Interview Versus Performance Assessment of Cognition as Predictors of Real-World Outcomes in a Large-Scale Cross-Sectional Study in Schizophrenia.

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). It is approved as a coprimary measure of performance-based instruments, such as the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Recent research highlights negative symptoms, social cognition, and functional capacity as mediators of cognitive impairment's impact on functioning. This study compared mediation analysis outcomes using CAI or MCCB scores, providing insights into the utility of interview-based tools in research and clinical practice. The study included 618 individuals diagnosed with schizophrenia, recruited from 24 Italian psychiatric clinics. Neurocognitive assessments utilized both CAI and MCCB. Mediation analyses explored negative symptoms, social cognition, and functional capacity as mediators of the impact of neurocognition on real-life functioning domains. The study's results extend the validation of the CAI as a coprimary measure that provides valid information on the impact of cognitive impairment on real-life functioning and its possible mediators, complementing the information obtained using the MCCB. Interview-based cognitive assessment might be essential for understanding schizophrenia complexity and its impact on various cognitive and functional domains for clinicians, patients, and caregivers.

Radiological evaluation of response in patients with locally advanced/metastatic soft tissue sarcoma treated with trabectedin.

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32-78). The median number of trabectedin cycles administered was four (range 2-50) for a median follow up of 5.83 months (range 1-60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7-4.6); median overall survival was 34.3 months (CI95% 0-75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen's kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.

Real-World Survival Impact of New Treatment Strategies for Lung Cancer: A 2000-2020 French Cohort.

Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all patients consecutively treated at Institute Curie for metastatic lung cancer. Diagnosis date was used to define three periods, based on the approvals of novel treatment strategies in the first-line setting, including targeted therapies in 2010 and immunotherapy in 2018. Endpoints included Overall survival (OS), survival rate of 2 years and 5 years, and a conditional survival rate of 2 years (if still alive at 6 months from treatment initiation). A total of 673 patients were identified for Period 1-2000 to 2009, 752 for Period 2-2010 to 2017, and 768 for Period 3-2018 to 2020. Median OS in the whole cohort was 11.1, 15.5, and 16.2 months, respectively. Median OS for patients with NSCLC or SCLC was 11.2, 17.2, and 18.2 months, or 10.9, 11.7, and 11.2 months, respectively. The two-year conditional survival was more favorable for NSCLC than SCLC patients. Outcomes were statistically higher for women as compared to men in all periods and all subgroups. Survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC, along with the implementation of novel treatment strategies.

Real-Life Use of Automated Insulin Delivery in Individuals With Type 2 Diabetes.

BACKGROUND: The objective of this work is to document performance of automated insulin delivery (AID) during real-life use in type 2 diabetes (T2D). METHODS: A retrospective analysis was performed of continuous glucose monitoring and insulin delivery data from 796 individuals with T2D, who transitioned from 1-month predictive low-glucose suspend (PLGS) use to 3-month AID use, in real-life settings. Primary outcome was change of time in range (TIR = 70-180 mg/dL) from PLGS to AID. Secondary outcomes included time above/below range (TAR/TBR) and total daily insulin (TDI). RESULTS: Compared with PLGS, AID increased TIR on average from 63.2% to 72.6%, decreased TAR from 36.2% to 26.8%, and increased TDI from 70.2 to 76.3 U (all P < .001), without significant change to TBR. Glycemic improvements were more pronounced in those with worse glycemic control during PLGS use (P < .001). CONCLUSIONS: Real-life use of AID led to a rapid and sustained improvement of glycemic control in individuals with T2D.

Optimizing Data Extraction: Harnessing RAG and LLMs for German Medical Documents.

