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Background: Identifying germline predisposition in CNS malignancies is of increasing clinical importance, as it contributes to diagnosis and prognosis, and determines aspects of treatment. The inclusion of germline testing has historically been limited due to challenges surrounding access to genetic counseling, complexity in acquiring a germline comparator specimen, concerns about the impact of findings, or cost considerations. These limitations were further defined by the breadth and scope of clinical testing to precisely identify complex variants as well as concerns regarding the clinical interpretation of variants including those of uncertain significance. Methods: In the course of conducting an IRB-approved protocol that performed genomic, transcriptomic and methylation-based characterization of pediatric CNS malignancies, we cataloged germline predisposition to cancer based on paired exome capture sequencing, coupled with computational analyses to identify variants in known cancer predisposition genes and interpret them relative to established clinical guidelines. Results: In certain cases, these findings refined diagnosis or prognosis or provided important information for treatment planning. Conclusions: We outline our aggregate findings on cancer predisposition within this cohort which identified 16% of individuals (27 of 168) harboring a variant predicting cancer susceptibility and contextualize the impact of these results in terms of treatment-related aspects of precision oncology.
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[This corrects the article DOI: 10.3389/fimmu.2024.1384623.].
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Modelos Animales de Enfermedad , Viroterapia Oncolítica , Animales , Viroterapia Oncolítica/métodos , Ratones , Inmunoterapia/métodos , Humanos , Virus Oncolíticos/inmunología , Virus Oncolíticos/genética , Terapia CombinadaRESUMEN
BACKGROUND: Macrophages play important roles in phagocytosing tumor cells. However, tumors escape macrophage phagocytosis in part through the expression of anti-phagocytic signals, most commonly CD47. In Ewing sarcoma (ES), we found that tumor cells utilize dual mechanisms to evade macrophage clearance by simultaneously over-expressing CD47 and down-regulating cell surface calreticulin (csCRT), the pro-phagocytic signal. Here, we investigate the combination of a CD47 blockade (magrolimab, MAG) to inhibit the anti-phagocytic signal and a chemotherapy regimen (doxorubicin, DOX) to enhance the pro-phagocytic signal to induce macrophage phagocytosis of ES cells in vitro and inhibit tumor growth and metastasis in vivo. METHODS: Macrophages were derived from human peripheral blood monocytes by granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Flow cytometry- and microscopy-based in-vitro phagocytosis assays were performed to evaluate macrophage phagocytosis of ES cells. Annexin-V assay was performed to evaluate apoptosis. CD47 was knocked out by CRISPR/Cas9 approach. ES cell-based and patient-derived-xenograft (PDX)-based mouse models were utilized to assess the effects of MAG and/or DOX on ES tumor development and animal survival. RNA-Seq combined with CIBERSORTx analysis was utilized to identify changes in tumor cell transcriptome and tumor infiltrating immune cell profiling in MAG and/or DOX treated xenograft tumors. RESULTS: We found that MAG significantly increased macrophage phagocytosis of ES cells in vitro (p < 0.01) and had significant effect on reducing tumor burden (p < 0.01) and increasing survival in NSG mouse model (p < 0.001). The csCRT level on ES cells was significantly enhanced by DOX in a dose- and time-dependent manner (p < 0.01). Importantly, DOX combined with MAG significantly enhanced macrophage phagocytosis of ES cells in vitro (p < 0.01) and significantly decreased tumor burden (p < 0.01) and lung metastasis (p < 0.0001) and extended animal survival in vivo in two different mouse models of ES (p < 0.0001). Furthermore, we identified CD38, CD209, CD163 and CD206 as potential markers for ES-phagocytic macrophages. Moreover, we found increased M2 macrophage infiltration and decreased expression of Cd209 in the tumor microenvironment of MAG and DOX combinatorial therapy treated tumors. CONCLUSIONS: By turning "two keys" simultaneously to reactivate macrophage phagocytic activity, our data demonstrated an effective and highly translatable alternative therapeutic approach utilizing innate (tumor associated macrophages) immunotherapy against high-risk metastatic ES.
