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Background: Newborn screening (NBS) is a simple, non-invasive test that allows for the early identification of genetic diseases within the first days of a newborn's life. The aim of NBS is to detect potentially fatal or disabling conditions in newborns as early as possible, before the onset of disease symptoms. Early diagnosis enables timely treatments and improves the quality of life for affected patients., Results: A pilot project for dried blood spot (DBS) NBS of lysosomal storage diseases (LSDs), including Mucopolysaccharidosis I (MPSI, IDUA α-L-iduronidase deficiency), Pompe disease (GAA α-glucosidase acid deficiency), Gaucher disease (GBA β-glucosidase deficiency) and Fabry disease (GLA α-galactosidase deficiency), was conducted using the digital microfluidic (DMF) technique. DBS were analyzed in a multiplexed assays for the enzymatic activities of four lysosomal enzymes (IDUA, GAA, GBA, GLA), and subjects identified as deficient in any of these enzymes were referred to the clinical reference center for diagnosis confirmation. From June 6th, 2022, to May 12th, 2023, a total of 7650 newborns were analyzed and 1 subject affected by Pompe disease was identified together with two additional subjects, suspected of Pompe and Fabry disease respectively, for whom continued follow-up is mandatory to determine the phenotype., Conclusions: The pilot project for DBS NBS of four LSDs in Campania Region validated the effectiveness of DMF method, established enzymatic activity cut-offs, and identified newborns referred to the clinical center for integrated diagnostics, including genetic analyses. The results suggest that this technique can effectively detect potentially affected newborns, who will require further diagnostic confirmation and clinical follow-up. This diagnostic flow chart provides the opportunity to initiate early treatments and improve LSD patients' life span., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Newborn screening (NBS) programs have significantly improved the health and outcomes of patients with inherited metabolic disorders (IMDs). Methods based on liquid chromatography/mass spectrometry (LC-MS/MS) analysis are viewed worldwide as the gold standard procedure for the expanded NBS programs for these disorders. Advanced molecular technologies point to genomic sequencing as an alternative and feasible strategy for the screening of genetic diseases, including IMDs. However, each of the two approaches has potential limitations when used as a first-tier analysis. In this study, we tested a workflow-based parallel biochemical and sequencing analyses to determine whether this approach could improve the diagnostic outcome., Results: For each patient identified by LC-MS/MS as positive, we performed both the biochemical confirmatory tests and next-generation sequencing (NGS) procedures from the same Dried Blood Spot (DBS). NGS analysis was based on applying Exome Sequencing libraries, limiting the analysis to 105 actionable genes involved in IMDs. This allows overtaking the actual limitations of NBS on DBS, enhancing our capacity to identify variants that can drive a genetic disease. Through this approach, we could reach 100% of cases solved, with 37.9% of cases (41/108) for which the combination of the biochemical and NGS analysis was indispensable for a correct diagnosis. In total, we could identify 17 affected, 34 false positives, 12 individuals referred to us for maternal conditions. In 45 newborns the molecular analysis showed heterozygosity for mutations in one or more of the genes analyzed, with results compatible with the biochemical profile indicative of NBS positivity., Conclusions: In this study, we validated the performance of the proposed workflow. The advantage of this approach is limiting molecular analysis only to positive newborns and using a restricted panel of 105 genes relevant for the expanded NBS, with a 100% rate of diagnosis and potential reduction of the costs related to NBS procedures and reduced impact on patients and families., Competing Interests: Declarations. Ethics approval and consent to participate: NBS for both biochemistry and genetics was performed according the Italian national law 167/2016 [9] Ethics approval from the local ethical committee (Campania 3) was also obtained: GENOMED study (nr. 3/2023). The research conformed to the principle of the Helsinki Declaration. Consent for publication: Not applicable. Competing interests: Davide Cacchiarelli is the founder, shareholder, and consultant of NEGEDIA Srl. Sara Riccardo, Patrizia Annunziata, and Chiara Colantuono are employees of NEGEDIA Srl. The other authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We re-analyzed the series after a median of 119 months, adding retrospectively patients' molecular features., Methods: Follow-up of all patients was updated. DNA copy number analysis and gene-fusion detection could be completed for 94/160 patients, methylation