In the field of medical data analysis, converting unstructured text documents into a structured format suitable for further use is a significant challenge. This study introduces an automated local deployed data privacy secure pipeline that uses open-source Large Language Models (LLMs) with Retrieval-Augmented Generation (RAG) architecture to convert medical German language documents with sensitive health-related information into a structured format. Testing on a proprietary dataset of 800 unstructured original medical reports demonstrated an accuracy of up to 90% in data extraction of the pipeline compared to data extracted manually by physicians and medical students. This highlights the pipeline's potential as a valuable tool for efficiently extracting relevant data from unstructured sources.

SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma.

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06-30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24-14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04-1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71-76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10-19-NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58-91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7-75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16-73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

How comparative studies can inform treatment decisions for Crohn's disease.

INTRODUCTION: As new therapies for the treatment of Crohn's disease (CD) are approved, there is an increasing need for evidence that clarifies their positioning and sequencing. AREAS COVERED: Comparative effectiveness research (CER) aims to inform physicians' decisions when they choose which intervention (drug or treatment strategy) to administer to their patients. Pragmatic head-to-head trials represent the best tools for CER, but only a few have been published in the IBD field. Network meta-analyses can point toward the superiority of one drug over another, but they do not reflect everyday clinical practice. Finally, real-world evidence complements that coming from head-to-head trials and network meta-analyses, assessing the real-life effectiveness of therapeutic interventions. EXPERT OPINION: There is insufficient evidence to create a definitive therapeutic algorithm for CD, but some general considerations can be made. Anti-TNF-α agents seemingly represent the most 'sustainable' first-line choice, considering benefit-harm ratio and costs; vedolizumab, ustekinumab, and risankizumab may be considered as first-line choice when safety issues become prominent. In the event of pharmacodynamic failure, out-of-class swap is to be preferred - possibly with anti-IL23p19 as the best option, with unclear data regarding upadacitinib positioning; a second anti-TNF-α could be considered, as a second choice, after pharmacokinetic failure.

Coordination and Referral Platforms for Children Aged 7 and Under with Suspected Neurodevelopmental Outcome: What Data for Research on Care and Developmental Trajectories?

At the core of the child's medical, social, and educational pathway, coordination and referral platforms (CRPs) for neurodevelopmental disorders (NDDs) have been gradually deployed in France since 2018 and support the early detection of NDDs in children. The 112 nationwide CRPs do not benefit from a common electronic health record system. Our aim was to propose an HER model for CRP to enable real-life data reuse, optimize care pathway management and conduct pre-screening for research. CRP data were collected (n=34) into an application enriched by a NLP tool extracting standardized scales for NDDs assessments from medical and paramedical professionals. NLP tool evaluation presented a precision of 86.4% and recall of 90.5%. CRP support was provided to 195 children included between 1 September 2022 and 31 August 2023, aged 4 years, with a sex ratio of 2.8, with delays reported in language (75%) and concerned by global developmental delays (16%). Children's ND phenotype and care pathway description could be automated by a harmonized and structured EHR. While many clinical situations are at an impasse, real-life data-driven evidence is particularly relevant in the context of NDDs, where early intervention plays such a key role in children's development and prognosis. A harmonized and enriched CRP database could benefit both individual and public health levels with pathway monitoring, intervention proposals and research pre-screenings.

Does the PedsQL reflect the real-time quality of life in autistic adolescents? A comparison with the experience sampling methodology.

