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Congenital heart diseases (CHD) are the most frequently associated anomalies with anorectal malformations (ARM). Nevertheless, many specific aspects of CHD in ARM patients have yet to be studied. The aims of this study were to evaluate the prevalence and distribution of CHD in neonates-infants with ARM, and to explore whether the severity of ARM, and the presence of VACTERL association, had an impact on CHD rate, severity, and timing at first cardiac surgery. All consecutive newborn-infants with ARM managed in our tertiary center (January-1999; December-2021) were collected from a prospective database and retrospectively analyzed. Prevalence and distribution of CHD in ARM patients were assessed. Patients were divided into groups depending on ARM severity and presence of VACTERL association. Pairwise comparison for CHD prevalence, severity, and timing at first cardiac surgery was performed between groups. Of 396 ARM patients identified, those with severe ARM showed a higher number of overall CHD compared to patients with non-severe ARM (36.7 % vs. 25.2 %, p = 0.032). VACTERL + patients had a significantly higher prevalence of CHD (73.4 % vs. 16.4 %; p <0.001) and major CHD (51.7 % vs. 26.9 %; p = 0.008) when compared with VACTERL-patients. Furthermore, VACTERL + patients underwent first cardiac surgery at a significantly younger age than VACTERL-patients (5.2 ± 15.2 months vs. 11.9 ± 6.3, p = 0.039). Patients with severe ARM had a higher number of CHD compared to patients with non-severe ARM. VATERL + patients had significantly more CHD and more severe CHD than VACTERL-patients. Early screening for CHD is strongly recommended in all newborns diagnosed with ARM before surgery. III retrospective comparative study. [ABSTRACT FROM AUTHOR]

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of its management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the second part of guidelines, focused on the multidisciplinary tumor board of experts and non-surgical treatments of HCC. [ABSTRACT FROM AUTHOR]

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC. [ABSTRACT FROM AUTHOR]

Tool condition monitoring has emerged as an essential approach in the machining industry to drive cost reductions and enhance productivity. In the era of Industry 4.0, tool wear monitoring can be done using various Internet of Things sensors, such as those recording acoustic emission, vibration, temperature, and pressure. Signals acquired can be processed by extracting numeric features or converting them into images. In this study, experimental milling campaigns with different input machine parameters were conducted, leading to the creation of a dataset based on tool wear measurements and acoustic emission registrations. Then we investigated a deep convolutional neural networks approach to classify image representations of the registered acoustic signals, aiming to predict the status of tool wear. Since the dataset was imbalanced, a class weights approach was used to improve model performance. An accuracy exceeding 90% was reached, demonstrating a great potential of the model in predicting tool wear state. [ABSTRACT FROM AUTHOR]

Controversy exists regarding the optimal duration of the extended adjuvant endocrine treatment (ET) in patients with early-stage breast-cancer (eBC). We performed a systematic review and trial-level meta-analysis of all randomized clinical trials (RCTs) comparing a "limited-extended" adjuvant ET (defined as more than 5 but less than 7.5 years of treatment overall) versus a "full-extended" adjuvant ET (defined as more than 7.5 years of treatment overall) in eBC. To be eligible, RCTs had to i) compare a "limited-extended" adjuvant ET versus a "full-extended" adjuvant ET in patients with eBC; and ii) report disease-free survival (DFS) hazard ratio (HR) according to the disease nodal-status [i.e., nodal-negative (N-ve) versus nodal-positive (N + ve)]. The primary endpoint was to assess the difference in efficacy of full-versus limited-extended ET, measured in terms of the difference in DFS log-HR, according to the disease nodal-status. Secondary endpoint was the difference in efficacy of full-versus limited-extended ET according to tumor size (i.e., pT1 vs pT2/3/4), histological grade (i.e., G1/G2 vs G3), patients' age (i.e., ≤60 vs > 60 years) and previous type of ET (i.e., aromatase inhibitors vs tamoxifen vs switch strategy). Three phase III RCTs fulfilled the inclusion criteria. A total of 6689 patients were included in the analysis, of which 3506 (53%) had N + ve disease. The full-extended ET provided no DFS-benefit as compared with the limited-extended ET in patients with N-ve disease (pooled DFS-HR = 1.04, 95%CI: 0.89 to 1.22; I2 = 18%). Conversely, in patients with N + ve disease the full-extended ET significantly improved DFS, with a pooled DFS-HR of 0.85 (95%CI: 0.74 to 0.97; I2 = 0%). There was a significant interaction between the disease nodal-status and the efficacy of the full-versus limited-extended ET (p-heterogeneity = 0.048). The full-extended ET provided no significant DFS-benefit as compared with the limited-extended ET in all the other subgroups analyzed. Patients with eBC and N + ve disease can obtain a significant DFS-benefit from the full-extended as compared with the limited-extended adjuvant ET. [Display omitted] • The full-extended Endocrine Therapy (ET) significantly improved DFS in nodal positive disease. • The full-extended ET provided no DFS benefit in patients with nodal negative disease. • No other subgroups explored (younger age, higher T-stage or histological grade) derived benefit from the the full-extended ET. [ABSTRACT FROM AUTHOR]

• Magnamosis represents a minimally invasive treatment for LGEA with limited knowledge available. • A prospective evaluation of 5 LGEA patients consecutively treated with magnetic anastomosis is here reported. • Also highlighting 6-months postoperative outcomes. Aim of study is to report our preliminary experience with magnetic anastomosis (magnamosis) treating long-gap esophageal atresia (LGEA), the most challenging condition of esophageal atresia continuum. Magnamosis has been reported in 20 patients worldwide as an innovative and marginally invasive option. Prospective evaluation of all LGEA patients treated with magnamosis was performed (study registration number: 2535/2021). Main outcomes considered were demographic and surgical features, postoperative complications and feeding within 6-month of follow-up. Between June 2020 and January 2021, 5 LGEA patients (Type A, Gross classification) were treated. Median preoperative gap was 5 vertebral bodies. Magnetic bullets were placed at an average age of 81 days of life, leading to successful magnamosis in all cases: 4 infants had primary magnetic repair (one after thoracoscopic mobilization of the pouches), 1 patient had a delayed magnamosis after Foker's procedure. Esophageal anastomosis was achieved after an average of 8 days. No anastomotic leak was found. All patients developed anastomotic stenosis at 6-month follow-up, requiring a mean of 6 dilations each. Full oral feeding was achieved in 3 patients, while 2 were still on oral-gastrostomy feeding. One patient experienced small esophageal perforation after dilation (3 months after magnamosis), distal to the anastomotic stricture and subsequently developed oral aversion. Our preliminary results suggest magnamosis a safe and effective minimally invasive option in patients with LGEA. Absence of postoperative esophageal leaks may represent a major advantage of magnamosis over conventional surgery, although possible high rate of esophageal stenosis should be further evaluated. IV (Case series with no comparison group) [ABSTRACT FROM AUTHOR]

