Real-life Patients Research Articles

Measurable residual disease study through three different methods can anticipate relapse and guide early interventions in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer among children. Measurable residual disease (MRD, previously named minimal residual disease) study can guide therapy adjustments or preemptive interventions that might avoid hematological relapse. Clinical decision making and patient outcome were evaluated in 80 real-life childhood ALL patients, according to the results observed in 544 bone marrow samples analyzed with three MRD methods: multiparametric flow cytometry (MFC), fluorescent in-situ hybridization (FISH) on B or T-purified lymphocytes and patient-specific nested reverse transcription polymerase chain reaction (RT-PCR). Estimated 5year overall survival and event-free survival were 94% and 84.1%, respectively. A total of 12 relapses in 7 patients were associated with positive MRD detection with at least one of the three methods: MFC (p < 0.00001), FISH (p < 0.00001) and RT-PCR (p = 0.013). MRD assessment allowed the anticipation of relapse and adapted early interventions with different approaches including chemotherapy intensification, blinatumomab, HSCT and targeted therapy to halt relapse in five patients, although two of them relapsed afterwards. MFC, FISH and RT-PCR are complementary methods for MRD monitoring in pediatric ALL. Although, our data clearly show that MDR positive detection is associated with relapse, continuation of standard treatment, intensification or other early interventions were able to halt relapse in patients with different risks and genetic background. More sensitive and specific methods are warranted to enhance this approach. However, whether early treatment of MRD can improve overall survival in patients with childhood ALL needs to be evaluated in adequately controlled clinical trials.

Prescriptive behavior of non-vitamin K oral anticoagulants in patients affected by atrial fibrillation in general practice

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and in recent years the pharmacological approach has been strongly implemented; in Italy, the prescription of the non-vitamin K oral anticoagulants (NOAC) was also extended to General Practitioners (GPs) since 2020. The aim of the present study was to investigate the GPs prescribing behaviour of NOACs. An observational study was performed by using the computerized medical record of 14 GPs in Sicily: patients affected by AF were selected and stratified according to the prescribed antithrombotic drugs. Patients were considered inadequately managed if antithrombotic treatment was not adherent to recent ESC guidelines. A total of 467 (2.7 %) patients were affected by AF, 276 (59.1 %) were treated with an oral anticoagulant (OAC) regardless the high stroke risk (OR 1.64; 95 %CI 0.74–3.62; p = 0.226). The NOAC users were 236 patients as follow: Rivaroxaban 33.5 %, Apixaban 33,1 %, Dabigatran 17,4 %, Edoxaban 16.1 %. In 7 patients an inappropriate NOAC treatment was observed. Among Vitamin-K antagonist users, 25.0 % were considered inappropriate. Patients not treated with OAC were 191, of them 81.7 % were at high stroke risk and did not receive any OAC despite the indication to treat. In addition, the probability to be not properly managed significantly increased in older and in patients with atherosclerosis. Conversely, patients with at least one reported cardiology counselling significantly reduced the likelihood to be not properly managed (OR 0.38, 95 %CI 0.25–0.58; p 0.01). Our results suggest the need to optimize the management of real-life AF patients by improving prescribing adherence to ESC guidelines.

Patient-specific hemodynamic feature of central venous disease intervened by stent: A numerical study.

Central venous disease (CVD) with stenosis or occlusion is a severe and prevalent complication for chronic hemodialysis (HD) patients, resulting in dialysis access dysfunction. Percutaneous transluminal angioplasty with stent placement (PTS) has become one of the first-line treatments for CVD. In clinical practice, the extra stents would be used if the curative efficacy of a single stent were unsatisfactory. Aiming to evaluate the therapeutic effect of different PTS schemes, computational fluid dynamics (CFD) simulations on four patients were performed to compare the hemodynamic characteristics of real-life HD patients after stent placement. The three-dimensional central vein's models of each patient were built using computational tomography angiography (CTA) images, and idealized models were constructed as contrast. Two inlet velocity modes were imposed to imitate the blood flow rate of healthy and HD patients. The hemodynamic parameters for different patients were investigated, including wall shear stress (WSS), velocity, and helicity. The results showed that the implantation of double stents is able to improve flexibility. When subjected to external force, the double stents have better radial stiffness. This paper evaluated the therapeutic efficacy of stent placement and provided a theoretical basis for CVD intervention in hemodialysis patients.

