Real-life Population Of Patients Research Articles

Intracranial Efficacy of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in Real-World Patients with Non-Small-Cell Lung Cancer and EGFR or ALK Alterations.

Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients fit to receive ABCP after targeted therapy and quantify its clinical effect in patients with brain metastases. Patients treated in Cheshire and Merseyside between 2019 and 2022 were identified. Data were collected retrospectively. A total of 34 patients with actionable EGFR or ALK alterations had treatment with a median age of 59 years (range 32-77). The disease control rate was 100% in patients with PDL1 ≥ 1% (n = 10). In total, 19 patients (56%) had brain metastases before starting ABCP, 17 (50%) had untreated CNS disease, and 4 (22%) had PDL1 ≥ 1%. The median time to symptom improvement was 12.5 days (range 4-21 days), with 74% intracranial disease control rates and 89.5% synchronous intracranial (IC) and extracranial (EC) responses. IC median Progression Free Survival (mPFS) was 6.48 months, EC mPFS was 10.75 months, and median Overall Survival 11.47 months. ABCP in real-life patients with brain metastases (treated or untreated) was feasible and showed similar efficacy to that described in patients without actionable mutations treated with upfront chemo-immunotherapy.

Challenges for the Practitioner in using Biomarkers and Genetics in Clinical Diagnosis and Treatment of Alzheimer's Disease

The underdiagnoses of cognitive impairment and dementia are well documented and when the diagnosis is made it is often late in the disease course. These facts have serious consequences highlighted by the recent approval of the monoclonal antibodies for amyloid treatment for Alzheimer’s disease. The slow uptake and even serious pushback from many stakeholders may reflect their equipoise about early and accurate detection of dementia let alone its specific etiology. The Genetic marker, Apolipoprotein ε4, good clinical acumen, and biomarkers for amyloid and tau, can provide confidence in an Alzheimer’s disease diagnosis even at the mildest stages. Low utilization of these biomarkers highlights the limited knowledge of dementia care providers around mechanisms of disease and pharmacologic action. The use of biomarkers can provide confidence in clinical assessment and diagnosis, selection of agents, and assessment of safety. Disease staging using both clinical evaluation and biomarkers may soon be required to select interventions fully. Designing trials that use recognized methods for subject selection and include a wider range of outcomes, measures of patient satisfaction, and costs may improve the utilization of approved medications. Additionally, education about targeted pathologies, molecular diagnoses, and measurement of benefits can be developed for both the provider and the patient population. The presentation will highlight challenges for the practitioner in translating the clinical trial results to real-life patient populations.

Particularities of coronary physiology in patients with atrial fibrillation: insights from combined pressure and flow indices measurements.

Symptoms suggestive of myocardial ischemia are frequently encountered in patients with atrial fibrillation (AF) even in the absence of obstructive coronary artery disease. Nevertheless, an in-depth characterisation of coronary physiology in patients with AF is currently lacking. We aim to provide an insight into the characteristics of coronary physiology in AF, by performing simultaneous invasive measurements of coronary flow- and pressure- indices in a real-life population of patients with AF and indication of coronary angiography. This is a prospective open label study including patients with permanent or persistent AF and indication of coronary angiography showing intermediate coronary stenosis requiring routine physiological assessment (n = 18 vessels from 14 patients). We measured FFR (fractional flow reserve), and Doppler-derived coronary flow indices, including CFR (coronary flow reserve) and HMR (hyperaemic microvascular resistance). From the analysed vessels, 18/18 vessels (100%) presented a pathological CFR (<2.5), indicative of coronary microvascular dysfunction (CMD), and 3/18 (17%) demonstrated obstructive epicardial coronary disease (FFR ≤ 0.8). A large proportion of vessels (15/18; 83%) showed discordant FFR/CFR with preserved FFR and low CFR. 47% of the coronary arteries in patients with AF and non-obstructive epicardial coronary disease presented structural CMD (HMR ≥ 2.5 mmHg/cm/s), and were associated with high BMR and an impaired response to adenosine. Conversely, vessels from patients with AF and non-obstructive epicardial coronary disease with functional CMD (HMR < 2.5 mmHg/cm/s) showed higher bAPV. The permanent AF subpopulation presented increased values of HMR and BMR compared to persistent AF, while structural CMD was more often associated with persistent symptoms at 3 months, taking into account the limited sample size of our study. Our findings highlight a systematically impaired CFR in patients with AF even in the absence of obstructive epicardial coronary disease, indicative of CMD. In addition, patients with AF presented more prevalent structural CMD (HMR ≥ 2.5 mmHg/cm/s), characterized by reduced hyperaemic responses to adenosine, possibly interfering with the FFR assessment.