Neoadjuvant chemoimmunotherapy (NACIT) has been shown to improve pathologic complete response (pCR) rates and survival outcomes in stage II-III triple-negative breast cancer (TNBC). Promising pCR rate improvements have also been documented for selected patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC). However, one size does not fit all and predicting which patients will benefit from NACIT remains challenging. Accurate predictions would be useful to minimize immune-related toxicity, which can be severe, irreversible, and potentially impact fertility and quality of life, and to identify patients in need of alternative treatments. This review aims to capitalize on the existing translational and clinical evidence on predictors of treatment response in patients with early-stage BC treated with neoadjuvant chemotherapy (NACT) and NACIT. It summarizes evidence suggesting that NACT/NACIT effectiveness may correlate with pre-treatment tumor characteristics, including mutational profiles, ER expression and signaling, immune cell presence and spatial organization, specific gene signatures, and the levels of proliferating versus quiescent cancer cells. However, the predominantly qualitative and descriptive nature of many studies highlights the challenges in integrating various potential response determinants into a validated, comprehensive, and multimodal predictive model. The potential of novel multi-modal approaches, such as those based on artificial intelligence, to overcome current challenges remains unclear, as these tools are not free from bias and shortcut learning. Despite these limitations, the rapid evolution of these technologies, coupled with further efforts in basic and translational research, holds promise for improving treatment outcome predictions in early HER2- BC. [ABSTRACT FROM AUTHOR]

• What is currently known about this topic? Concerns have been addressed about a higher risk of anastomotic leak and mediastinitis in neonates operated on for EA/TEF who required non-invasive ventilation after extubation in previous studies, with contrasting results. • What new information is contained in this article? Post-operative non-invasive respiratory support could be safely used in EA/TEF infants without a significant increase in risk of anastomotic leak. This should be considered especially in preterm infants in which a prolonged invasive ventilation contribute to the development of bronchopulmonary dysplasia and therefore it should be carefully shifted to non-invasive ventilation as soon as possible, using low pressures and, if necessary, a mild sedation. Infants affected by Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) may require non-invasive ventilation (NIV) in the post-operative period after elective extubation, especially if born preterm. The aim of the paper is to evaluate the role of different ventilation strategies on anastomotic complications, specifically on anastomotic leak (AL). Retrospective single Institution study, including all consecutive neonates affected by EA with or without TEF in a 5-year period study (from 2014 to 2018). Only infants with a primary anastomosis were included in the study. All infants were mechanically ventilated after surgery and electively extubated after 6–7 days. The duration of invasive ventilation was decided on a case-by-case basis after surgery, based on the pre-operative esophageal gap and intraoperative findings. The need for non-invasive ventilation (NCPAP, NIPPV, and HHHFNC) after extubation and extubation failure with the need for mechanical ventilation in the post-operative period were assessed. The primary outcome evaluated was the rate of anastomotic leak. 102 EA/TEF infants were managed in the study period. Sixty-seven underwent primary anastomosis. Of these, 29 (43.3%) were born preterm. Patients who required ventilation (n = 32) had a significantly lower gestational age as well as birthweight (respectively p = 0.007 and p = 0.041). 4/67 patients had an AL after surgical repair, with no statistical differences among post-operative ventilation strategies. We found no significant differences in the rate of anastomotic leak (AL) according to post-operative ventilation strategies in neonates operated on for EA/TEF. [ABSTRACT FROM AUTHOR]

Breast cancer risk associated with germline likely pathogenic/pathogenic variants (PV) varies by gene, often by penetrance (high >50% or moderate 20–50%), and specific locus. Germline PVs in BRCA1 and BRCA2 play important roles in the development of breast and ovarian cancer in particular, as well as in other cancers such as pancreatic and prostate cancers and melanoma. Recent studies suggest that other cancer susceptibility genes, including ATM, CHEK2, PALB2, RAD51C and RAD51D confer differential risks of breast and other specific cancers. In the era of multigene panel testing, advances in next-generation sequencing technologies have notably reduced costs in the United States (US) and enabled sequencing of BRCA1/2 concomitantly with additional genes. The use of multigene-panel testing is beginning to expand in Europe as well. Further research into the clinical implications of variants in moderate penetrance genes, particularly in unaffected carriers, is needed for appropriate counselling and risk management with data-driven plans for surveillance and/or risk reduction. For individuals at high risk without any pathogenic or likely pathogenic variant in cancer susceptibility genes or some carriers of pathogenic variants in moderate-risk genes such as ATM and CHEK2, polygenic risk scores offer promise to help stratify breast cancer risk and guide appropriate risk management options. Cancer patients whose tumours are driven by the loss of function of both copies of a predisposition gene may benefit from therapies targeting the biological alterations induced by the dysfunctional gene e.g. poly ADP ribose polymerase (PARP) inhibitors and other novel pathway agents in cancers with DNA repair deficiencies. A better understanding of mechanisms by which germline variants drive various malignancies may lead to improvements in both therapeutic and preventive management options. • The interpretation of genetic testing results requires careful attention. • ATM, CHEK2, RAD51D and BARD1 correlated with breast and other cancers risk. • European and American guidelines discrepancies. • Support European healthcare providers in interpreting and managing female carriers. [ABSTRACT FROM AUTHOR]