Efficacy and safety study of osimertinib in advanced non-small cell lung cancer (NSCLC) with EGFR mutation.

e21150 Background: The frequency of transmission on EGFR is more frequent in women and non-smokers. It is characteristic of the Asian population (10% in the Caucasian race). EGFR tyrosine kinase domain inhibitors (EGFR-TKIs) are the standard first-line therapy in non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of osimertinib (third generation TKI-EGFR) were evaluated in the FLAURA phase III clinical trial, comparing it against first and second generation TKI-EGFR (erlotinib and gefitinib) in patients with advanced NSCLC. The objective is to evaluate the efficacy and safety of osimertinib in routine clinical practice at the Juan Ramon Jimenez Hospital. Methods: Descriptive observational, and retrospective study of patients with advanced NSCLC and EGFR + treated TKI-EGFR in the period 2015-2022. We analyzed (IBM SPSS Statistics 22) sociodemographic and clinical variables, toxicity profile, objective response rate (ORR), treatment response and progression-free survival (PFS) with Kappan-Meier curves. Results: We included 41 patients (p). 24 women (58.5%). The median age 66 years. 61% had a smoking habit (39% active smokers and 22% ex-smokers). 1p South American race, rest Caucasians. Present histologies: adenocarcinoma (87.8%), squamous cell (4.9%) and signet ring cells (2.4%). EGFR mutations: 53.7% exon 19 deletion and 36.6% exon 20 mutation and 9.8% were not specified. In 10 p the T790 mutation was analyzed, positive in 14.6%. Stage at diagnosis: IV (87.8%); III (12.2%). Symptoms at diagnosis: persistent cough (22%), pain (22%), dyspnea (19.5%) and constitutional syndrome (12.2%). Status Performance: 0-1 (85.4%). Pulmonary (48.8%), bone (36.6%), lymph node (29.3%), liver (22%), brain (22%), and adrenal (14.6%) metastases. 58.5% received osimertinib in the first line, 17.1% in the second. ORR: 77.4% partial response, 9.7% complete response and 12.9% disease progression. Toxicity (T) 90.9%. Digestive T: Diarrhea: grade G1 36.7%, G2 13.3%, G3 6.7%; nausea: G1 3.3%; hyporexia: G1 25.8%; hypertransaminasaemia: G1 3.2%. Dermal T: skin dryness: G1 20.7%, G2 10.3%, G3 3.4%; onycholysis: G1 19.4%. Asthenia: G1 25.8%, G2 12.9%, G3 12.9%. Pneumonitis: G1 3.2%, G2 3.2%, G3 6.5%. Hematological T: anemia: G1 6.5%, G2 16.1%, G3 3.2%. Dose reduction to 40 mg (37.5%). 12.5% discontinued osimertinib. mPFS in 1st line (L): 14 m (m). mPFS in 2nd L: 8 m. 95% CI (0-31.5). 95% CI (9.8- 18.1. mOS: 21 m (95% CI: 17.73-24.26). Conclusions: Osimertinib presents an adequate safety profile for patients with G1, G2 toxicities, generally easy to manage in clinical practice. A very low percentage of patients had to discontinue treatment. No fatal adverse event was reported. Our results in OS and PFS, although favorable, are somewhat lower than those of the FLAURA clinical trial, possibly due to dealing with real-life patients and/or the size of the sample, which is not entirely sufficiently representative.

Impact of first-line immunotherapy on survival and intracranial outcomes from a real-world cohort of patients with non-small cell lung cancer with brain metastases at diagnosis.

