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Specific learning disorders (SLDs) are the most frequently diagnosed developmental disorders in childhood. Different neurocognitive patterns have been found in patients with overweight and obesity, but no data on childhood obesity and SLDs have been reported. To increase our understanding of the relationship between neuropsychological developmental and obesity, we assessed the prevalence of SLD in a pediatric population with obesity. We retrospectively included 380 children and adolescents with obesity. For all participants, auxological, metabolic, demographic features, relationship and social skills, anamnestic data on pregnancy and the perinatal period, stages of development and family medical history were reviewed. SLD was defined according to the DSM-5 criteria. A group of 101 controls of normal weight was included. The overall prevalence of SLD was 10.8%, and SLD was more prevalent in patients with obesity (p < 0.001), with male predominance (p = 0.01). SGA was associated with SLD (p = 0.02). Speech retardation (p < 0.001), limited relationships with peers (p < 0.001) and didactic support (p < 0.001) were noted in the SLD group compared to the group without SLD. A higher prevalence of family history of neuropsychiatric disorders was observed in the SLD group (p = 0.04). A higher fasting glucose level was detected in patients with obesity and SLD compared to subjects without SLD (p = 0.01). An association between obesity and SLD could not be excluded, and an overlap of pathogenic factors for both conditions should be considered. [ABSTRACT FROM AUTHOR]

Recently, thanks to the greater discovery of the mechanisms of facial aging, an alternative to invasive plastic surgery has found space with less invasive aesthetic procedures, also based on an increasingly pressing request. We are specifically referring to dermal filler injection into or under the skin which leads to immediate rejuvenation and aesthetic improvements. In this study, we wanted to analyze the results obtained through the use of NEAUVIA Organic Stimulate, particularly with regard to its effectiveness, which is a cross-linked polymeric hydrogel, containing stabilized sodium hyaluronate 26 mg/mL and calcium hydroxyapatite (1%), glycine and L-proline in buffer pyrogen-free water, in its main indication, namely, the temporary correction of congenital and acquired deficiencies of the soft tissues of the face by intradermal injection. Initially, 70 patients were enrolled, but 10 did not complete the study due to non-observance of the investigation rules, so they were excluded from the protocol. The collected data demonstrate an efficient mechanical effect of the pegylated polymeric acid matrix enriched with low concertation of calcium hydroxyapatite and in accordance with other evidence in vitro and in vivo, and the mechanical support of the interstitial connective space improves the homestays of the anatomical layer rebalancing the physiological activity of the dermis cells. [ABSTRACT FROM AUTHOR]

Congenital lung malformations (CLMs) involve anomalies of the lungs and respiratory tree such as congenital pulmonary airway malformation (CPAM), pulmonary sequestration (PS), bronchogenic cysts, congenital lobar emphysema, and bronchial atresia (BA). Although symptomatic lesions require surgical resection, the appropriateness of surgery for patients with asymptomatic malformations is a matter of ongoing debate. Limited data are available concerning the long-term follow-up of affected subjects. In this study, we sought to evaluate the long-term clinical and functional respiratory outcomes in children with CLMs who underwent surgical resection. We carried out a retrospective analysis of 77 children with CLMs who underwent pulmonary resection with at least one year of follow-up. The most common diagnoses were CPAM (50.65%), hybrid lesions (25.97%), lobar emphysema (11.69%), and PS (5.19%). The most common surgical approaches were lobectomy (61.3%), segmentectomy (10.7%), and pneumonectomy (5.3%). Acute post-surgery complications occurred in 31.2% of children. In addition, 73.7% experienced long-term complications, and we found no correlation between the presence of these complications and the sex of the patients, their age at time of surgery, the type of surgery undergone, the presence of symptoms prior to intervention, or acute complications after surgery. Pulmonary function tests revealed FEV1 Z-scores of <−2 SDs in 16 patients, and we found a significant correlation between pneumonectomy and the development of lung function deficit (p = 0.031). In conclusion, clinical and functional respiratory complications may occur in children with CLMs who undergo surgical resection. Long-term monitoring is needed to improve the management of asymptomatic patients. [ABSTRACT FROM AUTHOR]