the assessment of fibrosis in Crohn's disease (CD) bowel lesions helps to guide therapeutic decisions. Real-time elastography (RTE) and delayed-enhancement magnetic resonance enterography (DE-MRE) have demonstrated good accuracy in quantifying CD-related ileal fibrosis as compared with histological examination. To date no study has compared DE-MRE and RTE. we aimed to evaluate the agreement between RTE and DE-MRE on quantifying CD-related ileal fibrosis. consecutive patients with ileal or ileocolonic CD underwent RTE and DE-MRE. Ileal fibrosis was quantified by calculating the strain ratio (SR) at RTE and the 70s-7 min percentage of enhancement gain (%EG) of both mucosa and submucosa at DE-MRE. A SR ≥2 was applied to define severe fibrosis. Clinically relevant outcomes occurring at follow-up were recorded. 40 CD patients were enrolled. A significant linear correlation was observed between SR and submucosal %EG (r = 0.594, p < 0.001). Patients with severe fibrosis (SR ≥2) had significantly higher submucosal %EG values than patients with low/moderate fibrosis (median values 26.4% vs. 9.5%, p < 0.001). During a median 43.8-month follow-up relevant disease outcomes occurred more frequently in the severe-fibrosis group (75% vs. 36%, HR 5.4, 95% CI 1.2–24.6, p = 0.029). the study demonstrates an excellent agreement between RTE and DE-MRE in assessing ileal fibrosis in CD. [ABSTRACT FROM AUTHOR]

We report here for the first time, a comprehensive characterization of biological and clinical features of early-stage triple negative Invasive Lobular Carcinomas(TN-ILCs) We analyzed all consecutive patients with early-stage TN-ILC operated at two reference cancer-centers between 1994 and 2012. Primary objective was to assess the invasive disease-free survival(iDFS). Co-primary objective was to assess biological features of TN-ILCs, including molecular intrinsic subtypes based on PAM-50 assay, expression of androgen receptor (AR) and mutational status of ERBB2 -gene. Additionally, DNA mutational status of an independent cohort of 45 TN-ILCs from three databases were analyzed, to confirm mutations in ERBB2 -gene and to identify other recurrently mutated genes. Among 4152 ILCs, 74(1.8%) were TN and were analyzed. The iDFS at 5 and 10 years of FUP were 50.4%(95%CI,38.0–61.6) and 37.2%(95%CI,25.5–48.8), respectively. The molecular subtype was defined through PAM50-classifier for 31 out of 74 TN-ILCs: 48% were Luminal-A(15/31), 3% luminal-B(1/31), 32% HER2-enriched (10/31), and only 16% basal-like(5/31). Luminal tumors expressed AR more frequently than non-luminal tumors (AR≥1% in 94% of luminal tumors versus 53% in non-luminal tumors; p-value = 0.001). 20% of TN-ILCs analyzed(7/35), harbored a pathogenetic and actionable mutation in the ERBB2 -gene. Analysis of the independent cohort of 45 TN-ILCs from three different databases, confirmed similar percentage of pathogenetic and actionable mutations in ERBB2 -gene(20%; 9/45). Among the top 10 molecular pathways significantly enriched for recurrently mutated genes in TN-ILCs(FDR<0.05), there were ErbB-signaling and DNA-damage-response pathways. TN-ILCs are rare tumors with poor prognosis. Their specific biological features require newly defined targeted therapeutic strategies • Triple-negative ILCs are distinct from both TN-IDCs and endocrine-responsive ILC. • TN-ILCs are enriched for actionable mutations in ErbB2 gene and DNA Damage Response genes. • The Luminal Androgen Receptor (LAR) is the most prevalent subtype in TN-ILCs. [ABSTRACT FROM AUTHOR]

Background: No specific features of nevus-associated melanoma (NAM) are currently defined.Objective: To identify clinical/dermoscopic features of NAM.Methods: Retrospective evaluation of histopathologically diagnosed NAM.Results: Eighty of 165 NAMs had a clinically recognizable nevus component, often raised or nodular, most frequently characterized by different morphologic clones and/or colors. In 111 of 165 NAMs, dermoscopy showed a nevus component, prevalently characterized by regular dots/clods and structureless brown areas. Clinically, the melanoma component was eccentric/peripheral in 45 of 80 cases and central in 35 of 80; dermoscopically, the figures were 59 of 111 and 52 of 111, respectively. Melanomas associated with congenital nevi (C-NAMs) occur at a younger age and have a thicker Breslow depth than melanomas associated with acquired nevi (NC-NAMs). Dermoscopically, regular dots/globules characterize C-NAMs, and hypopigmented structureless areas characterize NC-NAMs.Limitations: Retrospective analysis.Conclusion: C-NAMs are more often central to a congenital nevus, with a clod/globular or structureless brown pattern, typical of young patients. NC-NAMs are frequently hypopigmented nodules/plaques, eccentric/peripheral, with hypopigmented structureless areas, typical of older patients. [ABSTRACT FROM AUTHOR]

To provide evidence explaining the poor association between pCR and patients' long-term outcome at trial-level in neoadjuvant RCTs for breast cancer (BC), we performed a systematic-review and meta-analysis of all RCTs testing neoadjuvant treatments for early-BC and reporting the hazard ratio of DFS (HR DFS) for the intervention versus control arm stratified by pathological response type (i.e., pCR yes versus no). The objective was to explore differences of treatment effects on DFS across patients with and without pCR. We calculated the pooled HR DFS in the two strata of pathological response (i.e., pCR yes versus no) using a random-effects model, and assessed the difference between these two estimates using an interaction test. Ten RCTs and 8496 patients were included in the analysis. Patients obtaining pCR in the intervention-arm had a higher, although not statistically significant, risk of DFS-event as compared with patients obtaining pCR in the control-arm: the pooled HR DFS for the experimental versus control arm was 1.23 (95%CI, 0.91–1.65). On the opposite, the risk of DFS-event was higher for control as compared with the intervention-arm in the stratum of patients without pCR: the pooled HR DFS was 0.86 (95%CI, 0.78–0.95). Treatment effect on DFS was significantly different according to pathological response type (interaction test p: 0.014). We reported new evidence that contributes to explaining the poor surrogacy value of pCR at trial-level in neoadjuvant RCTs for early-BC. • Pathological complete response (pCR) has been shown to be associated with long-term outcome at patient level but not at trial-level in neoadjuvant RCTs for breast cancer (BC). • One explanation could be that new neoadjuvant treatment regimens achieving substantially higher pCR rates might exert a dissociated effect on primary tumors versus micrometastases. • In this meta-analysis of recent RCTs testing neoadjuvant treatments for early-BC patients, there was a numerically higher risk of DFS-event for patients obtaining pCR in the intervention-arm as compared with those obtaining pCR in the control-arm. • On the opposite, the risk of DFS-event was higher for control as compared with the intervention-arm in the stratum of patients without pCR. [ABSTRACT FROM AUTHOR]

