Prognostic factors facilitating multiple food allergies and atopiv march occurrence in children with Non-IgE mediated gastrointestinal Food Allergy: results of two years follow up of the NIGEFA project

Objectives and Study: Non-IgE mediated gastrointestinal food allergies (non-IgE-GIFA) are an increasing problem in pediatric gastroenterology clinical practice. These conditions include food protein-induced: enterocolitis syndrome (FPIES), enteropathy (FPE), allergic proctocolitis (FPIAP), and motility disorders (FPIMD). The NIGEFA project is focused on the investigation of main clinical features, prognostic factors (presence atopic dermatitis (AD), multiple food allergies, diagnostic delay, and familial history of allergy), and natural history (atopic march (AM) prevalence and timing of immune tolerance acquisition). Methods: Prospective observational study evaluating children with non-IgE-GIFA diagnosed according to standard criteria observed at a tertiary center for pediatric gastroenterology and allergy (both sexes, aged <36 m, follow up 12 m after diagnosis). Main anamnestic, demographic, and clinical data were collected from all enrolled patients. Immune tolerance acquisition was evaluated by the result of oral food challenge. Results: A total of 100 patients were enrolled: 58% male, mean age at diagnosis (SD) 8.5(8.8) m. Non-IgE-GIFA conditions were: FPE (44%), FPIES (11%), FPIAP (18%), FPIMD (27%). Mean diagnostic delay was 5.3 (7.4) m. Multiple non-IgE-GIFA were observed in 47% at baseline. Familial history of allergy was observed in 64% of subjects. Presence of AD before the onset of non-IgE-GIFA was observed in 40% of subjects. The overall rate of immune tolerance acquisition at 12 m was 27%, with a higher rate in FPIAP (44%) compared with FPIMD (29.6%), FPE (22.7%) and FPIES (9.1%) subjects (p<0.05). The rate of immune tolerance acquisition at 12 m was significantly lower in children with familial history of allergy (-48%, estimated risk ratio (RR)0.52 (95% CI 0.28 to 0.99, p<0.05)) and in those with multiple non-IgE-GIFA (-61%, RR at 12 m 0.39 (95% CI 0.18 to 0.85, p<0.05)). At 12 m follow up, the rate of subjects presenting AM was 24% with no difference among the 4 disease groups. The occurrence of AM was significantly higher in subjects with multiple (38%) vs. mono non-IgE-GIFA (11%) (p<.001) at baseline, with an estimated RR of 3.38 (95% CI 1.47 to 7.81, p<0.01) at 12 m. Moreover, for every 1-month of diagnostic delay there was an increase of 1.04 RR(95% CI 1.01 to 1.07) of AM occurrence at 12 m. No associations with other potential predictors (sex, familial allergy risk, AD before the onset of GIFA, type of non-IgE-GIFA) were found. Conclusions: These data shed lights on prognostic factors and natural history of non-IgE-GIFA suggesting the importance of early diagnosis in preventing the occurrence of AM occurrence in these patients. Contac

Diabetes and colorectal cancer risk: A new look at molecular mechanisms and potential role of novel antidiabetic agents

Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated

Serum low density lipoprotein subclasses in asthma

Background: The levels of serum low-density lipoproteins (LDL) have been implicated in the inflammatory cascade in a murine model of asthma. Recent findings suggest that LDL may modulate the inflammatory state of the asthmatic airways in humans. Objective: We explored whether LDL subclasses are associated with the occurrence and severity of asthma. Methods: 24 asthmatics (M/F: 11/13) and 24 healthy individuals, with normal BMI and absence of metabolic syndrome, matched for age and gender. Serum concentrations of LDL subclasses were distributed as seven bands (LDL-1 and -2 defined as large, least pro-inflammatory LDL, and LDL-3 to 7 defined as small, most pro-inflammatory LDL), using the LipoPrintª System (Quantimetrix Corporation, Redondo Beach, CA, USA). Results: LDL-1 was similar in the two groups (56 ± 16% vs. 53 ± 11, p = NS), while LDL-2 was significantly lower in asthmatics as compared to controls (35 ± 8% vs. 43 ± 10%, p = 0.0074). LDL-3 levels were two-fold higher in the asthmatics, but the difference did not reach the statistical significance (8± 7.3% vs. 4±3%, p=NS). Smaller subclasses LDL-4 to LDL-7 were undetectable in controls. In asthmatics, LDL-1 was positively associated with VC% predicted (r=+0.572, pZ0.0035) and FEV1% predicted (r=+0.492, p=+.0146). LDL-3 was inversely correlated with both VC% predicted (r =-0.535, p =0.0071) and FEV1% predicted (r =-0.465, p = 0.0222). Conclusions: The findings of this pilot study suggest a role of LDL in asthma, and advocate for larger studies to confirm the association between asthma and dyslipidemia