BACKGROUND: The PedsQL is widely used to retrospectively evaluate quality of life (QoL) in autistic adolescents. However, concerns have arisen regarding its ability to reflect real-time QoL, considering their challenges in recollecting past experiences. OBJECTIVE: We examined the overall and social QoLs of autistic adolescents compared to neurotypical peers using the PedsQL and the experience sampling method (ESM), an ecological momentary assessment of QoL in real-time. Additionally, we explored the relationship between these measures in each group. METHODS: A total of 175 participants, including 117 autistic and 58 neurotypical adolescents aged 10-16, completed the PedsQL and an ESM protocol with a mobile device to record their real-time experiences seven times a day for seven days. We performed multiple linear regression and multilevel analyses to compare QoLs between groups and the association between the two measures. RESULTS: Autistic adolescents scored significantly lower than neurotypical peers on PedsQL overall and social QoL but not on the real-time experiences collected with ESM. Among neurotypical adolescents, we found significant associations between the Social Functioning score of the PedsQL and various aspects of real-time social experiences recorded with ESM. For autistic adolescents, only the real-time experience of 'loneliness' during social engagement was associated with Social Functioning on the PedsQL. CONCLUSIONS: The retrospective PedsQL does not entirely capture the real-time QoL via ESM. However, relying solely on ESM may overlook situations where participants opt out or could not complete surveys. Thus, using both retrospective and real-time assessments to examine QoL among autistic adolescents is recommended.

A 3-Year Experience with Tildrakizumab Treatment for Patients with Plaque Psoriasis in Clinical Practice.

INTRODUCTION: The efficacy and safety of tildrakizumab for the treatment of plaque psoriasis were demonstrated by randomized clinical studies, but the reappraisal of prolonged experiences in the clinical practice helps to optimize the use of this biologic drug. The aim of this study was to evaluate the long-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the real world. METHODS: This is a long-term retrospective observational study in a real-life setting. Overall, 136 adult patients with moderate-to-severe plaque psoriasis and treated with tildrakizumab were included. RESULTS: One hundred percent reduction of Psoriasis Area Severity Index (PASI100) was reached by 21.7% of patients at 4 weeks of therapy and by 51.2% at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We could not confirm a previous observation that patients naïve to biologic had a better response, but we observed that those with a short history of psoriasis had a higher probability of 90% PASI reduction (PASI90) or PASI 100 within 36 weeks, suggesting that early treatment could be useful. CONCLUSION: This long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years.

Safety and effectiveness of vortioxetine in patients with major depressive disorder in a real-life clinical setting in India: results from an interventional, flexible-dose study.

OBJECTIVE: Vortioxetine has demonstrated safety and efficacy in improving symptoms of major depressive disorder (MDD), including overall functioning in real-world settings. This is the first study in a real-life clinical setting in India to evaluate effectiveness and safety of vortioxetine in patients with MDD. METHODS: This interventional, open-label study consisted of a 12-week treatment period with flexible doses of vortioxetine (5-20 mg/day) in adult patients (aged 18-65 years) with a confirmed MDD diagnosis. Effectiveness outcomes included change from baseline to week 12 in Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression-Severity (CGI-S) scores, along with CGI-Improvement (CGI-I) scores at week 12, using a mixed model for repeated measures. Adverse events (AEs) were recorded for safety outcome assessments. RESULTS: Of 395 patients who received vortioxetine, 42.3% were women mean age 38.9 years; 322 patients completed the study. Significant improvement in depressive symptoms was observed in change from baseline to week 12 least squares (LS) mean (SE) PHQ-9 total score (-9.36 [0.276]; p<.0001) and CGI-S score (-2.14 [0.065]; p<.0001). LS mean (SE) CGI-I score showed significant improvement at week 12 (1.93 [0.067]; p<.0001). Subgroup analysis across age, sex, disease severity, and body mass index showed significant improvements in depression symptoms and severity. A total of 35.4% (n = 140) of patients experienced treatment-emergent AEs (mostly mild-moderate); nausea and pruritus were the most frequent (6.6%, n = 26 each). CONCLUSION: Safety and effectiveness of vortioxetine in improving symptoms of MDD over a 12-week period was demonstrated in a real-life clinical setting in India. CLINICAL TRIAL REGISTRATION INFORMATION: Open-label, flexible-dose study of vortioxetine in patients with major depressive disorder in India; Clinical Trials.gov ID: NCT04288895; https://www.clinicaltrials.gov/study/NCT04288895.

Evaluation of a New Telemedicine System for Early Detection of Cardiac Instability in Patients With Chronic Heart Failure: Real-Life Out-of-Hospital Study.