• Sex dimorphism could affect tumor microenvironment and anticancer immunity. • Possible role of sex dimorphism may occur when ICI is used as single agent. • Pregnancy leads to changes in the immune system and some may be permanent. • Fetal-maternal microchimerism affects cancer development and ICI activity. • Immunological memory to cancer-fetal shared antigens influence outcomes upon ICI. In the immunoncology era, growing evidence has shown a clear sex dimorphism in antitumor immune response with a potential impact on outcomes upon immunecheckpoint blockade (ICI) in patients with cancer. Sex dimorphism could affect tumor microenvironment composition and systemic anticancer immunity; however, the modifications induced by sex are heterogeneous. From a clinical perspective, six metanalyses have explored the role of sex in cancer patients receiving ICI with conflicting results. Environmental and reproductive factors may further jeopardize the sex-related heterogeneity in anticancer immune response. In particular, pregnancy is characterized by orchestrated changes in the immune system, some of which could be long lasting. A persistence of memory T-cells with a potential fetal-antigen specificity has been reported both in human and mice, suggesting that a previous pregnancy may positively impact cancer development or response to ICI, in case of fetal-antigen sharing from tumor cells. On the other hand, a previous pregnancy may also be associated with a regulatory memory characterized by increased tolerance and anergy towards cancer-fetal common antigens. Finally, fetal-maternal microchimerism could represent an additional source of chronic exposure to fetal antigens and may have important immunological implications on cancer development and ICI activity. So far, the role of pregnancy dimorphism (nulliparous vs parous) in women and the impact of pregnancy-related variables remain largely underexplored in cancer patients. In this review, we summarize the evidence regarding sex and pregnancy dimorphism in the context of immune response and anticancer immunotherapy and advocate the importance of analyzing pregnancy variables on ICIs clinical trials. [ABSTRACT FROM AUTHOR]

to demonstrate safety of ovarian stimulation with 52mg Levonorgestrel Intrauterine System (LNG-IUS) in situ in patients conservatively treated for atypical endometrial lesions prospective observational study. G ynecology department of University Federico II, Naples, Italy. young women with atypical endometrial hyperplasia (AEH),or FIGO IA G1-G2 endometrial cancer(EC-G1,EC-G2),who underwent fertility-sparing treatment and ovarian stimulation with LNG-IUS in situ. combined fertility-sparing treatment was performed:EC-G1 and EC-G2 were treated by three steps hysteroscopic technique, AEH by superficial endometrial resection. LNG-IUS was inserted after surgery. Hysteroscopic endometrial biopsies were performed at 3 and 6 months. If complete response (CR) was achieved, controlled ovarian stimulation with LNG-IUS in situ was started, oocytes retrieval performed, and mature oocytes cryopreserved. After removal of LNG-IUS, embryo transfer was performed. 23 young women with AEH(n=17), EC-G1(n=3), or EC-G2(n=3) were enrolled. CR was achieved in 14/16(87.5%) of AEH, 2/2(100%) of EC-G1 and 2/3(66.7%) of EC-G2 at 3-month follow up and in 11/14(78.6%) of AEH, 2/2(100%) of EC-G1 and 2/2(100%) of EC-G2 at 6-month follow up. 10 patients underwent ovarian stimulation with LNG-IUS in situ (experimental group) and compared with 10 infertile patients undergoing ovarian stimulation in absence of LNG-IUS (control group). The mean number of oocytes retrieved and mature oocytes was 8.10(± 2.77 SD) and 7.00(± 2.11 SD) in experimental group, compared with 6.30(± 3.3 SD) and 4.88(± 2.68 SD) in control group. There were no statistically significant differences in oocytes retrieved(p=0.19) and mature oocytes(p=0.05) between the two groups. Reproductive outcome (pregnancies and live birth rate) was also assessed. Pregnancy rate was 50%, live birth rate 37.5% and miscarriage rate 12.5%; 50% of patients experienced implantation failure. presence of LNG-IUS during ovarian stimulation has no negative effects on oocyte quality, balancing the potentially dangerous effect of hyperestrogenism on patients with atypical endometrial lesions. The combined approach confirmed as a safe and effective fertility-sparing approach. Promising pregnancy outcomes can be expected. [ABSTRACT FROM AUTHOR]

A series of naturally occurring 3,3-dimethylallyloxy- and geranyloxycoumarins and alkaloids were chemically synthesized and tested as anti-inflammatory agents for their inhibitory effects on nitric oxide production in LPS-stimulated RAW 264.7 cells. Results indicated that the alkaloid of fungal origin 3-methylbut-2-enyl-4-methoxy-8-[(3-methylbut-2-enyl)oxy]quinoline-2-carboxylate, commonly known as Ppc-1, and coumarins having an unsubstituted 2-benzopyrone ring exhibited the highest activity with IC 50 values from 23 to 34 μM without having poor or not detectable cytotoxicity. Indomethacine and L-NAME used as reference drugs provided by far less activities. [ABSTRACT FROM AUTHOR]

Background & Aims We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. Methods We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. Results We associated DILI with rs114577328 (a proxy for A*33:01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9−3.8; P = 2.4 × 10 −8 ) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6−2.5; P = 9.7 × 10 −9 ). The association with A*33:01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A*33:01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6−2.7; P = 4.8 × 10 −9 ). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0−9.5; P = 7.1 × 10 −9 ). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. Conclusions In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non−drug-specific risk factors. [ABSTRACT FROM AUTHOR]