Real-life use of cabozantinib as front-line therapy in metastatic renal cell carcinoma: The CabFRONT (Meet-URO 24) study.

e16539 Background: Cabozantinib is approved as first-line therapy for patients with intermediate-poor risk metastatic renal cell carcinoma (mRCC); however translating results from pivotal trials to an unselected real-world population remains a concern. Methods: CabFRONT is a retrospective observational multicentre Italian Network for Research in Urologic-Oncology (Meet-URO) study of a real-life population of treatment-naïve patients with intermediate-poor mRCC treated with cabozantinib as per clinical practice between September 2019 and September 2022. Results: 209 patients were enrolled. Median age was 65 years (36 - 85). 158 patients (76%) started with a dose of 60 mg, while 51 (24%) started with a dose of 40 mg. 140 patients (67%) were classified as intermediate and 69 (33%) as poor risk according to IMDC risk model. Clear-cell represented the most common histotype (172/209), followed by papillary (19/209), chromophobe (6/209) and NOS (4/209). Sarcomatoid features were present in 29 patients (14%). Lungs were the most frequent metastatic site, [137 (65%) patients], followed by lymph nodes [115 (55%)], and bones [72 (35%)]. 33 (16%) patients presented brain metastases. At a follow-up of 23 months (mo), the median progression-free survival (mPFS) was 9.6 mo (95% CI, 7.63-10.9 mo) and the median overall-survival was 21 mo (95% CI, 14-30 mo). As best overall response, 7 patients achieved a complete response, 73 a partial response and 77 stable disease for an objective response rate (ORR) of 38% and a disease control rate (DCR) of 75%. ORR for intermediate and poor population was respectively 29% and 10%, DCR was 56% for intermediate risk and 20% for poor risk population. mPFS for intermediate and poor population was respectively 12.73 and 5.27 mo (p &lt; 0.0001). mPFS for intermediate with 1 risk factor was 17.2 and for intermediate with 2 risk factors was 9.7 mo (p 0.0033). Subsequent antineoplastic treatments were received by 41% (86/209) of patients. Subsequent nivolumab was received by 87% of patients. 191 patients (91%) reported at least 1 grade (G) 1 to 2 adverse event (AE). The most common G1 to G2 AEs were fatigue (113 [60%]), mucositis (100 [52%]), hand-foot syndrome (HFS) (91 [47%]), diarrhoea (79 [41%]), hypertension (67 [35%]), and hypothyroidism (60 [31%]). 78 G3 AEs ere reported: the most common were fatigue (19 [24%]) and diarrhoea (18 [23%]). Permanent discontinuations from the study owing to AEs was observed in 7 patients: three for G3 diarrhea, one of which manifested also G3 renal injury, two for G3 asthenia, one for G3 HFS and one for G3 mucositis. At least 131 patients (63%) required a dose reduction and 86 (41%) required a transitory interruption to manage toxic effects. Conclusions: Our data confirmed that front-line Cabozantinib is effective and safe in an unselected real-life population of patients with intermediate-poor mRCC, including non-clear cell histologies.

Hemodynamic parameters of aortic valve prostheses - KRAK-AS registry analysis.

The treatment of choice for aortic stenosis is a valve replacement. Some patients have post-procedural increased pressure gradient on the implanted prosthesis because of patient-prosthesis mismatch (PPM), known to adversely influence prognosis. The PPM risk should be initially predicted and effort made to avoid this complication, specifically in large body size patients. To assess the frequency of PPM taking into account the valvular prosthesis type in a real-life population of consecutive patients included in the Krakow aortic stenosis registry. The KRAK-AS registry was conducted in July-October 2016. Patients were assessed before and after valve surgery and during the 3-year follow-up. Patients who underwent aortic valve intervention were clinically and echocardiographically evaluated within a month after surgery and divided into groups depending on the implanted prosthesis type. Analysis of patients with a smaller (< 23 mm) and larger than median (≥ 23 mm) valve diameter was performed. The valve implantation was performed in 229 patients (42 mechanical, 139 biological, 48 transcatheter). No differences between patient groups compared by PPM occurrence was seen at baseline. Median age was 70 years; 55.5% were men. At least moderate PPM (iEOA ≤ 0.85 cm2/m2) was observed in 40% of mechanical valves, 33% of biological valves, and was significantly less frequent (10%) in patients after transcatheter valve implantation, p = 0.0001. Severe PPM (iEOA < 0.65 cm2/m2) was found in 17.6% of mechanical valve PPM patients, 4.3% of biological ones, and no patients after transcatheter procedure. PPM is a frequent phenomenon in the real-life population of patients undergoing surgical aortic valve replacement, being significantly less frequent in the case of a transcatheter procedure.

