Jacobs Institute of Women's Health
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CT derived fractional flow reserve: Part 2 - Critical appraisal of the literature
No full textThe integration of computed tomography-derived fractional flow reserve (CT-FFR), utilizing computational fluid dynamics and artificial intelligence (AI) in routine coronary computed tomographic angiography (CCTA), presents a promising approach to enhance evaluations of functional lesion severity. Extensive evidence underscores the diagnostic accuracy, prognostic significance, and clinical relevance of CT-FFR, prompting recent clinical guidelines to recommend its combined use with CCTA for selected individuals with with intermediate stenosis on CCTA and stable or acute chest pain. This manuscript critically examines the existing clinical evidence, evaluates the diagnostic performance, and outlines future perspectives for integrating noninvasive assessments of coronary anatomy and physiology. Furthermore, it serves as a practical guide for medical imaging professionals by addressing common pitfalls and challenges associated with CT-FFR while proposing potential solutions to facilitate its successful implementation in clinical practice
Trained autologous cytotoxic T-cells derived from PBMCs or splenocytes for immunotherapy of neuroblastoma
No full textBACKGROUND: Pediatric solid tumors, particularly neuroblastoma, present significant treatment challenges due to the limited efficacy of existing therapies. Adoptive immunotherapy, which involves transferring immune cells has shown clinical promise. Optimizing the preparation of immune cells ex vivo is critical to enhancing tumor immunity. This study introduces a novel method for improving the efficacy of autologous peripheral blood mononuclear cells (PBMCs) for neuroblastoma treatment. METHODS: An IRB-approved protocol was used to collect tumor samples and PBMCs from eight patients undergoing neuroblastoma biopsy or resection. Primary tumor cells were isolated, cultured, and characterized using Phox2b and synaptophysin staining. Autologous PBMCs were co-cultured with irradiated tumor cells pre-treated with MYC inhibitors (I-BET726, JQ1) and a STING antagonist (C170) to enhance immunogenicity and train tumor-specific PBMCs. The immunogenicity and gene expression changes in treated tumor cells were assessed through multiplex ELISA and NanoString Tumor Signaling profiling. The phenotype and cytotoxicity of the trained PBMCs were evaluated by flow cytometry, IFN-γ ELISA, and IncuCyte assays. RESULTS: Trained PBMCs primarily induced potent tumor cell cytotoxicity in patient-derived cellular products. In a preclinical neuroblastoma mouse model, similarly trained splenocytes demonstrated powerful efficacy, mirroring the findings in patient-derived PBMCs. This approach generates immunogenic tumor cells through modulation with small molecule inhibitors and radiation, enabling PBMCs or splenocytes to induce cytotoxic trained autologous tumor-specific T cells under controlled in vitro conditions. These trained PBMCs and splenocytes exhibit potent cytotoxicity against neuroblastoma, with significant therapeutic effects as an adoptive cellular immunotherapy in vivo. CONCLUSIONS: This study provides preliminary evidence supporting the efficacy of a personalized, PBMC-based immunotherapy for neuroblastoma. These findings highlight the potential for further development of this approach as a novel treatment strategy, paving the way for improved clinical outcomes in pediatric oncology
An urgent need for diagnostic tools to address global mpox public health emergencies
No full textMonkeypox virus (MPXV) is the causative agent of mpox, a zoonosis formerly known as monkeypox. MPXV can be divided into clades I and II, which are further divided into subclades Ia, Ib, IIa, and IIb. Since May 2022, subclade IIb MPXV has rapidly spread outside Africa to more than 100 countries due to increased human-to-human transmission. Clade I is a more virulent MPXV endemic in Central Africa with up to 10% mortality in humans. Clade I has recently evolved into a novel subclade Ib and caused outbreaks in non-endemic neighboring countries and other continents. In response to mpox, the World Health Organization has declared Public Health Emergencies of International Concern in July 2022 (subclade IIb) and August 2024 (subclade Ib). The emergence and spread of the more virulent subclade Ib MPXV has caused a significant global public health threat, particularly in low- and middle-income countries (LMICs). The evolution of MPXV has outpaced the development of novel diagnostic assays, hampering the global response. There is an urgent need for additional diagnostic tools for the detection and surveillance of MPXV, especially subclade Ib MPXV, in LMICs. Herein, we provide the current epidemiology of mpox, analyze the diagnostic gaps for mpox, and evaluate the potential of additional detection strategies to be added to the suite of mpox assays. This commentary not only sheds light on the currently available diagnostic tools for mpox but also highlights the urgent need for additional diagnostic tools in response to the new global mpox public health threats