Phase contrast cine MRI with determination of pulsatile aqueductal cerebrospinal fluid (CSF) stroke volume and flow velocity has been suggested to assess intracranial pulsations in idiopathic normal pressure hydrocephalus (iNPH). We aimed to compare this non-invasive measure of pulsations to intracranial pressure (ICP) pulse wave amplitude from continuous ICP monitoring. We hypothesised that a significant correlation between these two markers of intracranial pulsations exists. Fifteen patients with suspected iNPH had continuous computerised ICP monitoring with calculation of mean ICP pulse wave amplitude (MWA) from time-domain analysis. MRI measured CSF aqueductal stroke volume and peak flow velocity. Mean MWA was 5.4 mmHg (range 2.3–12.4 mmHg). Mean CSF stroke volume and peak flow velocity were 65 μl (range 3–195 μl) and 9.31 cm/s (range 1.68–15.0 cm/s), respectively. No significant correlation between the invasive and non-invasive measures of pulsations existed (Spearman r = −0.30 and r = −0.27, respectively; p > 0.05). We observed marked intra-individual fluctuation of MWA during continuous ICP monitoring of an average of 6.0 mmHg (range 2.8–12.2 mmHg). The results suggest a complex interplay between measures of pulsations derived from snapshot MRI measurements and continuous computerised ICP measurements, as no significant relationship existed in our data. Further study is needed to better understand the temporal profile of CSF MRI flow studies, as substantial variation in MWA over the course of several hours of ICP monitoring is common, suggesting that these physiologic fluctuations might obscure MRI snapshot measures of intracranial pulsations. [ABSTRACT FROM AUTHOR]

Aim Esophageal atresia (EA) and tracheoesophageal fistula (TEF) consist of a spectrum of rare congenital abnormalities. Although EA surgical treatment is well established, the outcome of EA with proximal fistula (type B and D EA) or isolated H-type fistula (type E EA) is poorly explored. These forms of EA shared a common surgical step: the need of a cervical approach to close the fistula. Therefore, the aim of present study is to evaluate postoperative outcomes of patients treated for Gross type B–D and E EA, on regards of their cervical surgery. Materials and methods A retrospective case series analysis of all patients affected by type B–D and E EA, and admitted to our tertiary care center between January 2003 and December 2014 was performed. All patients underwent preoperative flexible laryngo-tracheobronchoscopy (LTBS) as part of our standardized preoperative diagnostic assessment to define the diagnosis, evaluate preoperative vocal cord motility and to cannulate the fistula when required. Fistula closure was always performed through a right cervical access. Analysis of all cases and comparison between type B–D and E EA were performed. Mann–Whitney test, Chi-squared test and unpaired t test were used as appropriate; p < 0.05 was considered significant. Results During the study period, 180 EA newborns were treated. Proximal or isolated TEF was found in 18 patients (10%): 7 type B, 11 type E EA. Patients affected by type B and E EA/TEF frequently present associated major malformations (27%), and major cardiac abnormalities (44%). Major postoperative complications were: vocal cord paralysis (5 patients), bilateral in 2 infants requiring tracheostomy, cerebral ischemia (1 patient), and cardiac failure (1 patient). Conclusion Patients affected by type B and E EA have a high rate of associated abnormalities, and risk of possible sequelae. Postoperative complications are common, with possible transient vocal cord dismotility, but in some cases persistent paralysis may require tracheostomy. Therefore, both preoperative and postoperative LTBS is highly recommended to evaluate the presence of a proximal fistula, and vocal cord motility, even in asymptomatic patients, to rule out any possible intraoperative “surprise” and any vocal cord abnormality and to possibly define its pathogenesis (congenital vs. iatrogenic). [ABSTRACT FROM AUTHOR]

The aim of this study is to develop a specific formula for the purpose of assessing skeletal age in a sample of Italian growing infants and children by measuring carpals and epiphyses of radio and ulna. A sample of 332 X-rays of left hand-wrist bones (130 boys and 202 girls), aged between 1 and 16 years, was analyzed retrospectively. Analysis of covariance (ANCOVA) was applied to study how sex affects the growth of the ratio Bo/Ca in the boys and girls groups. The regression model, describing age as a linear function of sex and the Bo/Ca ratio for the new Italian sample, yielded the following formula: Age = -1.7702 + 1.0088 g + 14.8166 (Bo/Ca). This model explained 83.5% of total variance (R(2) = 0.835). The median of the absolute values of residuals (observed age minus predicted age) was -0.38, with a quartile deviation of 2.01 and a standard error of estimate of 1.54. A second sample test of 204 Italian children (108 girls and 96 boys), aged between 1 and 16 years, was used to evaluate the accuracy of the specific regression model. A sample paired t-test was used to analyze the mean differences between the skeletal and chronological age. The mean error for girls is 0.00 and the estimated age is slightly underestimated in boys with a mean error of -0.30 years. The standard deviations are 0.70 years for girls and 0.78 years for boys. The obtained results indicate that there is a high relationship between estimated and chronological ages. [ABSTRACT FROM AUTHOR]

Background Newborn babies with esophageal atresia/tracheoesophageal fistula (EA/TEF) are prone to respiratory tract disorders. Functional residual capacity (FRC) and lung clearance index (LCI) are commonly considered useful and sensitive tools to investigate lung function and early detecting airways diseases. The aim of the present study is to report the first series of EA/TEF infants prospectively evaluated for FRC and LCI. Methods Prospective observational cohort study of all patients treated for EA/TEF. Lung volume and ventilation inhomogeneity were measured by helium gas dilution technique using an ultrasonic flow meter. Babies were studied both in assisted controlled ventilation (sedated) and in spontaneous breathing (quiet sleep). Three consecutive FRC and LCI measurements were collected for each test at three different time points: before surgery (T0), 24 hours after surgery (T1) and after extubation (T2). Results 16 EA newborns were eligible for the study between December 2011 and July 2013. Three were excluded because of technical problems. At T0 FRC values were in the normal range regardless the presence of TEF but worsened afterwards at T1, with a subsequent recovering after extubation; a significant improvement after surgery was observed concerning LCI while no differences were found in tidal volume. Conclusion Helium gas dilution technique is a suitable method to measure the effect of surgery on lung physiology, even in ventilated infants with EA. The changes observed could be related to the ventilatory management and lung compression during surgical procedure. [ABSTRACT FROM AUTHOR]