9058 Background: Although brain metastases (BM) at diagnosis are common in non-squamous NSCLC patients (ns-NSCLC), they have been mostly excluded from randomized trials. The aim of this retrospective study was to evaluate real-word outcomes of frontline immune checkpoint inhibitor (ICI) in these patients. Methods: We conducted a retrospective study to assess the intracranial and overall efficacy of first-line ICI-based therapy compared to chemotherapy (CT) in ns-NSCLC patients diagnosed with BM, showing no targetable alterations. Patients were divided according to systemic therapy: CT, ICI, or CT-ICI respectively. Primary endpoint was overall survival (OS), compared using Kaplan-Meier and Cox methodology. Secondary endpoint was intracranial progression free survival (icPFS). Results: Between 01-2018 and 05-2021, 118 newly diagnosed ns-NSCLC patients with BM were included (52 CT, 38 ICI and 28 CT-ICI). Median follow-up was 30.0 months [95% CI: 25.9-36.0]. Intracranial radiotherapy was delivered for 75.0%, 68.4% and 67.9% of patients for CT, ICI and CT-ICI groups (p = 0.805) respectively. OS rates at 24 months were respectively 25.3% (95% CI: 15.7-40.9), 44.6% (95% CI: 30.8-64.7) and 50.5% (95% CI: 34.3-74.4) in CT, ICI and CT-ICI groups (p = 0.048). Twelve-month icPFS was respectively 17.0% (95% CI: 9-32), 47% (95% CI: 33-66) and 45% (95% CI: 30-69) in CT, ICI and CT-ICI groups . After adjustment, ICI and CT-ICI were associated with a better OS compared to CT (HR = 0.46, 95%CI: 0.23-0.89, p = 0.021 and HR = 0.52, 95%CI: 0.27-1.01, p = 0.054 respectively). ICI and CT-ICI were associated with a significant reduction in the risk of intracranial progression by 54% (HR = 0.46, 95%CI: 0.25–0.84, p = 0.0123) and 59% (HR = 0.41, 95%CI: 0.23–0.77, p = 0.0050) compared to CT. Stereotactic radiosurgery was associated with an increased icPFS compared to systemic therapy alone (HR = 0.51, 95% CI: 0.29 – 0.92, p = 0.0247), whereas whole-brain was not (p = 0.096). Conclusions: Real-life ns-NSCLC patients with BM at diagnosis treated frontline with ICI presented OS and icPFS benefit compared to CT alone. A prospective assessment of the ideal type and sequence of systemic and local therapy should be conducted.

First-line immune checkpoint inhibitors alone or in combination with chemotherapy in real-life elderly patients with advanced non-small cell lung cancer (NEJ057).

9012 Background: Immune checkpoint inhibitor (ICI) plus chemotherapy is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. However, the efficacy and safety of ICI plus chemotherapy (ICI-chemo) in 75 years or older patients have not been elucidated. The aim of this study is to reveal the real-world choice of first-line drugs in elderly patients (pts) and evaluate the efficacy and safety of ICI-chemo. Methods: We conducted a multicenter (58 centers in Japan), retrospective cohort study of consecutive 75 years or older pts with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC who started first-line systemic therapy between December 2018 and March 2021. Pts with epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or whose first-line systemic therapy was molecular targeted therapy were excluded. Results: A total of 1245 pts were enrolled: median (range) age 78 (75-95) years; 278 (22%) female; 367 (29%) ECOG PS 0, 680 (55%) PS 1 and 171 (14%) PS 2; 678 (54%) adenocarcinoma; PD-L1 tumor proportion score 268 (22%) &lt;1%, 387 (31%) 1-49% and 410 (34%) ≥50%; 354 (28%) ICI-chemo, 425 (34%) ICI alone, 311 (25%) platinum-doublet chemotherapy and 155 (12%) single agent chemotherapy. The median overall survival (OS) was 20.0 months (95%CI, 17.1–23.6) in the ICI-chemo group, 19.8 months (95%CI, 16.5–23.8) in the ICI alone group, 12.8 months (95%CI, 10.7–15.6) in the platinum-doublet chemotherapy group and 9.5 months (95%CI, 7.4–13.4) in the single agent chemotherapy group, respectively. After propensity score matching, there was no difference in OS and progression-free survival (PFS) between ICI-chemo group (n=96) and ICI alone group (n=95) in PD-L1 ≥1% (OS: HR, 0.98; 95% CI, 0.67-1.42, PFS: HR, 0.92; 95% CI, 0.67-1.25). Regardless of PD-L1 subgroups (1-49% or ≥50%), no significant differences in OS and PFS were observed. Concerning safety, Grade 3 or higher immune-related adverse events (irAEs) occurred in 86 pts (24.3%) in the ICI-chemo group and 76 pts (17.9%) in the ICI alone group (p = 0.03). The number of pts who required steroids for irAEs was 115 (32.5%) in the ICI-chemo group and 105 (24.7%) in the ICI alone group (p = 0.02). Pneumonitis was reported in 83 pts (23.4%) in the ICI-chemo group and 66 pts (15.6%) in the ICI alone group (p = 0.006). Conclusions: In real-world data for pts aged 75 years or older, ICI-chemo did not improve survival and increased the incidence of grade 3 or higher irAEs compared to ICI alone. Based on our results, ICI alone is recommended for elderly pts with PD-L1 positive NSCLC. Clinical trial information: UMIN000046700 .

