cardiac cause is only 41%. Immediate CA in OHCA survivors, with pPCI if indicated, should be restricted to highly selected patients.

The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis.

The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca2+-activated K+ channel (KCNN3) and the voltage-independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca2+ homeostasis in epithelial cancers.

Assessment of global longitudinal strain at low-dose anthracycline-based chemotherapy for the prediction of subsequent cardiotoxicity.

OBJECTIVES: The aim of this study was to assess whether global longitudinal strain (GLS) measured early during treatment with anthracycline (at a cumulative dose of 150mg/m2) can predict subsequent alterations in left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Eighty-six patients suffering from Hodgkin's disease, non-Hodgkin's lymphoma or acute leukemia and receiving anthracyclines were prospectively included. They underwent complete echocardiography on four separate occasions: baseline (V1); after reaching a cumulative dose of 150mg/m2 (V2); end of treatment (V3); one year follow-up (V4). Six patients developed cardiotoxicity defined by a decrease in LVEF by more than 10 percentage points to a value of at least less than 53% at V4. Both GLS measured at V1 and at V2 were significantly lower in the cardiotoxicity group compared with the control group (P=0.042 and P=0.01, respectively). Compared to GLS at V1, GLS obtained at V2 provided implemental predictive information and appeared to be the strongest predictor of cardiotoxicity (area under the receiver operating characteristic curve, 0.823). At a threshold of -17.45% for GLS measured at V2, the sensitivity and specificity of detecting cardiotoxicity were 67% (95%CI: [33-100%]) and 97% (95%CI: [94-100%]) respectively. CONCLUSION: GLS>-17.45%, obtained after 150mg/m2 of anthracycline therapy, is a significant predictor of future anthracycline-induced cardiotoxicity. This study should encourage physicians to perform echocardiography earlier during treatment with anthracyclines.

[Intracoronary administration of antithrombotic agents via a perfusion balloon catheter in patients with ST-segment elevation myocardial infarction presenting with massive intraluminal thrombus and failed aspiration]. / Apport de l'administration intracoronaire d'antithrombotiques par cathéter à ballon de perfusion en phase aiguë d'infarctus du myocarde avec thrombus massif et échec de la thromboaspiration.

BACKGROUND: Massive intracoronary thrombus is associated with adverse procedural results including failed aspiration and unfavourable reperfusion. We aim to evaluate the effect of the intracoronary administration of antithrombotic agents via a perfusion catheter in patients with ST-segment elevation myocardial infarction (STEMI) presenting with a large thrombus burden and failed aspiration. METHODS: We retrospectively analyzed the thrombus burden, the TIMI grade flow, and the myocardial Blush in 25 consecutive STEMI patients with a large thrombus burden and failed manual aspiration, who received intracoronary infusion of glycoprotein IIb/IIIa inhibitors (N=17) or bivalirudine (N=8) via a 6F-infusion catheter (ClearWay™ RX) RESULTS: Mean age was 67±14 years, 16 patients (64 %) presented with anterior STEMI, and 7 (28 %) with cardiogenic shock. Immediately after intracoronary infusion, the TIMI flow grade improved of 2 grades in 7 patients (28 %), and 1 grade in 14 (56 %), a complete resolution of the thrombus was observed in 9 patients, and a >50 % resolution in 12. Blush was improved of 3 grades in 15 patients (60 %), of 2 grades in 7 (28 %), and Blush grade 0 remained in 3. At the end of procedure, we observed normal TIMI 3flow in most patients (92 %), a complete resolution of thrombus in 80 %, and a Blush grade 3 in 68 %. CONCLUSIONS: In STEMI patients presenting with a large thrombus burden and failed aspiration, intracoronary administration of glycoprotein IIb/IIIa inhibitors or bivalirudin via the perfusion catheter ClearWay™ RX significantly reduced the thrombus burden and improved the TIMI flow and the Blush grade, without bleeding.

[Evolution of the interventional reperfusion strategy and reperfusion times in acute ST-segment elevation myocardial infarction]. / Évolution de la prise en charge interventionnelle et des délais de reperfusion à la phase aiguë de l'infarctus du myocarde avec sus-décalage du segment ST.

