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Introduction: Despite advances in surgical techniques, the rate of early recurrence in perihilar cholangiocarcinoma (PCC) remains high. We sought to develop the Preoperative Recurrence Score (PRS), a model to estimate the risk of early recurrence after resection based on preoperative radiological characteristics., Materials and Methods: Data of patients who underwent surgery for PCC were retrospectively collected, and preoperative imaging was reviewed to assess tumor characteristics. A model to assess the risk of early recurrence based on preoperative radiologic characteristics was internally developed and externally validated on two cohorts of patients from two European major hepatobiliary surgery referral centers., Results: A total of 215 patients among three different patient cohorts were included in the study. Tumor size ≥18 mm (HR 2.70, 95 % CI 1.48-4.92, p = 0.001), macroscopic portal vein involvement (HR 2.28, 95%CI 1.19-4.34, p = 0.013), hepatic arteries involvement (HR 2.44, 95%CI 1.26-4.71, p = 0.008), and presence of suspicious lymph nodes (HR 1.98, 95%CI 1.02-3.83, p = 0.043) were significantly associated with recurrence-free survival (RFS). The model showed excellent discrimination both on the internal (AUC 0.83) and external validation cohorts (external 1: AUC 0.84; external 2: AUC 0.70). High PRS was associated with worse RFS among all three cohorts, with a 1-year recurrence probability of 80.1 %, 100.0 %, and 54.2 % in the internal and external validation cohorts 1 and 2, respectively., Conclusions: The PRS is a simple tool that can accurately assess the risk of early recurrence in patients with PCC. Up-front surgery should be carefully evaluated in patients with high PRS, as it could result in a futile resection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

In recent years, significant academic and commercial interest has focused on collagen derived from horse tendons, with potential applications across diverse sectors such as medicine, pharmaceuticals, and cosmetics. Nano collagen, with its enhanced wound penetration, improved cell contact, and heightened cellular regeneration and repair capabilities due to its high surface area, holds promise for a wide range of applications. In this study, we present a novel method for producing nano collagen from the equine tendon. Our approach is characterized by its speed, affordability, simplicity and environmentally friendly nature, with precise temperature-control to prevent collagen denaturation. We conducted a comprehensive characterization of the obtained samples, including assessments of morphology, chemical and thermal properties, particle size distribution and biocompatibility. Importantly, our results indicate improvements in thermal stability, and surface roughness of nano collagen, while preserving its molecular weight. These advancements expand the potential applications of nano collagen in various fields., Competing Interests: Declaration of competing interest This piece of the submission is being sent via mail., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Posttransplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3% to 14% of kidney transplants (KTs), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first 3 months after transplant and can be a manifestation of de novo disease or the recurrence of previous atypical hemolytic uremic syndrome (aHUS). Abnormalities in complement regulation genes could explain the increased susceptibility of some patients to PT-TMA. Eculizumab is a humanized monoclonal antibody that inhibits the formation of the membrane attack complex C5b-9. The aim of this study is to evaluate the efficacy of eculizumab as treatment for PT-TMA., Methods: We retrospectively analyzed clinical records of 45 KT patients who received eculizumab immediately after the clinical diagnosis of PT-TMA., Results: Kidney biopsy was performed in 91.1% of patients, and complement genetic study was performed in 64.4%. Of the kidney biopsies, 85.4% showed signs of TMA; genetic analysis revealed 1 pathogenetic variant, 2 variants of uncertain significance, 1 likely benign variant, 8 risk polymorphisms, and 27 risk haplotypes. After 2 weeks from the treatment starting, hemoglobin and platelets significantly increased. A remarkable improvement in kidney function was also observed. After 6 months, 28.8% of patients had a complete renal recovery whereas 44.4% had a partial recovery., Conclusion: This is, to our knowledge, the largest series of KT patients with PT-TMA treated with eculizumab. These data suggest that eculizumab is associated with a normalization of hemolysis indices and an important and progressive improvement of graft function.