Acute myeloid leukemia (AML) outcomes in the era of novel therapies: A 9-year single-institution experience.

e19053 Background: Recent advances and approval of multiple targeted and non-targeted agents have significantly transformed care for Acute Myeloid Leukemia (AML) over the past 5 years, particularly for older/unfit patients. While this has provided clinicians with several treatment options in both upfront and relapsed/refractory setting, it has also increased the complexity of clinical decision making. Although several trials have shown immense promise of these therapies, the real-world outcomes have not been reported. The primary aim of this study is to compare survival outcomes in newly diagnosed and relapsed AML before and after the introduction of the novel AML treatments that were granted FDA approval over the past 5 years. Methods: We performed a retrospective single-center analysis on adult patients (≥ 18 years) with newly diagnosed and relapsed AML treated at University of Florida Cancer Hospital between January 2012 and December 2020. Patients were stratified according to the time of diagnosis and Overall survival (OS) was estimated using Kaplan Meier method. Survival between groups was compared using log-rank test. Results: A total of 1617 patients were included in this analysis. Median age was 61 years (range 18-83) and 54.4% of patients were men. 71.4% patients were of white race. Median OS was 71.5 months with 1-year OS of 67.4%. Women had significantly better survival than men (1-year OS: 72% vs 63.6%, p=0.0043). 1-year OS for patients diagnosed in 2012-14, 2015-17 and 2018-20 was 73.5%, 67.6% and 58.1% respectively (p &lt; 0.0001). There were no significant differences in survival based on race. 21.4% (n=347) patients had relapse of AML. Median OS for AML relapse was 9.8 months with 1-year survival of 45.1%. There were no significant differences in survival of patients based on race, sex and year of diagnosis. Conclusions: Our study reports decline in 1-year survival of patients with AML in the modern era despite introduction of several novel therapies in recent years. Additionally, relapsed AML continues to have dismal outcomes despite the availability of multiple novel agents for R/R AML. These results are surprising given the reported good efficacy of these agents in clinical trials. Possible explanations include under-representation of real-life patients in clinical trials, poor tolerability of these therapies by the average patient, and/or barriers to access to these novel therapies in healthcare due to prohibitive high cost, inadequate insurance coverage, or limited availability. Larger-scale real-life population-based studies are needed to further investigate the validity of these findings. [Table: see text]

Real-world Experience of Approved Chimeric Antigen Receptor T-cell Therapies Compared to Clinical Trials Data.

Real-world Experience of Approved Chimeric Antigen Receptor T-cell Therapies Compared to Clinical Trials Data.