Thrombocytopenia after transcatheter aortic valve implantation: prognostic value and mechanisms

Abstract Funding Acknowledgements Type of funding sources: None. Background Thrombocytopenia post transcatheter aortic valve implantation (TPPT) in its most severe manifestation is an independent predictor of mortality. However, mechanisms that favors TPPT remain unknown. Purpose To establish the prognostic value and risk factors of TPPT in a real-life population of patients treated with transcatheter aortic valve implantation (TAVI) in a tertiary hospital. Methods We analyzed retrospectively clinical, laboratory, echocardiographic and procedure-related variables from 203 consecutive patients, treated with TAVI between January 2019 and October 2021. Results This cohort had mean age of 82,3 ±5,9 years, 56% male, 83% hypertensive, 62% dyslipidemia, 35% diabetic, 20% chronic kidney disease, 22% chronic obstructive pulmonary disease, 32% coronary artery disease, 20% had previous ICP, 38% Atrial Fibrillation (AF), 18% peripheral arterial disease, 12% neurovascular disease, 23% history of cancer, 10% pacemaker carriers. 50% of TAVIs were balloon-expandable and 50% self-expandable. Mean procedure duration was 138 ±109min, size 26,6±3mm, contrast dose 233 ±88mL. During in-hospital stay 192/203 patients had TPPT. Platelets before TAVI, 187.000 (IQR 148.000-222.000) Vs a minimum post-TAVI (PlqMin) of 135.000 (IQR 105.000-164.000); P&amp;lt;0,05. Platelet fall (DeltaPlq) 48.000 ±38.000. We observed a Minimum Kidney clearance (ClMin) 46 ±20,75mL/min/m2, a maximum ultrasensitive Troponin-T (Tr-TusMax) 250 ±450 pg/L, a Maximum C Reactive Protein (PCRMax) 6,68 ±6,4, and a Minimum Hemoglobin (HbMin) 9,8 ±1,7 g/dL. 31/203 (15,3%) patients were exitus at the end of follow-up. We observed a non-lineal statistically significant association between TPPT quartiles and all-cause mortality (P&amp;lt;0,05): 21 exitus occurred in the extreme quartiles (1 and 4) while only 11 at the central ones (2 and 3). DeltaPlq was associated with PCRMax (Pearson 0,25; P&amp;lt;0,001), CliMin (Pearson -0,23; P0,005), HbMin (Pearson -0,27; P 0,001), AF. The only protective factor for DeltaPlq was history of previous ICP. Among exitus patients PlqMin was observed later than in survivors (3,5 vs 2,2 days; P&amp;lt;0,05). TPPT’s quartiles, previous ICP, time to PlqMin, HbMin, PCRMax and Tr-TusMax were the variables found to be independent associated with all-cause mortality (P&amp;lt;0,05). Conclusions The non-linear association between TPPT and mortality, the temporal relation between TPPT and mortality and the linear correlation between TPPT and HbMin and PCRMax suggest that late TPPT may have a mortality prognostic value through an increased risk of low Hb in the context of an increased inflammatory status. The fact that history of ICP was associated with les platelet fall suggests that revascularization, or ICP associated drug therapy, may confer protection against after TAVI mortality.

Daratumumab in AL Amyloidosis: A Real-Life Experience of the "RTM" (Regional Tuscan Myeloma Network).

Systemic amyloidosis arises from monoclonal CD38+ plasma cells that produce misfolded immunoglobulin light chains, which form amyloid fibrils that are deposited into different tissues, leading to organ damage. Daratumumab is a human IgG/k monoclonal antibody that targets CD38, a glycoprotein uniformly expressed on human plasma cells. Daratumumab has been utilized in recent years with unprecedented responses in multiple myeloma. In patients with relapsed or refractory AL amyloidosis, daratumumab has shown promising efficacy in terms of hematologic responses and improvement in organ function. Here, we report real-life treatment with Daratumumab in 33 AL amyloidosis patients treated within the Regional Tuscan Myeloma network at 5 centers with associated MGUS or SMM (n = 15) or symptomatic MM (n = 18). Patients were treated at relapsed/refractory disease stages (n = 29) with a median of one previous line of therapy or at diagnosis (n = 4). Daratumumab showed good efficacy, representing 60% of good hematological responses and 50% of organ responses in a real-life population of patients with an acceptable toxicity profile.

