Real-life Observational Study Research Articles

The Size of a Thyroid Nodule with ACR TI-RADS Does Not Provide a Better Prediction of the Nature of the Nodule: A Single-Center Retrospective Real-Life Observational Study.

We investigated if thyroid nodule size has a predictive value of malignancy on a par with composition, echogenicity, shape, margin, and echogenic foci, and what would be the consequence of observing the rule of the American College of Radiology (ACR) to perform a fine-needle aspiration biopsy (FNAB). We conducted a retrospective real-life observational study on 86 patients who underwent surgery after a standardized diagnostic protocol. We divided the TR3, TR4, and TR5 classes into sub-classes according to the size threshold indicating FNAB (a: up to the threshold for no FNAB; b: over the threshold for FNAB suggested). We computed sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for the different sub-classes and Youden's index (Y) for the different possible cutoffs. Each sub-class showed the following PPV (0.67, 0.68, 0.70, 0.78, 0.72), NPV (0.56, 0.54, 0.51, 0.52, 0.59), and Y (0.20, 0.20, 0.22, 0.31, 0.30). In this real-life series, we did not find a significant difference in prediction of malignancy between the sub-categories according to the size threshold. All nodules have a pre-evaluation likelihood of being malignant, and the impact and utility of size thresholds may be less clear than suggested by the ACR TIRADS guidelines in patients undergoing standardized thyroid work up.

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

BackgroundAnti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life.MethodsIn this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies.ResultsA total of 162 patients were included, median age 68 years (range 65–87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%).ConclusionsAnti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice.Graphical

Effectiveness of salvage catheters in home parenteral nutrition: A single-center study and systematic literature review

There are sparse data regarding the rate of catheter salvage and long-term effectiveness of antibiotic lock treatment outcome after central line-associated bloodstream infections (CLABSI). Objectives were to analyze the effectiveness of central venous catheter (CVC) rescue strategy and its impact on catheter lifespan. Secondary objective included effectiveness of taurolidine+4% citrate in primary prevention, compared to a secondary prevention strategy, by analyzing infection incidence during two successive periods. Real-life 5-year observational study assessing CLABSI occurrence and CVC salvage outcomes in adult patients requiring Home Parenteral Nutrition (HPN) managed in a single-center Intestinal Failure Unit. Over the 5-year period, there were 106 confirmed infections (63/143 patients (44%)). Infection incidence was 0.92/1000 catheter-days. Incidence was 1.02/1000 catheter-days during the taurolidine+4% citrate period while lower at 0.84/1000 catheter-days (p=0.034) during the systematic taurolidine lock period. Of the total number of infections, 89 CVCs were immediately removed and 17 were salvaged. The success rate of catheter salvage with antibiotic lock was 82.4%, with 53% remaining CLABSI-free at one year. The salvage strategy extended catheter lifespan by a median 165 days (IQR 50-214). However, the rate of new infection was significantly higher in instances of salvage (71.4%) vs. removal (36%). Parenteral Nutrition (PN) ≥12 months (p=0.002), PN (vs. hydroelectrolytic support) (p=0.028) and self-management by patients (p=0.049) were independent risk factors of CLABSI. Catheter salvage appears to be an effective long-term strategy with >50% of CVCs remaining CLABSI-free at one year and a prolonged catheter life, although may expose to a more frequent and earlier infection recurrence. Cohort approved by the French CNIL (National Committee for Data Protection, authorization number CNIL 2015-25). referred to as "observational research", "non-interventional", or«non-RIPH ».

Efficacy, Tolerability, and Safety of Treatment With Perampanel in Pediatric Patients With Epilepsy Aged ≥4 Years: A Real-Life Observational Study.