Facilitators in treatment pathways for depression or anxiety among adults in Nepal: a qualitative study
No full textBACKGROUND: Depression and anxiety are prevalent mental health issues globally, yet many individuals in low- and middle-income countries lack access to treatment. Limited research exists on mental health service utilization in these regions. Understanding the factors that affect access to care and treatment pathways can improve mental health services. This study examines the factors that facilitate the initiation and continuation of treatment for depression or anxiety in Nepal. METHODS: The study was conducted in three districts in Nepal: Jhapa, Chitwan, and Kailali districts, representing the eastern, central, and far-western regions. The participants were adults receiving treatment for depression or anxiety from various healthcare providers. A total of 24 participants were purposively recruited, including 13 with symptoms of depression, 9 with symptoms of anxiety, and 2 with both conditions. We utilized the McGill Illness Narrative Interview, a semi-structured protocol commonly used in mental health research, to collect detailed narratives on symptom experiences, illness accounts, and help-seeking behaviors. Data analysis was performed using a framework and thematic analysis approach with NVIVO software. RESULTS: Treatment pathways for depression and anxiety in Nepal are complex, involving multiple service providers and recurrent treatment from the same providers. Out of a total of 137 sessions across 24 patients, the majority of sessions were with traditional faith healers (27.7%), followed by private hospitals (19.7%), primary healthcare facilities (16.1%), government hospitals (13.1%), neighboring countries (11.7%), and private clinics (8.0%). Traditional healers were the most popular choice for initial visits, followed by private clinics and government hospitals. Factors such as service quality, provider behavior, availability of trained providers, appointment process, confidentiality, and types of services offered influenced care-seeking decisions. Support from family or friends, awareness of mental health issues, and recommendations from trusted individuals also played a significant role. CONCLUSION: Treatment pathways for depression and anxiety disorders are complex, often involving multiple sessions with various service providers and a combination of services. It is crucial to improve healthcare providers\u27 behavior, appointment scheduling, and consultation quality to encourage individuals to seek care. Raising awareness about mental health conditions and available services through different channels and training traditional healers in mental health could help enhance access to care
Replicating and Extending the Reliability, Criterion Validity, and Treatment Sensitivity of the PANSS10 and PANSS20 for Pediatric Trials
No full textOBJECTIVE: Pediatric studies of schizophrenia have relied on the 30-item Positive and Negative Syndrome Scale (PANSS30) as a primary outcome measure. There have been many efforts to create shorter versions of it to reduce costs and burden. The present aim is to conduct a confirmatory investigation of the reliability and validity of 10- and 20-item abbreviated versions developed in a United States-based National Institute of Mental Health (NIMH) pediatric sample that reflects the 5-factor structure underlying the PANSS, adding more detailed examination of patient-level score reproducibility and extending the examination to a large, placebo-controlled, international pediatric trial. METHOD: We applied the same psychometric and treatment sensitivity analyses as in Findling et al. (2023) to an adolescent schizophrenia paliperidone randomized placebo-controlled trial (RCT), accessed via the Yale Open Data Access (YODA) secure data environment (described in Singh et al., 2011). Analyses included confirmatory factor analyses, graded response models, ω reliability coefficients, tests of convergent criterion validity, sensitivity to change, and Bland-Altman plots to evaluate score reproducibility. RESULTS: Using the paliperidone RCT dataset, with N = 201 participants between the ages of 12 and 17 years (mean age = 15.40, SD = 1.53 years; 59% male), the PANSS 10- or 20-item vs 30-item versions had similar average interitem correlations (0.11-0.15); ω reliabilities of 0.78 to 0.89 with reliability \u3e0.80 across patient presentations from mild residual symptoms to severe