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1.
Article in English | MEDLINE | ID: mdl-38717107

ABSTRACT

Background: Aedes aegypti, is the primary vector of dengue, Chikungunya, Zika, and yellow fever viruses. Both natural and human-impacted landscapes have selective pressures on Ae. aegypti, resulting in strong genomic structure even within close geographical distances. Materials and Methods: We assess the genetic structure of this medically important mosquito species at the northern leading edge of their distribution in Southwestern USA. Ae. aegypti were collected during 2017 in the urban communities of El Paso and Sparks, Texas (USA) and in the city of Ciudad Juárez, Mexico. Results: Thousands of nuclear loci were sequenced across 260 captured Ae. aegypti. First, we recovered the genetic structure of Ae. aegypti following geography, with all four major collection communities being genetically distinct. Importantly, we found population structure and genetic diversity that suggest rapid expansion through active-short distance dispersals, with Anapra being the likely source for the others. Next, tests of selection recovered eight functional genes across six outliers: calmodulin with olfactory receptor function; the protein superfamily C-type lectin with function in mosquito immune system and development; and TATA box binding protein with function in gene regulation. Conclusion: Despite these populations being documented in the early 2000s, we find that selective pressures on specific genes have already occurred and likely facilitate Ae. aegypti range expansion.

2.
Value Health Reg Issues ; 42: 100981, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38677063

ABSTRACT

OBJECTIVES: To review and describe alternative strategies for the supply of vaccines in Latin America. METHODS: We conducted a narrative review to explore and describe alternatives for equitable vaccine access in Latin America. We searched and considered the main access strategies reported in the literature through PubMed, Science Direct, and Google Scholar. Additionally, we reviewed the web sites of key stakeholders. The search was conducted using the following keywords: ("access" or "availability" or "acquisition" or "affordability" or "tiered pricing") and ("vaccine"). Subsequently, documents that met the inclusion criteria were selected. Finally, findings were grouped by means of a thematic analysis and an interpretative synthesis. RESULTS: Twenty-four publications were included. We identified 5 main topics: current supply strategies, challenges for the acquisition of vaccines, vaccine prices equity, alternative supply strategies, and the advantages and impact of a tiered pricing strategy. CONCLUSIONS: Our review suggests that tiered pricing can be an tool for accelerating the process of introducing vaccines in low-income countries at affordable prices and for countries that do not adhere to the current procurement mechanisms or are not eligible for Vaccine Alliance because giving countries prices for vaccines that reflect their ability to pay can result in better programmatic and financial planning for the purchase of these vaccines, and in return, vaccine manufacturers can gain access to wider markets However, this model has not been z improve access to vaccines that are aimed only at developing countries, mainly because the market in these countries is not profitable for producers.


Subject(s)
Costs and Cost Analysis , Health Services Accessibility , Vaccines , Humans , Latin America , Vaccines/economics , Vaccines/supply & distribution , Health Services Accessibility/economics , Developing Countries
3.
Curr Opin Pediatr ; 36(3): 282-287, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38655809

ABSTRACT

PURPOSE OF REVIEW: Over the past four decades, pediatric emergency Medicine (PEM) has witnessed significant global development, with a notable increase in training programs and official recognition by regulatory bodies. However, disparities persist in the recognition of PEM as an independent subspecialty, availability of training programs on a global scale, academic recognition, and the ability to provide high-quality care to children worldwide. There is paucity of published literature regarding development of PEM globally. This review explores the current trends and challenges in international pediatric emergency medicine. RECENT FINDINGS: Current trends in international pediatric emergency medicine encompass the provision of training in pediatric-focused emergency and acute care, increased propagation of evidence-based guidelines specific to the care of children, the growth of collaborative research networks and interest groups within national and international societies. Simultaneously, the field continues to face challenges such as the lack of recognition, inequities in access, and a lack of dissemination of global PEM initiatives. SUMMARY: While recent advancements have significantly enhanced the state of international pediatric emergency medicine, including pediatric specific research networks and training programs, barriers still hinder its overall quality. Many of these obstacles are not unique to pediatric emergency medicine but are directly affected by financial disparities and lack of governmental and public recognition of the essential role of pediatric emergency care.


