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Evidence-Based Practice (EBP) has increased the availability of psychological treatments, yet many people do not benefit from therapy, some report deteriorations in symptoms, and dropout rates remain high. Precision Mental Health (PMH) is proposed as an extension of EBP by combining systematic measurement with predictive analytics to support the right intervention, at the right time, for the right person. Recent advances in Artificial Intelligence (AI) make PMH increasingly feasible in routine psychotherapy; however, the implementation of these approaches in routine care is still incipient. In this context, the present article has two main aims. First, we summarize key advances in PMH, particularly measurement-based care and data-informed decision making. Second, we introduce the NOVA project (Navigating Outcomes via Analytics), a multi-phase translational program designed to implement PMH in real-world psychological services. Guided by the Implementing Precision Methods framework, NOVA integrates (i) stakeholder-informed work on clinician acceptability and intention to use, (ii) pragmatic evaluation of decision support tools in routine care, (iii) development of robust and interpretable predictive models, and (iv) training and dissemination activities aligned with responsible innovation and professional competencies for AI-supported precision care. By detailing NOVA’s implementation pathway, we aim to provide a concrete roadmap for bridging AI innovation and psychological practice, accelerating the sustainable adoption of PMH in real-world settings.

Importance Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive and potentially life-threatening infection that predominantly affects immunocompromised patients. Recent advances in diagnostic imaging, antifungal therapy, and surgical techniques may have altered its incidence, morbidity, and mortality. Objective To evaluate temporal trends in the pooled proportion, morbidity, and mortality of AIFRS in immunocompromised patients and assess the association of diagnostic and therapeutic advances. Data Sources Systematic searches of Ovid MEDLINE, Ovid Embase, PubMed, Scopus, Web of Science, Cochrane, and Google Scholar from 1977 through October 20, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study Selection Prospective, retrospective, and cross-sectional studies and case series reporting pooled proportion, morbidity, or mortality of AIFRS in immunocompromised patients were included. Non-English articles, reviews, editorials, and studies with fewer than 10 patients were excluded. Data Extraction and Synthesis Two independent reviewers extracted data using standardized templates; disagreements were resolved by consensus. Risk of bias was assessed using the Newcastle-Ottawa Scale and Murad tool for case series. Random-effects meta-analysis generated pooled proportion, morbidity, and mortality rates with 95% CIs. Heterogeneity was quantified using I 2 statistics. Meta-regression and sensitivity analyses evaluated temporal trends and study-level effects. Main Outcomes and Measures Pooled proportion, morbidity, and mortality rates of AIFRS stratified by publication period (1983-2012 vs 2013-2025). Results A total of 205 studies comprising 48 437 immunocompromised patients (median [range] age, 49.4 [5.2-68.8] years), including 10 311 (21.3%) with AIFRS, were analyzed. The pooled proportion was 11.8% (95% CI, 7.9%-17.2%), rising to 16.6% (95% CI, 8.7%-29.2%) in studies from 2013 to 2025. Overall mortality was 31.2% (95% CI, 28.3%-34.3%), declining from 41.9% (95% CI, 35.0%-49.1%) before 2013 to 28.2% (95% CI, 25.1%-31.4%) after 2013. Morbidity was 37.0% (95% CI, 32.9%-41.4%), with similar rates across periods (39.3% before 2013 vs 36.4% after 2013). The most common complications were vision loss, exophthalmos/proptosis, and orbital exenteration. Conclusions and Relevance This systematic review and meta-analysis suggests that the pooled proportion of AIFRS among immunocompromised patients has increased while mortality has declined, reflecting advances in diagnostic and therapeutic approaches. Early detection and aggressive management remain critical to improving outcomes.