Left atrial functional reverse remodeling assessed by speckle tracking echocardiography in a real-life population of patients with chronic heart failure after therapy with sacubitril/valsartan

Abstract Funding Acknowledgements Type of funding sources: None. Background Left atrial (LA) enlargement has been demonstrated to be a predictor of adverse cardiovascular outcomes, such as atrial fibrillation (AF), heart failure (HF), and cardiovascular death (1). Previous studies showed left atrial structural reverse remodeling (LARR), defined as &amp;gt;15% reduction in LA end-systolic volume index (LAESVi) (2), can be achieved after therapy with Sacubitril/Valsartan (S/V) in real-world settings. On the other hand, LA functional reverse remodeling is not well defined. Purpose We sought to investigate the association between left atrial (LA) structural and functional remodelling in patients with chronic heart failure after therapy with S/V. Methods Patients with chronic HF, LV dysfunction (EF &amp;lt; 35%), NYHA class II-III were followed up between September 2019 and March 2020. All patients underwent clinical and echocardiography follow up at baseline and after 6 months of therapy with S/V. Measures of LA structure [LA end-systolic volume index (LAESVi)] and function [left atrial ejection fraction (LAEF), peak atrial longitudinal strain (PALS), LA conduit strain, and peak atrial contraction strain (PACS)] were calculated. We divided our population into two subgroups based on whether reverse remodeling was achieved (LARR+) or not (LARR-). Results Forty-seven consecutive outpatients (mean age 66 ± 8 years; 85% males) were enrolled in the study. At follow-up visit, a positive LARR was found in nearly half of patients treated with S/V, resulting in line with previous studies (3). Furthermore, global PALS was significantly improved in both groups compared to baseline (15 ± 7 vs 19 ± 8 %, p &amp;lt; 0.001), but the LARR+ group showed an improvement that was twice higher (55 ± 66 vs 25 ± 26, p = 0.039), supporting the potential role of PALS as marker of functional LARR. Conclusions Treatment with S/V in patients with systolic dysfunction is associated with an improvement in LA structural and functional remodelling in a real-world scenario. Therefore, PALS could be the benchmark for the assessment of left atrial functional reverse remodeling.

10-year survival in patients undergoing cardiac resynchronization therapy

Abstract Background Advanced heart failure with reduced ejection fraction (HFrEF) is associated with poor prognosis. Cardiac resynchronization therapy (CRT) is an effective method of treatment for advanced HFrEF to reduce HF hospitalizations and mortality. Nonetheless, very long-term observation of HF patients undergoing CRT implantation is scarce. Aim To assess very long-term survival (≥10 years) and predictors of shorter survival (death within 10 years from CRT implantation). Methods We screened a large dataset of CRT population from a tertiary care university hospital comprising consecutive HF patients implanted with CRT from 2002 through 2019 to select those who were alive ≥10 years and those who died within 10 years since device implantation. We analyzed various patients' baseline, clinical and procedural characteristics and sought for predictors of mortality within 10 years from CRT implantation. Results Of 1059 CRT patients, 143 (13.5%) were alive ≥10 years since CRT implantation. On multivariable regression analysis the independent predictors for all-cause death up to 10 years from CRT implantation were as follows: age, HR 1.02, 95% CI 1.01–1.31; male sex, 1.27, 95% CI 1.01–1.60; primary prevention of sudden cardiac death (SCD), HR 0.72, 95% CI 0.58–0.89; ischemic cardiomyopathy, HR 1.41, 95% CI 1.76–1.70; NYHA class at implantation, HR 1.38, 95% CI 1.17–1.62; baseline left ventricle ejection fraction (EF), HR 0.97, 95% CI 0.96–0.98; severe mitral regurgitation, HR 1.38; 95% CI 1.08–1.75; baseline NT-proBNP concentration, HR 1.00, 95% CI 1.00–1.00; and creatinine level, HR 1.00, 95% CI 1.00–1.01. Conclusions In a real-life patient population with CRT only 13.5% survived over 10 years since device implantation. Independent predictors for death within 10 years since CRT implantation were older age, male sex, secondary prevention of SCD, ischemic and more advanced heart failure along with renal impairment. Funding Acknowledgement Type of funding sources: None.