Purpose: The safety and effectiveness of perampanel in clinical settings involving Chinese pediatric patients are limited, as perampanel has only recently been approved for use in China, in September 2019. We aimed to evaluate the efficacy and tolerability of perampanel as an adjunctive therapy for pediatric patients with epilepsy aged ≥ 4 years in Xinjiang, Northwest China. Methods: Efficacy was assessed by measuring changes in seizure frequency at 3-, 6-, and 12-month follow-up compared with baseline. The baseline was 3 months before the addition of perampanel, and the seizure frequency was based on the patients' seizure diary. The safety and tolerability depended on the type and frequency of any adverse event during epilepsy treatment across all pediatric patients. Results: Overall, 67 pediatric patients from 2 different hospitals were enrolled in the study. Among the pediatric patients with seizures during the baseline period, the effective rates for all seizure types at 3, 6, and 12 months were 59.1%, 58.7%, and 57.4%, respectively. During perampanel treatment, 34 patients (50.7%) experienced at least 1 adverse reaction. Conclusion: Overall, this real-world retrospective study of pediatric patients validated that perampanel is an effective treatment option as an adjunctive therapy among pediatric patients with epilepsy aged ≥4 years.

A Prospective Study of Costs Associated With the Evaluation of Allergic Reactions to Radiological Contrast Media.

The prevalence of hypersensitivity reactions to radiological contrast media (RCM) is increasing owing to the improved performance of diagnostic and therapeutic tests that require RCMs. Objective: We carried out a year-long real-life observational study to prospectively evaluate patients referred to the allergy department from primary care, the emergency department, and other specialties with suspected moderate-to-severe RCM hypersensitivity reactions. To study the costs of evaluating RCM hypersensitivity reactions, we systematically recorded direct and indirect costs. Sixty-nine patients with previous reactions to RCM were evaluated in the allergy department from June 1, 2017, to May 31, 2018.Total direct health care costs were €10 715.84, with a mean (SD) cost per patient of €155.30 (77.08). Specifically, direct non-health care costs reached €1605.42 (mean, €23.27 [41.14]), and indirect costs were €6490.85 (mean, €94.07 [110.61]). In summary, the total cost was €18 812.11, that is, a mean cost of €272.64 (164.77). Our study shows that the costs of an elective evaluation of hypersensitivity reactions to RCM are low, thus confirming that correct and safe management of affected patients are cost-effective. Therefore, our efforts should be directed toward ensuring the necessary logistics.

The use of a diversion tube to reduce blood culture contamination: A “real-life” quality improvement intervention study

BackgroundBlood culture contamination is associated with health care costs and potential patient harm. Diversion of the initial blood specimen reduces blood culture contamination. We report results of the "real-life" clinical implementation of this technique. MethodsFollowing an educational campaign, use of a dedicated diversion tube was recommended prior to all blood cultures. Blood culture sets taken from adults using a diversion tube were defined as "diversion sets," those without, "non-diversion" sets. Blood culture contamination and true positive rates were compared for diversion and nondiversion sets and to nondiversion historical controls. A secondary analysis investigated efficacy of diversion by patient age. ResultsOut of 20,107 blood culture sets drawn, the diversion group included 12,774 (60.5%) and the nondiversion group 8,333 (39.5%) sets. The historical control group included 32,472 sets. Comparing nondiversion to diversion, contamination decreased by 31% (5.5% [461/8333] to 3.8% [489/12744], P < .0001]. Contamination was also 12% lower in diversion than historical controls [3.8% (489/12744) vs 4.3% (1,396/33,174) P = .02)]. The rate of true bacteremia was similar. In older patients, contamination rate was higher, and the relative reduction associated with diversion decreased (54.3% amongst 20-40-year-olds vs 14.5% amongst >80-year-olds). ConclusionsUse of a diversion tube in the ED reduced blood culture contamination in this large real life observational study. Efficacy decreased with increasing age, which requires further investigation.

Injections Site Reactions and Biologics for Psoriasis: A Questionnaire Based Real Life Study.

Biologic selection for psoriasis treatment should take into account numerous factors including injection site reactions (ISRs) such as swelling at the injection site, pain, burning, erythema, all possibly reducing patient adherence. A 6-months observational real life study was performed involving psoriasis patients. Inclusion criteria were age ≥ 18 years, moderate-to-severe psoriasis diagnosis since at least 1 year, patients being on biologic treatment for psoriasis ≥ 6 months. A 14-item questionnaire was administered to all patients enrolled to assess whether the patient ever experienced ISRs after the injection of the biologic drug. 234 patients were included: 32.5% received an anti-TNF-alpha drug, 9.4% received anti-IL12/23, 32.5% received an anti-IL17, 25.6% received an anti-IL23. 51.2% of study population reported at least one symptom related to ISR. 35.9% of patients experienced pain, 31.6% swelling, 28.2% burning sensation and 17.9% erythema. 3.4% of the surveyed population experienced anxiety or fear of the biologic injection due to ISRs symptoms. The greater incidence of pain was registered in anti-TNF-alpha and anti-IL17 groups (47.4% and 42.1%, p<0.01). Ixekizumab proved to be the drug with the highest rate of patients experiencing pain (72.2%), burning (77.7%) and swelling (83.3%). No patients reported biologics discontinuation or delay for ISRs symptoms. Our study highlighted that each different class of biologics for psoriasis was linked to ISRs. These events are more frequently reported with anti-TNF-alpha and anti-IL17.