BACKGROUND: In patients with acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), the recommended times (first medical contact-to-balloon (M2B) <120 or <90min, and door-to-balloon (D2B) <45min) are reached in less than 50% of patients. PURPOSE: To compare the interventional reperfusion strategy and reperfusion times between two series of consecutive STEMI patients referred for pPCI within 12hours of symptom onset, in 2007 and 2012. METHODS: Retrospective study of 182 patients, 87 admitted from January 2007 to March 2008 (period 1), and 95 admitted from January to December 2012 (period 2). The procedural characteristics and the different times between onset of pain and mechanical reperfusion were gathered and compared by non-parametric tests. RESULTS: Radial access, thromboaspiration, and drug eluting stents were more frequent, and cardiogenic shock was less common during period 2, compared with the period 1. The median time from first medical contact to balloon (M2B) decreased by 26% (135min, [quartiles: 113-183] in 2007 versus 100 [76-137] in 2012, P<0.001), in relation to the reduction in both prehospital times and time in the catheterization laboratory (D2B: 51 [44-65] and 44min [37-55], respectively, P<0.01). CONCLUSIONS: The D2B and M2B times significantly decreased in our centre between 2007 and 2012, and reached the recommended values in >60% of the cases. This may be explained by better coordination between emergency medical units and interventional cardiologists, and by the presence of two paramedics in the catheterization laboratory for 24/24 7/7 pPCI since 2010 in France, in accordance with recent national regulation.

[Usefulness of transesophageal echocardiography to optimize treatment after ischemic stroke]. / Intérêt de l'échocardiographie trans-œsophagienne dans l'optimisation de la stratégie thérapeutique après un accident vasculaire cérébral ischémique.

AIM OF THE STUDY: In the setting of ischemic stroke, the place of transesophageal echocardiography (TEE) is still matter of debate. The aim of the study is to evaluate the therapeutic impact provided by TEE and to characterize patients in whom TEE is warranted. PATIENTS AND METHOD: Three hundred and fifty-nine consecutive patients were included in the study. "Decisive TEE" (DTEE) was defined by echographic findings resulting in a change of treatment, whereas "informative TEE" (ITEE) was defined by TEE revealing a potential cardiac or aortic source of embolism. RESULTS: Three hundred and forty-one patients underwent TEE. Twenty-eight patients (8.2%) had DTEE and 184 (53.9%) had ITEE. DTEE were as follows: thrombus in the left atrial appendage in 6 patients, complex aortic plaques in 10 patients, patent foramen ovale (PFO) associated with atrial septal aneurism (ASA) and an important right to left shunt (3 patients), FOP associated with ASA and lower limb phlebitis (1 patient), 4 cases of endocarditis and 4 patients with intense spontaneous echo contrast in the left atrium. In most cases of DTEE (67.8%), the patient was given anticoagulation drugs. Left atrial dilatation (P=0.005) and multivessel territory stroke (P=0.018) were statistically predictive of DTEE. CONCLUSIONS: In the setting of ischemic stroke, TEE provides important additional informations, but modifies therapeutic strategy in less than 10% of cases. Multivessel territory stroke, and left atrial dilatation were predictive of DTEE.

[Undifferentiated sarcoma: usefulness of multimodality cardiac imaging in characterizing a rare intracardiac mass]. / Sarcome cardiaque indifférencié : intérêt de l'imagerie multimodale dans la caractérisation d'une masse intracardiaque.

We report the case of a man presenting with a Pierre Marie-Bamberger syndrome. This paraneoplastic syndrome revealed an undifferentiated intracardiac sarcoma. This case emphasizes the need for multimodality imaging to characterize intracardiac tumor.

[Evaluation of a selective strategy for glycoprotein IIb/IIIa inhibitors administration in non-ST segment elevation acute coronary syndromes]. / Évaluation d'une stratégie sélective de prescription des antagonistes de la glycoprotéine IIb/IIIa dans les syndromes coronariens aigus sans sus-décalage du segment ST.