Background Near-infrared spectroscopy (NIRS) is a noninvasive technique for monitoring tissue oxygenation and perfusion. The aim of this study was to evaluate cerebral and splanchnic NIRS changes in CDH operated infants enrolled into the VICI trial and therefore randomized for ventilatory modalities. Materials and methods CDH newborns enrolled into the VICI trial (Netherlands Trial Register, NTR 1310) were randomized at birth for high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) according to the trial. Cerebral oxygenation (rSO 2 C) and splanchnic oxygenation (rSO 2 S) were obtained by NIRS (INVOS 5100; Somanetics, Troy, MI) before and after surgery. Variations in rSO 2 C and rSO 2 S were evaluated. Mann–Whitney test and one-way ANOVA were used as appropriate. p < 0.05 was considered significant. Results Thirteen VICI trial patients underwent surgical repair between March 2011 and December 2012, and were enrolled in the study. Seven patients were assigned to HFOV and six to CMV group respectively. During surgery, a significant reduction in rSO 2 C (p = 0.0001) and rSO 2 S (p = 0.005) were observed. HFOV patients experienced prolonged reduction in rSO 2 C value (p = 0.003) while rSO 2 S did not vary between HFOV and CMV (p = 0.94). Conclusions Surgical CDH repair was associated with decrease of cerebral and splanchnic oxygenation, regardless of ventilation. Patients ventilated by HFOV need a longer time interval to recovery normal rSO 2 C values, than those ventilated by CMV. This may be owing to a different impact of HFOV on patients' hemodynamic status with a higher impairment on total venous return and its negative consequences on cardiac output. [ABSTRACT FROM AUTHOR]

Introduction Refractory chylothorax is a severe clinical issue, particularly in neonates. Conventional primary approach is based on diet with medium-chain fatty acids and/or total parenteral nutrition. In nonresponders, proposed second line treatments include chemical or surgical pleurodesis, thoracic duct ligation, pleuroperitoneal shunting and pleurectomy but none of these have been shown to be superior to other in terms of resolution rate and safety. Our aim is to report our experience on povidone–iodine use for chemical pleurodesis in newborn infants with chylothorax unresponsive to conservative treatment. Our aim is to report our experience on povidone–iodine use for chemical pleurodesis in newborn infants with chylothorax unresponsive to conservative treatment. Methods Since 2013, povidone–iodine pleurodesis was attempted in all patients with persistent chylothorax who failed conservative treatment (no response to at least 10 days of total parenteral nutrition and maximum dosage of intravenous octreotide). Pleurodesis consisted in the injection of 2 ml/kg of a 4% povidone–iodine solution inside the pleural space, leaving the pleural tube clamped for the subsequent 4 hours. Results Five patients were treated with chemical pleurodesis of persistent chylothorax. Four of 5 patients had their pleural effusion treated by one single povidone–iodine infusion. Median time for resolution was 4 days. A patient with massive superior vena cava thrombosis did not benefit from pleurodesis. None of the patients experienced long term side effects of the treatment. Conclusion Our data suggest that povidone–iodine pleurodesis may be considered a safe and effective option to treat refractory chylothorax in newborns. [ABSTRACT FROM AUTHOR]

Objective: The Depression Anxiety Stress Scales-21 (DASS-21) is the short version of a self-report measure that was originally developed to provide maximum differentiation between depressive and anxious symptoms. Despite encouraging evidence, the factor structure and other features of the DASS-21 are yet to be firmly established. Method: A community sample of 417 participants and two clinical groups (32 depressive patients and 25 anxious patients) completed the Italian version of the DASS-21 along with several measures of psychopathology. Results: Confirmatory factor analyses suggested that the DASS-21 is a measure of general distress plus three additional orthogonal dimensions (anxiety, depression, and stress). The internal consistency and temporal stability of the measure were good; each DASS-21 scale correlated more strongly with a measure of a similar construct, demonstrating good convergent and divergent validity. Lastly, the DASS-21 demonstrated good criterion-oriented validity. Conclusion: The validity of the Italian DASS-21 and its utility, both for community and clinical individuals, are supported. [ABSTRACT FROM AUTHOR]

Introduction Postpneumonectomy syndrome (PPS) is an ominous complication, caused by mediastinal shift following massive lung resection. Presentation of the case A neonate with oesophageal atresia and tracheo-oesophageal fistula developed acute respiratory distress shortly after surgery, despite mechanical ventilation. The patient was found to have an associated oesophageal right lung that collapsed after oesophageal atresia repair and a left pulmonary artery sling causing left main bronchus stenosis mimicking a postpneumonectomy syndrome. Discussion We will describe the diagnostic work-up and the therapeutic measures used both in the acute phase and as definitive treatment in this challenging case. Conclusions Neonatologists and paediatric surgeons should be aware of this rare association that may cause acute life threatening and worsening of patient’s clinical status. Prompt realignment of the mediastinum in the normal position is critical to obtain rapid improvement of the patient’s clinical conditions. [ABSTRACT FROM AUTHOR]

Introduction Multilevel cervical myelopathy without surgical treatment is generally poor in the neurological deficit without surgical decompression. The two main surgical strategies used for the treatment of multilevel cervical myelopathy are anterior decompression via anterior corpectomy or posterior decompression via laminctomy/laminoplasty. Presentation of case We present the case of a 62 year-old lady, harboring rheumatoid artritis (RA) with gait disturbances, pain, and weakness in both arms. A C5 and C6 somatectomy, C4–C7 discectomy and, instrumentation and fusion with telescopic distractor “piston like”, anterior plate and expandable screws were performed. Two days later the patient complained dysfagia, and a cervical X-ray showed hardware dislocation. So a C4 somatectomy, telescopic extension of the construct up to C3 with expandible screws was performed. After one week the patient complained again soft dysfagia. New cervical X-ray showed the pull out of the cranial screws (C3). So the third surgery “one stage combined” an anterior decompression with fusion along with posterior instrumentation, and fusion was performed. Discussion There is a considerable controversy over which surgical approach will receive the best clinical outcome for the minimum cost in the compressive cervical myelopathy. However, the most important factors in patient selection for a particular procedure are the clinical symptoms and the radiographic alignment of the spine. the goals of surgery for cervical multilevel stenosis include the restoration of height, alignment, and stability. Conclusion We stress the importance of a careful patients selection, and invocated still the importance for 360° cervical fixation. [ABSTRACT FROM AUTHOR]