Pulsed field ablation in real-life atrial fibrillation patients: 1-year clinical recurrence, operator learning curve and re-do procedural findings

Abstract Funding Acknowledgements Type of funding sources: None. Pulsed field ablation (PFA) is a novel method of cardiac ablation demonstrated in early preclinical and clinical settings. The aim of this study was to report the safety and clinical efficacy of pulmonary vein isolation (PVI) with PFA for real-world atrial fibrillation (AF) patients. Methods and results All-comer AF patients (n=121, 59% paroxysmal) were prospectively included and underwent PFA with 100% HD voltage maps performed after PVI. PVI was achieved with PFA-only in 119 (98%) of the cases. During the implementation phase the mean procedure and fluoroscopy time was reduced from 85 ± 34 to 72 ± 18 minutes (p=0.044) and 22 ±9 to 16 ±4 (p=0.034). We observed one phrenic nerve palsy with only partial remission at follow-up. Other adverse events were numerically comparable to standard PVI procedures. Over a mean follow-up of 308 ± 87 days a total of 22/121 (18.2%) cases experienced clinically significant recurrence or initiation of anti-arrhythmic drugs with Kaplan-Meier event-free estimate at 365 days of 80% (88% for paroxysmal versus 69% for persistent) Figure 1. HD mapping post-PVI showed insufficient acute lesion formation in up to 20% (60% of these right sided) resulting in additional PFA for sufficient isolation. In four of six re-do procedures significant gaps were located at the right pulmonary veins. Conclusion PFA was a highly efficient method to achieve PVI with reductions in procedure time and fluoroscopy over the implementation period. The safety, procedural data and clinical recurrence rates from initial trials were confirmed in real-life non-selected AF patients. More data is needed to investigate and understand the lesion durability and limitations of PFA.

Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry.

CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real-life patients. Retrospective analysis of AML patients treated with CPX-351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. Median age of 79 patients treated with CPX-351 was 67 years old (interquartile range 62-71), 53 were MRC-AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX-351 was 52%, 60-days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3-year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX-351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX-351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18-0.59), p < 0.001. Larger post-authorization studies may provide evidence of the clinical benefits of CPX-351 for AML in the real-life setting.

P71 SGLT2I IN THE REAL WORLD: DATA FROM THE PONTE (BRIDGE) HF PROJECT (PDTA FOR INTEGRATED TERRITORY HOSPITAL FOLLOW–UP OF PATIENTS WITH HEART FAILURE)

Abstract Background The DAPA–HF and the EMPEROR reduced trials showed that sodium–glucose cotransporter type 2 inhibitors (SGLT2i) dapagliflozin and empagliflozin, on best medical therapy, resulted in a reduced incidence of the combined primary outcome cardiovascular death and worsening heart failure (–26%) and a preventive effect on renal function decline. Based on this evidence, the 2021 ESC guidelines have included SGLT2i in class I recommendations in combination with angiotensin and neprilysin receptor inhibitors (ARNI) or ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB), beta–blockers (BB), and mineral corticoid receptor antagonists (MRA). However, the effect of adding SGLT2i in real–life patients is just partly known. The aim of the study was therefore to evaluate the impact of SGLT2i in a real world population of patients with heart failure and reduced left ventricular ejection fraction (HFrEF). Methods 220 consecutive patients with HFrEF, treated with SGLT2i and with 6 months of follow–up already enrolled in the PONTE (BRIDGE) HF project (PDTA FOR THE INTEGRATED FOLLOW–UP IN THE HOSPITAL TERRITORY OF THE PATIENT WITH HEART FAILURE), a care model implemented in Puglia region (Italy) based on hospital–territory integration aimed at the optimized management of patient with HF after hospitalization, were considered for the study. Demographic, clinical, laboratory and instrumental characteristics and changes in NYHA class, creatinine, NT proBNP, loop diuretic dose, LVEF after initiation of therapy with SGLT2i were evaluated. Results The 220 enrolled patients (mean age of 62 years, 72% hypertensive, 38% diabetic, 67% with ischemic heart disease, 50% with ICD/CRT, 44% with atrial fibrillation, 5.6% in NYHA class I, 61% class II, 33% class III, mean LVEF 30±11%) were in treatment with BB in 93% of cases, with MRA in 94%, with ACE/ARB in 24% and with ARNI in 80%. At 6–month follow–up of, a reduction of patients in NYHA class III from 33 to 20%, an increase in patients in NYHA class II from 61 to 70%, and in NYHA class I from 5.6 to 10% were observed; the LVEF (30 vs 37.2%) and creatinine values (1.3 vs 1.5) increased significantly, while loop diuretic doses decreased (35 vs 97.5). Conclusions Data from patients treated with SGLT2i from real world seem to confirm the efficacy of this class of drugs already in a short term follow–up, with a positive effect on NYHA class, LVEF, and renal function.