Background: In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig livers and reseeded them with allogeneic porcine mesenchymal stromal cells (pMSCs) to understand whether extracellular matrix (ECM) can influence and/or promote differentiation into hepatocyte-like cells (HLCs). Methods: After decellularisation with SDS, the integrity of ECM-scaffolds was examined by histological staining, immunofluorescence and scanning electron microscope. DNA quantification was used to assess decellularisation. pMSCs were plated on scaffolds by static seeding and maintained in in vitro culture for 21 days. At 3, 7, 14 and 21 days, seeded ECM scaffolds were evaluated for cellular adhesion and growth. Moreover, the expression of specific hepatic genes was performed by RT-PCR. Results: The applied decellularisation/recellularisation protocol was effective. The number of seeded pMSCs increased over the culture time points. Gene expression analysis of seeded pMSCs displayed a weak induction due to ECM towards HLCs. Conclusions: These results suggest that ECM may address pMSCs to differentiate in hepatocyte-like cells. However, only contact with liver-ECM is not enough to induce complete differentiation. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) patients show a higher risk of developing metabolic and cardiovascular diseases due to the presence of systemic low-grade chronic inflammation. Exercise can improve cardiovascular fitness and modulate the inflammatory processes. We evaluated the physical activity (PA) level and the fitness performance of children and adolescents with IBD. Patients and methods: We considered 54 pediatric patients with IBD (14.6 ± 2.2; 22 M), including CD (n = 27) UC (n = 24) and IBD unclassified (n = 3), and 70 healthy children. In all children, the Physical Activity Questionnaire (PAQ-C) and the International Fitness Enjoyment Scale were self-reported and recorded. Results: PAQ-C showed significant difference in PA levels in patients with IBD compared to controls (p < 0.001). A decrease in general fitness (p = 0.003), cardiorespiratory fitness (p = 0.002), strength (p = 0.01), speed agility (p = 0.003), and flexibility (p = 0.01) were also detected between patients and controls. Speed agility was related to age (p = 0.02) and BMI z-score (p = 0.01), and flexibility to BMI z-score (p = 0.05). We noted a correlation between PA levels and physician global assessment (p = 0.021) and activity disease severity (p = 0.025). Conclusions: A poorer PA level and poor physical competence were found in patients with IBD compared to healthy children and adolescents. Monitored exercise could provide multiple benefits at both physical and psychological levels. [ABSTRACT FROM AUTHOR]

Background: The primary aim of our study was to assess the correlation between an improved version of the attenuation coefficient available on the Arietta 850 ultrasound system (iATT, Fujifilm Healthcare, Tokyo, Japan) and controlled attenuation parameter (CAP). The secondary aim was to assess whether focusing only on iATT acquisition without following the strict protocol for liver stiffness measurements would affect iATT measurement. Methods: Consecutive individuals were enrolled. Pearson's r was used to test the correlation between ATT and CAP values. The concordance between iATT and CAP was tested using Lin's concordance correlation coefficient (CCC). Results: 354 individuals (203 males, 151 females) were studied. The overall Pearson correlation between CAP and iATT values obtained following or not following the liver stiffness measurement protocol, respectively, were r = 0.73 and r = 0.71. The correlation was affected by the interquartile range/median (IQR/M) of the 10 measurements: it was r = 0.75 for IQR/M ≤ 15% and r = 0.60 for IQR/M > 15%. CCC showed that there was a moderate to good concordance between iATT and CAP values. Conclusion: iATT shows a strong correlation with CAP that does not decrease when the protocol for liver stiffness acquisition is not followed. The correlation between iATT and CAP values is higher when the IQR/M ≤ 15%. [ABSTRACT FROM AUTHOR]

Tacrolimus (TAC) is an immunosuppressant drug approved both in the US and in the EU, widely used for the prophylaxis of organ rejection after transplantation. This is a critical dose drug: low levels in whole blood can lead to low exposure and a high risk of acute rejection, whereas overexposure puts patients at risk for toxicity and infection. Both situations can occur at whole-blood concentrations considered to be within the narrow TAC therapeutic range. We assumed a poor correlation between TAC trough concentrations in whole blood and the incidence of acute rejection; therefore, we propose to study TAC concentrations in endomyocardial biopsies (EMBs). We analyzed 70 EMBs from 18 transplant recipients at five scheduled follow-up visits during the first year post-transplant when closer TAC monitoring is mandatory. We observed five episodes of acute rejection (grade 2R) in three patients (2 episodes at 0.5 months, 2 at 3 months, and 1 at 12 months), when TAC concentrations in EMBs were low (63; 62; 59; 31; 44 pg/mg, respectively), whereas concentrations in whole blood were correct. Our results are preliminary and further studies are needed to confirm the importance of this new strategy to prevent acute rejection episodes. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥ 45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ± 4.4%, LV global longitudinal strain −22.1%, TAPSE 20.1mm, s' wave 0.13m/s, RV free wall longitudinal strain −27.8%) with normal LV diastolic function (E/A 1.5, E/e' 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (−21.1% vs. −22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction. [ABSTRACT FROM AUTHOR]