Subject(s)
Pediatric Emergency Medicine , Humans , Child , Global Health , Internationality , International Cooperation , Emergency Medicine/education , Emergency Medicine/trends
4.
Reprod Sci ; 31(7): 1861-1867, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38448741

ABSTRACT

Pathogenic variants of the SOHLH1 gene are responsible for an autosomal recessive form of ovarian dysgenesis; this gene encodes a transcription factor expressed early in spermatogonia and oocytes and contributes to folliculogenesis. Previously, four affected women from two unrelated families reported homozygous variants in the SOHLH1 gene, but none had a history of gonadal malignancy or a histologic description. We present two sisters and their paternal great-aunt with a history of primary amenorrhea, pubertal delay, and hypergonadotrophism who came from an inbred Mexican family. The proband was the younger sister who was referred for bilateral dysgerminoma. She had a normal blood karyotype, and whole-exome sequencing analysis revealed a novel homozygous missense variant, c.275C>T, in SOHLH1; several family members were also analyzed. In addition to pure dysgerminoma, histopathological analysis revealed an ovarian cortex with fibrosis and almost total absence of follicles. This work confirms the inheritance of ovarian dysgenesis 5, supports the occurrence of cell loss in mouse models, and suggests that affected women should undergo periodic imaging surveillance due to the likely risk of tumor development.


Subject(s)
Dysgerminoma , Pedigree , Humans , Female , Dysgerminoma/genetics , Dysgerminoma/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Adult , Gonadal Dysgenesis/genetics , Adolescent , Mutation, Missense , Young Adult
5.
Plant Dis ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38422440

ABSTRACT

Xanthomonas phaseoli pv. manihotis (Xpm) is a plant pathogenic bacterium known as the causal agent of cassava bacterial blight (CBB). CBB is the most limiting bacterial disease affecting cassava (Manihot esculenta Crantz), characterized by diverse symptoms including angular water-soaked leaf lesions, blight, wilting, stem exudates, stem cankers and dieback. CBB has been reported in most cassava-growing regions around the world, and, under conducive conditions, crop yield losses can reach up to 100% (Zárate-Chaves et al. 2021). While Xpm genetic diversity is remarkably high in South America (Bart et al. 2012) and cassava originates and was domesticated in the Amazon basin (Allem 2002), reports of CBB in the Amazonian region are missing. To fill this gap, in October 2018 we surveyed for CBB symptoms in cassava fields of the Orellana Province, located in the Amazon forest of the Republic of Ecuador. Adult cassava plants exhibiting typical angular, water-soaked leaf lesions were found in polyculture plots, i.e. intercrops of cassava with other species such as plantains and fruit trees (a.k.a. chakras). After surface disinfection with 5% sodium hypochlorite followed by 70% ethanol, white Xpm-like colonies were isolated from diseased leaf tissues of four plants on YPGA medium (yeast extract, 5 g/l; peptone, 5 g/l; glucose, 5 g/l; agar-agar, 15 g/l) supplemented with cephalexin (40 mg/l) and cycloheximide (50 mg/l). Pathogenicity tests were performed on peat-potted, 2-month-old cassava plants of the cultivar 60444. Bacterial suspensions were adjusted to an OD600 of 0.2 (2 × 108 CFU/ml) in sterile 10-mM MgCl2 and syringe infiltrated in fully-expanded leaves. In parallel, 20 µl of each bacterial suspension adjusted to an OD600 of 0.02 (2 × 107 CFU/ml) were inoculated on stems inside a hole previously punched with a sterile needle in the junction of the third-top petiole. Sterile 10-mM MgCl2 was used for mock inoculations in both leaves and stems, and experiments were replicated in three plants. Plants were incubated in a greenhouse at 28 ± 1°C with a 12-h photoperiod. Infiltrated leaves developed watersoaking 3 days post inoculation, while wilted leaves, stem exudates, and dieback were observed 21 days after stem inoculation. Control plants remained symptomless. White Xpm-like colonies were re-isolated from symptomatic leaves (Fig S1). One colony of each of the four Xpm isolates (before and after re-isolation) was assessed using diagnostic PCRs (Bernal-Galeano et al. 2018; Flores et al. 2019), using strain Xam668 as positive control. All four candidates were positive for both diagnostic tools. The sequences of the housekeeping genes atpD, dnaK, efp, glnA, gyrB and rpoD of our isolates were extracted from full genome sequences obtained through Oxford Nanopore Technologies (ONT) (GenBank OR288194 to OR288217) and compared to their homologs in four close Xanthomonas species and a reference Xpm strain (Table S1). The sequences of the tested strains aligned with that of Xpm CIO151 (GCA_004025275.1) (Arrieta-Ortiz et al. 2013) with nucleotide identity above 99.92% (Fig S2). The four strains were named CIX4169, CIX4170, CIX4171 and CIX4172, stored in the IRD Collection of Xanthomonas, where they are available upon request. To our knowledge, this is the first report of CBB in the Amazonian region and in Ecuador, where cassava is a central element for local culture and economy. Further surveys will be necessary to evaluate the distribution and prevalence of CBB in other ecozones of Ecuador where cassava is cultivated.