Background: Venous air embolism (VAE) is a potentially catastrophic complication during neurosurgical procedures, particularly in the sitting position. As practices vary widely, we conducted a survey to describe the global practice patterns for intraoperative detection and management of VAE. Methods: Following institutional review board (IRB) approval, we conducted a cross-sectional study using a 48-question online survey that was distributed via a snowball sampling approach, initially to the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) community and subsequently to international collaborators. Descriptive statistics summarized responses, and proportional comparisons between high-income and low- and middle-income country respondents were assessed using a χ 2 or the Fisher exact tests, as appropriate. Results: Of 307 responses, 297 were analyzed, representing 40 countries. Survey response rate was 25% among SNACC members. End-tidal carbon dioxide (EtCO 2 ) monitoring was the most frequently reported VAE monitoring modality, particularly for sitting craniotomies. Common barriers to implementing advanced monitoring included limited equipment availability and a lack of a transesophageal echocardiography (TEE) specialist. Decision-making for cases at VAE risk relied on team consensus (62%), review articles and primary literature (48%), and institutional protocols (42%). Among respondents, 89% expressed interest in consensus guidelines for VAE management. Conclusions: There is substantial global variability in both the preparation for and management of VAE during neurosurgical procedures. EtCO 2 is the preferred monitoring approach in routine practice, as resource limitations prevent the broader adoption of more sensitive techniques, such as TEE. The high interest in consensus guidelines underscores an opportunity for professional societies to standardize approaches and improve patient safety.

Abstract Introduction: Indolent systemic mastocytosis (ISM) is a clonal mast cell disease driven by the KIT D816V mutation in ~95% of cases and is associated with symptoms of mast cell activation and tissue infiltration. It can cause chronic, debilitating symptoms − including life-threatening anaphylaxis and impaired bone health. While historically most patients have relied on symptom-directed best supportive care (BSC) therapies, avapritinib is used as a new standard of care targeting KIT D816V, the primary driver for SM. Avapritinib is an oral, potent, selective KIT D816V inhibitor, and the first and only approved targeted therapy for adult patients with ISM in the USA and the EU. Approval was based on results from the phase 2 PIONEER trial. Here, we present the findings from ~3.5-year long-term follow-up. Methods: Adults with centrally confirmed ISM and uncontrolled moderate-to-severe symptoms who completed the randomized dose-finding (Part 1), or randomized, double-blind, placebo-controlled (Part 2) portions of PIONEER (NCT03731260) rolled over to the open-label, long-term extension (Part 3). This cumulative analysis includes patients who initiated avapritinib at the recommended dose of 25 mg once daily (QD) in either Parts 1, 2, or 3. All patients received BSC. Per investigator discretion and based on disease burden, dose titration up to 50 mg QD of avapritinib was permitted in Part 3. Long-term efficacy was assessed by measuring changes in symptoms and QoL, using the ISM-Symptom Assessment Form (ISM-SAF; ©2018 Blueprint Medicines, a Sanofi Company) and the Mastocytosis Quality-of-Life Questionnaire (MC-QoL). Safety was also assessed. Results: Overall, 226 patients initiated avapritinib 25mg QD across Parts 1, 2, and 3. This longer-term analysis is inclusive of 65 patients who dose titrated from 25 mg to 50 mg QD in Part 3. Median (range) treatment duration was 40.0 months (0.7‒67.2) as of February 21, 2025. Longer-term efficacy data with ~3.5 years of follow-up demonstrated sustained disease-related symptom improvements. The mean change (standard deviation [SD]) in total symptom score (TSS, per ISM-SAF), was −19.80 (19.81) at Week 144 (Month 33) and −20.43 (20.57) at Week 168 (Month 39) from a baseline of 48.08 (19.47). Additionally, avapritinib-treated patients demonstrated durable improvement in their most severe symptoms (mean change [SD] from baseline of −3.35 [3.02] at Month 33 and −3.47 [3.19] at Month 39) per ISM-SAF. Sustained responses were observed across all individual symptom domains (0–30) with mean changes (SD) at Month 33 and Month 39 of −3.77 (5.52) and −3.84 (6.05) for the gastrointestinal domain, −8.21 (7.70) and −8.20 (7.85) for the skin domain, and −4.66 (6.24) and −4.87 (6.51) for the neurocognitive domain. The mean percent change (SD) in MC-QoL was −34.67 (40.16) at Month 33 and −40.72 (33.24) at Month 39 from a baseline of 54.24 (18.32). Treatment with avapritinib was well tolerated, and its safety profile was similar to the previously reported placebo-controlled portion. Most treatment-related adverse events (TRAEs) were Grades 1–2, and 7% of patients experienced Grade ≥3 TRAEs of which diarrhea, neutrophil count decrease, and weight increase occurred in >1 patient. No Grade ≥3 TRAEs of increase in transaminases were observed. Edema (peripheral and periorbital), the most frequently reported TRAE, was mostly Grade 1 and occurred most frequently during the first 3–4 months of treatment. Three patients (1%) experienced serious adverse events assessed as treatment related. However, none led to treatment discontinuation and no trends were observed. After approximately 3.5 years of follow-up, low rates of treatment discontinuations (n=7, 3%) due to TRAEs were observed. Conclusion: Longer follow-up of patients with ISM treated on the PIONEER trial, including some on avapritinib for up to 5 years, demonstrates that prolonged avapritinib therapy continues to be effective and well tolerated. Additional prospective analyses will be needed to determine effects of selective KIT D816V-inhibition on anaphylaxis. These data support a favorable benefit-risk profile of avapritinib as a chronic treatment for adult patients with ISM.