Adherence, reliability, and variability of home spirometry telemonitoring in cystic fibrosis.

Forced spirometry is the gold standard to assess lung function, but its accessibility may be limited. By contrast, home spirometry telemonitoring allows a multi-weekly lung function follow-up but its real-life adherence, reliability, and variability according to age have been poorly studied in patients with CF (PwCF). We aimed to compare real-life adherence, reliability and variability of home spirometry between children, teenagers and adults with CF. This real-life observational study included PwCF followed for six months in whom lung function (i.e, forced expiratory volume maximum in 1 s (FEV1), forced vital capacity (FVC), forced mid-expiratory flow (FEF) and FEV1/FVC ratio) was monitored by both conventional and home spirometry between July 2015 and December 2021. The adherence, reliability and variability of home spirometry was assessed in all PwCF and compared between children (<12years old), teenagers (12-18 years old) and adults. 174 PwCF were included (74 children, 43 teenagers and 57 adults). Home spirometry was used at least one time per week by 64.1 ± 4.9% PwCF, more frequently in children and teenagers than in adults (79.4 ± 2.9%, 69.2 ± 5.5% and 40.4 ± 11.5% respectively). The reliability to conventional lung function testing was good for all assessed parameters (e.g., FEV1: r = 0.91, p < 0.01) and the variability over the 6 months of observation was low (FEV1 coefficient of variation = 11.5%). For each parameter, reliability was better, and the variability was lower in adults than in teenagers than in children. Home spirometry telemonitoring appears to be a reliable tool for multi-weekly lung function follow-up of PwCF.

73TiP Niraparib maintenance in first-line ovarian cancer: MITO 40, an observational real-life study

73TiP Niraparib maintenance in first-line ovarian cancer: MITO 40, an observational real-life study

P494 Impact of early optimization of ustekinumab on mid-term targets in severe Crohn’s disease: THE MUST study

Abstract Background As a substantial proportion of patients with Crohn’s disease (CD) experiences a refractory disease course, immediate drug intensification may be an option to optimize the effectiveness of current biotherapies. Aim : to compare the one-year efficacy of immediate dose escalation of ustekinumab 90 mg to 4-weekly with that of 8-weekly dosing after intravenous (iv) induction in severe active CD patients. Methods The MUST (meta-optimization of Ustekinumab) study is a real-life multicenter observational French retrospective cohort study including patients with severe active CD. All patients from three academic IBD centers who received induction therapy with IV ustekinumab followed with subcutaneous (sc) UST 90 mg, either 4-weekly (MUST group) or 8-weekly (STD group) were included from Jan 2019 to Dec 2020. The choice of treatment regimen was left at the physician’s discretion. Severe active CD was defined by HBI &amp;gt; 16 and stool frequency (SF) ≥ 4 and abdominal pain (AP) ≥ 2 over one week and at least one objective evidence of inflammation (CRP ≥ 5 mg/L and/or FCal ≥ 250 μg/g and/or radiologic and/or endoscopic signs of disease activity). The primary endpoint was PRO-2 based clinical remission defined by SF≤2-8 and AP ≤1, and either FCal &amp;lt;250 μg/g and/or CRP &amp;lt;5 mg/L at week 52. Key secondary endpoints were PRO-2 remission, endoscopic improvement and steroid-free clinical remission at week 52. Results 203 adult patients were included, either in the MUST group (n = 59) or in the STD group (n = 144). Baseline patient demographics and disease characteristics were similar between groups. Median disease duration was 9 years (IQR: 5 – 14 yrs), 66% were females. Disease location according to the Montreal classification was L1 and L3 in 36% and 44 % of patients. All had previously been exposed to more than one biotherapy, 27% experienced perianal CD, and 35% had undergone previous CD-related surgery. At week 52, the adjusted difference between the two groups for the primary endpoint was 15.8% (95% confidence interval (CI) 0.21 – 0.94; p = 0.029) with significantly higher clinical remission in the MUST group. The adjusted difference for PRO-2 remission was 3.7% (CI 0.45 - 1.66; p = 0.64). All patients, except one in the STD group, were weaned off steroids at week 52. Endoscopic improvement was similar in both groups (61.9% vs. 61.5%, p=0.98). Adverse events were not significantly different in both arms (42.4% vs 34.7%, p=0.338). Conclusion In the treat-to-target era, our real-life study shows that immediate escalation of ustekinumab therapy to 4-weekly dosing could achieve higher clinical remission at one year than 8-weekly dosing in severe CD. These findings should be confirmed in a dedicated prospective randomized trial.