Therapeutic monitoring of direct oral anticoagulants — an 8-year observational study

Introduction: For years, anticoagulants have been the basic group of drugs that slow down, inhibit or prevent blood clotting by inhibiting thrombin formation or reducing its activity. Treatment with DOACs does not require routine anticoagulation monitoring due to their wide therapeutic index. However, there are circumstances where it may be necessary to know the drug levels to manage the risk of side effects or to confirm laboratory efficacy. In such a situation, an indication for DOAC laboratory testing could be the suspicion of excessively high or low DOAC levels. The aim of this article was to determine trends in concentrations of DOACs in a real life population of patients. Material and methods: Consultations in clinical pharmacology extended with DOAC level assessments were performer in the Department of Cardiology and Clinical Pharmacology. The trial was designed as a retrospective analysis of laboratory analyses and included 480 laboratory tests performed in 236 patients. Results: Mean CHA 2 DS 2- VASc scoring 3.91 ±1.92 and HAS-BLED scoring 3.57 ±1.75 indicated high risks of both thrombosis and bleeding. Geometric mean of trough concentrations for dabigatran, rivaroxaban and apixaban were 91.53 ng/mL, 62.74 ng/mL and 124.81 ng/mL, whereas peak concentrations for all DOACs were significantly higher, at 220.80 ng/mL ( p &lt; 0.0001), 116.59 ng/mL ( p &lt; 0.0001) and 186.18 ng/mL ( p =0.0354), respectively. Values for males and females did not differ significantly. Dose adjustment, performed according to rules described for every drug in registered drug characteristics, did not change significantly concentrations. Trough concentrations higher than 20 ng/mL were found at the 10 th percentile for all DOACs, but higher at 40 ng/mL at the 5 th percentile was found only for apixaban. Peak concentration lower than 400 ng/mL were for the 95 th percentile for apixaban and for the 90 th percentile for dabigatran and rivaroxaban. Conclusion: Monitoring-based pharmacotherapy with DOACs should be restricted only to specific clinical settings; in the general population, it is not necessary. Recently, in many experienced centers, therapeutic drug monitoring of DOACs has gained great importance in selected clinical settings and it very likely will soon become commonplace in clinical practice.

Remodelling is inversely proportional to left ventricular dimensions in a real-life population of patients with chronic heart failure after therapy with sacubitril/valsartan

Background Left ventricular (LV) remodelling is a major mechanism underlying disease progression in patients with heart failure (HF) with reduced ejection fraction (EF). Previous studies that LVEF improvement and reverse remodelling can be achieved after therapy with Sacubitril/Valsartan in real-world settings. Therefore, we sought to investigate possible predictors of LV remodelling, in particular echocardiographic parameters derived by Tissue Doppler Imaging. Methods Patients with chronic HF, LV dysfunction (EF < 35%), NYHA class II–III were followed up between September 2016 and January 2019. All patients underwent clinical and echocardiography follow up at baseline and after 12 months of therapy with sacubitril/valsartan. Results Fifty-four consecutive outpatients were enrolled in the study. At follow-up visit LVEF (38 ± 9 vs. 30 ± 5%, p < 0.0001), LVEDD (61 ± 8 vs. 62 ± 8 mm, p = 0.0085), LVESV (114 ± 57 vs. 130 ± 56 mm3, p = 0.0001), mitral regurgitation severity (1 ± 1 vs. 2 ± 1, p < 0.0001), and left atrial area (23 ± 6 vs. 24 ± 6 mm2, p = 0.0121) changed compared to the baseline value. Changes in LVEF (follow up vs baseline) correlated with baseline levels of heart rate (r = 0.24, p = 0.048), LVEDD (r= −0.33, p = 0.004), LVEDV (r= −0.39, p = 0.001), LVESV (r = 0.37, p = 0.002), and changes in LVESV (r=−0.34, p = 0.006). Correlations remained significant even after correction at multivariate analysis including age and gender. Conclusions Treatment with sacubitril/valsartan in patients with systolic dysfunction is associated with an improvement in LVEF in a real world scenario. Smaller LV volumes are associated with better reverse LV remodelling.

Prevalence of Nonradiographic Sacroiliitis in Patients With Psoriatic Arthritis: A Real-life Observational Study.

