Laryngeal Cancer Cells Metabolize 25-Hydroxyvitamin D3 and Respond to 24R,25-dihydroxyvitamin D3 via a Mechanism Dependent on Estrogen Receptor Levels.

Studies have evaluated vitamin D3's therapeutic potential in estrogen-responsive cancers, with conflicting findings. We have shown that the proliferation of breast cancer cells is regulated by 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) depending on estrogen receptor alpha 66 (ERα66) expression, suggesting that this could also be the case for estrogen-sensitive laryngeal cancer cells. Accordingly, we examined levels of ERα isoforms in ERα66-positive UM-SCC-12 and ERα66-negative UM-SCC-11A cells and their response to 24R,25(OH)2D3. 24R,25(OH)2D3 stimulated proliferation, increased the expression of metastatic markers, and inhibited apoptosis in UM-SCC-12 cells while having the opposite effect in UM-SCC-11A cells. To evaluate if vitamin metabolites could act via autocrine/paracrine mechanisms, we assessed the expression, protein levels, and activity of vitamin D3 hydroxylases CYP24A1 and CYP27B1. Both cell types expressed both mRNAs; but the levels of the enzymes and their activities were differentially regulated by estrogen. ERα66-negative UM-SCC-11A cells produced more 24,25(OH)2D3 than UM-SCC-12 cells, but comparable levels of 1,25(OH)2D3 when treated with 25(OH)D3 These results suggest that the regulation of vitamin D3 metabolism in laryngeal cancer cells is modulated by ERα66 expression, and support a role for 24R,25(OH)2D3 as an autocrine/paracrine regulator of laryngeal cancer. The local metabolism of 25(OH)D3 should be considered when determining the potential of vitamin D3 in laryngeal cancer.

Pharmacokinetics/pharmacodynamics of benralizumab in chronic rhinosinusitis with nasal polyps: Phase III, randomized, placebo-controlled OSTRO trial.

AIMS: Benralizumab, a humanized, afucosylated monoclonal antibody against the interleukin 5 receptor, α subunit, causes rapid depletion of eosinophils by antibody-dependent cellular cytotoxicity. We investigated the pharmacokinetic and pharmacodynamic effects of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) from the phase III OSTRO trial. METHODS: Patients received a placebo or 30 mg of benralizumab by subcutaneous injection every 8 weeks (first three doses every 4 weeks) to week 48; a subset of patients continued in an extended follow-up period to assess treatment durability to week 80. Serum benralizumab concentrations and blood eosinophil and basophil counts were assessed to week 80. Biomarker assessments were performed on nasal polyp tissue biopsies at week 56 and nasal lining fluid at weeks 24 and 56 to examine changes in immune cells and inflammatory mediators. RESULTS: Among 185 patients in this analysis, 93 received benralizumab. Serum benralizumab concentrations reached a steady state by week 24 (median concentration 385.52 ng mL-1); blood eosinophils were almost fully depleted and blood basophils were reduced between weeks 16 and 56. Nasal polyp tissue eosinophils decreased with benralizumab from 57.6 cells mm-2 at baseline to 0 cells mm-2 at week 56 (P < .001 vs placebo), and tissue mast cells were numerically reduced. In nasal lining fluid, eosinophil-derived neurotoxin was significantly reduced at weeks 24 and 56 (P < .001) and interleukin-17 at week 56 (P < .05) with benralizumab. CONCLUSION: Benralizumab treatment led to rapid, sustained, nearly complete depletion of eosinophils from blood and nasal polyp tissue in patients with CRSwNP.

Laneth Acetates.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1982 and a previous re-review in 2002, along with updated information regarding product types and concentrations of use. Considering this information, the Panel confirmed that Laneth-9 Acetate and Laneth-10 Acetate are safe for topical application to humans in the present practices of use and concentration as described in this report.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Different Methods to Modify the Hydrophilicity of Titanium Implants with Biomimetic Surface Topography to Induce Variable Responses in Bone Marrow Stromal Cells.