Tight control in patients with rheumatoid arthritis treated with targeted therapies across the COVID-19 pandemic era

Objectives To analyze the impact of different patterns of healthcare delivery on remission of rheumatoid arthritis (RA) patients treated with targeted therapies during the first wave (2020) and second/third waves (2021) of the pandemic compared to the pre-pandemic period (2019). Methods In this observational real-life study, data from RA patients treated with biologic or targeted synthetic drugs were extracted from a longitudinal registry. Clinical Disease Activity Index (CDAI) was analyzed in the same period from the 22nd of February to the 18th of May for three consecutive years. These three periods were characterized by different patterns of healthcare delivery: (1) before the pandemic (2019) only in-person visits, (2) during the first wave (2020) both in-person visits and telehealth, and (3) during the second/third waves (2021) only in-person visits. A generalized linear model with the binomial error was fitted to evaluate the difference in the proportion of patients in CDAI remission. Quantile regression was used to compare the median of CDAI in difficult-to-treat (D2T) patients. Results In the three periods, we included 407, 450, and 540 RA patients respectively. The percentages of patients in CDAI remission were similar in the three periods (prevalence ratio 1.07, p value 0.423 between 2020 and 2019, and 1.01, p-value 0.934 between 2021 and 2019). The CDAI remission rate was 40.55% (N = 163), 43.18% (N = 155) and 40.82% (N = 220) in 2019, 2020 and 2021, respectively. Among our cohort of D2T patients, CDAI remission was similar across the three periods (N = 30, 22.22%; N = 27, 23.68%; and N = 34, 21.52% respectively). Conclusion Although the pandemic has imposed changes in our healthcare delivery, these different strategies seem to be effective in ensuring satisfactory management of RA treated with targeted therapies. The approaches modulated in the context of the different periods have been a feasible compensation for ensuring disease control even in D2T patients.

Real-Life Effectiveness and Safety of Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: A Single-Center 16-Week Study.

The treatment of severe atopic dermatitis (AD) includes cyclosporine and recently approved biologics and small molecules. Among these, upadacitinib is a selective inhibitor of Janus kinase 1, approved for the treatment of severe AD in adolescents/adults. Upadacitinib has shown efficacy and safety in several phase 3 clinical trials, but data on real-life patients are still lacking. We conducted a retrospective real-life observational study to evaluate the effectiveness and safety of upadacitinib up to week 16 in a cohort of both bio-naïve and bio-experienced patients. This study was carried out by analyzing the AD database records of an Italian referral hospital. Thirty-eight patients were included in this study, and 35 completed 16weeks of treatment. At week 16, out of 35 patients, the percentages of Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90 and EASI 100 responses were 94.29, 91.43, 74.29, and 60%, respectively. A decrease of at least 4 points from baseline of itch-NRS was reported by 94.74 and 91.43% of patients at weeks 8 and 16. Regarding the safety of upadacitinib, 26.32% of patients experienced at least one adverse event (AE), and a total of 13 AEs were recorded, including blood test abnormalities and papulopustular acne. None of our patients interrupted the drug because of an AE. We observed higher rates of EASI75/EASI90/EASI100 responses at week 16, compared with data from clinical trials. The safety profile of upadacitinib was favorable, as no AEs leading to discontinuation were experienced by our patients up to week 16.