Background: Physical fitness (PF) is positively related to skeletal and metabolic health, and it had an inverse relation with obesity. Adolescents with obesity have the worst performance in PF and speed-agility (SA) that contributes to an augmented risk to develop pathologies. To the best of our knowledge, many studies analyzed the trends of obesity and SA separately, but there is a lack of data about SA ability trends in adolescents with obesity. We aimed to investigate SA trends in children with obesity in the last few decades to define the association between body weight and physical performance. Methods: We recruited 3.923 Caucasian children across the period 1985–2010 in the same school in Northern Italy, near Milan. Once a year, at the ages of 11–12- and 13-years-old, we collected anthropometric measures and SA performance. We pooled the data into 5-year-period study waves and then stratified our analysis into test-sex-age BMI-z-score specific groups. Results: We reported an undetermined trend across years. The 4×5 m run test significantly decreased in adolescents with overweight/obesity, while we did not report a decline in 30 m and 60 m run tests. Conclusions: Fitness tests highlighted differences in normal weight compared to overweight/obese children, suggesting that it is crucial to carefully monitor PF capacities through the years. [ABSTRACT FROM AUTHOR]

Body mass index (BMI), usually used as a body fatness marker, does not accurately discriminate between amounts of lean and fat mass, crucial factors in determining metabolic syndrome (MS) risk. We assessed the predictive ability of the estimate of FM (eFM) calculated using the following formula: FM = weight − exp(0.3073 × height² − 10.0155 ×d-growth-standards/standards/bodymass-index-for-age-bmi-for-age weight− 1 + 0.004571 × weight − 0.9180 × ln(age) + 0.6488 × age0.5 + 0.04723×male + 2.8055) (exp = exponential function, score 1 if child was of black (BA), south Asian (SA), other Asian (AO), or other (other) ethnic origin and score 0 if not, ln = natural logarithmic transformation, male = 1, female = 0), to detect MS in 185 prepubertal obese children compared to other adiposity parameters. The eFM, BMI, waist circumference (WC), body shape index (ABSI), tri-ponderal mass index, and conicity index (C-Index) were calculated. Patients were classified as having MS if they met ≥ 3/5 of the following criteria: WC ≥ 95th percentile; triglycerides ≥ 95th percentile; HDL-cholesterol ≤ 5th percentile; blood pressure ≥ 95th percentile; fasting blood glucose ≥ 100 mg/dL; and/or HOMA-IR ≥ 97.5th percentile. MS occurred in 18.9% of obese subjects (p < 0.001), with a higher prevalence in females vs. males (p = 0.005). The eFM was correlated with BMI, WC, ABSI, and Con-I (p < 0.001). Higher eFM values were present in the MS vs. non-MS group (p < 0.001); the eFM was higher in patients with hypertension and insulin resistance (p < 0.01). The eFM shows a good predictive ability for MS. Additional to BMI, the identification of new parameters determinable with simple anthropometric measures and with a good ability for the early detection of MS, such as the eFM, may be useful in clinical practice, particularly when instrumentation to estimate the body composition is not available. [ABSTRACT FROM AUTHOR]

Frailty (FI) and metabolic syndrome (MS) are each associated with adverse health outcomes. A relationship between FI and MS has previously been described in adults. We considered the prevalence of a metabolically unhealthy phenotype (MUP) in malnourished children with neurological impairment and in subjects with obesity in comparison to a group of elderly individuals at risk of FI, and we did so in order to define the potential similarities that may underline the risk of FI in specific children. We considered 50 undernourished (defined as having a body mass index of BMI ≥ 2, standard deviation score, SDS, according to World Health Organization) disabled children; 50 children with obesity (BMI ≤ 2 SDS); 50 children who were a normal weight (1 SDS ≤ BMI ≤ +1 SDS); 21 patients who were >75 years old. MUP was defined as the presence of at least one of the following risk factors: hypertension, hyperglycemia or diabetes, hypercholesterolemia, and hypertriglyceridemia. In children with a disability and obesity, a higher prevalence (p < 0.001) and risk (disability OR 54.88, obesity OR 13.37) of MUP was noted compared to children of a normal weight. Compared to elderly patients, the prevalence of MUP did not differ in disabled children. On the contrary, MUP was lower in children with obesity (p < 0.001) and in pediatric subjects of a normal weight (p < 0.01). MS might play a key role in "pediatric" frailty. The extremities of the aging process and malnutrition are likely key factors in the development of FI. A multidisciplinary approach to FI may represent an important milestone for pediatric care. [ABSTRACT FROM AUTHOR]