The osteoblastic differentiation of bone marrow stromal cells (bMSCs), critical to the osseointegration of titanium implants, is enhanced on titanium surfaces with biomimetic topography, and this is further enhanced when the surfaces are hydrophilic. This is a result of changing the surface free energy to change protein adsorption, improving cell attachment and differentiation, and improving bone-to-implant contact in patients. In this study, we examined different methods of plasma treatment, a well-accepted method of increasing hydrophilicity, and evaluated changes in surface properties as well as the response of bMSCs in vitro. Commercially pure Ti and titanium-aluminum-vanadium (Ti6Al4V) disks were sand-blasted and acid-etched to impart microscale and nanoscale roughness, followed by treatment with various post-processing surface modification methods, including ultraviolet light (UV), dielectric barrier discharge (DBD)-generated plasma, and plasma treatment under an argon or oxygen atmosphere. Surface wettability was based on a sessile water drop measurement of contact angle; the elemental composition was analyzed using XPS, and changes in topography were characterized using scanning electron microscopy (SEM) and confocal imaging. The cell response was evaluated using bMSCs; outcome measures included the production of osteogenic markers, paracrine signaling factors, and immunomodulatory cytokines. All plasma treatments were effective in inducing superhydrophilic surfaces. Small but significant increases in surface roughness were observed following UV, DBD and argon plasma treatment. No other modifications to surface topography were noted. However, the relative composition of Ti, O, and C varied with the treatment method. The cell response to these hydrophilic surfaces depended on the plasma treatment method used. DBD plasma treatment significantly enhanced the osteogenic response of the bMSCs. In contrast, the bMSC response to argon plasma-treated surfaces was varied, with an increase in OPG production but a decrease in OCN production. These results indicate that post-packaging methods that increased hydrophilicity as measured by contact angle did not change the surface free energy in the same way, and accordingly, cells responded differently. Wettability and surface chemistry alone are not enough to declare whether an implant has an improved osteogenic effect and do not fully explain how surface free energy affects cell response.

Zinc Phenolsulfonate.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1986 and a previous re-review in 2004, along with updated information regarding product types and concentrations of use. Considering this information, the Panel confirmed that Zinc Phenolsulfonate is safe as a cosmetic ingredient in the present practices of use and concentration as described in this report.

Prevalence and anatomical factors associated with stent under-expansion in non-severely calcified lesions.

BACKGROUND: Stent underexpansion, typically related to lesion calcification, is the strongest predictor of adverse events after percutaneous coronary intervention (PCI). Although uncommon, underexpansion may also occur in non-severely calcified lesions. AIM: We sought to identify the prevalence and anatomical characteristics of underexpansion in non-severely calcified lesions. METHODS: We included 993 patients who underwent optical coherence tomography-guided PCI of 1051 de novo lesions with maximum calcium arc <180°. Negative remodeling (NR) was the smallest lesion site external elastic lamina diameter that was also smaller than the distal reference. Stent expansion was evaluated using a linear regression model accounting for vessel tapering; underexpansion required both stent expansion <70% and stent area <4.5mm2. RESULTS: Underexpansion was observed in 3.6% of non-heavily calcified lesions (38/1051). Pre-stent maximum calcium arc and thickness were greater in lesions with versus without underexpansion (median 119° vs. 85°, p = 0.002; median 0.95 mm vs. 0.78 mm, p = 0.008). NR was also more common in lesions with underexpansion (44.7% vs. 24.5%, p = 0.007). In the multivariable logistic regression model, larger and thicker eccentric calcium, mid left anterior descending artery (LAD) location, and NR were associated with underexpansion in non-severely calcified lesions. The rate of underexpansion was especially high (30.7%) in lesions exhibiting all three morphologies. Two-year TLF tended to be higher in underexpanded versus non-underexpanded stents (9.7% vs. 3.7%, unadjusted hazard ratio [95% confidence interval] = 3.02 [0.92, 9.58], p = 0.06). CONCLUSION: Although underexpansion in the absence of severe calcium (<180°) is uncommon, mid-LAD lesions with NR and large and thick eccentric calcium were associated with underexpansion.

MELTEMI and COLUMBA: 5-Year Comparative Safety Analysis of Benralizumab and Mepolizumab.