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Inmunoterapia , Macrófagos , Sarcoma de Ewing , Sarcoma de Ewing/inmunología , Sarcoma de Ewing/patología , Sarcoma de Ewing/terapia , Sarcoma de Ewing/tratamiento farmacológico , Animales , Ratones , Humanos , Macrófagos/inmunología , Macrófagos/metabolismo , Inmunoterapia/métodos , Antígeno CD47/metabolismo , Línea Celular Tumoral , Fagocitosis , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Inmunidad Innata , Modelos Animales de EnfermedadRESUMEN
OBJECTIVES: To measure the effect of routine vaccination on serum amyloid A (SAA) concentration in apparently healthy horses. We hypothesized that routine vaccination would increase SAA in healthy horses. ANIMALS: 21 apparently healthy client-owned horses and 15 Kansas State University College of Veterinary Medicine-owned horses. METHODS: In experiment 1 (n = 8 horses), a blinded, randomized, prospective, crossover study was performed. Horses were either vaccinated (rabies, tetanus, West Nile, Eastern and Western equine encephalomyelitis, equine herpesvirus-1/-4, influenza) or administered saline, and SAA was measured at 6, 12, and 24 hours and daily until day 10 with a commercial lateral-flow immunoassay. In experiment 2 (n = 28 horses), a prospective, observational study measured SAA after vaccination at 12 and 24 hours and daily until day 10. A linear mixed-effect model with repeated measures over time blocked by horse tested the effect of treatment on SAA. A repeated-measures correlation tested the correlation between SAA and temperature. RESULTS: Over time, vaccinated horses had increased model-adjusted SAA compared to unvaccinated horses without clinical evidence of adverse reaction (P < .01). In experiment 1, the model-adjusted SAA after vaccination peaked on day 2 (median, 1,872 µg/mL; IQR, 1,220.8 to 2,402.5 µg/mL) and returned to normal (< 20 µg/mL) by day 9 (median, 6 µg/mL; IQR, 0.8 to 23.5 µg/mL) after vaccination. In experiment 2, vaccinated horses had increased SAA over time; temperature and SAA were not correlated (P = .78). CLINICAL RELEVANCE: Results of this study indicated that routine vaccination results in increased SAA concentration and provided evidence for a period of convalescence following vaccination. Measuring SAA for 10 days following vaccination cannot be used as an indicator of illness.
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Estudios Cruzados , Proteína Amiloide A Sérica , Vacunación , Animales , Caballos , Proteína Amiloide A Sérica/análisis , Femenino , Vacunación/veterinaria , Masculino , Enfermedades de los Caballos/prevención & control , Estudios Prospectivos , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunologíaRESUMEN
Introduction: Malignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness. Methods: Here we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy's antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others. Results: Myelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment. Discussion: In summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.
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Modelos Animales de Enfermedad , Viroterapia Oncolítica , Microambiente Tumoral , Animales , Viroterapia Oncolítica/métodos , Ratones , Microambiente Tumoral/inmunología , Virus Oncolíticos/inmunología , Virus Oncolíticos/genética , Línea Celular Tumoral , Inmunoterapia/métodos , Humanos , Terapia Combinada , Femenino , Ratones Endogámicos C57BL , Neoplasias de la Vaina del Nervio/terapia , Neoplasias de la Vaina del Nervio/inmunología , Neoplasias de la Vaina del Nervio/genética , Aminopiridinas , PirrolesRESUMEN
A growing proportion of individuals adopt family caregiving roles. Family caregivers are the primary providers of long-term care in the United States yet limited federal policy supports exist, despite the known negative impacts of caregiving. There is also limited information about the prevalence of youth/young adult caregivers and the impacts of caregiving at formative ages in the United States. Our objective is to estimate the prevalence of youth caregivers and examine the association of caregiving with educational investments. We use the American Time Use Survey (2013-2019) to identify and describe youth caregivers (aged 15-18) and young adult caregivers (aged 19-22) and compare them with non-caregiving peers. We estimate that there are approximately 1,623,000 youth caregivers and 1,986,000 young adult caregivers, corresponding to 9.2% and 12.7% of these age groups, respectively. However, there is a wide range in the estimated prevalence per year, from approximately 364,000 to 2.8 million youth caregivers and from 353,000 to 2.2 million young adult caregivers, depending on caregiver definition. Unlike adult caregivers, we find that young men and women were nearly equally likely to provide care. We also find that non-White individuals are disproportionately represented as youth caregivers. Compared with non-caregiving peers, both youth and young adult caregivers are less likely to be enrolled in school and, among those enrolled in school, spend significantly less time on educational activities. Considering the association of caregiving among youth/young adults and education, policies supporting youth and young adult caregivers are critical.