This study analyses the geological reasons that supported the relocation of the Cavallerizzo village (Calabria, southern Italy) to a new area after the landslide event in 2005 to examine whether the institutional ordinance of displacing the entire village was the right choice. This study is based on new geological and geomorphological field investigations, on a new reading of the existing borehole data and new data collected by multi-temporal synthetic aperture radar interferometry. The results obtained reveal that only the areas bordering the Cavallerizzo village are affected by active landslides, whereas, in the historical centre, geomorphological evidence for an active landslide capable of involving the entire settlement is not found. Nowadays, 17 years after the 2005 landslide event, more than 85% of the Cavallerizzo village is completely intact, lacking evidence of instability or important damage to ancient buildings. Furthermore, in the historical urban area, very low ground displacements by InSAR investigation are observed, highlighting that the instability conditions of Cavallerizzo are less severe than those recognised in nearby villages. This evidence along with the strong negative economic and socio-cultural impacts that the village settlement had on the community involved led to the reconsideration of the adequacy of the relocation ordinance issued by the National Civil Protection. These findings can contribute to useful advice and best practices to state-run organisations and stakeholders for disaster management planning in urban sites, such as Cavallerizzo, subject to hydrogeological hazards. [ABSTRACT FROM AUTHOR]

Continuous input of plastic litter in ocean and coastal environments achieved alarming levels that are exposing new settings in natural systems. While novel plastic debris pollution, with rock-like appearance, has been reported worldwide, fundamentally geological analyses are still lacking. We surveyed the first occurrence of multiple associated plastic debris on a single outcrop located in a remote site (Trindade Island, SE Atlantic Ocean). Even though all plastic debris forms consisted of polypropylene and polyethylene, through a sedimentary approach (cross section, macro, and micro analyses) distinct types were identified. We detected plastiglomerates, geogenic analogous to conglomerates, divided into in situ and clastic types, and formed over beach sediment. We identified plastistones as a new type with homogeneous composition (lacking incorporated materials), geogenic-looking igneous rocks, divided into in situ and clastic types, and formed over rock surfaces. We linked pyroplastics, geogenic analogous to clasts, to clastic plastiglomerates/plastistones, therefore representing clastic types of plastic debris forms. This association was correlated in a depositional system model, which suggests that plastic debris forms are rock synthetic equivalents in which humans act as depositional and post-depositional agents. [Display omitted] • Marine pollution has triggered a novel situation in Earth Sciences. • First sedimentary approach to plastic debris forms found on a single site. • Field observations linked plastic debris forms to different substrate types. • Plastistone is a novel plastic debris form. • Humans became geological agents in processes considered essentially natural. [ABSTRACT FROM AUTHOR]

Although most patients with esophageal atresia (EA) and tracheo-esophageal fistula (TEF) may benefit from “standard” management, which is deferred emergency surgery, some may present unexpected elements that change this paradigm. Birth weight, associated anomalies, and long gap can influence the therapeutic schedule of the patients with EA/TEF and can make their treatment tricky. As a consequence, detailed information on these aspects gives the power to develop a decision-making process as correct as possible. In this article, we will review the most important factors influencing the treatment of patients with EA/TEF and will share our experience on the diagnostic and therapeutic tips that may provide pivotal help in the management of such patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Near infrared spectroscopy (NIRS) gradually became the gold standard to guide anesthetic conduction during cardiac surgery, and nowadays, it is commonly utilized to monitor cerebral oxygenation during invasive procedures. Preterm babies also benefit from this non-invasive monitoring to prevent neurological sequelae. However, few data are available on NIRS perioperative changes in newborn operated on for major non-cardiac malformations. Aim of the present study is to evaluate the usefulness of NIRS assessment during and after esophageal atresia (EA) correction and its correlation with clinical behavior. Patients and Methods: All patients treated for EA from May 2011 were prospectively enrolled in the study. All infants underwent “open” correction of EA and cerebral and splanchnic NIRS was applied up to 48h after surgery. Body temperature, blood pressure, pH, paSO2, paCO2, and urine output, were recorded during NIRS registration. Mann–Whitney test and 1-way ANOVA (Kruskal–Wallis and Dunn’s multiple comparison tests) were used as appropriate. Results: Seventeen patients were enrolled into the study and 13 were available for the analysis. Four patients were excluded because of poor NIRS registration. Cerebral and renal NIRS values significantly decreased at 24h post-operatively (p<0.05). Interestingly, all parameters studied as possible confounders in NIRS remained stable during the study period. Urine output significantly decreased. Conclusion: Our data confirmed that perioperative monitoring of tissue oxygenation during neonatal esophageal surgery is feasible. Cerebral and renal NIRS evaluation, as for cardiac patients, may guide anesthetic conduction and postoperative care. Out data suggest a newly observed hemodynamic reorganization during esophageal surgery involving renal and, probably, splanchnic blood flow redistribution, demonstrated by the observed subsequent significant post-operative transitory decrease in urinary output. Reducing the decrement in cerebral and renal NIRS values may improve, and ideally eliminate, the well-known late sequelae linked to hemodynamic changes during surgery. More studies are needed to better understand the causes of the NIRS described hemodynamic changes and, therefore, correct them. [Copyright &y& Elsevier]

In edge computing environments, microservices are typically deployed in the form of containers. To maintain proximity between edge computing services and mobile users, containers need to be migrated between nodes. When migrating containers, however, it is important to consider that they typically have ongoing communications with client endpoints. Moreover, in case of connection-oriented protocols, communicating endpoints share a state (i.e., the connection), which needs to be migrated as well. Connection-oriented protocols like TCP were not designed having connection migration in mind, thus their connections cannot survive a change of IP address or port number. On the other hand, QUIC, a transport protocol recently standardised by IETF, provides a mechanism for client-side connection migration, whereas a server-side connection migration is not yet implemented nor investigated. In this work, we propose an extension of QUIC to support server-side connection migration when a container is migrated between servers. We designed three different strategies, fitting a diverse set of scenarios, wherein the migration procedure is either or not supported by a centralised entity, e.g., an orchestrator. We implemented and verified the proposed extension. Besides, we evaluated it on a real testbed, showing how each of the three strategies is impacted by different container migration techniques and container sizes. To conclude, we compared our solution against two alternatives based on TCP+DNS and MPTCP respectively, demonstrating performance improvements in terms service-migration time. [ABSTRACT FROM AUTHOR]