Real-World Safety and Efficacy Clinical Data of an Improved Allergen-Specific Immunotherapy Product for the Treatment of Bee Venom Allergy.

The aim of this study is to explore the safety and efficacy of bee venom immunotherapy without HSA, in real-life patients. Methods: This is an observational retrospective study developed in seven hospitals in Spain, where patients treated with this immunotherapy were included. They gathered the protocol used to initiate the immunotherapy, adverse reactions, field re-stings, and the patient clinical data (clinical history, biomarkers, and skin prick test). Results: A total of 108 patients were included. In total, 4 protocols were used (5 weeks reaching 200 μg, and 4, 3, and 2 weeks reaching 100 μg). An incidence of systemic adverse reactions for each 100 injections of 1.5, 1.7, 0, and 0.58, respectively, was found. The demographic data showed not to directly affect the appearance of adverse reactions, except for those having a grade 2 systemic reaction with immunotherapy previously had a grade 4 systemic reaction; the IgE to Apis mellifera was 3 times higher in patients with systemic reactions of grade 1 than in the general group, and other specific IgEs were lower in those with systemic reactions. Most of the patients recognized Api m 1 followed by Api m 10. In the sample, 32% experienced spontaneous re-stings, without presenting systemic reactions, after a year of treatment.

P140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response

The p140Cap adaptor protein is a tumor suppressor in breast cancer associated with a favorable prognosis. Here we highlight a function of p140Cap in orchestrating local and systemic tumor-extrinsic events that eventually result in inhibition of the polymorphonuclear myeloid-derived suppressor cell function in creating an immunosuppressive tumor-promoting environment in the primary tumor, and premetastatic niches at distant sites. Integrative transcriptomic and preclinical studies unravel that p140Cap controls an epistatic axis where, through the upstream inhibition of β-Catenin, it restricts tumorigenicity and self-renewal of tumor-initiating cells limiting the release of the inflammatory cytokine G-CSF, required for polymorphonuclear myeloid-derived suppressor cells to exert their local and systemic tumor conducive function. Mechanistically, p140Cap inhibition of β-Catenin depends on its ability to localize in and stabilize the β-Catenin destruction complex, promoting enhanced β-Catenin inactivation. Clinical studies in women show that low p140Cap expression correlates with reduced presence of tumor-infiltrating lymphocytes and more aggressive tumor types in a large cohort of real-life female breast cancer patients, highlighting the potential of p140Cap as a biomarker for therapeutic intervention targeting the β-Catenin/ Tumor-initiating cells /G-CSF/ polymorphonuclear myeloid-derived suppressor cell axis to restore an efficient anti-tumor immune response.

A new lung cancer detection method based on the chest CT images using Federated Learning and blockchain systems

With an estimated five million fatal cases each year, lung cancer is one of the significant causes of death worldwide. Lung diseases can be diagnosed with a Computed Tomography (CT) scan. The scarcity and trustworthiness of human eyes is the fundamental issue in diagnosing lung cancer patients. The main goal of this study is to detect malignant lung nodules in a CT scan of the lungs and categorize lung cancer according to severity. In this work, cutting-edge Deep Learning (DL) algorithms were used to detect the location of cancerous nodules. Also, the real-life issue is sharing data with hospitals around the world while bearing in mind the organizations' privacy issues. Besides, the main problems for training a global DL model are creating a collaborative model and maintaining privacy. This study presented an approach that takes a modest amount of data from multiple hospitals and uses blockchain-based Federated Learning (FL) to train a global DL model. The data were authenticated using blockchain technology, and FL trained the model internationally while maintaining the organization's anonymity. First, we presented a data normalization approach that addresses the variability of data obtained from various institutions using various CT scanners. Furthermore, using a CapsNets method, we classified lung cancer patients in local mode. Finally, we devised a way to train a global model cooperatively utilizing blockchain technology and FL while maintaining anonymity. We also gathered data from real-life lung cancer patients for testing purposes. The suggested method was trained and tested on the Cancer Imaging Archive (CIA) dataset, Kaggle Data Science Bowl (KDSB), LUNA 16, and the local dataset. Finally, we performed extensive experiments with Python and its well-known libraries, such as Scikit-Learn and TensorFlow, to evaluate the suggested method. The findings showed that the method effectively detects lung cancer patients. The technique delivered 99.69 % accuracy with the smallest possible categorization error.