Type I collagen is commonly recognized as the gold standard biomaterial for the manufacturing of medical devices for health-care related applications. In recent years, with the final aim of developing scaffolds with optimal bioactivity, even more studies focused on the influence of processing parameters on collagen properties, since processing can strongly affect the architecture of collagen at various length scales and, consequently, scaffolds macroscopic performances. The ability to finely tune scaffold properties in order to closely mimic the tissues' hierarchical features, preserving collagen's natural conformation, is actually of great interest. In this work, the effect of the pepsin-based extraction step on the material final properties was investigated. Thus, the physico-chemical properties of fibrillar type I collagens upon being extracted under various conditions were analyzed in depth. Correlations of collagen structure at the supramolecular scale with its microstructural properties were done, confirming the possibility of tuning rheological, viscoelastic and degradation properties of fibrillar type I collagen., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open-label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (1:1) to receive a single pretransplant intravenous infusion of third-party bone marrow-derived MSC or standard of care alone. The primary endpoint was the safety profile of MSC administration during the 1-year follow-up. In all, 19 patients completed the study, and none of those who received MSC experienced infusion-related complications. The incidence of serious and non-serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56 bright NK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC-treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance-associated transcripts in 1-year protocol biopsies were similar in the two groups. In conclusion, pretransplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.gov identifier: NCT02260375., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Despite recent studies suggest that, among patients operated on for colorectal liver metastases (CLM), the primary tumor location may impact on postoperative survivals, results are still contrasting., Objective: evaluating survivals (overall (OS) and (DFS)) following liver resection of CLM from Right colon Cancer (RcC-CLM) versus Left colon Cancer (LcC-CLM), among patients undergoing preoperative chemotherapy (pCHT), identifying survival predictors, and investigating impact of recurrent disease pattern and management on survival., Methods: Among 727 patients operated for CLM(1989-2016), after excluding patients with primary transverse colon/rectum tumor and patients not receving pCHT, 297 patients were identified. Among them, 81 with RcC-CLM were matched 1:1 with LcC-CLM, according to CLM number and diameter, disease-free interval between primary tumor and CLM diagnosis, primary tumor N-status, and the presence of extrahepatic disease., Results: Overall, 66.7% of patients had multiple CLM, 21% had CLM>5 cm, 82.7% had DFI<12 months, 67.9% had N+ primary tumor, and 11.1% had extrahepatic disease at time of hepatectomy. RcC-CLM patients were similar to LcC-CLM in terms of demographic, clinical, perioperative, and pathologic characteristics. Patients operated for RcC-CLM, compared to LcC-CLM, had significantly shorter 5y-DFS(18% versus 39%) and 5y-OS(38% vs 65%). At multivariate analysis, being operated for RcC-CLM, compared to LcC-CLM, was the strongest predictor of recurrence (Hazard Ratio:2.265,p < .001) and death (HR:2.234,p = .001). Among 107 patients experiencing recurrent disease, curative recurrence resection was associated with higher 5y-OS(64% vs 17%; p < .001). However, recurrence resection was less frequently feasible among RcC-CLM(26%) patients, compared to LcC-CLM(44%,p = .05)., Conclusions: resection of RcC-CLM, compared to LcC-CLM, is associated with worse survivals, probably related to a different pattern of recurrence precluding recurrence resection among RcC-CLM patients., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: To examine the relationships among participants' demographic, social, and health characteristics and positive screening scores for symptoms of postpartum depression (PPD); to examine the feasibility of referring to a case management program women with symptoms of PPD who are accessing Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) services; and to identify barriers to screening and treatment programs for women with symptoms of PPD., Design: Descriptive, cross-sectional study followed by a process evaluation., Setting: Two WIC clinics in a large southeastern U.S. city., Participants: One group (n = 302) included women with infants younger than 12 months who were screened for symptoms of PPD. The second group (n = 31) included case managers (n = 7), nutritionists (n = 12), advisory board members (n = 7), and student volunteers (n = 5) who participated in focus groups., Methods: We conducted an initial screening of women for symptoms of PPD using the two-item Patient Health Questionnaire (PHQ-2). Participants with scores of 2 or greater (n = 73) were asked to complete the nine-item PHQ (PHQ-9) and the Edinburgh Postnatal Depression Scale. Participants were referred for case management services if they scored 10 or greater on the PHQ-9 or Edinburgh Postnatal Depression Scale (n = 29) and agreed to the referral (n = 19). We transcribed and analyzed the qualitative data recorded during focus groups., Results: Participants with no health insurance and limited support in caring for their infants were more likely to report symptoms of PPD. Overall, 302 women were screened for PPD, indicating the feasibility of PPD screening in WIC clinics. Of the 19 participants referred to case management, 47% (n = 9) accessed care. The results of focus groups illuminated barriers to screening and treatment programs for women at the individual, local, and macrosystem levels., Conclusion: Our findings show the feasibility of PPD screening in WIC clinics. However, some participants did not receive mental health services after referral because of various barriers, which highlights the need to integrate mental health providers into WIC clinics., (Copyright © 2020. Published by Elsevier Inc.)