Acanthosis nigricans (AN) is associated with obesity and type 2 diabetes, where insulin resistance (IR) is considered a predisposing factor. IR can also affect patients with type 1 diabetes (T1D). We evaluated the prevalence of AN in patients with T1D compared to subjects with obesity in order to define the interplay between IR and excess weight. We considered 138 pediatric patients who presented with T1D and 162 with obesity. As controls, 100 healthy normal-weight subjects were included. A physical examination with the detection of AN and biochemical assessments was performed. IR was calculated by using the homeostasis model assessment for IR in patients with obesity and the estimated glucose disposal rate in T1D. The AN prevalence was higher in T1D and obese subjects compared with controls in whom AN was not detected (p = 0.02 and p < 0.001, respectively). A greater number of AN cases were observed in subjects with obesity compared with T1D (p < 0.001). Patients with AN were older than subjects without AN (p = 0.005), and they had higher body mass index (BMI) values, waist circumference (WC), fasting triglycerides and blood pressure (all p < 0.001). Thirty-five patients with AN exhibited IR with an association between AN presence and IR in patients with obesity (p < 0.001). In T1D, there was an association between AN and being overweight/obese (p = 0.02), independently of IR. AN is a dermatological condition associated with obesity. In T1D, the presence of AN was significantly associated with overweight status or obesity but not IR. The presence of AN in the absence of IR supports the interplay role between impaired insulin signaling, IR and excess weight in the pathogenic mechanism. [ABSTRACT FROM AUTHOR]

New indexes of adiposity have been introduced to evaluate body-fat distribution and cardiometabolic risk. However, data on the correlation between Insulin Resistance (IR) and these new indexes are limited. We therefore evaluated the relationship between IR and adiposity indexes in children and adolescents with obesity, focusing on gender differences. We retrospectively enrolled 586 patients with obesity (10.80 ± 2.63; 306F/279M). As adiposity indexes we considered body mass index (BMI), BMI-z score, WC, waist-to-height ratio (WHtR), a body shape index (ABSI), triponderal mass index (TMI), visceral adiposity index (VAI) and conicity index (ConI). The homeostasis model assessment for insulin resistance (HOMA-IR), HOMA of percentage β-cell function (HOMA-β), quantitative insulin sensitivity check index (QUICKI), and triglyceride and glucose index (TyG-index) were measured and recorded as IR surrogates. In both sexes, WC and VAI significantly correlated with all IR measurements (p < 0.001). BMI significantly correlated (p < 0.001) with all IR parameters except for the TyG-index in females. Fat mass and TMI correlated with IR parameters only in females, BMI-z score with IR markers except for HOMA-β in males, WHtR with HOMA-β in both sexes (p < 0.05), free fat mass with HOMA-IR and QUICKI only in females (p < 0.01), ConI correlated with the TyG index in females (p = 0.01). Tryglicerides and SBP were correlated with all IR measurements (p < 0.001), in both sexes. Correlations between different sex parameters were significantly more evident in middle puberty. The relationship between IR surrogates and obesity indexes is influenced by gender in pediatrics. Sex-specific differences in obesity-related complications should be considered in preventive intervention decision-making. [ABSTRACT FROM AUTHOR]

Background: Long-term negative sequelae of esophageal atresia (EA) may induce poor growth and impaired nutritional status in childhood. We describe the nutritional profile and energy metabolism of children with repaired EA to identify malnutrition risk factors and optimize growth management. Methods: Twenty-one children (>4 years) were included, and anthropometric measurements, nutritional assessment, and energy metabolism were considered. The subjects were defined as undernourished if they met BMI < 2 standard deviation (SD). To grade undernutrition, we defined the prevalence of underweight, stunting, and wasting (cut-off level of <2 SD). Medical records were reviewed for the type of EA and surgery and perinatal data. Results: Malnutrition was detected in 28.6% of children. Underweight was detected in 23.8% of patients (all with undernutrition p < 0.01). Wasting was noted in 28.6% of patients, of these 5 children were undernourished (p < 0.001) and stunting was noticed in only one patient with malnutrition (p = 0.5). Resting expenditure energy (REE) was lower in undernourished subjects compared to subjects with adequate nutritional status (p < 0.001). Malnutrition was associated to: type of EA (p = 0.003, particularly type A and C); intervention including deferred anastomosis due to long-gap repair (p = 0.04) with/or without jejunostomy (p = 0.02), gastric pull-up (p = 0.04), primary anastomosis (p = 0.04), pyloromyotomy in long-gap (p < 0.01); small for gestational age condition (p = 0.001). Conclusions: undernutrition risk factors, beyond the type of malformation, surgery, and perinatal factors, must be early considered to personalize nutritional programming. Energy metabolism is important to monitor the nutritional requirements. The management of nutritional issues is surely a contributory factor able to counteract the poor growth of children with EA. [ABSTRACT FROM AUTHOR]