Characteristics of severe asthma patients on biologics: a real-life European registry study.

The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs. We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies. Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids. A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.

Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: the multicenter, prospective, real-life FRIEND2 study

BackgroundTo verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM: ≥ 15 days/month), and multiple preventive treatment failures.MethodsThis is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21–24 compared to baseline. Secondary endpoints encompassed changes in monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS, HIT-6 and MIDAS scores at the same time interval. Changes in MMDs/MHDs, monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS and HIT-6 scores at week 4 were also monitored.ResultsFour hundred ten patients who had received ≥ 1 dose of fremanezumab were considered for safety analysis while 148 patients treated for ≥ 24 weeks were included in the efficacy analysis. At weeks 21–24, fremanezumab significantly (p < 0.001) reduced MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM compared to baseline. The proportions of ≥ 50%, ≥ 75% and 100% responders at weeks 21-24were 75.0%, 30.8%, 9.6% (HFEM), and 72.9, 44.8 and 1% (CM). A significant (p < 0.001) decrease in MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM was already present at week 4. The proportions of ≥ 50%, ≥ 75%, and 100% responders at week 4 were 67.6%, 32.4%, 11.8% (HFEM) and 67.3%, 40%, 1.8% (CM). CM remitted to episodic migraine and medication overuse to no-medication overuse in 83.3 and 75% of patients at week 24, and in 80 and 72.4% at week 4. Adverse events were rare (2.4%), mild and transient. No patient discontinued treatment for any reason.ConclusionsFremanezumab is characterized by an early and sustained efficacy in HFEM and CM patients with multiple preventive treatment failures in real-life, revealing an optimal safety and tolerability profile.

Exposure-Response Analyses of Olaparib in Real-Life Patients with Ovarian Cancer.

Olaparib is given in a fixed dose of twice-daily 300mg in patients who are diagnosed with ovarian cancer, breast cancer, prostate cancer or pancreas cancer and has a high interpatient variability in pharmacokinetic exposure. The objective of this study was to investigate whether pharmacokinetic exposure of olaparib is related to efficacy and safety in a real-life patient' cohort. A longitudinal observational study was conducted in patients who received olaparib for metastatic ovarian cancer of whom pharmacokinetic samples were collected. A Kaplan-Meier analyses was used to explore the relationship between olaparib exposure, measured as (calculated) minimum plasma concentrations (Cmin), and efficacy, Univariate and multivariate cox-regression analyses were performed. Also, the Cmin of patients who experienced toxicity was compared with patients who did not experience any toxicity. Thirty-five patients were included in the exposure-efficacy analyses, with a median olaparib Cmin of 1514ng/mL. There was no statistical significant difference in PFS of patients below and above the median Cmin concentration of olaparib, with a hazard ratio of 1.06 (95% confidence interval: 0.46-2.45, p = 0.9)). For seven patients pharmacokinetic samples were available before toxicity occurred, these patients had a higher Cmin of olaparib in comparison with patients who had not experienced any toxicity (n = 33), but it was not statistically significant (p = 0.069). Our study shows that exposure of olaparib is not related to PFS. This suggests that the approved dose of olaparib yields sufficient target inhibition in the majority of patients.

Prospective evaluation of plasma phosphorylated tau in a real-life memory clinic in Thailand.