BACKGROUND: For a decade, despite results from many studies, telemedicine systems have suffered from a lack of recommendations for chronic heart failure (CHF) care because of variable study results. Another limitation is the hospital-based architecture of most telemedicine systems. Some systems use an algorithm based on daily weight, transcutaneous oxygen measurement, and heart rate to detect and treat acute heart failure (AHF) in patients with CHF as early on as possible. OBJECTIVE: The aim of this study is to determine the efficacy of a telemonitoring system in detecting clinical destabilization in real-life settings (out-of-hospital management) without generating too many false positive alerts. METHODS: All patients self-monitoring at home using the system after a congestive AHF event treated at a cardiology clinic in France between March 2020 and March 2021 with at least 75% compliance on daily measurements were included retrospectively. New-onset AHF was defined by the presence of at least 1 of the following criteria: transcutaneous oxygen saturation loss, defined as a transcutaneous oxygen measurement under 90%; rise of cardiac frequency above 110 beats per minute; weight gain of at least 2 kg; and symptoms of congestive AHF, described over the phone. An AHF alert was generated when the criteria reached our definition of new-onset acute congestive heart failure (HF). RESULTS: A total of 111 consecutive patients (n=70 men) with a median age of 76.60 (IQR 69.5-83.4) years receiving the telemonitoring system were included. Thirty-nine patients (35.1%) reached the HF warning level, and 28 patients (25%) had confirmed HF destabilization during follow-up. No patient had AHF without being detected by the telemonitoring system. Among incorrect AHF alerts (n=11), 5 patients (45%) had taken inaccurate measurements, 3 patients (27%) had supraventricular arrhythmia, 1 patient (9%) had a pulmonary bacterial infection, and 1 patient (9%) contracted COVID-19. A weight gain of at least 2 kg within 4 days was significantly associated with a correct AHF alert (P=.004), and a heart rate of more than 110 beats per minute was more significantly associated with an incorrect AHF alert (P=.007). CONCLUSIONS: This single-center study highlighted the efficacy of the telemedicine system in detecting and quickly treating cardiac instability complicating the course of CHF by detecting new-onset AHF as well as supraventricular arrhythmia, thus helping cardiologists provide better follow-up to ambulatory patients.

Real-Life Study on the Efficacy and Tolerance of a Preservative-Free Surfactant-Free Latanoprost Eye Drop in Patients with Glaucoma.

INTRODUCTION: The purpose of this study is to assess the real-life efficacy and tolerance of a new preservative-free, surfactant-free latanoprost (PFSF-LAT) formulation. METHODS: Retrospective, multicentre, non-comparative, observational study in patients with ocular hypertension or open angle glaucoma, naïve or non-naïve to previous intraocular pressure (IOP)-lowering treatment, and treated for at least 3 months with the study eye drop. IOP for worse eye, ocular signs and symptoms, and concomitant use of artificial tears were collected at study drug initiation and at last visit under treatment. Reasons for discontinuing the study eye drop (if relevant) and investigators' satisfaction were also assessed. RESULTS: In the per protocol population (103 eyes; 63 naïve, 39 switched, 1 not classified because of missing data), IOP decreased significantly (p < 0.001) from 21.6 ± 5.0 mmHg at baseline to 16.1 ± 3.5 mmHg at the end of the study (mean reduction of - 5.5 ± 4.6 mmHg; - 25.5%). IOP in naïve patients was significantly improved, with a mean reduction of 7.1 mmHg (- 30.7%), which was within expected latanoprost IOP-lowering effect. Interestingly, in previously treated patients, switching to PFSF-LAT also allowed for a further 2.9 mmHg decrease in IOP (p < 0.001). The incidence of ocular side effects at study initiation was significantly (p < 0.001) reduced from 31.1% to 11.3% in the overall population, and from 65.0% to 7.5% in switched patients. This included conjunctival hyperaemia and superficial punctate keratitis (from 42.5% to 2.5% and from 37.5% to 2.5% in switched patients, respectively). According to investigators, tolerance and efficacy of the study eye drop were satisfactory or very satisfactory in 98.1% and 83.2% of patients, respectively. CONCLUSION: PFSF-LAT is an efficient treatment for patients with glaucoma with an improved tolerance profile. It can be considered as initial therapy in naïve patients or in patients with poor ocular tolerance to previous IOP-lowering eye drops.