To establish the prevalence of nonradiographic sacroiliitis within a real-life sample of patients with psoriatic arthritis (PsA), using pelvic radiographs and magnetic resonance imaging (MRI) of sacroiliac joints (SIJs). This cross-sectional study included 107 consecutive adults with PsA (Classification Criteria for Psoriatic Arthritis criteria). Participants completed clinical and laboratory evaluation, pelvic radiographs scored for radiographic sacroiliitis according to the modified New York (mNY) criteria, and noncontrast MRI of SIJs, scored by the Berlin score and categorized into active sacroiliitis using the 2016 Assessment of Spondyloarthritis international Society (ASAS) criteria and the presence of structural sacroiliitis. Radiographic sacroiliitis/mNY criteria were detected in 28.7% (n = 29), confirmed by MRI-detected structural lesions in 72.4% (n = 21). Active sacroiliitis was detected by MRI in 26% (n = 28) of patients, with 11% (n = 11) qualifying for nonradiographic sacroiliitis. Patients with radiographic and nonradiographic sacroiliitis had similar clinical characteristics, except for a longer duration of psoriasis (PsO) and PsA in the radiographic subgroup (PsO: 23.8 ± 12.5 vs 14.1 ± 11.7 yrs, P = 0.03; PsA: 12.3 ± 9.8 vs 4.7 ± 4.5 yrs, P = 0.02, respectively). Inflammatory back pain (IBP) was reported in 46.4% (n = 13) with active sacroiliitis and 27% (n = 3) with nonradiographic sacroiliitis. The sensitivity of IBP for detection of nonradiographic sacroiliitis was low (27%) and moderate for radiographic sacroiliitis (52%), whereas specificity ranged from 72% to 79% for radiographic and nonradiographic sacroiliitis, respectively. The prevalence of active sacroiliitis among a real-life population of patients with PsA was 26%. However, the prevalence of nonradiographic sacroiliitis was low (11%) compared to the radiographic sacroiliitis (28.7%) seen in patients with longer disease duration. IBP was not a sensitive indicator for the presence of early-stage sacroiliitis that was commonly asymptomatic.

Outcome of a Real-Life Population of Patients With Acute Promyelocytic Leukemia Treated According to the PETHEMA Guidelines: The Polish Adult Leukemia Group (PALG) Experience

BackgroundAcute promyelocytic leukemia (APL) has a favorable prognosis. However, results of randomized studies do not necessarily reflect the outcomes of a real-life population. Patients and MethodsWe analyzed 283 unselected APL patients treated in 20 Polish hospitals between 2005 and 2017. All patients were intended to be treated with PETHEMA (Programa Español para el Tratamiento de las Hemopatías Malignas) protocols based on all-trans retinoic acid plus chemotherapy. ResultsThe probability of overall survival at 4 years was 67%, while event-free survival was 64%. The early death (ED) rate was 20.1% (n = 57), while 3.5% (n = 10) patients died before induction therapy was started. The main causes of ED included hemorrhage (45.6%), infections (17.5%), and differentiation syndrome (14.5%). Of 273 treated patients, 214 (78.4%) experienced hematologic morphologic remission, 2 (0.7%) were found to have resistant disease, 47 (17.2%) could not be evaluated for response because of ED, and in 6 (3.7%) no data concerning the response were available. Multivariate analyses showed that predictors of ED and overall survival were Eastern Cooperative Oncology Group performance status > 2, age > 60 years, and all types of bleeding episodes that occurred before starting therapy, while an additional predictor of event-free survival was high white blood cell count (> 10 109/L). ConclusionED remains a major problem in APL patients, especially in a real-life population. Shortening of the time between the initial contact with a health care professional, and all-trans retinoic acid administration and the use of appropriate supportive care could improve the outcome of unselected APL population, mainly by reducing the ED rate.

Determinants of anticoagulant therapy in atrial fibrillation at discharge from a geriatric ward: cross sectional study

Oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), but they are often underused in this particularly high-risk population. The aim of the study was to identify health and functional determinants of oral anticoagulant therapy (OA) in AF at discharge from a geriatric sub-acute ward. A cross-sectional study was conducted and patients who presented with atrial fibrillation were analyzed. They were interviewed, examined, assessed with comprehensive geriatric assessment protocol, and had their hospital records analyzed. Relative risks for OA were counted and multivariable logistic regression model was built. 95 patients took part in the study (22.8% of 416 consecutively admitted to the department, 31.9% men, 73.7% 80 + year-old). 25.8% of them were on antiplatelet drugs and 58.9% on OACs. The percentage on OACs increased significantly to 73.7% at discharge (p = 0.004), mainly due to the new OACs prescription (from 11.8 to 33.3%; p < 0.001). Severe frailty (7 point Clinical Frailty Scale ≥ 6) and anemia presence, but not the risk of bleeding according to the HAS-BLED score, significantly decreased the probability of OACs prescription at discharge. There was also a trend for an association of OACs prescription with the higher total score of CHA2DS2-VASc scale. We conclude that in the real-life population of patients with AF comprehensive geriatric assessment might allow to increase significantly the number of patients on OACs, but it is limited by patient’s frailty status and anemia diagnosis.