Despite the substantial accuracy of plasma p-tau in diagnosing Alzheimer's disease (AD) in research cohorts, data on real-life memory clinic patients are lacking. Memory clinic patients at their early symptomatic stages were prospectively enrolled to undergo routine clinical assessment, plasma p-tau181 quantification (Simoa), amyloid and tau-positron emission tomography (PET). The diagnostic performance of plasma p-tau181, neurocognitive specialists, and regional tau-PET were compared head-to-head using amyloid-PET as the reference standard. Plasma p-tau181 has the area under the curve (AUC), sensitivity, specificity, and accuracy of 0.84 (95% confidence interval [CI] 0.73-0.94), 0.80 (95% CI 0.64-0.90), 0.75 (95% CI 0.51-0.90), and 0.78 (95% CI 0.65-0.88) for detecting amyloid-PET positivity in early symptomatic patients, respectively. The AUC of clinical diagnosis and tau-PET were 0.70 (95% CI 0.56-0.85) and 0.88 (95% CI 0.79-0.97), respectively. Plasma p-tau181 also performed well in real-life memory clinic settings and its role in clinical practice is supported.

Increasing the COVID-19 immunization rate through allergy testing.

Vaccination of the population is required to combat the COVID-19 pandemic. Allergy testing could reduce anxiety towards COVID-19 vaccination and thereby may increase vaccination rate, however, its effectiveness remains unclear. One hundred and thirty prospective real-life patients in need of but not daring to get vaccinated asked for allergy workup for COVID-19 vaccine hypersensitivity in 2021/2022. Characterization of patients, identification of anxieties, decrease of patient's anxiety levels, overall vaccination rate and adverse reactions after vaccination were assessed. Tested patients were characterized by being female (91.5%) and having a high rate of previous allergies (e.g. to food 55.4%, drugs 54.6%, or previous vaccinations 50%) and dermatological disease (29.2%) but not always had medical contraindications for COVID-19 vaccination. Sixty one patients (49.6%) were highly concerned (4-6, Likert scale 0-6) about vaccination and 47 (37.6%) expressed resolving thoughts about vaccinaion anaphylaxis (3-6, Likert scale 0-6). However only 35 patients (28.5%) were scared of getting COVID-19 within 2 months (4-6, Likert scale 0-6) and only 11 (9%) patients had high expectations of getting COVID-19 (4-6, Likert scale 0-6). Allergy testing significantly (p< 0.01 to p< 0.05 respectively) reduced the median anxiety of allergic symptoms following vaccination: dyspnoea (4.2-3.1), to faint (3.7-2.7), long-term consequences (3.6-2.2), pruritus (3.4-2.6), skin rash (3.3-2.6) and death (3.2-2.6). After allergy testing, most patients (108/122, 88.5%) let themselves be vaccinated within 60 days. Revaccinated patients with previous symptoms experienced a reduction of symptoms (p< 0.05) upon revaccination. Patients not daring to get vaccinated have more anxiety towards vaccination than to acquire COVID-19. For those, allergy testing excludes vaccine allergy, and is a tool to increase vaccination willingness and thereby helps to combat vaccination hesitancy.

Hipoxemia y el riesgo de hipertensión arterial en apnea obstructiva del sueño

Introduction: there is limited information about the role of hypoxemia degree as a risk factor for hypertension (HTN) in patients with obstructive sleep apnea (OSA). The objective of this study is to assess hypoxemia as an independent risk factor for HTN in a work model based on real-life patients examined at sleep unit. Methods: this retrospective study consisted of a predictive model using multiple logistic regression to establish the relationship between HTN and age, sex, body mass index (BMI), apnea/hypopnea index (AHI) and time below SO2 ≤ 90% (T90 ≥ 3%). Results: we included 3.854 patients (median age: 55 years), mostly men (61.5%). According to the model, the variables that were significantly associated with HTN were: age (OR: 3.27 – 3.29, CI95% 2.83 – 3.80, p &lt; 0.0001), male sex (OR 1.35, CI95% 1.17 – 1.56, p &lt; 0.001), Obesity (OR 1.83, CI95% 1.59 – 2.11, p &lt; 0.0001), AHI &gt; 15 events per hour (OR 1.22, CI95% 1.05 – 1.43, p &lt; 0.01) and T90 ≥ 3% (OR 1.56 – 1.57, CI95% 1.32 – 1.84, p &lt; 0.0001). Conclusion: in a clinical population of subjects suspected of OSA, nocturnal hypoxemia measure as T90 ≥ 3% was associated with HTN.