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Cuidadores , Escolaridad , Humanos , Cuidadores/estadística & datos numéricos , Adolescente , Estados Unidos , Masculino , Femenino , Adulto Joven , Prevalencia , Factores Socioeconómicos , Factores Sociodemográficos , Adulto , Factores de EdadRESUMEN
Low-grade glioma (LGG) is the most common brain tumor affecting pediatric patients (pLGG) and BRAF mutations constitute the most frequent genetic alterations. Within the spectrum of pLGGs, approximately 70%-80% of pediatric patients diagnosed with transforming pleomorphic xanthoastrocytoma (PXA) harbor the BRAF V600E mutation. However, the impact of glioma BRAF V600E cell regulation of tumor-infiltrating immune cells and their contribution to tumor progression remains unclear. Moreover, the efficacy of BRAF inhibitors in treating pLGGs is limited compared with their impact on BRAF-mutated melanoma. Here we report a novel immunocompetent RCAS-BRAF V600E murine glioma model. Pathological assessment indicates this model seems to be consistent with diffuse gliomas and morphological features of PXA. Our investigations revealed distinct immune cell signatures associated with increased trafficking and activation within the tumor microenvironment (TME). Intriguingly, immune system activation within the TME also generated a pronounced inflammatory response associated with dysfunctional CD8+ T cells, increased presence of immunosuppressive myeloid cells and regulatory T cells. Further, our data suggests tumor-induced inflammatory processes, such as cytokine storm. These findings suggest a complex interplay between tumor progression and the robust inflammatory response within the TME in preclinical BRAF V600E LGGs, which may significantly influence animal survival.
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Genesis of skeletal muscle relies on the differentiation and fusion of mono-nucleated muscle progenitor cells into the multi-nucleated muscle fiber syncytium. The temporally-controlled cellular and morphogenetic changes underlying this process are initiated by a series of highly coordinated transcription programs. At the core, the myogenic differentiation cascade is driven by muscle-specific transcription factors, i.e., the Myogenic Regulatory Factors (MRFs). Despite extensive knowledge on the function of individual MRFs, very little is known about how they are coordinated. Ultimately, highly specific coordination of these transcription programs is critical for their masterfully timed transitions, which in turn facilitates the intricate generation of skeletal muscle fibers from a naïve pool of progenitor cells. The Mediator complex links basal transcriptional machinery and transcription factors to regulate transcription and could be the integral component that coordinates transcription factor function during muscle differentiation, growth, and maturation. In this study, we systematically deciphered the changes in Mediator complex subunit expression in skeletal muscle development, regeneration, aging, and disease. We incorporated our in vitro and in vivo experimental results with analysis of publicly available RNA-seq and single nuclei RNA-seq datasets and uncovered the regulation of Mediator subunits in different physiological and temporal contexts. Our experimental results revealed that Mediator subunit expression during myogenesis is highly dynamic. We also discovered unique temporal patterns of Mediator expression in muscle stem cells after injury and during the early regeneration period, suggesting that Mediator subunits may have unique contributions to directing muscle stem cell fate. Although we observed few changes in Mediator subunit expression in aging muscles compared to younger muscles, we uncovered extensive heterogeneity of Mediator subunit expression in dystrophic muscle nuclei, characteristic of chronic muscle degeneration and regeneration cycles. Taken together, our study provides a glimpse of the complex regulation of Mediator subunit expression in the skeletal muscle cell lineage and serves as a springboard for mechanistic studies into the function of individual Mediator subunits in skeletal muscle.