pathology; correlations of 0.92 and 0.98 with the 30-item total; partial eta-squared (η) values for time, treatment, and time by treatment; and also correlations with Clinical Global Impression (CGI) severity and Children\u27s Global Assessment Scale (CGAS) ratings. Per-item scores differed by 0.04 points on average on the PANSS10 and by 0.01 points for the PANSS20 vs the PANSS30, all not significant. CONCLUSION: Results replicated reliability and validity findings for the PANSS10 and PANSS20 short forms in an international pediatric randomized placebo-controlled trial. Findings extend prior work by being the first to apply modern reliability models (ω) for multi-factor composites, also using Bland-Altman methods to evaluate patient-level score reproducibility. Scores based on the PANSS10 or PANSS20 reproduce traditional scores with high fidelity and low bias, offering substantial savings in terms of time, cost, and burden, especially when used for tracking progress or outcomes. CLINICAL GUIDANCE: • Consider using the 10-item or 20-item PANSS for regular monitoring and assessment of pediatric schizophrenia patients. These shorter versions maintain high reliability and can streamline the evaluation process, making it more efficient.• Patient and family engagement: Use the abbreviated PANSS versions to engage more effectively with patients and their families. The reduced length of the assessment can alleviate the stress and fatigue associated with longer evaluations, potentially improving patient cooperation and the quality of the data collected
Health Literacy Among Sexual and Gender-Diverse Adolescents in New York City
No full textThis study explored sexual orientation and gender identity as predictors of health literacy among adolescents attending New York City (NYC) public high schools. Many studies have demonstrated disparities in sexual health among sexual and gender minority (SGM) adolescents. However, little is known about their health literacy. Health literacy, defined as the capacity to acquire, understand, appraise, and apply health information, especially in health decision-making, is a known predictor of health. Data came from a quantitative cross-sectional survey (N = 1,438) collected at 15 high schools in the Bronx, NYC. Four aspects of health literacy were explored: (1) knowledge of sexually transmitted infections (STIs), (2) knowledge of sexual health rights in New York State, (3) health access literacy and self-efficacy, and (4) health communication. Linear regression analysis was used to test predictors of health literacy. Contrary to our hypothesis, SGM adolescents did not score significantly lower on the health literacy variables compared with cisgender heterosexual adolescents. SGM adolescents scored significantly higher on knowledge of STIs and knowledge of health rights compared with cisgender heterosexual young men. Adolescents who were questioning their sexual identity scored significantly lower compared with both SGM and cisgender heterosexual adolescents on all four health literacy scales. Interventions are needed to ensure that in-school curricula are inclusive and address health literacy among questioning adolescents and cisgender heterosexual young men. Addressing the health needs of questioning adolescents is particularly important because adolescence is a critical time of decision-making around sexuality and health
Neonatal Neurocardiac Care: Strategies to Optimize Neurodevelopmental Outcomes in Congenital Heart Disease
No full textNeonates with critical congenital heart disease are at high risk for brain injury and neurodevelopmental disabilities. Neurocardiac care is a developing field, and there are few guidelines for front-line providers regarding neuromonitoring and neuroprotection. Understanding influences on early brain development, risk for seizures and brain injury, and long-term developmental outcomes can help providers formulate appropriate action plans for individual patients. Current evidence suggests that prenatal diagnosis, minimizing medical risk factors, monitoring for brain injury and seizures, providing individualized developmental care, supporting parental mental health, and referral to long-term developmental follow-up are components of care that may improve outcomes
Medical Child Abuse: Clinicians as Healers, Abusers, and Expert Witnesses
No full textMedical child abuse (MCA) occurs when a caregiver falsifies signs and symptoms resulting in a child receiving unnecessary and harmful or potentially harmful medical care. Like other conditions, MCA can be diagnosed using traditional diagnostic methods. MCA carries significant risk of morbidity and mortality. Collaboration between clinicians, and when necessary, between clinicians and Child Protective Services increases the likelihood of diagnosis and successful management