The main ingredients of biscuit fillings are sugar and lipids. Any modification of their formulation is a gastronomical challenge as it may affect the properties and the acceptability of the product. The objective of the present work was to develop a new filling formulation by partially replacing refined sugar and lipids with honey. In order to obtain a good quality cream, different formulations were evaluated. For the first time, the effects of each component were detailed studied by specific statistical tools and the predictive models of the texture characteristics were developed. The statistical analysis showed that honey significantly increased the antioxidant content in the biscuit fillings (P ≤ 0.05) and played a major role in their adhesiveness, cohesiveness, firmness and elasticity suggesting that it significantly contributed to structure of the cream (P ≤ 0.05). The predictive models were successfully applied to optimize a new cream formulation with honey addition and low levels of lipids and sugar. This formulation presented an excellent sensory acceptability and a high purchase intention. Besides, the shelf life evaluation indicated that the product was secure after 6 months at 20 °C and the texture and the antioxidants amount remained stable (P > 0.05). In conclusion, new biscuits fillings similar to the ones commercially available were developed. Besides, results showed that this food matrix would be an excellent alternative to preserve bioactive compounds such as antioxidants. [Display omitted] [ABSTRACT FROM AUTHOR]

The use of drugs in high dilutions and the principle of similarity (or "similia") are two basic tenets of homeopathy. However, the plausibility of both is a subject of debate. Although several models have been proposed to explain the similia principle, it can be best understood and appreciated in the framework of complexity science and dynamic systems theory. This work applies a five-node Boolean network to show how self-organization and adaptation are relevant to rationalizing this traditional medical principle. Simulating the trajectories and attractors of the network system in the energy state-space provides a rudimentary and qualitative illustration of how targeted external perturbations can have pathological effects, leading to permanent, self-sustaining alterations. Similarly, changes that conversely enable the system to find its way back to the original state can induce therapeutic effects, by causing specific shifts in attractors when suitable conditions are satisfied. Extrapolating these mechanisms to homeopathy, we can envisage how major changes in the evolution of homeodynamic systems (and, eventually, healing of the entire body) can be achieved through carefully selected remedies that reproduce the whole symptom pattern of the ill state. [ABSTRACT FROM AUTHOR]

Abstract: Pleomorphic xanthoastrocytoma (PXA) is a rare tumor with good prognosis after surgery. Few cases of anaplastic PXA (either de novo or secondary to transformation of a recurrent low grade PXA) have been reported. Moreover, primary anaplastic PXA with dissemination at diagnosis has been described only in two patients, to our knowledge. We report the first case of primary multicentric anaplastic PXA and discuss its atypical features and the pertinent literature. [Copyright &y& Elsevier]

Background & Aims: Drug-induced liver injury (DILI), especially from antimicrobial agents, is an important cause of serious liver disease. Amoxicillin-clavulanate (AC) is a leading cause of idiosyncratic DILI, but little is understood about genetic susceptibility to this adverse reaction. Methods: We performed a genome-wide association study using 822,927 single nucleotide polymorphism (SNP) markers from 201 White European and US cases of DILI following AC administration (AC-DILI) and 532 population controls, matched for genetic background. Results: AC-DILI was associated with many loci in the major histocompatibility complex. The strongest effect was with an HLA class II SNP (rs9274407, P = 4.8 × 10−14), which correlated with rs3135388, a tag SNP of HLA-DRB1*1501-DQB1*0602 that was previously associated with AC-DILI. Conditioned on rs3135388, rs9274407 is still significant (P = 1.1 × 10−4). An independent association was observed in the class I region (rs2523822, P = 1.8 × 10−10), related to HLA-A*0201. The most significant class I and II SNPs showed statistical interaction (P = .0015). High-resolution HLA genotyping (177 cases and 219 controls) confirmed associations of HLA-A*0201 (P = 2 × 10−6) and HLA-DQB1*0602 (P = 5 × 10−10) and their interaction (P = .005). Additional, population-dependent effects were observed in HLA alleles with nominal significance. In an analysis of autoimmune-related genes, rs2476601 in the gene PTPN22 was associated (P = 1.3 × 10−4). Conclusions: Class I and II HLA genotypes affect susceptibility to AC-DILI, indicating the importance of the adaptive immune response in pathogenesis. The HLA genotypes identified will be useful in studies of the pathogenesis of AC-DILI but have limited utility as predictive or diagnostic biomarkers because of the low positive predictive values. [ABSTRACT FROM AUTHOR]

Objectives: To describe the prevalence and pathogenesis of symptomatic vocal cord paresis/paralysis (VCP) in patients treated for esophageal atresia (EA), tracheo-esophageal fistula (TEF) or both. Study design: Retrospective study of all patients treated for EA/TEF in our center (1995 to 2009). Patients with and without symptomatic VCP were compared for gestational age, birth weight, associated anomalies, referrals, long-gap EA (>3cm or 3 vertebral bodies), cervical esophagostomy, anastomotic leakage, length of ventilation, and major cardiac surgery. Prevalence or median (IQR) is reported. Results: Of 174 patients, 7 (4%) had symptomatic VCP. Prevalence of referrals (5/7 versus 21/167; P = .0009), long gap (5/7 versus 41/167; P = .0146), previous cervical esophagostomy (5/7 versus 7/167; P < .0001), and anastomotic leakage (3/7 versus 10/167; P = .0097) was higher, and ventilation longer (8.5 days [7.0 to 15.5] versus 6.0 days (5.0 to 7.0); P = .0072) in patients with VCP. Conclusions: In infants treated for EA/TEF, VCP should be ruled out in case of persistent respiratory morbidity or, when present, cautiously monitored. Surgical risk factors should be actively controlled. Further studies are needed to define the prevalence of acquired and congenital VCP in patients with EA/TEF. [ABSTRACT FROM AUTHOR]

Abstract: Congenital chylous ascites is a rare entity, and surgical treatment is confined to selected intractable cases. We report 2 cases of refractory congenital chylous ascites successfully treated with preoperative administration of lipophilic dye (Sudan III) followed by abdominal systematic surgical exploration, cauterization, and fibrin glue application. [Copyright &y& Elsevier]