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PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax. PATIENTS AND METHODS: In this study, we report the findings of four patients enrolled onto the NeoVax clinical trial (NCT0342209). RESULTS: Immune reactivity to NeoVax neoantigens was assessed in peripheral blood mononuclear cells pre- and post-NeoVax for patients 1 to 3 using IFNγ-ELISPOT assay. A statistically significant increase in IFNγ producing T cells at the post-NeoVax time point for several neoantigens was observed. Furthermore, a post-NeoVax tumor biopsy was obtained from patient 3 and, upon evaluation, revealed evidence of infiltrating, clonally expanded T cells. CONCLUSIONS: Collectively, our findings suggest that NeoVax stimulated the expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine-based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in patients with GBM.
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Antígenos de Neoplasias , Vacunas contra el Cáncer , Glioblastoma , Medicina de Precisión , Vacunas de Subunidad , Humanos , Glioblastoma/inmunología , Glioblastoma/terapia , Glioblastoma/genética , Glioblastoma/patología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/uso terapéutico , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/uso terapéutico , Medicina de Precisión/métodos , Antígenos de Neoplasias/inmunología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Adulto , Anciano , Inmunoterapia/métodos , Vacunas de Subunidades ProteicasRESUMEN
OBJECTIVE: Endoscopic management of subglottic stenosis (SGS) includes a wide range of techniques. This 17-year review compares treatment outcomes between carbon dioxide (CO2) laser and cold steel. STUDY DESIGN: Retrospective chart review. SETTING: Single tertiary care center. METHODS: A chart review was performed for all patients undergoing endoscopic treatment of SGS at Cleveland Clinic between July 12, 2000 and September 1, 2017. Data collected included demographics, stenosis etiology, stenosis severity, comorbidities, treatment modality, and airway procedure history. The primary endpoint was repeated treatment-free survival (RTFS) within 2 years using a Kaplan-Meier analysis and Cox proportional hazard model. RESULTS: A total of 139 patients (median [interquartile range] aged 48.7 [37.8, 57.0] years; 83.4% female) were included in the analysis, with etiologies including idiopathic (56.8%), granulomatosis with polyangiitis (25.2%), and intubation (16.5%). All patients underwent either cold steel (107 patients) or CO2 laser (32 patients) lysis of stenosis with concurrent dilation. RTFS within 2 years was 50.2% for CO2 laser and 31.9% for cold steel (hazard ratio [HR] and 95% confidence interval [CI]: 1.69, 0.96-2.97, P = .07). In patients with no prior airway procedures, there was no difference in RTFS between laser and cold knife (P = .41). However, in patients with prior airway procedures, RTFS was significantly greater in the laser group, even after adjusting for age, smoking history, and stenosis etiology (50.0% vs 16.8%, adjusted HR and CI: 2.82, 1.14-6.98, P = .025). CONCLUSION: Endoscopic lysis of SGS with CO2 laser should be considered in revision cases.
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Laringoestenosis , Láseres de Gas , Humanos , Laringoestenosis/cirugía , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Masculino , Láseres de Gas/uso terapéutico , Adulto , Resultado del Tratamiento , Laringoscopía/métodos , Terapia por Láser/métodosRESUMEN
BACKGROUND: Cancers exhibit complex transcriptomes with aberrant splicing that induces isoform-level differential expression compared to non-diseased tissues. Transcriptomic profiling using short-read sequencing has utility in providing a cost-effective approach for evaluating isoform expression, although short-read assembly displays limitations in the accurate inference of full-length transcripts. Long-read RNA sequencing (Iso-Seq), using the Pacific Biosciences (PacBio) platform, can overcome such limitations by providing full-length isoform sequence resolution which requires no read assembly and represents native expressed transcripts. A constraint of the Iso-Seq protocol is due to fewer reads output per instrument run, which, as an example, can consequently affect the detection of lowly expressed transcripts. To address these deficiencies, we developed a concatenation workflow, PacBio Full-Length Isoform Concatemer Sequencing (PB_FLIC-Seq), designed to increase the number of unique, sequenced PacBio long-reads thereby improving overall detection of unique isoforms. In addition, we anticipate that the increase in read depth will help improve the detection of moderate to low-level expressed isoforms. RESULTS: In sequencing a commercial reference (Spike-In RNA Variants; SIRV) with known isoform complexity we demonstrated a 3.4-fold increase in read output per run and improved SIRV recall when using the PB_FLIC-Seq method compared to the same samples processed with the Iso-Seq protocol. We applied this protocol to a translational cancer case, also demonstrating the utility of the PB_FLIC-Seq method for identifying differential full-length isoform expression in a pediatric diffuse midline glioma compared to its adjacent non-malignant tissue. Our data analysis revealed increased expression of extracellular matrix (ECM) genes within the tumor sample, including an isoform of the Secreted Protein Acidic and Cysteine Rich (SPARC) gene that was expressed 11,676-fold higher than in the adjacent non-malignant tissue. Finally, by using the PB_FLIC-Seq method, we detected several cancer-specific novel isoforms. CONCLUSION: This work describes a concatenation-based methodology for increasing the number of sequenced full-length isoform reads on the PacBio platform, yielding improved discovery of expressed isoforms. We applied this workflow to profile the transcriptome of a pediatric diffuse midline glioma and adjacent non-malignant tissue. Our findings of cancer-specific novel isoform expression further highlight the importance of long-read sequencing for characterization of complex tumor transcriptomes.