6.
J Neurooncol ; 166(2): 321-330, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38263486

ABSTRACT

PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ. RESULTS: The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009). CONCLUSION: Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM. CLINICALTRIALS: gov Identifier: NCT03344250.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Temozolomide/therapeutic use , Leukocytes, Mononuclear/pathology , Brain Neoplasms/genetics , T-Lymphocytes/pathology , Glioblastoma/drug therapy , ErbB Receptors , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Alkylating/pharmacology
9.
Front Psychol ; 14: 1217178, 2023.
Article in English | MEDLINE | ID: mdl-37663334

ABSTRACT

The left and right hemispheres of the brain process emotion differently. Neuroscientists have proposed two models to explain this difference. The first model states that the right hemisphere is dominant over the left to process all emotions. In contrast, the second model states that the left hemisphere processes positive emotions, whereas the right hemisphere processes negative emotions. Previous studies have used these asymmetry models to enhance the classification of emotions in machine learning models. However, little research has been conducted to explore how machine learning models can help identify associations between hemisphere asymmetries and emotion processing. To address this gap, we conducted two experiments using a subject-independent approach to explore how the asymmetry of the brain hemispheres is involved in processing happiness, sadness, fear, and neutral emotions. We analyzed electroencephalogram (EEG) signals from 15 subjects collected while they watched video clips evoking these four emotions. We derived asymmetry features from the recorded EEG signals by calculating the log ratio between the relative energy of symmetrical left and right nodes. Using the asymmetry features, we trained four binary logistic regressions, one for each emotion, to identify which features were more relevant to the predictions. The average AUC-ROC across the 15 subjects was 56.2, 54.6, 51.6, and 58.4% for neutral, sad, fear, and happy, respectively. We validated these results with an independent dataset, achieving comparable AUC-ROC values. Our results showed that brain lateralization was observed primarily in the alpha frequency bands, whereas for the other frequency bands, both hemispheres were involved in emotion processing. Furthermore, the logistic regression analysis indicated that the gamma and alpha bands were the most relevant for predicting emotional states, particularly for the lateral frontal, parietal, and temporal EEG pairs, such as FT7-FT8, T7-T8, and TP7-TP8. These findings provide valuable insights into which brain areas and frequency bands need to be considered when developing predictive models for emotion recognition.

10.
Cancers (Basel) ; 15(12)2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37370865

ABSTRACT

Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019. With survival as the primary endpoint, we calculated the U-RPA and generated estimates using Kaplan-Meier curves and hazard ratios. Of 862 eligible patients, 752 received BDT and 110 received best supportive care (BSC). Median overall survival with BDT and BSC was 9.3 and 1.3 months, respectively. Patients in RPA class 1, 2A, 2B and 3 who underwent BDT had median survival of 28.1, 14.7, 7.6 and 3.3 months, respectively. The median survival for patients in RPA 3 who received BDT (n = 147), WBRT (n = 79) and SRS (n = 54) was 3.3, 2.9 and 4.1 months, respectively. The U-RPA defines prognosis estimates, independent of tumor type and treatment modality, which can assist to make value-based care treatment decisions. The prognosis for patients in U-RPA class 2B and 3 remains poor, with consideration for early palliative care involvement in these cases.

11.
Polymers (Basel) ; 15(9)2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37177247

ABSTRACT

Thermoplastic starch (TPS) has emerged as an essential alternative to produce environmentally friendly packaging; however, retrogradation is a disadvantage that affects its shelf life. This study analyzed the co-plasticizing effect of isosorbide on the mechanical, thermal, physicochemical, and microstructural properties and the retrogradation of films obtained by blown film extrusion from thermoplasticized starch with mixtures of glycerol and isosorbide in different ratios (3:0, 2:1, 1:2, and 0:3, respectively). The results showed that the higher concentration of isosorbide significantly increased the tensile strength; however, it reduced the elongation. Retrogradation modeled using the Avrami equation showed that the presence of isosorbide reduced the retrogradation rate (k) and modified the recrystallization mechanism (n). The relative crystallinity in the plasticized TPS films was reduced to 89%, and the adsorption significantly decreased. Isosorbide was very important in reducing the retrogradation of TPS. The best performance was obtained with the 2:1 ratio of glycerol/isosorbide due to the synergistic effect between the plasticizers. The results would allow tuning the properties of TPS films by combining glycerol/isosorbide in different ratios, which enables the design of materials tailored to potential application requirements.