EUS guided liver biopsy in patients with suspected cACLD and cirrhosis: a real-life observational study

EUS guided liver biopsy in patients with suspected cACLD and cirrhosis: a real-life observational study

Utility of Procalcitonin and Interleukin-6 As Severe Infection Biomarkers in Adulthematological and Oncological Patients. Real-Life Single Center Prospective Observational Study

Introduction: Hematological and oncology patients represent a vulnerable population to opportunistic infections, mainly due to the disease itself and chemotherapy-induced neutropenia. Therefore, timely antibiotic treatment becomes of even greater importance in order to prevent sepsis related mortality. Serum C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) have been widely used to facilitate sepsis diagnosis, but their diagnostic and prognostic values are limited. Methods: The purpose of our prospective study was to evaluate the diagnostic accuracy of the above-mentioned biomarkers that were monitored during fever episode for early diagnosis of severe infection and sepsis in immunosuppressed patients in course of chemotherapy. Adult oncological or hematological patients with fever or other clinical signs of infectious episode were included in the study. The study was approved by the independent ethics committee and patients provided written informed consent for the acquisition of biomarker samples. Results: The study population consisted of 51 patients with a median age of 56 year, 59% being male. Around 40% had previous infectious episode including eight patients with sepsis, with 28 patients affected from either lymphoma or multiple myeloma, while others had oncological disease. The patients were hospitalized in course of study for infectious episode in 40% of cases, while others were receiving chemotherapy with a median hospitalization duration of 12 days. Sixty percent of the study population was in disease progression at study entry. Fever was present as a clinical sign in all but two patients, that had low-grade fever (&lt;38°C), with 10 patients having neutropenic fever. More than half of the population had body temperature &gt;39°C, with a median of two daily fever spike episodes and median fever duration of two days. Both lung infection in CT scan and positive blood culture were evidenced in approximately 30% of patients. Twelve patients passed away, ten due to infection while disease progression was the cause of death in two of them.Mean baseline and peak PCT values were 4.2 ng/mL and 15.5 ng/mL (range 0.01-150), mean baseline and peak IL-6 values were 262 pg/mL and 299 pg/mL (range 5.5-1500), while mean baseline and peak CRP values were 115 mg/L and 152 mg/L (range 1-775) respectively. Interestingly, both baseline and peak IL-6 and peak CRP values were associated with survival outcome with p&lt;0.05 (Figure 1A and B) using Wilcoxon-Mann-Whitney test. Furthermore peak CRP values were predictive of blood culture positivity (p=0.0005). Conclusions: Serum biomarker monitoring in onco-hematological patients with infectious episode can be of aid in order to evaluate the severity and use it as a guide of antibiotic treatment response. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Additional Value of Lower Respiratory Tract Sampling in the Diagnosis of COVID-19: A Real-Life Observational Study.

Background: Since December 2019, SARS-CoV-2 has been causing cases of severe pneumonia in China and has spread all over the world, putting great pressure on health systems. Nasopharyngeal swab (NPS) sensitivity is suboptimal. When the SARS-CoV-2 infection is suspected despite negative NPSs, other tests may help to rule out the infection. Objectives: To evaluate the yield of the lower respiratory tract (LRT) isolation of SARS-CoV-2. To evaluate the correlations between SARS-CoV-2 detection and clinical symptoms, and laboratory values and RSNA CT review scores in suspect patients after two negative NPSs. To assess the safety of bronchoscopy in this scenario. Method: A retrospective analysis of data from LRT sampling (blind nasotracheal aspiration or bronchial washing) for suspected COVID-19 after two negative NPS. Chest CT scans were reviewed by two radiologists using the RSNA imaging classification. Results: SARS-CoV-2 was detected in 14/99 patients (14.1%). A correlation was found between SARS-CoV2 detection on the LRT and the presence of a cough as well as with typical CT features. Typical CT resulted in 57.1% sensitivity, 80.8% accuracy and 92.3% NPV. Neither severe complications nor infections in the personnel were reported. Conclusions: In suspect cases after two negative swabs, CT scan revision can help to rule out COVID-19. In selected cases, with consistent CT features above all, LRT sampling can be of help in confirming COVID-19.

Efficacy of anti-severe acute respiratory syndrome coronavirus 2 mRNA vaccines in adults with severe acquired aplastic anemia with or without allogeneic hematopoietic stem cell transplantation.