AIMS: We evaluated the impact of a selective strategy for glycoprotein IIb/IIIa inhibitors administration in non ST-segment elevation acute coronary syndrome. PATIENTS AND METHOD: Between February 1st, 2007, and February 1st, 2009, 331 consecutive patients were prospectively included in the study. Criteria for upstream glycoprotein IIb/IIIa inhibitors administration were as follows: transient ST elevation greater than 1mm, ST-segment depression greater than 2mm, ischemic recurrence, TIMI risk score greater than 5. Global mortality and cardiovascular outcomes were assessed at Day 7 and Day 30. RESULTS: The overall use of glycoprotein IIb/IIIa inhibitors was 16%. The procedure was successfully applied in 98%. Compared with non eligible patients (group 1, n = 254), eligible patients (group 2, n = 77) had a higher risk profile, median age: 73 versus 66, p < 0.01, TIMI risk score: 4 versus 3, p < 0.001. Eligible patients (66%) actually received the treatment. Among the 26 eligible but untreated patients, 19% had major bleeding risk, 34% had an unfavourable risk-benefit ratio and 34% were not suitable for an invasive strategy. Cardiovascular events occurred in 5.1% at Day 7 (Group 1, 1.6%), and 6.0% at Day 30 (group 1, 2.4%). Overall mortality at Day 30 was 1.2% (0.4% in Group 1). CONCLUSION: A strategy for glycoprotein IIb/IIIa inhibitors administration in non ST-segment elevation acute coronary syndrome restricted to 4 very high risk situations may be considered, without evidence for a loss of chance in intermediate risk patients, untreated although eligible for treatment according to the current guidelines.

[Radiation protection and arterial route in interventional cardiology]. / Radioprotection et voies d'abord en cardiologie interventionnelle.

Since its introduction as a routine arterial route for interventional cardiology, the radial route has been associated with higher X-rays doses, either to the patient and the operator. There is less evidence for this association in recent studies, probably due to the learning curve for this approach, improvement in radiological equipments and in radiation protection techniques. Coronary angiography and percutaneous coronary interventions can be performed by radial route routinely with very low levels of exposure for the patient (<50% of the reference levels). However, for a fixed dose to patient, the operator's exposure remains higher by radial route, compared to femoral route. Optimized individual radiation protection devices for operators are mandatory when procedures are performed by radial approach.

Validation of UBE2C protein as a prognostic marker in node-positive breast cancer.

BACKGROUND: We recently identified and validated UBE2C RNA as a prognostic marker in 252 node-positive (N+) breast cancers by means of a microarray study. The aim of this study was to validate UBE2C protein as a prognostic marker in N+ breast cancer by immunohistochemistry (IHC). METHODS: To this end, 92 paraffin-embedded blocks were used. The impact of UBE2C IHC value on metastasis-free survival (MFS) and overall survival (OS) was evaluated and compared with Ki-67 and Nottingham prognostic index (NPI) performances. RESULTS: In accordance with genomic data, UBE2C IHC had a significant impact both on MFS and OS (hazard ratio=6.79 - P=0.002; hazard ratio=7.14 - P=0.009, respectively). Akaike information criterion proved that the prognostic power of UBE2C IHC was stronger than that of Ki-67 (and close to that of NPI). Furthermore, multivariate analyses with NPI showed that, contrary to Ki-67 IHC, UBE2C IHC remained an independent factor, both for MFS (adjusted P=0.02) and OS (adjusted P=0.04). CONCLUSION: We confirmed that UBE2C protein measured by IHC could be used as a prognostic marker in N+ breast cancer. The potential predictive interest of UBE2C as a marker of proteasome activity needs further investigations.

[Pulmonary embolism and right diaphragmatic paralysis: "one train can hide another"]. / Embolie pulmonaire et paralysie diaphragmatique droite "un train peut en cacher un autre".

The authors report the case of an 84 year old woman admitted for a mild pulmonary embolism associated with severe hypoxaemia. The association of a right diaphragmatic paralysis with renewed patency of a foramenovale and creation of a right-to-left shunt is probably an underestimated cause of refractory hypoxaemia.