126 research outputs found
Strikingly high activity of metronomic chemotherapy in a patient with locally advanced, life-threatening cutaneous squamous-cell cancer â case report and discussion of the literature
The current treatment of choice in patients with advanced or metastatic squamous-cell carcinoma (SCC) of the skin is immunotherapy based on anti-PD1/L1 antibodies. For many years, there has been a consensus, that SCC of the skin is a chemorefractory neoplasm. However, despite a recent approval of checkpoint inhibitors for the treatment of cutaneous SCC, their extremely high cost makes them unavailable for many patients worldwide, and additionally, in many patients, their use may be contraindicated by patientsâ clinical conditions. This article provides strong arguments that optimized and well-matched chemotherapy still represents an active treatment option even in the era of novel therapies
Development and maturation of the immune system in preterm neonates : results from a whole genome expression study
To expand the knowledge about the consecutive expression of genes involved in the immune system development in preterm neonates and to verify if the environment changes the gene expression after birth we conducted a prospective study that included three cohorts: (A) extremely (gestational age (GA): 23â26 weeks; n=41), (B) very (GA: 27â29 weeks; n=39), and (C) moderately preterm infants (GA: 30â32 weeks; n=33). Blood samples were drawn from the study participants on the 5th and 28th day of life (DOL). The mRNA samples were evaluated for gene expression with the use of GeneChip Human Gene 1.0ST microarrays. Differential expression analysis revealed small subsets of genes that presented positive or negative monotone trends in both the 5th (138 genes) and 28th DOL (308 genes) in the three subgroups of patients. Based on pathway enrichment analysis, we found that most of the pathways that revealed a positive monotone trend were involved in host immunity. The most significantly GA dependent pathways were T-cell receptor signaling pathway and intestinal immune network for IgA production. Overall 4431 genes were differentially expressed between the 5th and 28th DOL. Despite differences in gestational age, patients with the same postconceptional age have a very similar expression of genes
Relationship between stereoscopic vision, visual perception, and microstructure changes of corpus callosum and occipital white matter in the 4-year-old very low birth weight children
Aim. To assess the relationship between stereoscopic vision, visual perception, and microstructure of the corpus callosum (CC) and occipital white matter, 61 children born with a mean birth weight of 1024âg (SD 270âg) were subjected to detailed ophthalmologic evaluation, Developmental Test of Visual Perception (DTVP-3), and diffusion tensor imaging (DTI) at the age of 4. Results. Abnormal stereoscopic vision was detected in 16 children. Children with abnormal stereoscopic vision had smaller CC (CC length: 53±6âmm versus 61±4âmm; p<0.01; estimated CC area: 314±106âmm2 versus 446±79âmm2; p<0.01) and lower fractional anisotropy (FA) values in CC (FA value of rostrum/genu: 0.7±0.09 versus 0.79±0.07; p<0.01; FA value of CC body: 0.74±0.13 versus 0.82±0.09; p=0.03). We found a significant correlation between DTVP-3 scores, CC size, and FA values in rostrum and body. This correlation was unrelated to retinopathy of prematurity. Conclusions. Visual perceptive dysfunction in ex-preterm children without major sequelae of prematurity depends on more subtle changes in the brain microstructure, including CC. Role of interhemispheric connections in visual perception might be more complex than previously anticipated
Fractional exhaled nitric oxide in preterm-born subjects: A systematic review and meta-analysis
Background
Decreased lung function is common in pretermâborn survivors. Increased fractional exhaled nitric oxide (FeNO) appears to be a reliable test for eosinophillic airway inflammation especially in asthma. We, systematically, reviewed the literature to compare FeNO levels in pretermâborn children and adults who did or did not have chronic lung disease of prematurity (CLD) in infancy with termâborn controls.
Methods
We searched eight databases up to February 2018. Studies comparing FeNO levels in pretermâborn subjects (<37â
weeksâ gestation) in childhood and adulthood with and without (CLD) with termâborn subjects were identified and extracted by two reviewers. Data were analysed using Review Manager v5.3.