classification for 68., Results: Progression-free survival (PFS) and overall survival (OS) at 5/10 years were 66/58%, and 80/73%. Ten patients had late relapses (range 66-126 mo), surviving after relapse no longer than those relapsing earlier (0-5 y). On multivariable analysis a better PFS was associated with grade II tumor and complete surgery at diagnosis and/or at radiotherapy; female sex and complete resection showed a positive association with OS. Posterior fossa (PF) tumors scoring ≥0.80 on DNA methylation analysis were classified as PFA (n = 41) and PFB (n = 9). PFB patients had better PFS and OS. Eighteen/32 supratentorial tumors were classified as RELA, and 3 as other molecular entities (anaplastic PXA, LGG MYB, HGNET). RELA had no prognostic impact. Patients with 1q gain or cyclin-dependent kinase inhibitor 2A (CDKN2A) loss had worse outcomes, included significantly more patients >3 years old (P = 0.050) and cases of dissemination at relapse (P = 0.007)., Conclusions: Previously described prognostic factors were confirmed at 10-year follow-up. Late relapses occurred in 6.2% of patients. Specific molecular features may affect outcome: PFB patients had a very good prognosis; 1q gain and CDKN2A loss were associated with dissemination. To draw reliable conclusions, modern ependymoma trials need to combine diagnostics with molecular risk stratification and long-term follow-up., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To evaluate the effects of high intra-abdominal pressure (IAP) during hyperthermic intraperitoneal chemotherapy (HIPEC) on cisplatin uptake by residual tumor and normal tissues, pharmacokinetics, and short-term surgical outcomes., Patients & Methods: Patients with peritoneal metastasis from colorectal cancer or pseudomyxoma peritonei were randomized to closed-abdomen HIPEC with low-IAP or high-IAP, after complete cytoreduction. High-IAP was obtained increasing the volume of perfusate maintaining constant the cisplatin concentration (42 mg/L). We determined the Platinum concentration using an Inductive Coupled Plasma Mass Spectrometry System. Randomization was stratified according to tumor type. To consider the multiple sampling in the three tissues types of interest, we performed linear mixed models to assess the differences of cisplatin concentration between study arms. We also compared AUC perfusate/plasma ratios (Wilcoxon-Mann-Whitney) and perioperative severe complication rates (chi-square) between study arms., Results: 38 cases were randomly assigned to IAP arms (n = 19 each). Median IAPs were 19 mmHg and 11 mmHg in the high and low arms, respectively. Cisplatin concentrations did not differ in the tumor residual tissues and in the muscular fascia [22.8 ng/mg (SD: 25.5) vs. 15.9 ng/mg (SD: 13.3), p = 0.181] and [50.3 ng/mg (SD: 40.1) vs. 42.0 ng/mg (SD: 38.3), p = 0.426, respectively], whereas in the mesenteric peritoneum it did [5.4 ng/mg (SD: 7.82) vs. 2.7 ng/mg (SD: 2.9), p = 0.048]. Pharmacokinetic advantage did not differ between the two arms. High-IAP did not increase perioperative severe complications rate (NCI-CTCAE.v3)., Conclusions: high-IAP HIPEC increases cisplatin distribution in the mesenteric peritoneum, is safe, and could be considered to obtain microscopic cytoreduction., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Aircraft noise may cause several non-auditory health effects, including annoyance, sleep disorders, hypertension, cardiovascular diseases, and impaired cognitive skills in children., Objectives: To perform a cross-sectional study among adult residents near the Orio al Serio International Airport (BGY), Italy to investigate the association between aircraft noise, annoyance, sleep disorders, blood pressure levels, and prevalence of hypertension., Methods: Residential addresses of subjects aged 45-70 years were geocoded and classified in three groups according to noise levels: <60 (Reference), 60-65 (Zone A), and 65-75 dBA (Zone B). A sample of subjects was invited to undergo a personal interview and blood pressure measurements. Multiple linear and robust Poisson regression models were used to analyze quantitative and categorical variables, respectively., Results: Between June and September 2013, we enrolled 400 subjects (166 in the Reference Zone, 164 in Zone A, and 70 in Zone B). Compared to the Reference Zone, we found elevated adjusted annoyance scores (day and night) in Zone A (+2.7) and Zone B (+4.0) (p<0.001) and about doubled proportions of severely annoyed subjects (p<0.001). Reported sleep disorders in the previous month were also more frequent in Zones A and B. Sleep disorders in general were 19.9% in the Reference Zone, 29.9% in Zone A, and 35.7% in Zone B (p<0.001)., Conclusions: We found a strong association between aircraft noise levels, annoyance, and sleep disorders among adult residents near the Orio al Serio International Airport. We found no relationship with blood pressure levels and prevalence of hypertension.