Adaptive changes in oxygenation and hemodynamics are evaluated during pediatric laparoscopy. The children underwent laparoscopy (LAP Group, n=20) or open surgery (Open Group, n=10). Regional cerebral (rScO2) and peripheral oxygen saturation (SpO2), heart rate (HR), diastolic (DP) and systolic pressure (SP) were monitored at different intervals: basal (T0); anesthesia induction (T1); CO2PP insufflation (T2); surgery (T3); CO2PP cessation (T4); before extubation (T5). At T1, in both the LAP and Open groups significant changes in rScO2, DP and SP were recorded compared with T0; a decrease in SatO2 was also observed at T5. In the LAP group, at T2, changes in HR related to CO2PP pressure and in DP and SP related to IAP were noted; at T4, a SP change associated with CO2PP desufflation was recorded. Open group, at T3 and T5 showed lower rScO2 values compared with T1. Pneuperitoneum and anesthesia are influent to induce hemodynamics changes during laparoscopy. [ABSTRACT FROM AUTHOR]

Immunoglobulin light-chain amyloidosis (AL) is caused by misfolded light chains produced by a small B cell clone. Mesenchymal stromal cells (MSCs) have been reported to affect plasma cell behavior. We aimed to characterize bone marrow (BM)-MSCs from AL patients, considering functional aspects, such as proliferation, differentiation, and immunomodulatory capacities. MSCs were in vitro expanded from the BM of 57 AL patients and 14 healthy donors (HDs). MSC surface markers were analyzed by flow cytometry, osteogenic and adipogenic differentiation capacities were in vitro evaluated, and co-culture experiments were performed in order to investigate MSC immunomodulatory properties towards the ALMC-2 cell line and HD peripheral blood mononuclear cells (PBMCs). AL-MSCs were comparable to HD-MSCs for morphology, immune-phenotype, and differentiation capacities. AL-MSCs showed a reduced proliferation rate, entering senescence at earlier passages than HD-MSCs. The AL-MSC modulatory effect on the plasma-cell line or circulating plasma cells was comparable to that of HD-MSCs. To our knowledge, this is the first study providing a comprehensive characterization of AL-MSCs. It remains to be defined if the observed abnormalities are the consequence of or are involved in the disease pathogenesis. BM microenvironment components in AL may represent the targets for the prevention/treatment of the disease in personalized therapies. [ABSTRACT FROM AUTHOR]

Epigenetic changes, including miRNAs deregulation, have been suggested to play a significant role in development of obliterative bronchiolitis (OB) in transplanted lungs. Many studies have tried to identify ideal candidate miRNAs and the downstream pathways implicated in the bronchiolar fibro-obliterative process. Several candidate miRNAs, previously indicated as possibly being associated with OB, were analyzed by combining the quantitative real time-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) of lung tissues of OB affected patients. Disease and OB-lesion-specific expression of miR-21-5p was confirmed and by computational analysis we were able to identify the network of genes most probably associated miR-21-5p in the context of OB fibrogenesis. Among all potentially associated genes, STAT3 had a very high probability score. Immunohistochemistry showed that STAT3/miR-21-5p were co-over expressed in OB lesions, thus, suggesting miR-21-5p could regulate STAT3 expression. However, miR-21-5p inhibition in cultures of bronchiolitis obliterans syndrome (BOS) derived myofibroblasts did not significantly affect STAT3 mRNA and protein expression levels. This study demonstrates the specificity of miR-21-5p over-expression in OB lesions and contributes to existing knowledge on the miR-21-5p downstream pathway. Activation of STAT3 is associated with miR-21-5p upregulation, however, STAT-3 network activation is most likely complex and miR-21-5p is not the sole regulator of STAT3. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea, especially in hospitalized elderly patients, representing a global public health concern. Clinical presentations vary from mild diarrhea to severe pseudomembranous colitis that may progress to toxic megacolon or intestinal perforation. Antibiotic therapy is recognized as a risk factor and exacerbates dysbiosis of the intestinal microbiota, whose role in CDI is increasingly acknowledged. A clinically challenging complication is the development of recurrent disease (rCDI). In this study, using amplicon metagenomics, we compared the fecal microbiota of CDI and rCDI patients (sampled at initial and recurrent episode) and of non-infected controls. We also investigated whether CDI severity relates to specific microbiota compositions. rCDI patients showed a significantly decreased bacterial diversity as compared to controls (p < 0.01). The taxonomic composition presented significant shifts: both CDI and rCDI patients displayed significantly increased frequencies of Firmicutes, Peptostreptococcaceae, Clostridium XI, Clostridium XVIII, and Enterococcaceae. Porphyromonadaceae and, within it, Parabacteroides displayed opposite behaviors in CDI and rCDI, appearing discriminant between the two. Finally, the second episode of rCDI was characterized by significant shifts of unclassified Clostridiales, Escherichia/Shigella and Veillonella. No peculiar taxa composition correlated with the severity of infection, likely reflecting the role of host-related factors in determining severity. [ABSTRACT FROM AUTHOR]