Efficacy of anti-severe acute respiratory syndrome coronavirus 2 mRNA vaccines in adults with severe acquired aplastic anemia with or without allogeneic hematopoietic stem cell transplantation.

Secukinumab in Patients with Psoriasis and a Personal History of Malignancy: A Multicenter Real-Life Observational Study.

IntroductionThere is limited evidence to guide clinicians on the treatment of psoriasis with biologics in patients with a history of malignancy who are often excluded from clinical trials investigating biologics. The aim of this work is to report a multicenter real-life experience of secukinumab treatment in patients with psoriasis and a personal history of cancer.MethodsThis retrospective observational study included adult patients with moderate-to-severe plaque psoriasis treated with secukinumab for at least 24 weeks and a previous diagnosis of cancer at 15 Italian referral centers. The primary endpoint of the study was tumor recurrence or progression and new cancer diagnosis during treatment. Secondary outcome assessment of secukinumab effectiveness (reduction of Psoriasis Area and Severity Index [PASI] score, improvement of Dermatology Life Quality Index [DLQI], itch and pain).ResultsForty-two patients (27 male) were included. Malignancy was diagnosed in the previous 5 years in 21 (56.8%) and in the previous 10 years in 37 (88.1%). The mean interval between cancer diagnosis and the start of secukinumab treatment was 3.5 ± 3.3 years. No tumor recurrence nor progression occurred over a mean of 56 ± 31.7 weeks of treatment. Three patients developed a new malignancy not related to the previous cancer. At week 48, PASI 90 was reached by 64.7% of patients and PASI 100 by 38.2%. Mean DLQI, itch, and pain VAS scores significantly improved during treatment.ConclusionsOur multicenter real-life experience is the largest reported to date focusing on a specific biologic and adds evidence to the safety of secukinumab in psoriatic patients with a personal history of cancer.

Real-life second-line epirubicin-paclitaxel regimen as treatment of relapsed small-cell lung cancer: EpiTax study.

Few therapeutic options are approved as second-line treatment after failure of platinum-based chemotherapy for patients with extensive-stage small-cell lung cancer (ES-SCLC). Topotecan widespread use remains challenged by the risk of severe toxicities in a pretreated population. Little is known about the efficacy and safety of epirubicin-paclitaxel doublet in second-line and beyond and especially cerebral outcomes. EpiTax is a retrospective multicenter observational real-life study. We evaluated the efficacy of epirubicin 90 mg/m2 combined with paclitaxel 175 mg/m2 every 3 weeks in SCLC patients after failure of at least one line of platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), intracranial control rate (ICR), and safety. A total of 29 patients were included. The median of previous systemic therapy lines was 2 (1-4). Eleven patients received the treatment in the second line. Characteristics of patients were a median age of 60 years (45-77), 65.5% of males with 72.4% of PS 0-1. Fifteen patients had a history of brain metastases. Median PFS and OS achieved 11.0 (95% CI, 8.1-16.3) and 23 (95% CI, 14.1-29.6) weeks, respectively. ORR was 34.5% and DCR was 55.2%. ICR was 3/15 (20%). Grade 3-4 adverse events were mainly hematological and concerned 7 patients. No case of febrile neutropenia or toxic death was reported. Epirubicin-paclitaxel association highlighted promising efficacy with PFS and OS of 11 and 23 weeks, respectively, ORR of 34.5%, and a tolerable safety profile. This doublet could represent another valuable therapeutic option for ES-SCLC patients treated in the second line and beyond.

Grade 3-4 Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer (NSCLC) Patients Are Correlated with Better Outcome: A Real-Life Observational Study.

