NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool.

OBJECTIVE: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy. METHODS: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques. RESULTS: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-deoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom. SIGNIFICANCE: Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision-making.

NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021.

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

Comparison of heat inactivation and cell disruption protocols for identification of mycobacteria from solid culture media by use of vitek matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Two novel protocols for inactivation and extraction were developed and used to identify 107 Mycobacterium clinical isolates, including Mycobacterium tuberculosis complex, from solid cultures using Vitek matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The protocol using heat inactivation with sonication and cell disruption with glass beads resulted in 82.2% and 88.8% species and genus level identifications, respectively.

Mycobacteria-primed macrophages and dendritic cells induce an up-regulation of complement C5a anaphylatoxin receptor (CD88) in CD3+ murine T cells.

Complement C5a anaphylatoxin is a potent activator of macrophages, neutrophils, and dendritic cells (DC) and binds the C5a receptor (C5a-R; CD88). Although C5a is chemotactic for T cells, expression of C5a-R on murine T cells has been disputed. We report here that naïve, Con A-activated, and cytokine (IL-12, IL-18)-stimulated murine CD3+ T cells from three strains of mice [C57Bl/6, B10.nSn (C5+/+), B10.on (C5-/-)] lacked C5a-R, as evaluated by immunophenotyping with an anti-C5a-R mAb. Ligation of CD3 induced a modest up-regulation with 3% of CD3+ T cells expressing cell surface C5a-R. T cells primed by APC differentiate into effector T cells. Activation of mycobacteria [bacillus Calmette-Guerin (BCG)]-sensitized T cells through MHC II and TCR interactions via BCG-infected macrophages enhanced the expression of C5a-R with approximately 14% of CD3+ T cells positive for C5a-R. Comparable expression was found in C5+/+ as well as C5-/- strains of mice (14% and 15%, respectively). Furthermore, anti-CD3-activated T cells were primed by BCG-infected DC, and a larger proportion of the primed T cells expressed C5a-R (30-40%). Finally, mice infected with BCG showed significant numbers of CD3+ T cells expressing C5a-R in the spleens during infection. As APC, such as macrophages and DC, can secrete C5 and cleave C5 to C5a and C5b through a peptidase, we suggest that macrophage and DC-T cell interactions can up-regulate C5a-R on T cells through MHC II-TCR and provide a C5a peptide for additional local activation of T cells via C5a-R.

Clinical and experimental applications of NIR-LED photobiomodulation.

This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as "photobiomodulation," uses light in the far-red to near-infrared region of the spectrum (630-1000 nm) and modulates numerous cellular functions. Positive effects of NIR-light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction.

IMERT deployment to Baton Rouge, Louisiana in response to Hurricane Katrina, September 2005.

An Illinois volunteer emergency response team was deployed to assist in the disaster care efforts following Hurricane Katrina. The team joined local care providers to establish a field hospital on the campus of Louisiana State University in Baton Rouge, Louisiana. The team worked to support local providers, establish order, and assist more than 3000 evacuees. The challenges and lessons learned from this deployment are identified.

Innate immunity for biodefense: a strategy whose time has come.

Defense against biothreat agents requires a broad-spectrum approach. Modulation of the innate immune system might fulfill this requirement. Hackett's previous review of innate immune activation as a broad-spectrum biodefense strategy identified several unresolved questions. The current article is a systematic approach to answering those questions with the focused participation of research groups developing this technology. Our team of academic and industry participants reviewed the promising agents and came to the following conclusions. It is feasible to construct a biodefense platform combining synergistic agents that activate the innate immune system against a broad range of pathogens on the basis of conserved microbial components by using a nasal spray for immune activation in the respiratory and gastrointestinal tracts because these are the most likely routes of attack. It might also be possible to include agents that inhibit molecular events leading to septic shock. Innate immune-activating agents designed to activate Toll-like and other receptors will probably provide protection against the biothreat pathogen spectrum for periods ranging from 2 to 14 days for IFNs up to 26 weeks for immunomodulatory oligonucleotides. Initial treatment is proposed on the first index case or biosensor alert. Boost doses would be required. Harmful inflammation is possible, but thus far, only transient fever has been observed. Autoimmune reaction and retroviral activation have not been seen thus far in preclinical and human trials of many of these compounds. Toll-like receptor agonists caused cytokine production in all subjects tested, but genetic polymorphism reduced the response to IFN in African American subjects.

Differences in race, ethnicity, and socioeconomic status in schoolchildren dispensed injectable epinephrine in 3 Massachusetts school districts.

BACKGROUND: Published surveys depicting the increase in the incidence of food allergy, especially peanut or tree nut allergy, in children have not reported any differences in race, ethnicity, or socioeconomic status. OBJECTIVE: To analyze the demographics of schoolchildren with diverse racial, ethnic, and socioeconomic characteristics dispensed injectable epinephrine. METHODS: School nurses in 44 schools enrolling 21,875 students recorded the characteristics of students dispensed injectable epinephrine in the 2003-2004 school year. Surveyed school districts included 2 affluent suburban districts enrolling 5,855 students (> 92% white) and 1 urban district enrolling 16,020 students (60% nonwhite). RESULTS: A total of 181 students in all 3 districts were dispensed injectable epinephrine; 118 of these children had peanut or tree nut allergy. Males were more likely to be dispensed injectable epinephrine than females (odds ratio [OR], 1.44; P < .02). Whites were more likely to have been dispensed injectable epinephrine than nonwhites (OR, 4.76; P < .001). Whites were nearly 5 times more likely to be dispensed injectable epinephrine for peanut or tree nut allergy than nonwhites (OR, 4.5; P < .001). Most students (75%) dispensed injectable epinephrine for peanut or tree nut allergy were enrolled in prekindergarten through grade 5 (P < .001). Whites were more likely than nonwhites to be dispensed injectable epinephrine for stinging insect allergy (OR, 8.7; P < .001). CONCLUSIONS: This study found significant racial, ethnic, and socioeconomic differences in the prevalence of childhood allergic disorders, especially peanut or tree nut allergy, requiring prescribed injectable epinephrine in a school setting. Additional studies are needed to determine whether minority children are being underdiagnosed or undertreated for allergic disorders requiring injectable epinephrine or whether they truly have a lower incidence of such allergic disorders.