BACKGROUND: Benralizumab and mepolizumab are IL-5Rα/IL-5-targeted monoclonal antibodies indicated as add-on treatments for patients with uncontrolled severe eosinophilic asthma (SEA). OBJECTIVE: To evaluate and compare the safety of benralizumab and mepolizumab among patients with SEA treated in MELTEMI and COLUMBA open-label, long-term extension studies, respectively. METHODS: MELTEMI was an extension study of benralizumab Q4W or Q8W for adults (aged 18-75 years) with SEA. MELTEMI participants transitioned from the BORA extension, preceded by participation in 1 of 3 placebo-controlled studies (SIROCCO, CALIMA, or ZONDA). COLUMBA was an extension study of mepolizumab for patients (aged ≥12 years) with SEA who transitioned from the dose-ranging DREAM study. Safety endpoints were presented as drug exposure patient years (MELTEMI, Q4W 784.28, Q8W 797.03; COLUMBA 1,201) for nonserious adverse events (AEs), serious adverse events (SAEs), and infections; malignancies were counted numerically. RESULTS: This analysis included 446 MELTEMI patients (benralizumab Q4W, 220; benralizumab Q8W, 226) and 347 COLUMBA patients (mepolizumab Q4W). Viral upper respiratory tract infection was the most common nonserious AE in both studies (MELTEMI Q8W, 46.5%; Q4W, 47.3%; COLUMBA, 48.7%). Asthma-related events were the most common SAE in both studies: MELTEMI 8.0% (Q8W) and 8.6% (Q4W) and COLUMBA 9.5%. Serious infections included pneumonia (MELTEMI Q8W, 2 [0.9%]; COLUMBA, 6 [1.7%]); cellulitis (MELTEMI Q8W, 1 [0.4%]; COLUMBA, 2 [0.6%]); and respiratory tract infections (COLUMBA, 2 [0.6%]). COLUMBA reported 6 malignancies and MELTEMI reported 4 malignancies in each group. CONCLUSIONS: This analysis demonstrated generally similar safety events between mepolizumab and benralizumab in patients with SEA.

Posterior vascular anatomy of the encephalon: a comprehensive review.

PURPOSE: This article presents a comprehensive exploration of neurovascular anatomy of the encephalon, focusing specifically on the intricate network within the posterior circulation and the posterior fossa anatomy; enhancing understanding of its dynamics, essential for practitioners in neurosurgery and neurology areas. METHOD: A profound literature review was conducted by searching the PubMed and Google Scholar databases using main keywords related to neurovascular anatomy. The selected literature was meticulously scrutinized. Throughout the screening of pertinent papers, further articles or book chapters were obtained through additional assessment of the reference lists. Furthermore, four formalin-fixed, color latex-injected cadaveric specimens preserved in 70% ethanol solution were dissected under surgical microscope (Leica Microsystems Inc, 1700 Leider Ln, Buffalo Grove, IL 60089, USA), using microneurosurgical as well as standard instruments, and a high-speed surgical drill (Stryker Instruments 1941 Stryker Way Portage, MI 49002, USA). Ulterior anatomical dissection was performed. RESULTS: Detailed examination of the basilar artery (BA), a common trunk formed by the union of the left and right vertebral arteries, denoted a tortuous course across the basilar sulcus. Emphasis is then placed on the Posterior Inferior Cerebellar Artery (PICA), Anterior Inferior Cerebellar Artery (AICA) and Superior Cerebellar Artery (SCA). Each artery's complex course through the posterior fossa, its divisions, and potential stroke-related syndromes are explored in detail. The Posterior Cerebral Artery (PCA) is subsequently unveiled. The posterior fossa venous system is explained, categorizing its channels. A retrograde exploration traces the venous drainage back to the internal jugular vein, unraveling its pathways. CONCLUSION: This work serves as a succinct yet comprehensive guide, offering fundamental insights into neurovascular anatomy within the encephalon's posterior circulation. Intended for both novice physicians and seasoned neuroanatomists, the article aims to facilitate a more efficient clinical decision-making in neurosurgical and neurological practices.

Reduced osseointegration in disuse and denervation rat models results from impaired cellular responses to multiscale microstructured titanium surfaces.

Immobilization-induced skeletal unloading results in muscle atrophy and rapid bone loss, thereby increasing the risk of falling and the need for implant therapy in patients with extended bed rest or neuromuscular injuries. Skeletal unloading causes bone loss by altering bone growth and resorption, suggesting that implant performance might be affected. To test this, we focused on early events in implant osseointegration. We used the rat sciatic neurectomy-induced disuse model under two different settings. In Study 1, 16 Sprague Dawley rats (SD) were separated into control, sham operated+cast immobilization, and sciatic neurectomy+casting groups; titanium implants with multiscale microtextured topography and hydrophilic chemistry (modSLA) were inserted in the distal femoral metaphysis. Neurectomy surgeries and casting were performed at the same surgical setting as implant placement; rats were euthanized 4 weeks post-implantation. In Study 2, we established the unloaded condition before implantation. A total of 12 SD rats were divided into control and sciatic+femoral neurectomy groups. A total of 24 days after sciatic and femoral neurectomy surgery, rats received implants. Study 2 rats were euthanized at 4 weeks post-implantation. MicroCT and histomorphometry showed that trabecular bone and osseointegration were reduced when disuse was established before implantation. Osteoblasts isolated from Study 1 sciatic neurectomy tibial bones exhibited impaired differentiation on modSLA culture disks, revealing a possible mechanism responsible for the decreased osseointegration observed in the Study 2 rats. This study addressed the importance of considering the mechanical unloading and muscle function history before implant insertion and suggests that implant performance was reduced due to poor cellular ability to regenerate.