12.
Mol Syndromol ; 14(2): 143-151, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37064331

ABSTRACT

Introduction: PACS1-related neurodevelopmental disorder (PACS1-related NDD) is caused by pathogenic variants in the PACS1 gene and is characterized by a distinctive facial appearance, intellectual disability, speech delay, seizures, feeding difficulties, cryptorchidism, hernias, and structural anomalies of the brain, heart, eye, and kidney. There is a marked facial resemblance and a common multisystem affectation with patients carrying pathogenic variants in the WDR37 and PACS2 genes, although they vary in terms of severity and eye involvement. Case Presentation: Here, we describe 4 individuals with PACS1-related NDD from Mexico, all of them carrying a de novo PACS1 variant c.607C>T; p.(Arg203Trp) identified by exome sequencing. In addition to eye colobomata, this report identified corneal leukoma, cataracts, and tortuosity of retinal vessels as ophthalmic manifestations not previously reported in patients with PACS1-related NDD. Discussion: We reviewed the ocular phenotypes reported in 74 individuals with PACS1-related NDD and the overlaps with WDR37- and PACS2-related syndromes. We found that the 3 syndromes have in common the presence of colobomata, ptosis, nystagmus, strabismus, and refractive errors, whereas microphthalmia, microcornea, and Peters anomaly are found only among individuals with PACS1-related NDD and WDR37 syndrome, being more severe in the latter. This supports the previous statement that the so-called WDR37-PACS1-PACS2 axis might have an important role in ocular development and also that the specific ocular findings could be useful in the clinical differentiation between these related syndromes.

13.
Public Health Nutr ; 26(6): 1125-1142, 2023 06.
Article in English | MEDLINE | ID: mdl-37009657

ABSTRACT

OBJECTIVE: Children are frequently exposed to unhealthy food marketing on digital media. This marketing contains features that often appeal to children, such as cartoons or bold colours. Additional factors can also shape whether marketing appeals to children. In this study, in order to assess the most important predictors of child appeal in digital food marketing, we used machine learning to examine how marketing techniques and children's socio-demographic characteristics, weight, height, BMI, frequency of screen use and dietary intake influence whether marketing instances appeal to children. DESIGN: We conducted a pilot study with thirty-nine children. Children were divided into thirteen groups, in which they evaluated whether food marketing instances appealed to them. Children's agreement was measured using Fleiss' kappa and the S score. Text, labels, objects and logos extracted from the ads were combined with children's variables to build four machine-learning models to identify the most important predictors of child appeal. SETTING: Households in Calgary, Alberta, Canada. PARTICIPANTS: 39 children aged 6-12 years. RESULTS: Agreement between children was low. The models indicated that the most important predictors of child appeal were the text and logos embedded in the food marketing instances. Other important predictors included children's consumption of vegetables and soda, sex and weekly hours of television. CONCLUSIONS: Text and logos embedded in the food marketing instances were the most important predictors of child appeal. The low agreement among children shows that the extent to which different marketing strategies appeal to children varies.


Subject(s)
Advertising , Internet , Humans , Child , Pilot Projects , Marketing/methods , Food , Vegetables , Television , Alberta , Food Industry , Beverages
14.
J Neurooncol ; 162(1): 45-57, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36884200

ABSTRACT

INTRODUCTION: Brain metastases are a common cause of morbidity and mortality in patients with breast cancer. Local central nervous system (CNS) directed therapies are usually the first line treatment for breast cancer brain metastases (BCBM), but those must be followed by systemic therapies to achieve long-term benefit. Systemic therapy for hormone receptor (HR+) breast cancer has evolved in the last 10 years, but their role when brain metastases occur is uncertain. METHODS: We performed a systematic review of the literature focused on management of HR+ BCBM by searching Medline/PubMed, EBSCO, and Cochrane databases. The PRISMA guidelines were used for systematic review. RESULTS: Out of 807 articles identified, 98 fulfilled the inclusion criteria in their relevance to the management of HR+ BCBM. CONCLUSIONS: Similar to brain metastases from other neoplasms, local CNS directed therapies are the first line treatment for HR+ BCBM. Although the quality of evidence is low, after local therapies, our review supports the combination of targeted and endocrine therapies for both CNS and systemic management. Upon exhaustion of targeted/endocrine therapies, case series and retrospective reports suggest that certain chemotherapy agents are active against HR+ BCBM. Early phase clinical trials for HR+ BCBM are ongoing, but there is a need for prospective randomized trials to guide management and improve patients' outcome.