Abstract Background: Systemic mastocytosis (SM) comprises a spectrum of subtypes characterized by neoplastic mast cell (MC) infiltration of tissues and release of MC mediators. Non-advanced SM (NonAdvSM), including indolent SM (ISM), smoldering SM (SSM), and bone marrow mastocytosis (BMM) subtypes, is the most prevalent form of SM. NonAdvSM can be associated with debilitating symptomology which can significantly impair quality of life. The gain-of-function somatic KIT c.2447 C>T (p.D816V) mutation is found in up to 95% of patients with SM. Bezuclastinib (CGT9486) is an oral, potent, and selective type 1 tyrosine kinase inhibitor with activity against KIT D816V. Results from Summit (NCT05186753) Part 1 informed the recommended phase 2 dose (100 mg QD bezuclastinib) for Part 2. We report topline results from the 24-week assessment of Summit Part 2. Methods: Summit is a multi-center, randomized, double-blind, placebo (PBO)-controlled Phase 2 trial of bezuclastinib in patients with NonAdvSM who had inadequate symptom control despite best supportive care (BSC) medications. The primary endpoint was 24-week mean change from baseline in Mastocytosis Symptom Severity Daily Diary (MS2D2) total symptom score (TSS) (range 0–110), which is a fit-for-purpose patient-reported outcome measure of NonAdvSM symptom severity. Key secondary endpoints included the proportion of patients with ≥50% reduction in serum tryptase, KIT p.D816V variant allele frequency (VAF), bone marrow (BM) MC burden, and MS2D2 TSS, ≥30% TSS reduction. Patients were randomized 2:1 to receive 100mg QD bezuclastinib + BSC or PBO + BSC. Results: As of May 22, 2025, 179 patients were enrolled in Part 2: 119 were randomized to receive bezuclastinib and 60 to placebo. Patients enrolled were representative of the NonAdvSM population with moderate to severe symptoms. Median age (range) was 51 (23-78) years; 65.9% female; mean (SD) baseline MS2D2 TSS 55.6 (19.8); 82% of patients had ISM, 11% had BMM, and 7% had smoldering SSM. At baseline, median (range) KIT p.D816V VAF in whole blood, BM MC burden, and serum tryptase was 0.25% (0-34%), 10% (1-75%), and 40 (6-692) ng/mL, respectively. Bezuclastinib demonstrated statistically significant superiority to placebo on all primary and key secondary endpoints. At Week 24, bezuclastinib led to significantly greater symptom improvement vs placebo (LS mean [95% CI] MS2D2 TSS change: –24.3 [–27.6 to –21.1] vs –15.4 [–19.6 to –11.2]; placebo-adjusted difference: –8.9 points; P=0.0002). A ≥50% reduction in serum tryptase was achieved in 87.4% of bezuclastinib-treated patients vs 0% on placebo (P<0.0001). Significantly more patients receiving bezuclastinib achieved ≥50% reductions in KIT D816V VAF, serum tryptase, BM MCs (P<0.0001), MS2D2 TSS (P=0.01), and ≥30% reduction in MS2D2 TSS (P=0.0004). Most treatment-emergent adverse events (TEAEs) were low grade (gr; 70% Gr 1) and reversible. The most common TEAEs (≥10%) in any treatment group and occurring in greater frequency in the bezuclastinib arm were hair color changes (69.5% vs 5.0%), altered taste (23.7% vs 0%), nausea (22.0% vs 13.3%), increased ALT/AST (22.0% vs 6.6%), headache (17.8% vs 11.7%), alopecia (11.9% vs 3.3%), and increased ALP (10.2% vs 3.3%). TEAEs (≥10%) that occurred more often in the placebo group were diarrhea (13% vs 18%), dizziness (10% vs 12%), fatigue (7% vs 12%), and arthralgia (6% vs 15%). ALT/AST elevations ≥Gr 3 were experienced by 5.9% of patients. The only hepatic