A primer to vascular anatomy of the brain: an overview on anterior compartment.

PURPOSE: Knowledge of neurovascular anatomy is vital for neurosurgeons, neurologists, neuro-radiologists and anatomy students, amongst others, to fully comprehend the brain's anatomy with utmost depth. This paper aims to enhance the foundational knowledge of novice physicians in this area. METHOD: A comprehensive literature review was carried out by searching the PubMed and Google Scholar databases using primary keywords related to brain vasculature, without date restrictions. The identified literature was meticulously examined and scrutinized. In the process of screening pertinent papers, further articles and book chapters were obtained through analysis and additional assessing of the reference lists. Additionally, four formalin-fixed, color latex-injected cadaveric specimens preserved in 70% ethanol solution were dissected under surgical microscope (Leica Microsystems Inc, 1700 Leider Ln, Buffalo Grove, IL 60089 USA). Using microneurosurgical as well as standard instruments, and a high-speed surgical drill (Stryker Instruments 1941 Stryker Way Portage, MI 49002 USA). Ulterior anatomical dissection was documented in microscopic images. RESULTS: Encephalic circulation functions as a complex network of intertwined vessels. The Internal Carotid Arteries (ICAs) and the Vertebral Arteries (VAs), form the anterior and posterior arterial circulations, respectively. This work provides a detailed exploration of the neurovascular anatomy of the anterior circulation and its key structures, such as the Anterior Cerebral Artery (ACA) and the Middle Cerebral Artery (MCA). Embryology is also briefly covered, offering insights into the early development of the vascular structures of the central nervous system. Cerebral venous system was detailed, highlighting the major veins and tributaries involved in the drainage of blood from the intracranial compartment, with a focus on the role of the Internal Jugular Veins (IJVs) as the primary, although not exclusive, deoxygenated blood outflow pathway. CONCLUSION: This work serves as initial guide, providing essential knowledge on neurovascular anatomy, hoping to reduce the initial impact when tackling the subject, albeit the intricate vasculature of the brain will necessitate further efforts to be conquered, that being crucial for neurosurgical and neurology related practice and clinical decision-making.

Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme.

BACKGROUND: Pivotal Phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. METHODS: XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). RESULTS: Of 1002 patients analysed, 380 were biologic-experienced. At Week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130/274) eliminated their use by Week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. CONCLUSION: In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

Variation in Health Status With Invasive vs Conservative Management of Chronic Coronary Disease.

BACKGROUND: The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients. OBJECTIVES: The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making. METHODS: One-year disease-specific health status was assessed in ISCHEMIA with the Seattle Angina Questionnaire (SAQ) Summary Score (SAQ SS) and Angina Frequency, Physical Limitations (PL), and Quality of Life (QL) domains (range 0-100, higher = less angina/better health status). RESULTS: Among 4,617 patients from 320 sites in 37 countries, mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year. Lower baseline SAQ SS and younger age were associated with better 1-year health status with invasive strategy (P interaction = 0.009 and P interaction = 0.004, respectively). For the individual domains, there were significant treatment interactions for baseline SAQ score (Angina Frequency, PL), age (PL, QL), anterior ischemia (PL), and number of baseline antianginal medications (QL), with more benefit of invasive in patients with worse baseline health status, younger age, anterior ischemia, and on more antianginal medications. Parsimonious prediction models were developed for 1-year SAQ domains with invasive or conservative strategies to support shared decision-making. CONCLUSIONS: In the management of chronic coronary disease, individual patient characteristics are associated with 1-year health status, with younger age and poorer angina-related health status showing greater benefit from invasive management. This prediction algorithm can support the translation of the ISCHEMIA trial results to individual patients. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Benralizumab in Severe Eosinophilic Asthma and Chronic Rhinosinusitis with Nasal Polyps: The Real-World, Multi-Country RANS Observational Study.

Purpose: Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting. Patients and Methods: RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥1-point reduction), SNOT-22 total (≥8.9-point reduction), ACQ-6 (≥0.5-point reduction) or ACT (≥3-point increase) scores, were reported. Results: A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was -1.2 (-1.7, -0.6) for NPS, and -19.8 (-23.6, -15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively. Conclusion: In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.

A systematic review of the psychometric properties of tools for measuring depression in youths with intellectual disability.