Subject(s)
Antineoplastic Agents , Brain Neoplasms , Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Retrospective Studies , Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy
15.
Clin Genet ; 104(1): 121-126, 2023 07.
Article in English | MEDLINE | ID: mdl-36896672

ABSTRACT

PKDCC encodes a component of Hedgehog signalling required for normal chondrogenesis and skeletal development. Although biallelic PKDCC variants have been implicated in rhizomelic shortening of limbs with variable dysmorphic features, this association was based on just two patients. In this study, data from the 100 000 Genomes Project was used in conjunction with exome sequencing and panel-testing results accessed via international collaboration to assemble a cohort of eight individuals from seven independent families with biallelic PKDCC variants. The allelic series included six frameshifts, a previously described splice-donor site variant and a likely pathogenic missense variant observed in two families that was supported by in silico structural modelling. Database queries suggested that the prevalence of this condition is between 1 of 127 and 1 of 721 in clinical cohorts with skeletal dysplasia of unknown aetiology. Clinical assessments, combined with data from previously published cases, indicate a predominantly upper limb involvement. Micrognathia, hypertelorism and hearing loss appear to be commonly co-occurring features. In conclusion, this study strengthens the link between biallelic inactivation of PKDCC and rhizomelic limb-shortening and will enable clinical testing laboratories to better interpret variants in this gene.


Subject(s)
Dwarfism , Osteochondrodysplasias , Humans , Hedgehog Proteins , Osteochondrodysplasias/pathology , Prevalence , RNA Splice Sites
16.
New Phytol ; 238(4): 1593-1604, 2023 05.
Article in English | MEDLINE | ID: mdl-36764921

ABSTRACT

Functional analysis of large gene families in plant pathogens can be cumbersome using classical insertional mutagenesis. Additionally, Cas9 toxicity has limited the application of CRISPR-Cas9 for directed mutagenesis in bacteria. Here, we successfully applied a CRISPR interference strategy to investigate the cryptic role of the transcription activator-like effector (tale) multigene family in several plant-pathogenic Xanthomonas bacterial species, owing to their contribution to pathogen virulence. Single guide RNAs (sgRNAs) designed against Xanthomonas phaseoli pv manihotis tale conserved gene sequences efficiently silenced expression of all tales, with concomitant decrease in virulence and TALE-induced host gene expression. The system is readily translatable to other Xanthomonas species infecting rice, citrus, Brassica, and cassava, silencing up to 16 tales in a given strain using a single sgRNA. Complementation with plasmid-borne designer tales lacking the sgRNA-targeted sequence restored molecular and virulence phenotypes in all pathosystems. Our results evidenced that X. campestris pv campestris CN08 tales are relevant for symptom development in cauliflower. They also show that the MeSWEET10a sugar transporter is surprisingly targeted by the nonvascular cassava pathogen X. cassavae, highlighting a new example of TALE functional convergence between phylogenetically distant Xanthomonas. Overall, this novel technology provides a platform for discovery and rapid functional understanding of highly conserved gene families.


Subject(s)
Oryza , Xanthomonas , Transcription Activator-Like Effectors/genetics , Xanthomonas/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Virulence/genetics , Biological Transport , Plant Diseases/microbiology , Oryza/genetics
17.
J Clin Oncol ; 41(3): 618-628, 2023 01 20.
Article in English | MEDLINE | ID: mdl-36288512

ABSTRACT

PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS: Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.


Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Focal Adhesion Protein-Tyrosine Kinases/genetics , Focal Adhesion Protein-Tyrosine Kinases/therapeutic use , Meningeal Neoplasms/drug therapy , Meningeal Neoplasms/genetics , Meningeal Neoplasms/pathology , Meningioma/drug therapy , Meningioma/genetics , Mutation , Neoplasm Recurrence, Local/drug therapy
18.
Neuroradiology ; 65(1): 121-129, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35953567

ABSTRACT

PURPOSE: Nearly all literature for predicting tumor grade in astrocytoma and oligodendroglioma pre-dates the molecular classification system. We investigated the association between contrast enhancement, ADC, and rCBV with tumor grade separately for IDH-mutant astrocytomas and molecularly-defined oligodendrogliomas. METHODS: For this retrospective study, 44 patients with IDH-mutant astrocytomas (WHO grades II, III, or IV) and 39 patients with oligodendrogliomas (IDH-mutant and 1p/19q codeleted) (WHO grade II or III) were enrolled. Two readers independently assessed preoperative MRI for contrast enhancement, ADC, and rCBV. Inter-reader agreement was calculated, and statistical associations between MRI metrics and WHO grade were determined per reader. RESULTS: For IDH-mutant astrocytomas, both readers found a stepwise positive association between contrast enhancement and WHO grade (Reader A: OR 7.79 [1.97, 30.80], p = 0.003; Reader B: OR 6.62 [1.70, 25.82], p = 0.006); both readers found that ADC was negatively associated with WHO grade (Reader A: OR 0.74 [0.61, 0.90], p = 0.002); Reader B: OR 0.80 [0.66, 0.96], p = 0.017), and both readers found that rCBV was positively associated with WHO grade (Reader A: OR 2.33 [1.35, 4.00], p = 0.002; Reader B: OR 2.13 [1.30, 3.57], p = 0.003). For oligodendrogliomas, both readers found a positive association between contrast enhancement and WHO grade (Reader A: OR 15.33 [2.56, 91.95], p = 0.003; Reader B: OR 20.00 [2.19, 182.45], p = 0.008), but neither reader found an association between ADC or rCBV and WHO grade. CONCLUSIONS: Contrast enhancement predicts WHO grade for IDH-mutant astrocytomas and oligodendrogliomas. ADC and rCBV predict WHO grade for IDH-mutant astrocytomas, but not for oligodendrogliomas.


Subject(s)
Astrocytoma , Brain Neoplasms , Isocitrate Dehydrogenase , Oligodendroglioma , Humans , Astrocytoma/diagnostic imaging , Astrocytoma/genetics , Astrocytoma/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Isocitrate Dehydrogenase/genetics , Magnetic Resonance Imaging , Mutation , Oligodendroglioma/diagnostic imaging , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Retrospective Studies , Neoplasm Grading
20.
Rev. Soc. Colomb. Oftalmol ; 56(1): 23-27, 2023. ilus
Article in Spanish | LILACS, COLNAL | ID: biblio-1444861

ABSTRACT

Objetivo: Reportar dos casos de endoftalmitis endógena por Klebsiella pneumoniae hipermucoviscosa y revisar las características clínicas de esta entidad que ha aumentado su prevalencia en países occidentales. Observaciones: Dos pacientes fueron diagnosticados con endoftalmitis endógena por K. pneumoniae con confirmación microbiológica de un origen abdominal, uno de ellos por un absceso hepático y el otro por un absceso renal. Ambos pacientes fueron sometidos a vitrectomía precoz, y a antibióticos intravítreos/intravenosos, no obstante uno requirió evisceración y el otro presentó una agudeza visual de percepción de luz. Conclusiones e importancia: K. pneumoniae es la primera causa de endoftalmitis endógena en Asia oriental, pero es poco frecuente en los países occidentales. Sin embargo su prevalencia en esta última población parece estar aumentando en asociación con las variantes hipermucoviscosas e hipervirulentas de este microorganismo. La detección temprana y el tratamiento temprano de esta enfermedad son fundamentales para preservar la anatomía del ojo.


Objective: To report two cases of hypermucoviscous Klebsiella pneumoniae endogenous endophthalmitis and to review the clinical characteristics of this aggressive disease whose prevalence appears to be increasing in western countries. Observations: Two patients were diagnosed with K. pneumoniae endogenous endophthalmitis with microbiological confirmation of an abdominal source, one from a hepatic abscess and the other with a renal abscess. Both patients underwent early vitrectomy, and intravitreal/intravenous antibiotics, nonetheless one required evisceration and the other presented a postoperative visual acuity of light perception. Conclusions and importance: K. pneumoniae is the first cause of endogenous endophthalmitis in eastern Asia, but it is rare in western countries. Nevertheless, its prevalence in the latter population appears to be increasing in association with the hypermucoviscous and hypervirulent variants of this microorganism. The early detection and early management of this disease are pivotal to preserve the anatomy of the eye.


Subject(s)
Humans , Male , Female , Middle Aged
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