Simple SummaryImmune checkpoint inhibitors (ICIs) recently became a standard treatment for advanced non-small-cell lung cancers (NSCLCs). Immune-related adverse events (irAEs) could occur in 10 to 80% of treated patients but were reported to associate with a better prognosis in clinical trials. However, the prognostic role of Grade 3–4 irAEs, occurring in 2 to 18% of cases, has not been specifically addressed in a real-life setting yet. In this observational study, we highlighted an association between high-grade irAEs and better outcomes in advanced NSCLC patients who received ICI treatment. Actually, a significantly longer overall survival was observed in patients with high-grade irAEs compared to the no-irAEs group. This observation thus suggests a direct link between anti-tumor efficacy and the level of immune activation leading to high-grade irAEs.Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3–4 irAEs on overall survival (OS). Methods: This observational study recruited advanced NSCLC patients who received ICIs at Bichat-Claude Bernard University Hospital and in a community hospital, Saint-Joseph Foundation (Paris), between 1 January 2016 and 31 December 2019. Immunotherapy as a single-agent or double-drug combination was applied in the first and later lines. Univariable and multivariable analyses were instrumental in evaluating the prognostic impact of irAEs. Results: Overall, 201 consecutive ICI-treated patients were enrolled. High-grade irAEs (Grades 3–4) occurred in 36 patients (17.9%), including 11 (30.5%) cases of pneumonitis, 8 (22.2%) of colitis, 4 (11.1%) hepatic, 3 (8.3%) dermatological, 2 (5.5%) neurological events, and 2 cases (5.5%) of poly-arthralgia. The median OS was 10.4 ± 1.36 months (95% CI:7.7–13.1), being significantly higher in patients with high-grade irAEs than those without, 27.8 months vs. 8.1 months, respectively (HR = 2.5; p < 0.0001). Multivariable analysis revealed an independent association between high-grade irAEs and longer OS (HR = 0.29, 95% CI: 0.2–0.6, p < 0.0001). Conclusions: Our real-life study confirms that high-grade irAEs predict longer OS in advanced NSCLC.

First Two-Year Observational Exploratory Real Life Clinical Phenotyping, and Societal Impact Study of Parkinson's Disease in Emiratis and Expatriate Population of United Arab Emirates 2019-2021: The EmPark Study.

Background: Phenotypic differences in Parkinson’s Disease (PD) among locals (Emiratis) and Expatriates (Expats) living in United Arab Emirates have not been described and could be important to unravel local aspects of clinical heterogenicity of PD pointing towards genetic and epigenetic variations. Objective: To investigate the range and nature of motor and nonmotor clinical presentations of PD and its impact on time to diagnosis, local service provisions, and quality of life in Emiratis and Expats in UAE, as well as address the presence of current unmet needs on relation to care and etiopathogenesis of PD related to possible genetic and epigenetic factors. Methods: a cross-sectional one point in time prospective, observational real-life study of 171 patients recruited from PD and Neurology clinics across United Arab Emirates from 2019–2021. Primary outcomes were sociodemographic data, motor and nonmotor symptoms (NMS), including cognition and sleep, and quality of life (QOL) assessments, Results: A total of 171 PD patients (52 Emiratis 119 Expats) were included with mean age (Emiratis 48.5 (13.1) Expats 64.15 (13.1)) and mean disease duration (Emiratis 4.8 (3.2) Expats 6.1 (2.9)). In the Emiratis, there was a significant mean delay in initiating treatment after diagnosis (Emiratis 1.2 (0.9) Expats 1.6 (1.1)), while from a clinical phenotyping aspect, there is a high percentage of akinesia 25 (48.1) or tremor dominant (22 (42.3)) phenotypes as opposed to mixed subtype 67 (56.3) in Expat cohorts; double tremor dominant, especially Emirati females (25%), had a predominant lower limb onset PD. Both Emirati (27.9 (24.0)) and Expat 29.4 (15.6) showed moderate NMS burden and the NMS profile is dominated by Sleep, Fatigue, Mood, Emotional well-being 3.0 (1.1) and Social Stigma 3.5 (0.9) aspects of PDQ8 SI measurements are predicted worse QOL in Emiratis, while lack of social support 2.3 (1.3) impaired QOL in Expat population. Awareness for advanced therapies was low and only 25% of Emiratis were aware of deep brain surgery (DBS), compared to 69% Expats. Only 2% of Emiratis, compared to 32% of Expats, heard of Apomorphine infusion (CSAI), and no (0%) Emiratis were aware of intrajejunal levodopa infusion (IJLI), compared to 13% of expats. Conclusion: Our pilot data suggest clinical phenotypic differences in presentation of PD in Emiratis population of UAE compared to expats. Worryingly, the data also show delayed treatment initiation, as well as widespread lack of knowledge of advanced therapies in the Emirati population.