Long-term neuropathy and quality of life in colorectal cancer patients treated with oxaliplatin containing adjuvant chemotherapy

Background: Oxaliplatin, combined with capecitabine (CAPOX) or infused 5-fluorouracil (FOLFOX), is standard of care in the adjuvant treatment of colorectal cancer (CRC). Prospective data on prevalence of oxaliplatin induced acute and long-term neuropathy in a real-life patient population and its effects on quality of life (QOL) and survival is limited, and scarce in CAPOX versus FOLFOX treated, especially in a subarctic climate.Methods: One hundred forty-four adjuvant CRC patients (all 72 CAPOX cases and 72 matched FOLFOX controls) were analyzed regarding oxaliplatin induced sensory neuropathy, which was graded according to NCI-CTCAEv3.0. Ninety-two long-term survivors responded to the QOL (EORTC QLQ-C30) and Chemotherapy-Induced Peripheral Neuropathy (EORTC CIPN20) questionnaires and were interviewed regarding long-term neuropathy.Results: Acute neurotoxicity was present in 94% (136/144) during adjuvant therapy and there was a significant association between acute neurotoxicity and long-term neuropathy (p < .001). Long-term neuropathy was present in 69% (grade 1/2/3/4 in 36/24/8/1%) at median 4.2 years. Neuropathy grades 2–4 did not influence global health status, but it was associated with decreased physical functioning (p = .031), decreased role functioning (p = .040), and more diarrhea (p = .021) in QLQ-C30 items. There were no differences in acute neurotoxicity, long-term neuropathy, or in QOL between CAPOX and FOLFOX treated. Neuropathy showed no pattern of variation according to starting and stopping month or treatment during winter.Conclusions: Neuropathy following oxaliplatin containing adjuvant chemotherapy is present in two-thirds, years after cessation, and impairs some QOL scales. There is no difference in severity of acute or long-term neuropathy between CAPOX and FOLFOX treated and QOL is similar. No seasonal variation in neuropathy was noted.

Importance of iron deficiency in patients with chronic heart failure as a predictor of mortality and hospitalizations: insights from an observational cohort study

BackgroundIron deficiency (ID) in patients with chronic heart failure (CHF) is considered an adverse prognostic factor. We aimed to evaluate if ID in patients with CHF is associated with increased mortality and hospitalizations.MethodsWe evaluated ID in patients with CHF at 3 university hospitals. ID was defined as absolute (ferritin < 100 μg/L) or functional (transferrin Saturation index < 20% and ferritin between 100 and 299 μg/L). We excluded patients who received treatment with intravenous Iron or Erythropoietin during follow-up. We evaluated if ID was a predictor of death or hospitalization due to heart failure or any cause using univariate and multivariate cox regression analysis.ResultsWe included 1684 patients, 65% males, 38% diabetics, median age of 72 years, 37% in functional class III-IV and 30% of patients with a left ventricular ejection fraction > 45%. Patients were well treated, with 87% and 88% of patients receiving renin-angiotensin inhibitors and beta-blockers, respectively. Median transferrin saturation index was 20%, median ferritin 155 ng/mL and median haemoglobin 13 g/dL. ID was present in 53% of patients; in 35% it was absolute and in 18% functional. Median follow-up was 20 months. ID was a predictor of death, hospitalization due to heart failure or to any cause in univariate analysis but not after multivariate analysis. No differences were found between absolute or functional ID regarding prognosis.ConclusionIn a real life population of patients with CHF and a high prevalence of heart failure with preserved ejection fraction, ID did not predict mortality or hospitalizations after adjustment for comorbidities, functional class and neurohormonal treatment.

Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study.

About one-third of patients with renal cell carcinoma (RCC) have detectable metastases at diagnosis. Among them, bone is the second most frequent metastatic site. Treatment of metastatic RCC mostly relies on anti-angiogenic (AA) therapies and, more recently, immunotherapy. Skeletal-related events (SREs) can be prevented with bone-targeted therapies such as denosumab (Dmab), which has demonstrated superiority when compared with zoledronic acid in solid tumors. However, there is limited available data on Dmab toxicity in combination with AA therapies in patients with kidney cancer. The objective of this study was to retrospectively analyze the toxicity profile (mainly osteonecrosis of the jaw [ONJ] and hypocalcemia) in patients with metastatic renal cell carcinoma (mRCC) treated with Dmab and AA therapy combination. We conducted a multicenter retrospective study among centers from the French Groupe d'Etudes des Tumeurs Uro Genitales (GETUG). Patients with bone metastases who received concurrently or sequentially AA therapy and Dmab were included in this study. A total of 41 patients with mRCC were enrolled. Although no patient presented with severe hypocalcemia, ONJ occurred in 7 (17%) of 41 patients. Interestingly, all patients with ONJ received the Dmab and AA combination in the first line of treatment; among these patients, 3 patients had no risk factor other than the Dmab and AA combination. The incidence of ONJ was high in this real-life population of patients with mRCC treated with AA therapies combined with Dmab. This toxicity signal should warn physicians about this combination in the mRCC population.