VALUTAZIONE DELLA CLEARANCE DI HCV-RNA SOTTO TRATTAMENTO ANTIVIRALE CON TRANSCRIPTION-MEDIATED AMPLIFICATION (TMA)

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In Vitro Evaluation of the Antibacterial Activity of the Peptide Fractions Extracted from the Hemolymph of Hermetia illucens (Diptera: Stratiomyidae)

Antimicrobial peptides (AMPs) are a chemically and structurally heterogeneous family of molecules produced by a large variety of living organisms, whose expression is predominant in the sites most exposed to microbial invasion. One of the richest natural sources of AMPs is insects which, over the course of their very long evolutionary history, have adapted to numerous and different habitats by developing a powerful innate immune system that has allowed them to survive but also to assert themselves in the new environment. Recently, due to the increase in antibiotic-resistant bacterial strains, interest in AMPs has risen. In this work, we detected AMPs in the hemolymph of Hermetia illucens (Diptera, Stratiomyidae) larvae, following infection with Escherichia coli (Gram negative) or Micrococcus flavus (Gram positive) and from uninfected larvae. Peptide component, isolated via organic solvent precipitation, was analyzed by microbiological techniques. Subsequent mass spectrometry analysis allowed us to specifically identify peptides expressed in basal condition and peptides differentially expressed after bacterial challenge. We identified 33 AMPs in all the analyzed samples, of which 13 are specifically stimulated by Gram negative and/or Gram positive bacterial challenge. AMPs mostly expressed after bacterial challenge could be responsible for a more specific activity

Leopard-like retinopathy and severe early-onset portal hypertension expand the phenotype of KARS1-related syndrome: a case report

Background: Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot–Marie–Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients. Case presentation: We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30&nbsp;months. Conclusions: Whole exome sequencing identified two rare variants in KARS1 gene. Our report expands the allelic and clinical features of tRNA synthase disorders. Moreover, with our report we confirm the usefulness of WES as first tier diagnostic method in infants with complex multisystem phenotypes

Minimally invasive mitral valve surgery: State-of-the-art and our experience

The minimally invasive approach is becoming the standard-of-care for surgery of the mitral valve. As any less invasive strategy, it entails an increased surgical complexity. Standard-of-care mitral repair using the totally videoscopic approach is indeed reproducible; however, few specific data on patients with complex mitral valve disease are available in the published literature. The purpose of the present paper is to provide an overview of the current state-of-the-art in minimally invasive cardiac surgery, and a summary of recent evidence on the topic, with particular regard to the surgical techniques and comparisons with conventional surgery. The experience of the GVM Care and Research network in the field is also briefly reported

Serum Vitamin D as a Biomarker in Autoimmune, Psychiatric and Neurodegenerative Diseases

Vitamin D is a steroid hormone regulating calcium-phosphorus homeostasis, immune response and brain function. In the past thirty years, an increasing number of cohort studies, meta-analyses and randomized controlled trials (RTCs) evaluated the serum levels of 25-hydroxyvitamin D [25(OH)D], which is considered the Vitamin D status biomarker, in patients affected by neurological, psychiatric and autoimmune diseases. Although an association between low 25(OH)D serum levels and the prevalence of these diseases has been found, it is still unclear whether the serum 25(OH)D measurement can be clinically useful as a biomarker for diagnosis, prognosis and predicting treatment response in neurodegeneration, mental illness and immune-mediated disorders. The lack of standardized data, as well as discrepancies among the studies (in the analytical methods, cut-offs, endpoints and study sets), weakened the findings achieved, hindered pooling data, and, consequently, hampered drawing conclusions. This narrative review summarizes the main findings from the studies performed on serum 25(OH)D in neurological, psychiatric and autoimmune diseases, and clarifies whether or not serum 25(OH)D can be used as a reliable biomarker in these diseases