Background and Aims: Uric acid (UA) is a byproduct of the high-energy purine metabolism and is conventionally regarded as a marker of cardio-metabolic impairment. Its potential relationship with energy homeostasis is unknown to date., Methods and Results: In a cross-sectional study on 121 otherwise healthy obese and 99 sex- and-age-matched lean subjects, UA levels were analyzed in relation to metabolic health, inflammatory markers, respiratory quotient (RQ) and resting energy expenditure (REE) as assessed by indirect calorimetry, fat mass (%FM) and fat-free mass (FFM) as determined by bioimpedance analysis. As expected, obese and lean subjects differed in BMI, glucolipid homeostasis, leptin and insulin levels, inflammatory markers, %FM and FFM (p < 0.001 for all). Likewise, UA levels (p < 0.001) and rates of hyperuricaemia (40.5% vs 3.0%, p < 0.0001) were also higher in obese than lean controls. Further, indirect calorimetry confirmed that obesity increased REE and decreased RQ significantly (p < 0.001). Beyond the expected metabolic correlates, in individual and merged groups UA levels were associated negatively with RQ and positively with REE (p < 0.0001 for both). In multivariable regression analysis, significant independent predictors of UA were BMI and sex. When BMI was replaced by measures of body composition, %FM and FFM emerged as significant predictors of serum UA (p < 0.0001)., Conclusions: A potential link relates serum UA to measures of resting energy expenditure and their determinants., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The majority of patients with stage III-IV epithelial ovarian cancer (EOC) relapse after initially responding to platinum-based chemotherapy, and develop resistance. The genomic features involved in drug resistance are unknown. To unravel some of these features, we investigated the mutational profile of genes involved in pathways related to drug sensitivity in a cohort of matched tumors obtained at first surgery (Ft-S) and second surgery (Sd-S)., Patients and Methods: Matched biopsies (33) taken at Ft-S and Sd-S were selected from the 'Pandora' tumor tissue collection. DNA libraries for 65 genes were generated using the TruSeq Custom Amplicon kit and sequenced on MiSeq (Illumina). Data were analyzed using a high-performance cluster computing platform (Cloud4CARE project) and independently validated., Results: A total of 2270 somatic mutations were identified (89.85% base substitutions 8.19% indels, and 1.92% unknown). Homologous recombination (HR) genes and TP53 were mutated in the majority of Ft-S, while ATM, ATR, TOP2A and TOP2B were mutated in the entire dataset. Only 2% of mutations were conserved between matched Ft-S and Sd-S. Mutations detected at second surgery clustered patients in two groups characterized by different mutational profiles in genes associated with HR, PI3K, miRNA biogenesis and signal transduction., Conclusions: There was a low level of concordance between Ft-S and Sd-S in terms of mutations in genes involved in key processes of tumor growth and drug resistance. This result suggests the importance of future longitudinal analyses to improve the clinical management of relapsed EOC., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy with manifestations of hemolytic anemia, thrombocytopenia, and renal impairment. Genetic studies have shown that mutations in complement regulatory proteins predispose to non-Shiga toxin-associated HUS (non-Stx-HUS). We undertook genetic analysis on membrane cofactor protein (MCP), complement factor H (CFH), and factor I (IF) in 156 patients with non-Stx-HUS. Fourteen, 11, and 5 new mutational events were found in MCP, CFH, and IF, respectively. Mutation frequencies were 12.8%, 30.1%, and 4.5% for MCP, CFH, and IF, respectively. MCP mutations resulted in either reduced protein expression or impaired C3b binding capability. MCP-mutated patients had a better prognosis than CFH-mutated and nonmutated patients. In MCP-mutated patients, plasma treatment did not impact the outcome significantly: remission was achieved in around 90% of both plasma-treated and plasma-untreated acute episodes. Kidney transplantation outcome was favorable in patients with MCP mutations, whereas the outcome was poor in patients with CFH and IF mutations due to disease recurrence. This study documents that the presentation, the response to therapy, and the outcome of the disease are influenced by the genotype. Hopefully this will translate into improved management and therapy of patients and will provide the way to design tailored treatments.

T cells (Ts-eff) induced in BALB/c mice by subcutaneous (sc) growth of syngeneic Meth A tumors can adoptively suppress the effector phase of delayed-type hypersensitivity (DTH) in Bacillus Calmette-Guérin (BCG)-primed and unprimed recipients which have been sensitized with irradiated Meth A cells but they do not inhibit the augmented DTH response in recipients inoculated with cyclophosphamide (CY) 2 days prior to sensitization. By reconstituting CY-treated immunized recipients with selected spleen cell populations, it has been demonstrated that Ts-eff suppress DTH by interacting with a second or auxiliary suppressor cell population present in immune but not normal spleens. These auxiliary suppressor cells (Ts-aux) are Thy+, Lyt 1-2+ and I-J+, phenotypically similar to Ts-eff. Their activity is not influenced by B-cell depletion. Unlike Ts-eff, Ts-aux do not bear receptors specific for Meth A cells. Ts-aux and Ts-eff share similar sensitivity to irradiation and high dose (100 mg/kg) CY but unlike Ts-eff, Ts-aux are cortisone sensitive, nondividing, nonadherent cells which are absent from the thymus. The phenotype and mechanism of action of Ts-aux resemble those of the auxiliary or Ts3 cells defined in models of contact sensitivity, DTH to simple haptens, and in vitro antibody responses.