Outcome of all-comers with STEMI based on the grade of ischemia in the presenting ECG

BackgroundGrade 3 ischemia (G3I) in the 12‑lead electrocardiogram (ECG) predicts poor outcome in patients with ST-elevation myocardial infarction (STEMI). The outcome of G3I in “real-life” patient cohorts is unclear. MethodsThe aim of the study was to establish the prognostic significance of grade 2 ischemia (G2I), G3I and the STEMI patients excluded from ischemia grading (No grade of ischemia, NG) in a real-life patient population. We assessed in-hospital, 30-day and 1-year mortality as well as other endpoints. ResultsThe NG patients had more comorbidities and longer treatment delays than the two other groups. Short-term and 1-year mortality were highest in patients with NG and lowest in patients with G2I. Maximum troponin level was highest in G3I, followed by NG and G2I. In logistic regression multivariable analysis, NG was independently associated with 1-year mortality. ConclusionsNG predicted poor outcome in STEMI patients. G2I predicted relatively favorable outcome.

MP28-19 DERMATOLOGIC FINDINGS AND FAMILY HISTORY ARE THE ONLY PREDICTORS OF A POSITIVE GENETIC TEST RESULT IN PATIENTS WITH A SUSPECTED HEREDITARY KIDNEY CANCER SYNDROME: EXPERIENCE FROM A PROVINCIAL GENETICS UNIT

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging I1 Apr 2018MP28-19 DERMATOLOGIC FINDINGS AND FAMILY HISTORY ARE THE ONLY PREDICTORS OF A POSITIVE GENETIC TEST RESULT IN PATIENTS WITH A SUSPECTED HEREDITARY KIDNEY CANCER SYNDROME: EXPERIENCE FROM A PROVINCIAL GENETICS UNIT Andrea Kokorovic, Aidan Thomas, Meghan Ferguson, and Ricardo A Rendon Andrea KokorovicAndrea Kokorovic More articles by this author , Aidan ThomasAidan Thomas More articles by this author , Meghan FergusonMeghan Ferguson More articles by this author , and Ricardo A RendonRicardo A Rendon More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.919AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The American College of Medical Genetics and Genomics and the National Society of Genetic Counselors (ACMG/NSGC) recommend genetic assessment for patients with renal cell carcinoma (RCC) who have high risk features: young age, bilateral/multifocal tumors, strong family history, non-clear cell histology, features suspicious for Cowden syndrome (CS) or tuberous sclerosis (TS). These recommendations are based on studies with individuals carrying known gene mutations but data assessing the outcomes of patients referred for genetic testing as per current guidelines are very limited. The only study available to date is from a single center (MSKCC) that found an association between young age and a positive genetic test in 43 patients evaluated for hereditary RCC. The purpose of our study is to delineate risk factors associated with a positive genetic test in a real-life cohort of patients referred to Medical Genetics for evaluation of hereditary RCC. METHODS A retrospective chart review of patients referred for genetic evaluation of a hereditary kidney cancer from 2006 to 2016 at the Division of Medical Genetics in Nova Scotia, Canada was performed. Univariate and multivariate analyses using Fisher's exact test were used to determine predictors of a positive test result. RESULTS 109 patients were referred to Medical Genetics, 85 were evaluated and 64 underwent testing. 5 were excluded from analysis (4 non-RCC; 1 unavailable result). 5 patients (8.5%) had a positive genetic test (3 Birt-Hogg-Dube, 1 CS, 1 TS). Mean age at time of RCC diagnosis was 54. 32 (54%) patients had multifocal/bilateral tumors, 26 (44%) had a positive family history, 26 (44%) had non-clear cell histology and 10 (17%) had tumors outside the kidney. Dermatologic findings (facial fibrofolliculomas) (p=0; OR=42) and family history of RCC or a genetic syndrome (p=0.037; OR=7.2) were the only predictors of a positive test. CONCLUSIONS This study identifies dermatologic findings and family history as the only predictors of a positive genetic test in patients undergoing evaluation for hereditary RCC. To date, our patient population represents the largest of its kind in the literature. A recent SEER database study reveals that 1 in 5 patients diagnosed with RCC should be referred for genetic counselling as per ACMG/NSGC guidelines. Our study suggests that current referral criteria may be too broad for application in a real-life patient population, however further evaluation with prospective trials is needed. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e364 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Andrea Kokorovic More articles by this author Aidan Thomas More articles by this author Meghan Ferguson More articles by this author Ricardo A Rendon More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Reversibility of severe mitral valve regurgitation after left ventricular assist device implantation: single-centre observations from a real-life population of patients.

This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. Of the 234 patients who received LVAD therapy in our centre during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7-28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283-848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). Preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival.