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Procedural success following tricuspid transcatheter edge-to-edge repair (TEER) has been defined variably over time; however, the consequences of achieving a tricuspid regurgitation (TR) grade of 0/1+ are still unclear. This study aimed to assess the predictors and prognostic impact of achieving TR 0/1+ after TEER and its role in clinical events. This multicenter registry included patients undergoing tricuspid TEER in 15 Spanish centers from June 2020 and May 2023. Patients were categorized into the following groups based on the TR grade after procedure: optimal (0/1+), acceptable (2+), and not acceptable (≥3+). The primary endpoint was the 1-year composite of all-cause death, heart failure hospitalization, and tricuspid reintervention. Secondary endpoints included each component of the primary endpoint assessed separately, NYHA functional class, and TR grade at follow-up. Among 280 enrolled patients, 120 (42.9%) had residual TR 0/1+, 111 (39.6%) had residual TR 2+, and 49 (17.5%) had residual TR ≥3+. Patients with TR 0/1+ experienced lower rates of the primary endpoint (13% vs 20% vs 31%; log-rank P = 0.036). Residual TR ≥3+ was an independent predictor of primary endpoint (HR: 2.277; P = 0.044). Higher rates of NYHA functional class I or II and sustained TR reduction were seen in the TR 0/1+ group (P < 0.001 for both). A small coaptation gap and absence of septal leaflet tethering were independent predictors of achieving TR 0/1+. An optimal procedural result after TEER might be associated with improved outcomes. TR coaptation gap and leaflet restriction may aid in assessing suitability for TEER. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To report our real-world experience using intravitreal faricimab, a novel anti-vascular endothelial growth factor (anti-VEGF) therapy, in eyes with neovascular age-related macular degeneration (nAMD) previously treated with other anti-VEGF therapy. Patients and Methods: A retrospective, single-center study of previously treated nAMD eyes treated with faricimab. Results: In 88 eyes (73 patients), mean baseline best-corrected visual acuity (BCVA) was 20/63 (range 20/20 to CF) with mean anti-VEGF injection interval of 6.1 + 2.0 weeks. Mean baseline central subfield thickness (CST) was 291 + 73 μm. During mean follow-up of 30.1 + 13.5 (range 7.0 to 50.3) weeks on faricimab, the eyes received an average of 5.1 + 2.4 injections (range 1 to 11). Mean BCVA remained at 20/63 (p=0.11), but injection interval increased to 7.4 + 2.6 weeks (p< 0.001), and CST decreased to 262 + 63 μm (p< 0.001). Multiple linear regression analysis revealed that higher number of different anti-VEGF drugs used at baseline was associated with a lower decrease in CST on faricimab (p=0.04) while total number of anti-VEGF injections at baseline (p=0.56) and time on faricimab (p=0.68) were not associated. Faricimab was discontinued in 23 eyes (26.1%), including 8 eyes for poor response, 2 eyes for persistent new floaters and 4 eyes for new vision decrease which reversed after stopping faricimab. Conclusion: In previously treated nAMD eyes, intravitreal faricimab was associated with increased mean treatment interval and decreased CST but no improvement in mean BCVA. The benefit of faricimab on CST reduction may be diminished in eyes previously treated with multiple different types of anti-VEGF therapy. [ABSTRACT FROM AUTHOR]

• Dual staining p16/Ki67 (DS) cytology is an alternative triage method of HPV+women. • This is a retrospective analysis of real-world experience with DS. • DS provided a better risk stratification than conventional PAP cytology. • DS positivity as referral criterion for colposcopy reduces of the referrals. • DS cytology may support the extension of the follow-up interval. Organized cervical cancer (CxCa) screening is the most effective secondary prevention method to decrease the disease incidence and mortality. Screening for infection with 14 high-risk HPV genotypes (hrHPV) is recommended as primary screening test. Since only ca. 6 % of HPV-positive (HPV+) women will develop a high-grade lesion in 5 years, triage is critical for risk stratification and management of colposcopy resources. Dual staining (DS) p16/Ki67 cytology is an alternative to Papanicolau cytology (PAP) for triage of HPV+women, with potential improvements in sensitivity and specificity, and optimization of colposcopy referrals. To compare PAP vs DS cytology in terms of (i) optimization of referrals for colposcopy and (ii) risk stratification to better define the follow-up interval. Retrospective analysis of the CxCa screening database of Centro Hospitalar Universitário de Coimbra (CHUC), one of the centralized diagnostic laboratories for the CxCa screening program of the central region of Portugal, between July 2019 and May 2023. At CHUC, since July 2019, all samples from hrHPV+women have been triaged with liquid PAP and tested with DS cytology. At baseline (1032 HPV+women), 1028 women were tested with DS: 739 women were DS negative (DS-) [70.7 % with normal PAP cytology (NILM) and 29.3 % with abnormal PAP cytology (ASC-US+)], and 289 were DS positive (DS+) (1.1 % NILM and 98.6 % ASC-US+). DS positivity as referral criterion for colposcopy instead of ASC-US+would have reduced the number of colposcopies by 39.4 % overall and by 48.3 % for other 12 hrHPV, while improving the number of colposcopies per HSIL (3.9 vs. 2.4 overall and 4.9 vs. 2.9 for other 12 hrHPV). In this cohort, if the follow-up interval for women positive for other 12 hrHPV+and DS- would have been extended from 1 to 3 years, 799 follow-up consultations, 799 HPV re-tests, and 277 colposcopies (−64.7 %) would have been avoided, with an overall risk of missed HSIL lesions of 2.2 %. Triage with DS allows the optimization of colposcopy referrals and a safe extension of the follow-up interval to 3 years for other 12 hrHPV+/DS- women, eliminating the need for annual re-testing for many women. [ABSTRACT FROM AUTHOR]

Introduction: Treatment for relapsed/refractory AL amyloidosis (AL) is an unmet need. The safety and efficacy of belantamab mafodotin (BLM) in multiple myeloma are known, whereas in AL data are limited. Methods: We report a multi-center cohort of AL patients receiving BLM, and review all previous data on BLM therapy in AL. Results: Twelve patients with a median of 3 (range 2–9) prior lines of therapy were included. The overall hematological response rate (ORR) was 75% (9/12), including 5 complete responses. Six of the 10 evaluable patients had organ responses. The median event-free survivals/overall survivals were 22.3 and 28.8 months, respectively. Grade 3 toxicities were mostly infections and keratopathy, occurring in 7/12 (58%). Hematological toxicities were rare. No grade 4/5 toxicities occurred. The review of the previous series reveals BLM provides an ORR of 60–83% with similar rates of corneal toxicity. Conclusion: BLM, being an off-the-shelf therapy, with acceptable toxicity even in frail patients, may be a valuable option in AL, with a high ORR, and a signal for durable responses and high-quality organ responses. [ABSTRACT FROM AUTHOR]

Summary: Idecabtagene vicleucel (ide‐cel), a chimeric antigen receptor T‐cell therapy targeting B‐cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real‐world registry‐based multicentre observational study in 11 French hospitals to evaluate ide‐cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR‐T registry. Of these, 159 patients (90%) received ide‐cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression‐free survival (PFS) from the ide‐cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra‐medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA‐targeted immunoconjugate or T‐cell‐redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide‐cel's feasibility, safety and efficacy in real‐life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection. [ABSTRACT FROM AUTHOR]

• Heaviest treated patients in the real world with onasemnogene abeparvovec. • Liver impairment and only transitory improvement in functional outcomes. • Risk-benefit considerations is required in treating older and heavier SMA patients. Spinal muscular atrophy (SMA) is an autosomal recessive disorder with progressive muscle atrophy and weakness, caused by biallelic mutations in the survival motor neuron 1 (SNM1) gene. Onasemnogene abeparvovec (OA) is an approved gene replacement therapy for patients with SMA. We report on two patients with SMA type 1, weighing 20 kg, previously treated with Nusinersen, who received OA infusion at 7 years of age. To our knowledge, these two patients are the heaviest treated in the real-world and we describe their different courses after gene therapy, including liver impairment requiring long-term steroid treatment and additional immunosuppression, with only transitory improvement in functional outcomes. Our cases illustrate how careful risk-benefit consideration is required in treating older and heavier SMA patients with OA, especially in view of the multiple treatment choices available for older patients with SMA. [ABSTRACT FROM AUTHOR]

Introduction: CD20-depleting therapies are a real milestone in the treatment of multiple sclerosis (MS). This study examined the ocrelizumab (OCR) use in patients with primary progressive (PP) and relapsing remitting (RR) MS, also evaluating the predictors of treatment response. Methods: Patients with MS treated with OCR between 2017 and 2022 were included, and OCR use trends examined. The patients' characteristics were assessed at baseline and after 24 months of OCR to assess the NEDA-3 status. Results: This study included 421 patients: 33 (7.9%) with PP and 388 (92.1%) with RR MS. Among these, 67 (17.3%) were naïve, while switchers from first- and second-line disease-modifying therapies (DMTs) were 199 (51.3%) and 122 (31.4%), respectively. An increasing trend in OCR use was reported. For six patients treated with rituximab, OCR was chosen to improve tolerability; for 390 switcher patients, the choice was due to ineffectiveness; and for 25, as an exit strategy from natalizumab due to JC virus positivity. NEDA-3 status was calculated for subjects exposed to 24 months of OCR and was achieved by 163/192 (84.9%) RR patients and 9/16 (56%) PP patients, with younger age (p = 0.048) and annualized relapse rate in the year previous to OCR (p = 0.005) emerging as determinants. For the 25 patients who switched to OCR after natalizumab, no clinical or MRI activity after 12 months was reported. Conclusion: OCR has been confirmed to be a highly efficacious option for patients with PP and RR MS, even proving to be a valid exit strategy for natalizumab. [ABSTRACT FROM AUTHOR]

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Background: Dupilumab is a monoclonal antibody approved for the treatment of moderate-to-severe atopic dermatitis (MtS-AD). Various clinical trials have established the effectiveness and safety of dupilumab for the treatment MtS-AD; however, the real-world experiences of patients treated with dupilumab with malignancy and other comorbidities are lacking. Objective: To assess the real-life effectiveness and safety of dupilumab in the treatment of MtS-AD within Canadian adult patient population, including those with other significant comorbidities such as malignancy. Methods: In this retrospective study, records of adult patients diagnosed with MtS-AD, with a Physician Global Assessment (PGA) score of 3 or 4, and treated with dupilumab for 52 weeks were reviewed and collected. Results: A total of 155 adult patients with atopic dermatitis (AD) treated with dupilumab were included in the study. Asthma was the most common comorbidity. One hundred twenty-three (80%) patients received either phototherapy and/or at least 1 systemic agent (methotrexate and cyclosporine) before initiation of dupilumab. PGA score of 0 or 1 was achieved by 64% of patients at week 52. Adverse effects including injection site reactions, ocular surface disease, facial and neck redness, and arthropathy occurred in 6%, 10%, 8%, and 6% of patients, respectively. Three patients continued receiving dupilumab throughout pregnancy, all maintaining PGA score of 0 or 1 with no impact on pregnancy, delivery, or the newborn. Twelve patients with prior or active malignancy were included, with no reported negative impact on malignancy. Conclusion: Dupilumab is an effective and safe option for patients with AD in real life, including patients with malignancy and other medical comorbidities.

Abstract Background Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice. Methods This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches. Results Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group. Conclusion Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup.

Ceftazidime-avibactam (CAZ-AVI) has been launched in Asian countries for five years, local real-world data about infections, patient characteristics, efficacy, and safety of CAZ-AVI in gram-negative bacterial infection is limited. We conducted a multicenter, retrospective cohort study to investigate the clinical characteristics, microbiology, and outcomes of patients treated with CAZ-AVI for gram-negative bacterial infection in Taiwan. Among the 472 patients treated by CAZ-AVI, 44.9% had respiratory tract infections, 21.2% had complicated urinary tract infections, 12.5% had complicated intra-abdominal infections, and 9.5% had primary bacteremia. Most patients receiving ceftazidime/avibactam in Taiwan are older, have a high SOFA score (mean 8.4), and have a high Charlson Comorbidity Index score (75.1%). 90% (425/472) of CAZ-AVI were used as targeted therapy for pathogens including Klebsiella pneumoniae (304/472, 64.4%), Pseudomonas aeruginosa (84/472, 17.8%), Escherichia coli (39/472, 8.3%), and Enterobacter spp. (11/472, 2.3%). The overall clinical success rate is 58.1%, and the in-hospital mortality rate is 41.1%. The logistic regression model revealed a significantly higher clinical success rate for those who initiated CAZ-AVI within 24 - 48 hours than those receiving CAZ-AVI > 72 hours. The multivariate logistic regression analysis revealed that receiving immunomodulators, higher SOFA score, and Enterobacter spp. infection were the significant factors associated with in-hospital mortality.

Simple Summary: Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions regarding effectiveness, safety, and cost of therapy. For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Bevacizumab re-mains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Overall, it is estimated that more than 3,500,000 patients have received Bevacizumab as part of systemic oncologic treatment. Bevacizumab and its biosimilars are currently marketed in over 130 countries. Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions with regard to effectiveness, safety, and cost of therapy. Methods: For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Results: The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60–65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8–9.6), and the median OS was 13.2 months (95% CI 11.5–14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Conclusions: Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy. [ABSTRACT FROM AUTHOR]

Background: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice. Methods: This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches. Results: Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group. Conclusion: Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup. [ABSTRACT FROM AUTHOR]

Objective: ESKALE is a French, multicentre, observational study of adults with treatment-resistant depression (TRD) treated with esketamine. This interim analysis describes baseline demographic and clinical characteristic evolution in patients included and treated from early access program to post-marketing launch. Methods: Data were collected from medical records and included patient characteristics, disease history at esketamine initiation, use of neurostimulation, the patient's care pathway, and the number of antidepressant treatment lines prescribed prior to esketamine initiation. Descriptive statistics were used for each cohort: the early access program 'Temporary Authorisation for Use' (ATU), post-ATU, and post-launch cohorts. Results: The overall ESKALE cohort (N = 160 included; n = 157 treated with esketamine; average age 49.0 years; 66.2% female) demonstrated moderate-to-severe depression according to clinical assessment and a mean Montgomery-Åsberg Depression Rating Scale score of 32.6 (8.0); however, severity, subtype, and comorbidities were heterogeneous across the cohorts. Earlier use of esketamine and prior to alternative treatments occurred during the later cohorts. Conclusion: These findings demonstrated a high burden of TRD in these patients and that esketamine is used in TRD treatment regardless of their disease severity, subtype, or existing comorbidities. These results also suggest that esketamine is potentially a clinically useful alternative treatment, particularly with healthcare professionals gaining greater familiarity with and easier access to esketamine. KEY POINTS: ESKALE is a long-term, French, multicentre, observational study based on secondary data in adult patients with treatment-resistant depression (TRD) who initiated esketamine treatment in one of three mutually exclusive cohorts: the Temporary Authorisation for Use (ATU), post-ATU, and post-launch cohorts. ESKALE is one of the largest European real-world studies investigating the profiles of more than 150 patients and their treatment with esketamine before and after marketing authorisation. A majority of patients had moderate to severe TRD, with multiple treatment failures with medications and/or neurostimulation prior to esketamine initiation. Esketamine nasal spray administration was undertaken more frequently in an outpatient setting, with the post-administration period monitoring being undertaken mostly by nurses. Esketamine was used in patients with TRD in real-world conditions regardless of their disease severity and subtype or existing comorbidities. These results highlight both the need for an effective treatment for TRD and the adoption of esketamine by multidisciplinary teams that are involved in esketamine prescription and administration. [ABSTRACT FROM AUTHOR]

Few data are known regarding the use of interim positron emission tomography (iPET) after the first two cycles (iPET2) of chemotherapy in treatment‐naïve classical Hodgkin lymphoma (cHL) in routine clinical practice, and about the real‐life adoption of intensification strategies for iPET positive patients. We conducted a multicenter retrospective study on cHL to investigate the use of iPET in the real‐life setting, its prognostic role and outcomes of patients early shifted to intensification. Six hundreds and forty‐one patients were enrolled (62% had advanced stage). iPET2 was positive in 89 patients (14%) including 8.7% and 17% early and advanced stage patients, respectively (p = 0.003). Among iPET 2 positive cases treatment was immediately modified in 19 cases; in 14 cases treatment was modified after an additional positive iPET4. Overall 56 iPET2 positive patients never received intensified therapies. Most frequently used intensified therapy was autologous stem cell transplantation followed by BEACOPP. After a median follow‐up of 72 months, the 5‐year progression‐free survival (PFS) was 82% with iPET2 positive patients showing a worse PFS compared with iPET2 negative cases: 31% versus 85%. Focusing on advanced stage patients with a positive iPET2, the 5‐year PFS was 59% for patients shifted to intensified therapy at any time point versus 61% for patients who never received intensified therapy. Our study confirmed the higher curability of naïve cHL patients in a real‐world setting, and the prognostic role of iPET2 in this setting. A poor adherence to response‐adapted strategy which however did not translate into a difference in patient outcomes. [ABSTRACT FROM AUTHOR]

Management of pediatric epilepsies poses unique challenges around diagnosis, treatment options, comorbidities, and the potential for these factors to interact with processes in the developing brain. In pediatric patients, broad-spectrum antiseizure medications (ASMs) with minimal potential for adverse events (AEs) and limited impact on cognition and behavior are preferred. Perampanel is a first-in-class ASM with broad-spectrum efficacy, a tolerable safety profile, minimal negative impact on cognitive function, and other features that make it a viable treatment option in this patient population. However, evidence and experience of its use in pediatric patients are less extensive than in adult patients. Experts in pediatric epilepsy across the region convened at a series of meetings to discuss the use of perampanel in pediatric patients, including dose optimization, AE prevention and management, and considerations in particular groups. This article summarizes key evidence for perampanel in the pediatric population and consolidates the experts' recommendations for using the ASM in managing pediatric epilepsies. [ABSTRACT FROM AUTHOR]

Purpose: The Nutritional Prognostic Score (NPS) is a composite indicator that effectively reflects the preoperative nutritional and inflammation status of patients. Its prognostic value has been extensively confirmed in various types of tumors. Our study aims to investigate the clinical implications of the NPS in the postoperative patients with cholangiocarcinoma (CCA). Patients and Methods: Data on clinicopathological characteristics were collected from CCA patients who underwent radical surgery between 2014 and 2019 at Harbin Medical University Cancer Hospital. NPS was calculated using relevant indicators to categorize the patients, and association of NPS with clinicopathological characteristics and survival outcomes were analyzed. To assess differences in survival rates between different groups, we utilized the Kaplan-Meier method. Independent prognostic risk factors were identified by Cox regression analysis. A CONomogram was created, and its accuracy in survival prediction was evaluated using receiver operating characteristic (ROC) curves. Independent verification was conducted in the validation group. Results: For this study, a cohort of 232 patients was enlisted and subsequently divided into training group (N=162) and validation group (N=70). An evident correlation was detected between NPS and preoperative malnutrition. Patients with higher NPS exhibited a worse overall survival (OS), with 5-year OS rates of 79.1%, 33.1%, and 10.6%. Multivariate analysis revealed that NPS was an independent risk factor for OS in resected CCA patients (P< 0.001). The NPS-based Nomogram was developed to accurately assess the risk of patients. Conclusion: The NPS was identified as a significant risk factor that impacts the prognosis of patients with resected CCA. In order to improve prognosis management, the NPS-based Nomogram has been demonstrated to be a precise and efficient tool. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) is a group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Impaired wound healing is central and can lead to serious clinical complications, deformities, and symptoms with a devastating impact on quality of life (QoL). Dressing changes and wound care are central to the management of EB. Recently Oleogel-S10 (also known as birch bark extract or birch triterpenes) was approved in Europe and the UK for treating EB wounds. This approval was based on data from the EASE phase 3 study, which demonstrated Oleogel-S10 accelerated wound healing, reduced total wound burden, and decreased the frequency of dressing changes in patients with EB. A retrospective analysis of medical records was conducted for up to 24 months in 13 patients with EB treated with Oleogel-S10 through an early access programme in Colombia. Effectiveness was assessed by measuring body surface area percentage (BSAP) and total body wound burden (EBDASI). Tolerability and safety were monitored throughout. This is the first report to evaluate the effectiveness of Oleogel-S10 in clinical practice. The results showed a reduction in percentage of BSA affected, from a mean of 27.3% at baseline to 10.4% at 24-month follow-up, despite treatment interruptions. A reduction in EBDASI skin activity score of − 16.2 (24 months) together with a reduced skin damage index score of − 15.4 (18 months) was also observed. Physicians, patients, and caregivers perceived faster wound closure. Adherence with therapy by patients was good, and patients expressed satisfaction with treatment and reported improvements in self-esteem, productivity, and social interaction. Oleogel-S10 was well tolerated; however, two patients reported worsening wounds related to gauze adherence. Two deaths during treatment interruption were reported and was not considered related to Oleogel-S10. This study supports the effectiveness of Oleogel-S10 in a real-world scenario in a country with scarce resources for the treatment of EB. [ABSTRACT FROM AUTHOR]

Abstract Background There is limited evidence over the real‐life secukinumab survival in psoriatic patients, especially in the long‐term bio‐naïve subjects, and to date biological treatments have been assessed in patients with a chronic and recalcitrant psoriasis. It has been hypothesised that early intensive treatment with biological therapies could decrease pathogenic tissue resident memory (TRm) cells migration and potentially modify the natural course of psoriasis and related comorbidities. Objectives To analyze long‐term secukinumab efficacy, safety and survival, and its predictive factors for psoriasis treatment determining also whether early intervention may result in better outcomes for patients. Methods Bio‐naïve psoriatic patients under treatment with secukinumab (n = 128 patients) in a daily practice setting were analyzed in a retrospective multicentric study and followed up to 8 years. Drug survival rate, efficacy, posology and safety were reported. Results The overall secukinumab survival was 81.9% for an average treatment exposure of 147.9 weeks. The approved posology was the most commonly prescribed regimen (78.7%), and 17.7% could be optimized. An absolut‐PASI ≤3 was reached by 86.6%, 82.6% and 91.7% at the weeks 48,156 and 264, respectively. The incidence of arthritis or psoriasis related comorbidities was low. The response was not influenced by weight, age (>65), gender or the presence of arthritis. No severe adverse events were reported. Conclusions In our bio‐naïve series, the high efficacy and long‐term survival rates observed and the low prevalence of arthritis and comorbidities might suggest that early intervention could contribute to modify the course of the disease, but further studies are needed.

Abstract Background Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, affecting predominantly the fair‐skinned older population exposed to high levels of ultraviolet light. Immune suppression is considered a significant risk factor. With the recent advances in the field of immunotherapy, the treatment paradigm for advanced MCC, traditionally based on chemotherapy, has largely shifted to anti‐PD‐L1 and PD‐1 agents such as avelumab and pembrolizumab, respectively. However, real‐world data remain sparse. The aim of this study was to assess real‐world evidence of the effectiveness of avelumab in a diverse group of patients with MCC in Israel. Methods The electronic databases of five university hospitals in Israel were searched for all consecutive patients with MCC treated with at least one dose of avelumab in 2018–2022. Data on baseline, disease‐related, treatment‐related, and outcome parameters were collected and analyzed. Results The cohort included 62 patients of whom 22% were immune‐suppressed. The overall response rate to avelumab was 59%. The median progression‐free survival was 8.1 months, and the median overall survival, 23.5 months, with no differences between immune‐competent and immune‐suppressed patients. Treatment was well tolerated; any‐grade toxicity developed in 34% of patients, and grade 3–4 toxicity, in 14%. Conclusions Avelumab was found to be effective and safe for the treatment of advanced MCC in a diverse group of patients, including some with immune suppression. Further studies are warranted to evaluate the optimal sequence and duration of treatment and to assess the potential role of avelumab for earlier stages of MCC.

(1) Background: The objective of this analysis was to evaluate the device usage rates and patterns of use regarding Tumor-Treating Fields (TTFields) for patients with malignant pleural mesothelioma (MPM) throughout the US. (2) Methods: We evaluated de-identified data from 33 patients with MPM enrolled in FDA-required HDE protocols at 14 institutions across the US from September 2019 to March 2022. (3) Results: The median number of total TTFields usage days was 72 (range: 6–649 days), and the total treatment duration was 160 months for all patients. A low usage rate (defined as less than 6 h per day, 25%) was observed in 34 (21.2%) months. The median TTFields usage in the first 3 months was 12 h per day (range: 1.9–21.6 h), representing 50% (range: 8–90%) of the potential daily duration. The median TTFields usage after 3 months decreased to 9.1 h per day (range: 3.1–17 h), representing 38% (range: 13–71%) of the daily duration, and was lower than usage in the first 3 months (p = 0.01). (4) Conclusions: This study represents the first multicenter analysis of real-world TTFields usage based on usage patterns for MPM patients in clinical practice. The real-world usage level was lower than the suggested daily usage. Further initiatives and guidelines should be developed to evaluate the impact of this finding on tumor control.

This article presents a research project that set out to better understand the transformational learning of students working with a real-world client in the design thinking process. The article presents a case study involving a partnership between Grand Valley State University and Founders Brewery to design, develop, market, and distribute a "Born and Brewed in Michigan" beer. The project involved a multi-level, qualitative research approach collecting data from Grand Valley State University students in INT-323: Design Thinking to Meet Real-World Needs and employees of Founders who were actively engaged in designing a beer and strategic marketing plan from January 2020 through April 2021. It is argued that students who engage in the design thinking process with a client in a real-world application develop a deeper understanding of theories associated with a course while refining skills that will transfer into their professional and personal lives. This article will provide insight into why design thinking ought to be adapted into interdisciplinary curriculum development. [ABSTRACT FROM AUTHOR]

IntroductionThis study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg) liquid, in 59 children (aged

Background: Despite the increased availability and use of novel therapies for multiple myeloma, early mortality is a pervasive challenge with a significant impact on older adults. Reported rates and predictors of early mortality have varied in the literature, with most studies seldom focusing on community‐treated patients. Methods: In this retrospective cohort analysis of a real‐world electronic health record–derived deidentified database of 7512 patients newly diagnosed with multiple myeloma between January 1, 2011, and February 2, 2021, and treated primarily in US‐based community oncology practices, factors associated with early mortality (defined as death within 6 months after the multiple myeloma diagnosis) were examined with the use of binary logistic regression. Results: The median age was 70 years overall. We found an overall early mortality rate of 8.3%, with 73% of early deaths occurring in those aged ≥70 years. Among the early deaths, only 49 patients (8.7%) had documented disease progression before death (median time to progression, 30 days [interquartile range, 7–53 days]). Baseline factors associated with higher odds of early mortality included an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, Revised International Staging System (R‐ISS) stage III, an age ≥ 70 years, receipt of proteasome inhibitor–doublet therapy, a light‐chain isotype, and the presence of renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Among those aged ≥70 years, ECOG PS ≥ 2 and R‐ISS stage III remained the strongest predictors of early mortality. Conclusions: Early mortality disproportionately affects older adults (aged ≥70 years) with multiple myeloma. Interventions to support this population are needed to reduce disparate survival outcomes. Plain language summary: Factors associated with an increased risk of dying within 6 months (early mortality) of a new diagnosis of multiple myeloma (MM) among 7512 mostly community‐treated patients with MM were evaluated.The early mortality rate was 8.3%; among those deaths, 49 patients (8.7%) had documented evidence of MM progression before death.The risk of early mortality was greatest for older patients (aged ≥70 years) and those with a poor performance status, poor kidney function, a higher disease stage, and light‐chain MM and those receiving two‐drug MM therapies.These findings highlight the need for supportive interventions geared toward older adults with MM. Approximately 9% of adults newly diagnosed with multiple myeloma will die within 6 months. Most early deaths occur in those aged 70 years or older and among those with advanced disease, a poor performance status, and kidney dysfunction and those who have received a proteasome inhibitor‐based doublet regimen. [ABSTRACT FROM AUTHOR]

Purpose: The safety and efficacy of subcutaneous immune globulin 20% (human) solution (Ig20Gly) were demonstrated in clinical trials. However, real-world evidence of the tolerability of self-administered Ig20Gly in elderly patients is lacking. We describe real-world patterns of Ig20Gly usage for 12 months in patients with primary immunodeficiency diseases (PIDD) in the USA. Methods: This retrospective chart review of longitudinal data from 2 centers included patients aged ≥ 2 years with PIDD. Ig20Gly administration parameters, tolerability, and usage patterns were assessed at initial and subsequent 6- and 12-month infusions. Results: Of 47 enrolled patients, 30 (63.8%) received immunoglobulin replacement therapy (IGRT) within 12 months before starting Ig20Gly, and 17 (36.2%) started IGRT de novo. Patients were predominantly White (89.1%), female (85.1%), and elderly (aged > 65 years, 68.1%; median age = 71.0 years). Most adults received at-home treatment during the study, and most self-administered at 6 months (90.0%) and 12 months (88.2%). Across all time points, infusions were administered at a mean rate of 60–90 mL/h/infusion, using a mean of 2 sites per infusion, on a weekly or biweekly frequency. No emergency department visits occurred, and hospital visits were rare (n = 1). Forty-six adverse drug reactions occurred in 36.4% of adults, mostly localized site reactions; none of these or any adverse events led to treatment discontinuation. Conclusion: These findings demonstrate tolerability and successful self-administration of Ig20Gly in PIDD, including elderly patients and patients starting IGRT de novo. [ABSTRACT FROM AUTHOR]

(1) Background: The objective of this analysis was to evaluate the device usage rates and patterns of use regarding Tumor-Treating Fields (TTFields) for patients with malignant pleural mesothelioma (MPM) throughout the US. (2) Methods: We evaluated de-identified data from 33 patients with MPM enrolled in FDA-required HDE protocols at 14 institutions across the US from September 2019 to March 2022. (3) Results: The median number of total TTFields usage days was 72 (range: 6–649 days), and the total treatment duration was 160 months for all patients. A low usage rate (defined as less than 6 h per day, 25%) was observed in 34 (21.2%) months. The median TTFields usage in the first 3 months was 12 h per day (range: 1.9–21.6 h), representing 50% (range: 8–90%) of the potential daily duration. The median TTFields usage after 3 months decreased to 9.1 h per day (range: 3.1–17 h), representing 38% (range: 13–71%) of the daily duration, and was lower than usage in the first 3 months (p = 0.01). (4) Conclusions: This study represents the first multicenter analysis of real-world TTFields usage based on usage patterns for MPM patients in clinical practice. The real-world usage level was lower than the suggested daily usage. Further initiatives and guidelines should be developed to evaluate the impact of this finding on tumor control. [ABSTRACT FROM AUTHOR]

Background: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, affecting predominantly the fair‐skinned older population exposed to high levels of ultraviolet light. Immune suppression is considered a significant risk factor. With the recent advances in the field of immunotherapy, the treatment paradigm for advanced MCC, traditionally based on chemotherapy, has largely shifted to anti‐PD‐L1 and PD‐1 agents such as avelumab and pembrolizumab, respectively. However, real‐world data remain sparse. The aim of this study was to assess real‐world evidence of the effectiveness of avelumab in a diverse group of patients with MCC in Israel. Methods: The electronic databases of five university hospitals in Israel were searched for all consecutive patients with MCC treated with at least one dose of avelumab in 2018–2022. Data on baseline, disease‐related, treatment‐related, and outcome parameters were collected and analyzed. Results: The cohort included 62 patients of whom 22% were immune‐suppressed. The overall response rate to avelumab was 59%. The median progression‐free survival was 8.1 months, and the median overall survival, 23.5 months, with no differences between immune‐competent and immune‐suppressed patients. Treatment was well tolerated; any‐grade toxicity developed in 34% of patients, and grade 3–4 toxicity, in 14%. Conclusions: Avelumab was found to be effective and safe for the treatment of advanced MCC in a diverse group of patients, including some with immune suppression. Further studies are warranted to evaluate the optimal sequence and duration of treatment and to assess the potential role of avelumab for earlier stages of MCC. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Due to the lack of structured and systematic information available, the aim of this study was to describe the epidemiology, diagnosis, healthcare processes, and treatment patterns of hereditary angioedema (HAE) in Mexico. To achieve this, different data sources were consulted regarding medical literature, structured health system databases, and angioedema-specialized physicians (AEP) opinion regarding HAE. Material and methods: A mixed methods approach was conducted in 4 phases: I) systematic literature review (SLR) and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; II) review of national health system (NHS) databases and systematic reports; III) physician survey; and IV) an epidemiologic model. ICD 10 D84.1 encoded records from the NHS were used to estimate the number of patients with HAE attended and treated during 2019. A survey was implemented to increase understanding of the clinical profile and treatments used. Results: A prevalence rate of 0.9/50 000 inhabitants was estimated for 2019. In the same year, an estimated 317 HAE type 1 patients were recorded in the NHS, aged ≥11 years old. The most frequent clinical symptoms were cutaneous edema (67.5%) and abdominal pain (47.9%). A severe episode with laryngeal edema appeared in 27.5% of cases. Acute episodes were mainly moderate to severe (77.0%), with an annual per capita frequency of emergency visits of 7.6 patient-year (range 1–12/patient-year). The main reasons for hospitalization corresponded to laryngeal facial, tongue, and abdominal edemas, representing 73.3% of annual ICD 10 D84.1 reported hospitalizations. The main treatments that patients with HAE received were fresh frozen plasma for acute attacks and danazol for short-term prophylaxis (STP). Conclusions: Despite efforts to make HAE visible, according to this study, cases recognized and treated in the NHS represent only 16.6% of the estimated prevalence.

Chin-Wei Huang,1 Kanokwan Boonyapisit,2 Suryani Gunadharma,3 Josephine Casanova-Gutierrez,4,5 Liri Jin,6 Dinesh Nayak,7 Naoki Akamatsu8,9 1Division of Epileptology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Division of Neurology, Department of Medicine, Siriraj Hospital, Bangkok, Thailand; 3Department of Neurology, Faculty of Medicine, Padjadjaran University, Hasan Sadikin Hospital, Bandung, Indonesia; 4Department of Internal Medicine, Section of Neurology, De La Salle University Medical Center and College of Medicine, Dasmariñas, Philippines; 5Department of Neurosciences, University of the Philippines College of Medicine–Philippine General Hospital, Manila, Philippines; 6Department of Neurology, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 7Department of Neurology, Gleneagles Global Health City, Chennai, India; 8Department of Neurology, International University of Health and Welfare, Narita, Japan; 9Epilepsy and Sleep Disorders Center, Fukuoka Sanno Hospital, Fukuoka, JapanCorrespondence: Naoki Akamatsu, Epilepsy and Sleep Disorders Center, Fukuoka Sanno Hospital, 3-6-45 Momochi-hama, Sawara-ku, Fukuoka, 814-0001, Japan, Tel +81 092-832-1100, Fax +81 092-832-3061, Email akamatsu@iuhw.ac.jpAbstract: Managing epilepsy in the elderly remains complicated largely due to factors related to aging. In this population, management practices are increasingly shifting towards the use of newer-generation anti-seizure medications (ASMs) as they are generally associated with better tolerability and safety profiles than older ones. Perampanel is a new ASM with broad-spectrum efficacy and a favorable safety profile. However, because of the lack of information and experience in its use, the prescription of perampanel has not been optimized in the elderly in the real-world setting in Asia. A group of epilepsy experts across the region convened at a series of virtual meetings to share their experience and discuss recommendations on perampanel use in elderly patients, including dose optimization, considerations with treatment initiation, and strategies to manage adverse events and maximize tolerability. This article summarizes key clinical and real-world evidence for perampanel in the elderly and consolidates the experts’ opinions on optimizing perampanel use in elderly Asian patients with epilepsy, providing practical guidance for clinicians to address challenges related to treatment initiation and tolerance.Keywords: perampanel, elderly, epilepsy, real-world experience, Asia

Background.: Oncology clinical trials demonstrate the risk of cardiotoxicity but are not sufficient to reveal the true risk. In this article, we compared the incidence of cardiotoxicity of crizotinib and osimertinib from a real-world study to data reported by phase 3 clinical trials. Methods.: Data from an ongoing real-world lung cancer study was used as a comparator. Patients were recruited retrospectively with the criteria of being diagnosed with non-small cell lung cancer and having received at least a course of treatment of tyrosine-kinase inhibitor and/or immune check-point inhibitor. Characteristics of the patients who developed cardiotoxicity associated with osimertinib and crizotinib in the real-world lung cancer study were analysed against the inclusion criteria of the corresponding phase 3 clinical trials. Variations of cardiotoxicity incidence among the real-world lung cancer study and clinical trials were investigated. Results.: 18%, n = 37/206, of the patients developed cardiotoxicity. QTc prolongation was the most frequently observed cardiotoxicity (n = 12/37). Osimertinib and crizotinib were the most cardiotoxic agents, each responsible for seven cases of cardiotoxicity. FLAURA, AURA3, PROFILE 1007 and PROFILE 1014 were the included clinical trials for analysis. None of the patients who developed cardiotoxicity in the real-world study would have been eligible to participate in FLAURA and PROFILE 1014 study whereas n = 4/7 and n = 5/7 patients were eligible to participate in AURA3 and PROFILE 1007 trials, respectively. Conclusion.: Although phase 3 clinical trials play an important role in understanding the effectiveness and give insights on side-effect profiles, real-world studies can show the real risk of cardiotoxicity more accurately and realistically. [ABSTRACT FROM AUTHOR]

Introduction: Plaque psoriasis is a chronic skin disease characterised by periods of remission and relapse and associated with considerable burden to patients and healthcare systems. For most patients, standard-of-care is reactive management (RM) with topical therapies, but, more recently, the benefits of proactive management (PAM) have been recognised. This study aimed to gain consensus on real-world use and consumption in RM versus PAM regimens, based on fixed-dose combination calcipotriol and betamethasone dipropionate (Cal/BD) foam which, following a recent update, is currently the only topical therapy for psoriasis with a long-term maintenance regimen in its label. Methods: The modified-Delphi approach was used to gain insights and consensus on real-world views, use and consumption in RM versus PAM from a panel of dermatologists with experience prescribing Cal/BD foam as PAM. The panel included 16 dermatologists, 4 each from France, Germany, Italy, and Spain, and included two questionnaire rounds and a meeting to obtain final consensus. Results: The panel agreed that topicals are burdensome to apply in clinical practice and that poor patient adherence, particularly long-term, is a barrier to effective psoriasis management. The panel advised that, as they prescribe a similar number of cans for RM and PAM over a given period, consumption is not a key driver influencing future decisions to prescribe PAM, even in instances where prescribing differences could be observed. Instead, the panel agreed that patient- and disease-related factors better determine patient suitability for PAM. Conclusion: This modified-Delphi study confirms that prescription of RM or PAM, with Cal/BD foam, is largely driven by patient-related factors and patient involvement is key to optimise outcomes. Real-world experiences captured in this study suggest that a PAM regimen does not increase overall consumption, and thus costs per patient for payers and prescribers, in comparison to RM. [ABSTRACT FROM AUTHOR]

Simple Summary: With the recent advances of immunotherapy in the modern oncology era, the landscape of malignant melanoma has changed. However, it is not clear from the data across the various trials how to design the best therapeutic strategy. Hence, we decided to study the role of potential predictive biomarkers in a real-world, unselected population from Romania and to analyze the results of the single agent Nivolumab as first-line treatment in metastatic melanoma patients. Based on our findings, we believe that further studies could be designed to better map the immune landscape in metastatic melanoma in order to provide further perspectives on treatment options and choice. We performed a retrospective study on 51 metastatic melanoma patients treated with Nivolumab in first line, at the Regional Institute of Oncology (RIO) Iasi, Romania between April 2017 and December 2019. We studied the efficacy and safety of anti-PD-1 immune checkpoint inhibitor therapy on a treatment-naive population. After a median follow-up of 36 months, the median progression free survival (PFS) was 26 months (95% CI, 15–36) and the median overall survival (OS) was 31 months (95% CI, 20.1–41.8). At 12 months after the initiation of immunotherapy, the percentage of patients alive was 70%, and at 24 months 62.5%. The most common adverse events observed were dermatological (23.5%) and grade ≥3 was identified in 4 (6.8%) patients. Multivariate analysis indicated that the presence of liver metastases (HR 4.42; 95% CI: 1.88–10.4, p = 0.001) and a neutrophils/lymphocytes ratio (NLR) were associated with poor survival (HR 3.21; 95% CI: 1.04–9.87, p = 0.04). Although retrospective data on a small group of patients were analyzed, we can conclude that our results in RIO are similar to those described in clinical trials and other real-world studies. Our study highlights the potential usefulness of liver metastases and NLR as novel predictive factors in clinical decision-making. [ABSTRACT FROM AUTHOR]

Objective: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. It is usually treated surgically, with very high cure rates. However, in 3%-7% of cases, cSCC metastasizes to lymph nodes or distant organs. Many of the affected patients are elderly with comorbidities who are not candidates for standard-of-care curative-intent treatment with surgery and/or radio-/chemotherapy. Immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) pathways, have recently emerged as a potent therapeutic option. The present report presents the Israeli experience with PD-1 inhibitors for the treatment of loco-regionally advanced or metastatic cSCC in a diverse and elderly population, with or without the addition of radiotherapy. Material and methods: The databases of two university medical centers were retrospectively searched for patients with cSCC treated with the PD-1 inhibitors cemiplimab or pembrolizumab between January 2019 and May 2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed. Results: The cohort included 102 patients of a median age 78.5 years. Evaluable response data were available for 93. The overall response rate was 80.6%: complete response in 42 patients (45.2%) and partial response in 33 (35.5%). Stable disease was recorded in 7 (7.5%) and progressive disease in 11 (11.8%). Median progression-free survival was 29.5 months. Radiotherapy was administered to the target lesion during PD-1 treatment in 22.5% of patients. mPFS was not significantly different in patients who treated with RT than patients how did not (NR vs 18.4 months, HR=0.93, 95%CI: 0.39 - 2.17, p<0.859). Any-grade toxicity was recorded in 57 patients (55%), including grade ‗3 in 25, of whom 5 (5% of cohort) died. Compared to toxicity-free patients, patients with drug toxicity had better progression-free survival (18.4 months vs not reached, HR=0.33, 95% CI: 0.13-0.82, p=0.012) and higher overall response rate (87% vs 71.8%, p=0.06). Conclusion: This retrospective real-world study showed that PD-1 inhibitors were effective in the treatment of locally advanced or metastatic cSCC and appeared to be amenable for use in elderly or fragile patients with comorbidities. However, the high toxicity warrants consideration against other modalities. Induction or consolidation radiotherapy may improve the results. These findings need to be corroborated in a prospective trial. [ABSTRACT FROM AUTHOR]

• In an observational study of ivacaftor in pwCF with non– G551D-CFTR gating mutations. • Lung function, BMI, and weight improved; improvements were maintained over 48 months. • Rates of PEx, antibiotic use due to PEx, and hospitalization decreased. • Percentage of people with cultures positive for respiratory pathogens decreased. • This supports ivacaftor's long-term real-world effectiveness with these mutations. VOCAL was an observational study of the effect of long-term ivacaftor on real-world clinical outcomes and healthcare resource utilization (HCRU) in people with cystic fibrosis (pwCF) in Italy, the Netherlands, and the UK. pwCF aged ≥6 years with non– G551D-CFTR gating mutations were eligible. Prospective data were collected up to 48 months after enrollment; retrospective data were collected to ensure that 12 months of pre-ivacaftor data were available. Endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV 1) and measures of nutritional status. Pulmonary exacerbation (PEx) rates, HCRU, and respiratory microbiology during ivacaftor treatment were compared with data from the 12-month period before initiation. Seventy-three eligible pwCF were enrolled and received ivacaftor; 65 (89.0%) completed the study (48 [65.8%] completed ≥48 months of ivacaftor). During the first 6 months of ivacaftor, ppFEV 1 , body mass index (BMI), and BMI-for-age z -score showed least-squares mean absolute improvements of 10.8 percentage points, 0.79 kg/m2, and 0.54, respectively; improvements were maintained through 48 months. Rates of PEx, antibiotic use due to PEx, and hospitalization decreased by >50% during ivacaftor treatment compared with before ivacaftor. The number of respiratory cultures and sputum was lower post-ivacaftor, as was the percentage of pwCF with positive respiratory cultures for 3 of 9 pathogens evaluated (Pseudomonas aeruginosa, Aspergillus fumigatus, Stenotrophomonas maltophilia). Reported safety results were consistent with CF and ivacaftor's known safety profile. These results demonstrate the positive long-term effectiveness of ivacaftor on clinical outcomes and HCRU in pwCF with non– G551D-CFTR gating mutations in real-world settings. [ABSTRACT FROM AUTHOR]

New methods and demonstrations of feasibility guide future implementation of genomic population health screening programs. This is the first report of genomic population screening in a primary care, non-research setting using existing large carrier and health risk gene sequencing panels combined into one 432-gene test that is offered to adults of any health status. This report summarizes basic demographic data and analyses patterns of pathogenic and likely pathogenic genetic findings for the first 300 individuals tested in this real-world scenario. We devised a classification system for gene results to facilitate clear message development for our Genomic Medicine Action Plan messaging tool used to summarize and activate results for patients and primary care providers. Potential genetic health risks of various magnitudes for a broad range of disorders were identified in 16% to 34% of tested individuals. The frequency depends on criteria used for the type and penetrance of risk. 86% of individuals are carriers for one or more recessive diseases. Detecting, reporting, and guiding response to diverse genetic health risks and recessive carrier states in a single primary care genomic screening test appears feasible and effective. This is an important step toward exploring an exome or genome sequence as a multi-purpose clinical screening tool. [ABSTRACT FROM AUTHOR]

To present the first real-world data of patients with treatment-resistant depression (TRD) treated with esketamine through a French cohort Temporary Authorisation for Use (ATUc) programme. In 2019, the French Health Authorities exceptionally granted the first ATUc in psychiatry for TRD patients. Clinical characteristics, safety and efficacy data were reported by physicians. The ATUc ended ∼6 months after initiation. The cohort (n = 66; median age 53.0 years; 62.1% female; 78.8% with severe major depressive episodes; resistance to a mean of 4.2 previous antidepressants) received esketamine treatment for a median of 30 days. Among 46 analysed patients, 22 (47.8%) achieved response (Montgomery–Åsberg Depression Rating Scale [MADRS] total score reduction ≥50.0%) and 17 (37.0%) achieved remission (MADRS total score of ≤12) at least once at a median of 18.5 (2.0–77.0) and 21.0 (2.0–46.0) days after initiation, respectively. By Week 4, patients had a 31.6% probability of achieving remission (Kaplan–Meier method). Sedation, somnolence, dizziness, hypertension, anxiety and dissociation were the most frequently reported (>10.0%) adverse events. No new safety signals were identified. Patient characteristics of this cohort demonstrate high-level treatment resistance. The safety and efficacy of esketamine in patients with TRD in real‐world clinical practice were consistent with Phase 3 trials. Patients with treatment-resistant depression (TRD) exceptionally received esketamine nasal spray ahead of its launch through a French cohort Temporary Authorisation for Use (ATUc) programme. The clinical characteristics of 66 adult patients with TRD included in this cohort demonstrated a high-level of resistance to conventional treatments at the time of treatment request prior to esketamine initiation. No new safety signals were observed with esketamine initiation during the ATUc period compared with the Phase 3 clinical trials. The safety and efficacy of esketamine in the real world remain consistent with that established in Phase 3 clinical trials. The data collected during this ATUc also provide the first real-world data on the management and practical use of esketamine in a hospital setting in France. [ABSTRACT FROM AUTHOR]

ObjectiveCutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. It is usually treated surgically, with very high cure rates. However, in 3%-7% of cases, cSCC metastasizes to lymph nodes or distant organs. Many of the affected patients are elderly with comorbidities who are not candidates for standard-of-care curative-intent treatment with surgery and/or radio-/chemotherapy. Immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) pathways, have recently emerged as a potent therapeutic option. The present report presents the Israeli experience with PD-1 inhibitors for the treatment of loco-regionally advanced or metastatic cSCC in a diverse and elderly population, with or without the addition of radiotherapy.Material and methodsThe databases of two university medical centers were retrospectively searched for patients with cSCC treated with the PD-1 inhibitors cemiplimab or pembrolizumab between January 2019 and May 2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed.ResultsThe cohort included 102 patients of a median age 78.5 years. Evaluable response data were available for 93. The overall response rate was 80.6%: complete response in 42 patients (45.2%) and partial response in 33 (35.5%). Stable disease was recorded in 7 (7.5%) and progressive disease in 11 (11.8%). Median progression-free survival was 29.5 months. Radiotherapy was administered to the target lesion during PD-1 treatment in 22.5% of patients. mPFS was not significantly different in patients who treated with RT than patients how did not (NR vs 18.4 months, HR=0.93, 95%CI: 0.39 - 2.17, p

Background and purpose: Chronic migraine is a highly disabling primary headache disorder that is the most common diagnosis of patients seen at tertiary headache centres. Typical oral preventive therapies are associated with many limitations that impact their therapeutic utility. Erenumab was the first available calcitonin gene‐related peptide monoclonal antibody in the UK. It had proven efficacy in migraine prevention in clinical trials and limited real‐world data in tertiary settings. Methods: We audited our first 92 patients (n = 73 females) with severely disabling chronic migraine who were given monthly erenumab 70 mg sc for 6 months between December 2018 and December 2019. Results: At 3 months, monthly migraine days were significantly reduced by a median of 4 days, and all other variables also showed significant improvement. The improvement was not affected by baseline analgesic use status. More than half of our patients experienced a clinically meaningful improvement in migraine days. No serious adverse events were reported. Conclusions: Our real‐world data with erenumab demonstrate it is effective and well tolerated in managing patients with chronic migraine in a tertiary care setting. [ABSTRACT FROM AUTHOR]

Yotin Chinvarun,1 Chin-Wei Huang,2 Ye Wu,3 Hsiu-Fen Lee,4 Surachai Likasitwattanakul,5 Jing Ding,6 Takamichi Yamamoto7 1Department of Neurology, Phramongkutklao Royal Army Hospital and Medical College, Bangkok, Thailand; 2Department of Neurology, National Cheng Kung University Hospital College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Pediatrics, Peking University First Hospital, Beijing, People’s Republic of China; 4Division of Pediatric Neurology, Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan; 5Division of Neurology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 6Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 7Department of Neurosurgery, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital, Hamamatsu, JapanCorrespondence: Takamichi YamamotoDepartment of Neurosurgery, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka, 430-8558, JapanTel +81 53 474 2222Fax +81 53 474 3094Email taka-yamamd@sis.seirei.or.jpAbstract: Perampanel is a once-daily, first-in-class AMPA receptor antagonist approved for the treatment of epilepsy and exhibits broad-spectrum efficacy in a range of seizure types when used as both monotherapy and adjunctive therapy. Clinical studies and real-world evidence have demonstrated the advantages of initiating perampanel at low doses and utilizing a slow titration strategy. Initiating perampanel at an early stage has also been shown to be associated with better patient outcomes. However, the optimal use and place of perampanel in clinical practice has not yet been clearly defined for the Asian patient population. Use of perampanel in clinical practice varies markedly across the Asia region because of variation in knowledge, attitudes, and practice. There is currently no specific guidance on best practices for prescribing perampanel in Asian patients or how to optimize treatment strategies to maximize adherence. A group of epilepsy experts attended a virtual meeting in September 2020 to discuss their experience with using perampanel in the Asian practice setting, including their views regarding appropriate patient populations, optimal starting and maintenance doses, optimal titration regimens, key barriers to adherence, and prevention and management of adverse events. This article summarizes key clinical and real-world evidence for perampanel and consolidates the experts’ opinions on optimization of perampanel prescribing and adherence in real-world practice, providing practical strategies for clinicians to implement to improve outcomes for people with epilepsy in Asia.Keywords: perampanel, epilepsy, real-world experience, Asia

Simple Summary: Vismodegib and sonidegib are targeted therapies inhibiting the hedgehog pathway, a key driver in the pathogenesis of basal cell carcinoma (BCC). Hedgehog inhibitors (HhIs) are first-line therapy for locally advanced basal cell carcinoma (laBCC), metastatic basal cell carcinoma (mBCC) and multiple BCCs, when surgery and radiotherapy are no longer feasible. Safety and efficacy of the HhIs vismodegib and sonidegib have been shown in large prospective clinical trials. However, treatment of advanced basal cell carcinoma (aBCC) in daily practice includes patients who do not meet strict inclusion criteria and poses an additional challenge for treating physicians. This study aims to give an insight into a real-world experience in our tertiary skin referral center. Background: The hedgehog inhibitors vismodegib and sonidegib are approved for the treatment of advanced basal cell carcinoma. This study reports the experiences with these therapies in a tertiary skin referral center in daily practice. Methods: A retrospective, observational, single-center study analyzing medical records of patients with aBCC treated with a smoothened (SMO) inhibitor outside a clinical trial for at least one month between 2013 and 2021. Results: In total, 33 patients were included: 21 (64%) patients were treated with vismodegib, 3 (9%) patients with sonidegib and 9 (27%) patients with both treatments subsequently. With vismodegib, the best overall response was complete response (CR) in 33% cases, and partial response (PR) in 33% cases. Under sonidegib, 42% patients achieved CR and 17% PR. Mean duration to next treatment was 33 and 14 months for vismodegib and sonidegib, respectively. Adverse events varied in frequency between continuous and intermittent dosing and they were the most common reason for therapy discontinuation. Conclusions: Our real-world data illustrate the pitfalls and benefits of HhIs as well as the impact of different dosing regimens on adverse events, patient adherence and response. Treatment duration remains limited by adverse events and resistance. Additional treatment options, including immunotherapy and drug combinations, are needed. [ABSTRACT FROM AUTHOR]

Dupilumab is a monoclonal antibody against interleukins 4 and 13 currently FDA approved for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents and severe AD in children aged 6–11 years. It is reported to be safe with the most common side effects described from clinical trials being conjunctivitis, nasopharyngitis and injection site reactions. Outside the clinical trial setting, there is insufficient data on the side effects of dupilumab in adults with AD, and much less among children and adolescents. The aim of this study was to analyze the spectrum of side effects in all patients receiving dupilumab for the treatment of AD and related conditions in a real‐world setting at a single tertiary referral center, and correlate any risk factors for the development of these side effects. A retrospective review of electronic medical records was conducted for all patients who had received dupilumab for a minimum of 2 months for the treatment of AD and related conditions in the department of dermatology at Rashid hospital, Dubai from February 2018 to November 2021. We analyzed the medical records of 128 patients who received dupilumab according to standard age‐related dosing. This included 78 adults (age range 18–81 years) and 50 children and adolescents (aged 6–17 years). There were 73 males and 55 females. The mean duration of dupilumab treatment was 14.9 months. The most common side effects encountered during dupilumab therapy were head and neck dermatitis in 25 (19.5%), conjunctivitis in 20 (15.6%), erythema, pruritus and peeling of skin in 14 (10.9%) and dryness of eyes in 10 (7.8%) patients, respectively. Overall, dupilumab was well‐tolerated in our patient population. Most of the side effects were mild and did not require discontinuation of dupilumab. These findings would enable dermatologists understand the side effects of dupilumab better, resulting in improved treatment plan decisions in clinical practice. [ABSTRACT FROM AUTHOR]