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Glioma , Transcriptoma , Humanos , Niño , Perfilación de la Expresión Génica/métodos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Empalme del ARN , Análisis de Secuencia de ARN , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
OBJECTIVE: There are several options for surgical management of subglottic stenosis, including endoscopic and open procedures. However, treatment algorithms, outcomes, and anesthetic management of subglottic stenosis during pregnancy are not well described. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane databases. REVIEW METHODS: A scoping review of management of subglottic stenosis during pregnancy was performed, and then reported in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria consisted of those with subglottic or tracheal stenosis aged greater than 18 years, those in whom management was performed during pregnancy, and those who reported delivery related outcomes. RESULTS: After systematic review and detailed search of 330 identified articles, 15 articles met inclusion criteria and were included in the final analysis. All studies were case reports or case series (level 4 evidence). This study identified 27 patients. The median age was 29 and the median gestational age at intervention was 28 weeks. Left lateral positioning and fetal heart rate monitoring were used in nearly every case. The most common intervention performed was endoscopic balloon dilation. In many cases, jet ventilation or transnasal humidified rapid insufflation ventilatory exchange was satisfactory for maintenance of the airway. Three women ultimately required tracheostomy prior to labor and delivery. There was no fetal death or complications reported in these studies, and all but one woman proceeded to deliver at term. CONCLUSION: Endoscopic balloon dilation during pregnancy is safe and effective, resulting in optimized respiratory outcomes for the mother and safe delivery of the fetus. The third trimester appears to be safe for airway intervention. Laryngoscope, 134:1014-1022, 2024.
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Laringoestenosis , Estenosis Traqueal , Embarazo , Humanos , Femenino , Anciano , Adulto , Lactante , Constricción Patológica/cirugía , Endoscopía/métodos , Traqueostomía , Estenosis Traqueal/cirugía , Tercer Trimestre del Embarazo , Laringoestenosis/cirugíaRESUMEN
Disabled Veterans commonly experience pain. The Program of Comprehensive Assistance for Family Caregivers (PCAFC) provides training, a stipend, and services to family caregivers of eligible Veterans to support their caregiving role. We compared ascertainment of veteran pain and pain treatment through health care encounters and medications (pain indicators) of participants (treated group) and non-participants (comparison group) using inverse probability treatment weights. Modeled results show that the proportion of Veterans with a pain indicator in the first year post-application was higher than that pre-application for both groups. However, the proportion of Veterans with a pain indicator was substantially higher in the treatment group: 76.1% versus 63.9% in the comparison group (p < .001). Over time, the proportion of Veterans with any pain indicator fell and group differences lessened. However, differences persisted through 8 years post-application (p < .001). PCAFC caregivers appear to help Veterans engage in pain treatment at higher rates than caregivers not in PCAFC.