Variations in the interferon sensitivity-determining region (ISDR) within the NS5A region were related to the development of hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV). The aim of the study was to investigate a relationship between ISDR/PKR substitutions and their association with liver fibrosis or HCC development. A total of 316 patients infected with HCV and treated with DAAs were evaluated. HCV RNA was quantified and sequenced before treatment. The liver fibrosis stage was assessed by transient elastography and equalized to METAVIR scores. Multivariate analysis showed that ≥3 substitutions in ISDR and ≥6 in PKR-bd were significantly associated with advanced fibrosis. Advanced fibrosis was observed in patients with higher substitutions in ISDR and PKR-bd. A higher correlation between advanced fibrosis and a high frequency of ≥3 substitutions in ISDR and ≥6 in PKR-bd was observed in patients infected with genotype 2c. In addition, in a higher proportion of HCC patients, advanced fibrosis (40.4% vs. 88.2%; p < 0.001) and ≥6 substitutions in PKR-bd (15.4% vs. 41.2%; p = 0.01) was observed. In conclusion, a higher number of substitutions in ISDR and PKR-bd were associated with advanced liver fibrosis, suggesting a use of like predictors for progression in the liver damage. A significantly higher number of PKR-bd substitutions was observed in HCC patients; in particular, in patients infected with HCV genotype 2c. [ABSTRACT FROM AUTHOR]

Background and Objectives: Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten in genetically-predisposed subjects carrying MHC-DQ2 and -DQ8 heterodimers, which are encoded by four HLA-DQ allelic variants, overall. This meta-analysis aims at providing further epidemiological support to the predominant relevance of one specific allele, namely HLA-DQB1*02, in the predisposition and genetic risk of CD. Materials and Methods: We performed a search of MEDLINE/PubMed, Embase, Web of Science, and Scopus, retrieving all publications (case-control study, cross-sectional, and retrospective cohort study) on the association between HLA class II polymorphisms and first-degree relatives (FDRs) of children with CD. After a critical reading of the articles, two investigators independently performed data extraction according to the following inclusion criteria: HLA class II genes, any DQ and DR molecules, and CD diagnosed following the current clinical guidelines. A third participant was consulted for discussion to reach an agreement concerning discrepancies. Results: Our search strategy selected 14 studies as being eligible for inclusion, and those were submitted for data extraction and analysis. These studies were published between 1999 and 2016 and, collectively, enrolled 3063 FDRs. Positive and negative likelihood ratios (LR+ and LR-, respectively) for CD diagnosis, according to the presence of the HLA-DQ genotype coding a complete MHC-DQ2 and/or MHC-DQ8 molecules, were 1.449 (CI 1.279-1.642) and 0.187 (CI 0.096-0.362), respectively. If only the isolated presence of HLA-DQB1*02 allele is considered, the pooled estimation of LR+ was 1.659 (CI 1.302-2.155) and, importantly, the LR- still showed a very good discriminatory power of 0.195 (CI 0.068-0.558). Conclusions: Through our differential meta-analysis, comparing the presence of the genotype coding the full MHC-DQ2 and/or DQ8 molecules with the isolated presence of HLA-DQB1*02 allelic variant, we found that the LR- of the latter analysis maintained the same value. This observation, along with previous evidences, might be useful to consider potential cost-effective widened screening strategies for CD in children.