Objective: We built and externally validated a nomogram for predicting the overall survival (OS) probability of advanced gastric cancer patients receiving second-line treatment., Methods: The nomogram was developed on a set of 320 Italian patients and validated on two independent sets (295 Italian and 172 Korean patients). Putative prognostic variables were selected using a random forest model and included in the multivariable Cox model. The nomogram's performance was evaluated by calibration plot and C index., Results: ECOG performance status, neutrophils to lymphocytes ratio, and peritoneal involvement were selected and included into the multivariable model. The C index was 0.72 (95% CI 0.68-0.75) in the development set, 0.69 (95% CI 0.65-0.73) in the Italian validation set, but only 0.57 (95% CI 0.52-0.62) in the Korean set. While Italian calibrations were quite good, the Korean one was poor. Regarding 6-month OS predictions, calibration was best in both Caucasian cohorts and worst the in Asian one., Conclusions: Our nomogram may be a useful tool to predict 3- or 6-month OS in Caucasian gastric cancer patients eligible for second-line therapy. Based on three easy-to-collect variables, the Gastric Life nomogram may help clinicians improve patient selection for second-line treatments and assist in clinical trial enrollment., (© 2018 S. Karger AG, Basel.)

The objective of this study is to investigate the relationship between epidural analgesia (EDA) in labor and the onset of lactation in healthy women after birth. In a Regional Perinatal Center in northern Italy, women who had had a vaginal delivery were recruited by convenience sampling. Analyses were carried out on the data of 366 women. 209 women received EDA and 157 women did not receive EDA or any other pharmacological analgesia. A structured follow-up was carried out interviewing women by telephone after 5 days and, a second time, 20 days after delivery. The primary outcome was the time (in hours) of the onset of lactation. Timing of the onset of lactation in the EDA and non-EDA groups did not statistically differ (p = 0.15), although the non-EDA group was more likely to initiate breastfeeding. On the basis of the results of this study, we concluded that intrapartum EDA does not have an effect on delays in the onset of lactation.

Backgrounds: In Europe 23.5% of the working-age population suffers from chronic or rare diseases, including Ehlers-Danlos syndrome (EDS), an inherited disorder of the connective tissue that frequently leads to impairment also at work., Objectives: We sought to evaluate the impairment of different functional areas in EDS subjects, using EDS-Disability Test (EDS-DT) (7 visual analogical scales: pain, stiffness, daily activities of life, in the home, outside the home, at work, in social relationships)., Methods: We administered the EDS-DT to 50 workers with EDS (classic type n=35, hypermobile n=14, vascular n=3) and 150 healthy workers (non-EDS)., Results: EDS subjects showed higher perceived disability (median 29.31 vs 7.22, p&lt; 0.0001) than non-EDS. We observed a trend suggesting that the hypermobile type has a higher level of pain (54 vs 42) and work impairment (62.5 vs 42.5) (p&gt;0.20), whereas the classic type has greater impairment of daily living activities (18.57 vs 11.43) and in the home (34.29 vs 25.71) (p&gt;0.20). Subjects reporting moderate-to-vigorous occupational physical activities (OPA) showed a higher disability level in the work area (p=0.04)., Conclusions: People with EDS suffer from chronic pain, impaired quality of life and employment difficulties. The hypermobile type seems more compromised in functional areas such as pain and work, while the classic type is more compromised in daily routine and home activities. The employment section was more impaired for EDS subjects who perform tasks with greater physical effort.

This study is the largest Italian survey on liver retransplantations (RET). Data report on 167 adult patients who received 2 grafts, 16 who received 3 grafts, and one who received 4 grafts over a 11 yr period.There was no statistically significant difference in graft survival after the first or the second RET (52, 40, and 29% vs 44, 36, and 18% at 1,5,and 10 yr, respectively: Log-Rank test, p = 0.30).Survivals at 1, 5, and 10 years of patients who underwent 2 (n = 151) or 3 (n = 15) RETs, were 65, 48,and 39% vs 59, 44, and 30%, respectively (p = 0.59).Multivariate analysis of survival showed that only the type of graft (whole vs reduced) was associated with a statistically significant difference (HR = 3.77, Wald test p = 0. 05); the donor age appeared to be a relevant factor as well, although the difference was not statistically significant (HR = 1.91, Wald test p = 0.08).Though late RETs have better results on long term survival relative to early RETs, no statistically significant difference can be found in early results, till three years after RET.Considering late first RETs (interval>30 days from previous transplantation) with whole grafts the difference in graft survival in RETs due to HCV recurrence (n = 17) was not significantly different from RETs due to other causes (n = 53) (65-58 and 31% vs 66-57 and 28% respectively at 1-5 and 10 years, p = 0.66).