Results
From 6042 article titles, 183 full articles were screened for inclusion. Nineteen studies met the inclusion criteria. Seventeen studies compared FeNO levels in pretermâ and termâborn children and adults; 11 studies (preterm nâ=â640 and term nâ=â4005) were included in a metaâanalysis. The mean FeNO concentration difference between the pretermâborn and termâborn group was â0.74 (95% CI â1.88 to 0.41) ppb. For the six studies reporting data on CLD (preterm nâ=â204 and term nâ=â211) the mean difference for FeNO levels was â2.82 (95% CI â5.87 to 0.22) ppb between the pretermâborn CLD and termâborn groups.
Conclusions
Our data suggest that preterm born children with and without CLD have similar FeNO levels to termâborn children suggesting an alternative mechanism to eosinophilic inflammation for symptoms of wheezing and airway obstruction observed in pretermâborn subjects
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Topical Mechlorethamine for the Treatment of Psoriasis: A Report of Two Cases and Literature Review
Introduction
Psoriasis is a common inflammatory skin disease that significantly impacts patientsâ psychosocial wellbeing. Despite increasingly effective treatment options, the recurrence of plaques after discontinuation of therapy in many patients highlights the need for additional therapies.
Methods
We report two cases of patients with concurrent psoriasis and mycosis fungoides who were treated with topical mechlorethamine (MCH). A literature review was performed by searching PubMed using the keywords psoriasis, mechlorethamine, chlormethine, and nitrogen mustard.
Results
Both patients had significant improvement in their psoriasis following treatment with topical MCH gel, which was well tolerated and maintained clearance after 1 and 3 years of follow-up. Seven prospective cohort studies investigating the use of topical MCH were identified through literature review. Out of five studies reporting clinical outcomes by patient, 68 of 77 patients (88%) experienced an improvement in their psoriasis, with 47 of 77 (61%) achieving complete or near-complete clearance. The remaining two studies reported clinical outcomes by lesion, demonstrating improvement in 40 of 45 lesions (88%) and complete or near-complete clearance in 32 of 42 lesions (76%). Contact dermatitis was the most frequent adverse effect, observed in 56 of 125 patients (45%).
Conclusions
Topical MCH may be an option for patients with psoriasis who fail or have incomplete responses to other treatments. Published studies are limited by lack of standardized treatment regimens and well-defined outcome measures, highlighting the need for prospective clinical trials to better understand the utility of this topical agent in psoriasis
Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia
Background: In this study, we aimed to analyze differences in plasma protein abundances between infants with
and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis
of this disease.
Methods: Cord and peripheral blood of neonates (†30 weeks gestational age) was drawn at birth and at the 36th
postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(â)
groups, according to the development of BPD.
Results: Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels
in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an
increased serotransferrin abundance in plasma at the 36 PMA.
Conclusions: BPD development is associated with the plasma proteome changes in preterm infants, adding further
evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes
in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins
related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD
Comparison of whole genome expression profile between preterm and full-term newborns
Objectives: Evaluate the time dependent expression of genes in preterm neonates and verify the influence of ontogenic maturation and the environmental factors on the gene expression after birth. Material and methods: The study was carried out on 20 full-term newborns and 62 preterm newborns (mean birth weight = 1002 [g] (SD: 247), mean gestational age = 27.2 weeks (SD: 1.9)). Blood samples were drawn from all the study participants at birth and at the 36th week postmenstrual age from the preterm group to assess whole genome expression in umbilical cord blood and in peripheral blood leukocytes, respectively. (SurePrint G3 Human Gene Expression v3, 8x60K Microarrays (Agilent)).
Results: A substantial number of genes was found to be expressed differentially at the time of birth and at 36 PMA in comparison to the term babies with more genes being down-regulated than up-regulated. However, the fold change in the majority of cases was < 2.0. Extremely preterm and very preterm infants were characterized by significantly down-regulated cytokine and chemokine related pathways. The number of down-regulated genes decreased and number of up-regulated genes increased at 36 PMA vs. cord blood. There were no specific gene expression pathway profiles found within the groups of different gestational ages.
Conclusions: Preterm delivery is associated with a different gene expression profile in comparison to term delivery. The gene expression profile changes with the maturity of a newborn measured by the gestational age
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