Focusing on positive listening experiences improves hearing aid outcomes in first-time hearing aid users: a randomized controlled trial.

OBJECTIVE: The objective of this study was to investigate whether positive focus (PF), an intervention that asks hearing aid users to focus on positive listening experiences, improves hearing aid outcomes for first-time hearing aid users. DESIGN: The participants were randomised into a control or PF group. They were fitted with hearing aids and followed for six months after fitting. The PF group was asked to report positive listening experiences in their daily life via an app. Participants in both groups were periodically prompted by the app to answer questionnaires about hearing aid satisfaction and benefit. Two follow-up visits at approximately one and six months were performed. STUDY SAMPLE: 20 adult first-time hearing aid users in the control and 18 in the PF group. RESULTS: Hearing aid satisfaction and benefit scores were significantly better in the PF group, already at two weeks and throughout the six months. In the PF group, the hearing aid outcomes were positively correlated with the number of submitted positive reports. CONCLUSIONS: These results point to the importance of asking first-time hearing aid users to focus on positive listening experiences and to reflect upon them. This can lead to improved short- and long-term hearing aid outcomes.

The use of biologics in patients suffering from chronic rhinosinusitis with nasal polyps - a 4-year real life observation.

PURPOSE: Antibody therapy for chronic rhinosinusitis with nasal polyps (CRSwNP) has been established in Germany since 2019. With limited long-term data on biologic treatment for CRSwNP, we conducted a comprehensive evaluation of our 4-year data. This monocentric study aims to assess the real-world effects of this treatment on clinical course, quality of life, treatment adherence, biologic switching, dual therapy, and comorbidities. METHODS: We retrospectively analysed biologic therapy data in patients with severe chronic rhinosinusitis with nasal polyps. 191 patients with CRSwNP treated with Dupilumab, Mepolizumab, or Omalizumab were observed for up to 4 years in a real-life setting. RESULTS: We observed clear symptom improvements with few side effects. No loss of efficacy or tolerability was noted during the 4-year period. Patients reported high satisfaction compared to previous therapies, with overall improved quality of life. Revision surgery or oral steroid use during biologic therapy was rare. Some patients prolonged injection intervals or discontinued steroid nasal spray. Biologic switching occurred infrequently due to side effects or inadequate response and was generally well tolerated. Many patients reported additional positive effects such as asthma or allergy symptom improvement and reduced medication intake. CONCLUSION: In summary, this study confirms the potency and tolerability of biologics for CRSwNP treatment, with sustained efficacy over 4 years. Biologic switching is a viable option for inadequate response or intolerable side effects. Therapy positively impacts Th2 comorbidities, corticosteroid requirements, surgery need, and overall compliance remains high. CLINICAL TRIAL REGISTRATION: Project No.: 22-0802. Registry name: Biologika bei Patient*innen mit chronischer Sinusitis mit Nasenpolypen.

Mothership versus Drip-and-Ship for stroke in a rural area: A French prospective observational study.