While youths with intellectual disability (ID) have increased vulnerability for depressive disorders, cognitive problems and combined functional barriers make them less prone to receive adequate treatments. A systematic review of the literature was conducted (PROSPERO Registration number: CRD42022347703) based on several databases from 1980 to 2022 to examine the quality of tools for measuring depression in children and adolescents with ID. The COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) checklist was used to assess several psychometric domains. Twelve studies evaluated the properties of six tools for measuring depression in youths with ID. The Center for Epidemiologic Studies Depression Scale-Intellectual Disability (CESD-ID) was the only scale with at least five domains of psychometric properties assessed to have strong or moderate evidence. Based on the reviewed findings, tools specifically developed for populations with developmental disabilities should be considered first in order to screen depression in youths with ID. Much work is required to confirm their validity in clinical samples with patients with a complex form of developmental disabilities. As a complement to self- and caregivers-report questionnaires, clinician rating scales were considered useful to catch the full picture of depression in youths with ID, in particular associated behavioral expressions. Their validity received little scrutiny and certainly deserve more attention to improve care practice of youths with ID.

Promoting emotional and behavioral interventions in ASD treatment: Evidence from EPIGRAM, A naturalistic, prospective and longitudinal study.

BACKGROUND: Prognostic factors from naturalistic treatment studies of children with Autism Spectrum Disorder (ASD) remain largely unknown. We aimed to identify baseline and treatment-related prognostic predictors at 1-year follow-up after Integrative Care Practices (ICPs). METHODS: Eighty-nine preschool children with severe ASD were given ICP combining nine therapeutic workshops based on children's needs. Participants were assessed at baseline and during 12 months follow-up with the Psycho-educational Profile-3-R, Children Autism Rating Scale, Parental Global Impression, and the Autistic Behaviors Scale. We assessed prognostic predictors using multivariable regression models and explored treatment ingredients influencing outcome using Classification and Regression Trees (CART). RESULTS: Multivariable models showed that being a child from first generation immigrant parents predicted increased maladaptive behaviors, whereas play activities had an opposite effect; severity of ASD symptoms and impaired cognitive functions predicted worse autism severity at follow-up; and lower play activities predicted worse parent impression. Regarding treatment effects, more emotion/behavioral interventions predicted better outcomes, and more communication interventions predicted lower autism severity, whereas more education and cognitive interventions had an opposite effect. CART confirmed that more hours of intervention in the emotion/behavioral domain helped classifying cases with better outcomes. More parental support was associated with decreased maladaptive behaviors. Sensorimotor and education interventions also significantly contributed to classifying cases according to outcomes but defined subgroups with opposite prognosis. CONCLUSION: Children who exhibited the best prognosis following ICPs had less autism severity, better cognition, and non-immigrant parents at baseline. Emotion/behavior interventions appeared key across all outcomes and should be promoted.

Etiologies and Impact of Exclusion Rates for Transcatheter Mitral and Tricuspid Valve Structural Heart Clinical Trials at a High-Volume Quaternary Care Hospital.

There are various devices under clinical investigation for transcatheter mitral valve intervention and transcatheter tricuspid valve intervention (TTVI); however, the exclusion rates remain high. We aimed to investigate the exclusion rates for transcatheter mitral valve repair (TMVr), transcatheter mitral valve replacement (TMVR), transcatheter tricuspid valve repair (TTVr), and transcatheter tricuspid valve replacement (TTVR). There were 129 patients who were referred to St. Francis Hospital & Heart Center valve clinic and completed screening between January 2021 and July 2022. The causes for exclusion were classified into 4 categories: patient withdrawal, anatomic unsuitability, clinical criteria, and medical futility. In 129 patients, the exclusion rates for TMVr, TMVR, TTVr, and TTVR were 81%, 85%, 91%, and 87%, respectively. Patient withdrawal and medical futility were leading etiologies for exclusion, followed by anatomic unsuitability. TMVr had the highest rate of patient withdrawal (64%) and the lowest anatomic unsuitability (5%) because of short posterior leaflet length. Replacement interventions have a higher anatomic unsuitability (33%) than repair interventions (17%) (p = 0.04). Most exclusions of anatomic unsuitability were because of mitral stenosis or small annulus size for TMVR and large annulus size for TTVR. A total of 50% of exclusions from TTVr were because of the presence of pacemaker/defibrillator leads. In patients excluded from their respective trials, patients being referred for TMVr had the highest recurrent hospitalization and repair group had a higher mortality (p <0.01 and p = 0.01, respectively). In conclusion, the exclusion rates for transcatheter mitral valve intervention and TTVI trials remain high because of various reasons, limiting patient enrollment and treatment. This supports the need for further device improvement or exploring alternative means of therapy.