adverse events (AEs) reported were transient lab abnormalities; none required hospitalization. Treatment-related AEs requiring dose reductions occurred in 11% of patients receiving bezuclastinib. All discontinuations (5.9%) due to treatment-related AEs were due to transaminase elevations; all fully resolved. Conclusions: At 24-weeks, bezuclastinib 100 mg QD demonstrated statistically and clinically significant improvements in symptom burden and biomarkers of disease vs placebo in patients with NonAdvSM. The treatment was generally well-tolerated and effective across a population that is representative of the real-world NonAdvSM population, including SSM. These results support the use of bezuclastinib to reduce SM burden and symptoms in pts with NonAdvSM, and a potentially disease-modifying impact.

Abstract Introduction Extramedullary hematopoiesis (EMH) is the production of blood cells outside of bone marrow. It is associated with myeloproliferative neoplasms such as myelofibrosis and chronic myeloid leukemia. Most common sites for EMH are liver and spleen, but other sites may be involved. Pulmonary EMH is extremely rare. It is associated with symptoms of dyspnea, cough or chest pain. Chest imaging may demonstrate pulmonary nodules or masses, alveolar septal thickening, ground glass opacities, and/or patchy consolidations. We present a case of a woman with primary myelofibrosis who developed pulmonary hypertension (PH) in the setting of pulmonary EMH. Case description 73-year-old woman with history of primary myelofibrosis (diagnosed via bone marrow biopsy, grade 3 fibrosis, being treated with hydroxyurea) presented with progressive exertional dyspnea for 1.5 years. Exam was notable for elevated jugular venous pressure and mild peripheral edema. Labs revealed anemia with hemoglobin 8.2 g/dL, thrombocytosis with platelets 549K/dL and no leukocytosis. Brain natriuretic peptide was elevated at 1361 ng/L. Chest CT demonstrated few peripheral wedge-shaped opacities in the bilateral lower lobes were noted. Pulmonary function tests revealed normal spirometry and lung volumes but moderately reduced diffusion capacity. Echocardiogram showed normal left ventricular (LV) size and function with ejection fraction 60%, moderately enlarged right ventricle (RV) and RV systolic pressure 63 mmHg. Right heart catheterization showed RA pressure:14 mmHg, PA: 49/26/36 mmHg, PCWP 15mmHg, thermodilution CO 5.5 L/min, CI 3.1L/min/m2, Fick CO 4.6 L/min, CI 2.6 L/min/m2, pulmonary vascular resistance 3.8-4.6 Woods Units. Given her history of myelofibrosis, Tc-99m bone marrow scan was performed which showed diffuse radiotracer uptake in both lungs suggestive of pulmonary EMH. She subsequently underwent radiation therapy with 100cGy to bilateral lungs. On a follow-up visit two months later, she reported symptomatic improvement. Repeat NM bone scan showed decreased tracer uptake in the lungs. Discussion PH associated with myeloproliferative neoplasia is classified as group 5 in the latest clinical classification. It can be due to thrombocytosis, hypercoagulability, left ventricular failure, portal hypertension and/or hematopoietic infiltration of the pulmonary parenchyma. Tc-99m sulfur colloid scanning can be used to detect hematopoietic tissue in the lung. Treatment is usually radiation-therapy to the lungs to control the hematopoiesis. In patients with myeloproliferative neoplasms presenting with dyspnea, consider screening for PH with echocardiogram.