BACKGROUND: The availability of mechanical thrombectomy (MT) is limited. Thus, there are two paradigms for patients living closer to a primary stroke center (PSC) than a comprehensive stroke center (CSC) capable of MT: "Mothership" (direct referral to a CSC) and "Drip-and-Ship" (referral to a PSC for imaging and thrombolysis and transfer to a CSC for thrombectomy or monitoring). We aimed to compare the prognosis of patients at three months between the two paradigms in a rural area. MATERIALS: From September 2019 to March 2021, we prospectively included patients living closer to a PSC than the one CSC, regardless of the type of stroke or reperfusion treatment. The proportion of patients with a good functional outcome (Rankin≤2) at three months was compared between the two initial orientations for all patients and for subgroups: patients with ischemic stroke and patients treated by MT. RESULTS: Among the 206 patients included, 103 were admitted directly to the CSC (82.5% had an ischemic stroke and 24.3% a MT) and 103 initially admitted to a PSC and then transferred to the CSC (100% had an ischemic stroke and 52.4% a MT). The proportion of patients with a good outcome was comparable between the two groups (54.5% vs. 43.7%, P=0.22). Among the 79 patients who underwent MT, the prognosis at three months was better in the Mothership group (49.3% vs. 15.3%, P=0.01). CONCLUSION: The functional prognosis is comparable between Mothership and Drip-and-Ship paradigms in our setting, despite a trend towards a better prognosis for the Mothership. As has been shown in urban settings, the mothership paradigm also leads to a better prognosis for patients treated with MT in a rural setting.

Aspergillus niger prolyl endopeptidase in celiac disease.

We comment here on the article by Stefanolo et al entitled "Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet", published in the World Journal of Gastroenterology. Celiac disease is a well-recognized systemic autoimmune disorder. In genetically susceptible people, the most evident damage is located in the small intestine, and is caused and worsened by the ingestion of gluten. For that reason, celiac patients adopt a gluten-free diet (GFD), but it has some limitations, and it does not prevent re-exposure to gluten. Research aims to develop adjuvant therapies, and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease (AN-PEP), which is able to degrade gluten in the stomach, reducing its concentration in the small intestine. The study found a high adherence to the GFD, but did not address AN-PEP as a gluten immunogenic peptide reducer, as it was only tested in patients following a GFD and not in gluten-exposing conditions. This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.

Reversion of chronic to episodic migraine in working age and botulinum toxin-resistant patients treated with fremanezumab: A real-life study.

OBJECTIVES: The objectives of this real-life study were to analyze the reversion of chronic migraine (CM) to episodic migraine (EM) with fremanezumab, evaluate its benefit on the symptomatology, and determine the influence of possible clinical features on the reversion. BACKGROUND: The clinical manifestations of CM have a high impact on the quality of life of patients, and monoclonal antibodies such as fremanezumab are used as prophylactic treatment. METHODS: Diagnosed CM patients treated for at least 3 months with monthly fremanezumab were interviewed. The data to assess efficacy were before treatment and at the time of the interview: monthly headache days (MHDs), daily headache hours (DHHs), monthly symptomatic medication days (MSMDs), percentage of patients with symptomatic medication overuse (SMO), and pain intensity with the numerical rating scale (NRS) score. Possible predictors of reversion were analyzed: percentage of patients treated for at least 12 months, hypertension, diabetes mellitus, depression, anxiety, symptomatic control with non-steroidal anti-inflammatory drugs (NSAIDs), triptans or both, and amitriptyline prophylaxis. RESULTS: A total of 54 patients were included, of whom 40 (74.1%) were converters to EM. There were significant improvements in converters compared to pre-treatment in MHDs (28.0 vs. 5.0 days), as well as on the variables DHHs, MSMDs, and SMO. The percentage of erenumab failures was significantly higher in non-converters than in converters, as was the percentage of patients with anxiety. CONCLUSIONS: High reversion from CM to EM was achieved with fremanezumab and notable symptomatological improvement, establishing previous failure to erenumab and anxiety as possible detrimental factors for reversion.

Impact of pembrolizumab treatment duration on overall survival and prognostic factors in advanced non-small cell lung cancer: a nationwide retrospective cohort study.