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Personas con Discapacidad , Veteranos , Humanos , Cuidadores , Servicios de Salud , DolorRESUMEN
Psychological stress poses a risk for sleep disturbances. Importantly, trauma-exposed individuals who develop posttraumatic stress disorder (PTSD) frequently report insomnia and recurrent nightmares. Clinical studies have provided insight into the mechanisms of these sleep disturbances. We review polysomnographic findings in PTSD and identify analogous measures that have been made in animal models of PTSD. There is a rich empirical and theoretical literature on rapid eye movement sleep (REMS) substrates of insomnia and nightmares, with an emphasis on REMS fragmentation. For future investigations of stress-induced sleep changes, we recommend a focus on tonic, phasic and other microarchitectural REMS measures. Power spectral density analysis of the sleep EEG should also be utilized. Animal models with high construct validity can provide insight into gender and time following stressor exposure as moderating variables. Ultimately, preclinical studies with translational potential will lead to improved treatment for stress-related sleep disturbances.
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Annual wellness visits (AWVs) are an important component of primary care as they provide preventive services and an opportunity to identify safety and health risk factors for Medicare beneficiaries. However, primary care practices are facing unprecedented demands with high patient volumes, multimorbidity, a rapidly growing aging population, and primary care provider (PCP) shortages. RN-led models of care are increasingly recognized as a major key to providing quality care while relieving PCP demands. This article describes the implementation of an RN-led model of care pilot in an urban family practice to increase Medicare AWV completion and alleviate PCP burden.
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Envejecimiento , Medicare , Anciano , Estados Unidos , Humanos , Calidad de la Atención de Salud , Factores de RiesgoRESUMEN
OBJECTIVE: The aim of this Meta-analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity, leptin hormone, and its associated metabolic dysregulation. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, were searched for studies from 1946 to October 2022, using predefined syntax. REVIEW METHODS: Outcome data for the meta-analysis were extracted on odds ratios (OR) of CRS prevalence based on the presence of overweight/obesity and mean serum leptin levels. A Meta-analysis was performed using the DerSimonian-Laird estimator to pool extracted data by the generalized inverse variance approach. Random effect models were utilized due to the small sample size. A qualitative synthesis was performed on articles that did not meet the inclusion criteria for the Meta-analysis. RESULTS: Thirty-six studies met the systematic review inclusion criteria out of 1113 articles screened. A total of 6 studies were included in the pooled Meta-analysis of the various outcome variables. Our pooled meta-analysis observed a positive association between overweight/obesity and the prevalence of CRS (OR = 1.33, 95% confidence interval [CI]: 1.17-1.51). The pooled ratio of the means analysis of the mean serum leptin levels between CRS with nasal polyposis and control patients was 2.21 (95% CI: 1.45; 3.36). CONCLUSION: Our pooled Meta-analysis indicates a positive association between overweight/obesity and CRS. Future prospective studies are needed to explore the association between CRS and obesity with an understanding of potential confounding comorbidities, including studies focused on assessing the underlying immunologic mechanism of this association.
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Rinosinusitis , Sinusitis , Humanos , Sobrepeso/epidemiología , Leptina , Obesidad/complicaciones , Obesidad/epidemiología , Sinusitis/complicaciones , Sinusitis/epidemiología , Enfermedad CrónicaRESUMEN
Insomnia is a prevalent and negatively impactful disorder among veterans. The Department of Veterans Affairs (VA) has committed significant resources to the development and dissemination of training related to cognitive behavioral therapy for insomnia (CBT-I), the recommended first-line intervention for chronic insomnia disorder. It has been established that VA clinicians can be effectively trained to deliver high fidelity CBT-I and that treatment results in significant improvements in insomnia. However, there is a paucity of research examining rates and predictors of veterans' participation in CBT-I in routine VA clinical care. In this study, we conducted a secondary analysis of data from VA electronic health records (EHR) to determine individual predisposing, enabling, and need factors associated with CBT-I participation. The sample included veterans who had at least one CBT-I templated note from the VA mid-Atlantic region of the United States (VISN4) between 2015 and 2019 in their chart (N = 2,801). CBT-I participation was defined by number of CBT-I templated notes occurring within a 6-month period from the initial note. Findings indicated that veterans most often completed only one session of CBT-I and, on average, completed approximately three sessions. Results from multinomial logistic regression identified significant associations of race, the presence of comorbid mental health disorders, rurality, presence of insomnia diagnosis, and insomnia medication with CBT-I participation; associations varied depending on how CBT-I participation was defined. More work is needed to better understand factors contributing to participation and reasons for completion and noncompletion of CBT-I. (PsycInfo Database Record (c) 2023 APA, all rights reserved).