Abstract Rationale Patients with pulmonary hypertension (PH) often require significant assistance from caregivers. Caregivers frequently help patients with numerous PH-related tasks, such as medication administration and insurance coordination, in addition to emotional and other forms of support. However, little is known about optimal strategies for engaging and empowering caregivers in PH. We sought to improve understanding of PH patients’ and caregivers’ perspectives on the role of caregiving to identify ways to better support them. Methods We performed a cross-sectional survey of PH patients and/or their adult caregivers participating in the Pulmonary Hypertension Association conference in August 2024. Questions focused on roles and perspectives towards caregiving. Study participation was voluntary without monetary or other compensation. Results Sixteen patients and 18 caregivers completed the survey, with 9 patient and caregiver pairs. Patient characteristics and responses are detailed in Table 1. The majority of patients (87.5%) reported that caregivers play a “very important” role in their lives. (Table 1) Most surveyed caregivers were patients’ significant others (10/18, 55.5%) or parents (7/18, 38.9%), with average age 59 years, and were employed full-(10/18, 55.5%) or part-time (3/18, 16.7%). Regarding their role(s), all caregivers (18/18) reported providing emotional support, 7/18 (38.9%) physical support (e.g. mobility, hygiene assistance), 7/18 (38.9%) help with medications, and 13/18 (72.2%) help with transportation to appointments. 4/18 (22.2%) caregivers reported they spend more than 20 hours/week on caregiving-related tasks while most reported they spend 5-20 hours/week. Caregivers detailed challenges regarding emotional support (e.g. “Spouse seems to be very short with me most of the time. I think she hates this disease and takes it out on others”), among others. However, they also reported caregiving to be rewarding (e.g. “Seeing my husband improve, and getting to be on his side to advocate for him and other patients.”) Caregivers had many suggestions for what they would like to see in a program focused on supporting them, including “Online education such as resources and experts such as new treatments, insurance information…How to advocate better. Tips for self care” and “Connection to therapist who understand chronic diseases and the challenges of long term caregivers.” Conclusions Caregivers play an integral and multifaceted role in the lives of patients with PH. Caregivers would appreciate additional education, resources and support.

Abstract RATIONALE: Many ICU patients experience physical, psychological, and cognitive impairments following resolution of critical illness, collectively referred to as post-intensive care syndrome (PICS). PICS has become widely recognized within the critical care field, but how to screen for PICS does not currently have consensus. Development of a validated, concise PICS screening tool would allow for rapid identification of this vulnerable and understudied population. Therefore, this study's goal was to develop and evaluate a screening tool to identify patients at risk for PICS. METHODS: We performed a prospective cohort study in a quaternary academic hospital. We included adults ≥ 18 years old with ≥48 hours spent in an ICU. Exclusion criteria were admission for suicide attempt, severe cognitive impairment/dementia, life expectancy <3 months, and non-English speaking. We assessed mental, cognitive, and physical function following ICU discharge and at 3 months using Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised, Montreal Cognitive Assessment-blind, and Barthel Index. Our team, including critical care physicians, psychiatrists, psychologists, physical and occupational therapists, and nurses, developed a brief 15-item PICS screening tool (5 questions/domain). This tool was administered after patients were discharged from ICU stay to general care to assess its effectiveness in predicting impairments in all 3 domains at discharge and again at three months after hospital discharge, in comparison to previously mentioned validated questionnaires. Youden index statistical methods were used to determine potential “cutoff” values (scores) for the tool to maximize sensitivity and specificity. RESULTS: A total of 194 patients from 6 ICUs were recruited and completed the initial questionnaire, and 109 (56%) patients completed 3-month follow-up. Median age was 65 years (IQR 57-72) and 49% (95/194) were female. Screening tool is depicted in Figure 1. Overall, the screening tool weakly-to-moderately correlated with continuous outcomes of the validated measures upon ICU discharge and 3-month follow-up. When evaluating sensitivity and specificity for individual domains, the tool had an area under the receiver operating curve of >0.7 for the following domains: cognitive, anxiety, and physical impairments, indicating moderate-to-good sensitivity and specificity. CONCLUSIONS: This PICS screening tool was correlated with validated measures of PICS upon ICU discharge and at 3-month follow-up for all three domains. The tool's strength lies in its concise nature, making it easier for those caring for this patient population to screen for long-term effects of an ICU stay. Our proposed next step is validation of the PICS screening tool in an external cohort.