Background: The efficacy of front-line pembrolizumab has been established in studies that limit treatment duration to 2 years, but decision to stop pembrolizumab after 2 years is often at physician's discretion. ATHENA is a retrospective cohort study using a comprehensive administrative database aimed firstly at exploring the optimal duration of pembrolizumab and secondly real-life prognosis factors in patients with advanced non-small cell lung cancer (NSCLC). Methods: Using the French National Health Insurance database (SNDS), we identified patients with incident lung cancer in France from 2015 to 2022. Treatments and patients' characteristics were extracted or inferred from hospital, outpatient care, pharmacy delivery reports. The duration's hazard ratio (HR) was estimated with Cox model weighted by inverse of propensity score to account for confounding. Prognostics factors in first line population were identified with Cox model selected by a LASSO procedure. Findings: 391,106 patients with lung cancer were identified, of whom 43,359 received up-front pembrolizumab for an advanced disease. There were 67% (29,040/43,359) of male and the median age at diagnosis was 65 years old. After a median follow-up time of 25.9 months (min-max, [0-97.6]), the median overall survival (OS) after pembrolizumab initiation in first line was 15.7 [CI 95, 15.3-16.0] months. In multivariable analysis, several covariables were independently associated with worse OS, including male sex with chemo-immunotherapy, age, hospital category, high deprivation index, inpatient hospitalization for first pembrolizumab, and history of diabetes, diuretic, beta blocker, painkiller prescription. At landmark time of 29 months after pembrolizumab initiation, continuation beyond 2 years was not associated with better OS than a fixed 2-year treatment, HR = 0.97 [0.75-1.26] p = 0.95. Interpretation: This study supports the notion that stopping pembrolizumab after 2 years could be safe for patients with advanced NSCLC. However, because observational studies are prone to confounding and selection bias, causality cannot be affirmed. Funding: This study did not receive any specific grant.

Feasibility and Safety of the "One-Week Breast Radiation Therapy" Program.

AIMS: FAST-Forward and UK-FAST-trials have demonstrated the safety and efficacy of five-fraction breast adjuvant radiation therapy (RT) and have become the standard of care for selected early breast cancer patients. In response to the additional burden caused by the COVID-19 pandemic, we implemented "One-Week Breast RT," an innovative program delivering five-fraction whole breast RT in a complete 5-day workflow. The primary objective of this study was to demonstrate the feasibility and safety of our program. The secondary objective was to evaluate cosmetic results. MATERIAL AND METHODS: A total of 120 patients treated from February 2021 to March 2022, received whole breast RT without lymph node irradiation nor boost, with 26 Gy in five fractions over one week. Inverse planning with restricted optimization parameters offers systematic deep inspiration breath-hold aimed to provide treatment plans compliant with FAST-Forward recommendations. Toxicity and cosmetic evaluations were prospectively registered prior (pre-RT), at the end (end-RT), and 6 months after RT (6 months) based on Common Terminology Criteria for Adverse Events v. 4.03 and Harvard scale. RESULTS: With a median age of 70 years (interquartile range (IQR): 66-74) and a median follow-up of 6 months (IQR: 6.01-6.25), most patients (93.3%) completed their RT in one week from baseline to the end of the treatment consultation. The most common acute toxicities (at end-RT) were skin-related: radio-dermatitis (72%), induration (35%), hyperpigmentation (8%), and breast edema (16%). The rate of radio-dermatitis decreased from end-RT to 6 months (71.7% vs 5.4%, P< 0.001). No patient experienced grade ≥3 toxicity. At 6 months, cosmetic results were generally good or excellent (94.1%). CONCLUSION: This study confirms the feasibility and acute safety of the "One-Week Breast RT" in real life. Favorable toxicity profiles and good cosmetic outcomes are in line with FAST-Forward results. A prospective national cohort, aimed at decreasing treatment burden, maintaining safety, efficacy, and improving RT workflow efficiency with longer follow-up is ongoing.