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Melanoma brain metastases present a major challenge in cancer treatment and reduce overall survival despite advances in managing primary melanoma. Immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 pathways have shown promise in treating advanced melanoma, but their efficacy for melanoma brain metastases is debated. This systematic review and meta-analysis summarize evidence on anti-PD-1/PD-L1 inhibitors for melanoma brain metastases. This systematic review and meta-analysis followed PRISMA guidelines. PICO criteria targeted melanoma brain metastasis patients treated with PD-1/PD-L1 inhibitors, assessing overall survival, progression-free survival, and complications. Inclusion criteria were English studies on humans using PD-1/PD-L1 inhibitors for melanoma brain metastases with > 10 patients. A total of 22 trials involving 1523 melanoma brain metastase patients treated with anti-PD-1/PD-L1 inhibitors were thoroughly analyzed. Our findings show the 6-month OS rate of 0.75 [95%CI:0.67-0.84], the 6-months PFS rate of 0.42 [95%CI:0.31-0.52], the 1-year OS rate of 0.63 [95%CI:0.52-0.74], the 1-year PFS rate was 0.45 [95%CI:0.32-0.58], the 18-months OS rate of 0.52 [95%CI:0.37-0.67], the 2-year OS rate of 50% [95% CI: (34%-65%)], the 2 year PFS rate of 0.36 (95%CI:0.23-0.50), the 3-year OS rate of 0.42 (95%CI:0.17-0.67), the 4-year PFS rate of 0.35 [95%CI:0.08-0.61], the 4-year OS rate of 0.29 [95%CI:0.01-0.56], the 5-year OS rate of 0.29 (95%CI:0.09-0.50), and the 5-year PFS rate of 0.11 (95%CI:0.03-0.19). The combined disease stability rate was 0.13 [95%CI:0.05-0.20], the progressive disease rate was 0.49 [95%CI:0.37-0.62], the partial response rate was 0.14 [95%CI:0.07-0.20], the object response rate was 0.35 [95%CI:0.24-0.46], and the complete response rate was 0.22 [95%CI:0.12-0.32]. In conclusion, our meta-analysis provides compelling evidence supporting the efficacy of PD-1/PD-L1 inhibitors in patients with melanoma brain tumors, as evidenced by favorable survival outcomes and disease control rates.
Assuntos
Antígeno B7-H1 , Neoplasias Encefálicas , Inibidores de Checkpoint Imunológico , Melanoma , Receptor de Morte Celular Programada 1 , Humanos , Melanoma/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno B7-H1/antagonistas & inibidoresRESUMO
An analytical method is presented for designing N-coupled multi-core fibers with zero differential group delay. This approach effectively reduces the problem to a system of N-1 algebraic equations involving the associated coupling coefficients and propagation constants, as obtained from coupled mode theory. Once the parameters of one of the cores are specified, the roots of the resulting N-1 equations can be used to determine the characteristics of the remaining waveguide elements. Using this technique, a number of pertinent geometrical configurations are investigated to minimize intermodal dispersion.
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Introduction: Copy number variations (CNVs), which are genetic factors responsible for human evolution, have emerged as underlying pathogenic factors for a number of diseases such as autism spectrum disorders (ASD). DUF1220 coding sequences have been shown to be positively associated with the severity of symptoms in familial/multiplex cases of autism. However, this association has not been confirmed in simplex autism, and the potential impact of gender/sex has not been studied. Methods: Using saliva samples taken from Iranian children with non-syndromic simplex autism, different ethnicity/race and genetic backgrounds from previous studies, we assessed the association between DUF1220 CNVs and Autism Diagnostic Interview-Revised (ADI-R) domain scores in both males and females. Results: In the male and female combined group with autism, in line with previous reports, our findings showed that there were no significant associations between DUF1220 CNVs with either total ADI-R score, social, communication, or repetitive diagnostic scores in simplex autism cases. Interestingly, however, in sex classified groups, despite the insignificant results, our findings in girls with autism showed a negative trend between DUF1220 CNVs and severity of symptoms for the social interaction and communication domains. By contrast, in male children with autism, the results showed a positive trend. Conclusion: It seems that association of DUF1220 CNV with the severity of symptoms in simplex children with autism may follow a sexually dimorphic pattern that needs to be re-examined in prospective studies.
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Autism spectrum disorders (ASD) are strikingly more prevalent in males, but the molecular mechanisms responsible for ASD sex-differential risk are poorly understood. Abnormally shorter telomeres have been associated with autism. Examination of relative telomere lengths (RTL) among non-syndromic male (N = 14) and female (N = 10) children with autism revealed that only autistic male children had significantly shorter RTL than typically-developing controls (N = 24) and paired siblings (N = 10). While average RTL of autistic girls did not differ significantly from controls, it was substantially longer than autistic boys. Our findings indicate a sexually-dimorphic pattern of RTL in childhood autism and could have important implications for RTL as a potential biomarker and the role/s of telomeres in the molecular mechanisms responsible for ASD sex-biased prevalence and etiology.
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Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Masculino , Feminino , Transtorno Autístico/genética , Transtorno do Espectro Autista/genética , Caracteres Sexuais , Biomarcadores , TelômeroRESUMO
We analyzed water samples to determine the prevalence of free-living Acanthamoeba in water sources from Gilan, greater area, Iran. A total of 27 surface water samples were collected from environmental sources, including natural (rivers, lakes, springs, and lagoon) and freshwater source. The samples were filtrated and transferred to non-nutrient agar plates seeded with Escherichia coli and incubated for 2 to 7 days at 30°C or 42°C. The plates were examined by microscopy to morphologically identify Acanthamoeba species. Following DNA extraction, PCR was used to confirm the microscopically identification. A total of 19 out of 27 samples (70.3%) were positive for Acanthamoeba species based on the morphological criteria, and 14 (73.7%) were confirmed by PCR method. The high frequency of Acanthamoeba spp. in different environmental water sources of Gilan is an alert for the public health related to water sources in Iran.
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Acanthamoeba/isolamento & purificação , Água Doce/parasitologia , Acanthamoeba/citologia , Acanthamoeba/genética , Acanthamoeba/crescimento & desenvolvimento , DNA de Protozoário/genética , Irã (Geográfico) , Microscopia , Parasitologia/métodos , Reação em Cadeia da Polimerase/métodos , Manejo de Espécimes/métodosRESUMO
A survey was conducted on man-made recreational water located in different regions of Tehran, Iran to detect the free-living amoebae present in ponds and fountains of parks and squares. Fifty water samples from 22 municipal districts of Tehran were screened for free-living amoebae and identified by morphological characters and polymerase chain reaction amplification. Amoebae detected were identified as Hartmannella vermiformis (12 %) and Vannella persistens (4 %), which are the first reports of these two amoebas in recreational water environments of Iran. Since, H. vermiformis, which is highly similar to strains serving as hosts for Legionella pneumophila, is a common component of the microbial community in fresh surface water. Although Vannella spp. is not proved to be pathogenic itself, they are capable of harboring pathogenic intracellular organisms. Due to some reports related to pathogenicity of these amoebas, the particular hazard related to these microorganisms should be taken into account in the encounter with drinking and washing in these waters. We recommend control strategies based on physical removal rather than on disinfection to be adopted where necessary.