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Background and Methods: Hereditary hemochromatosis in adults is usually characterized by mutations in the HFE gene on the short arm of chromosome 6. Most patients have a substitution of tyrosine for cysteine at position 282 (C282Y). We studied a large family from Italy that includes persons who have a hereditary iron-overload condition indistinguishable from hemochromatosis but without apparent pathogenic mutations in the HFE gene. We performed biochemical, histologic, and genetic studies of 53 living members of the family, including microsatellite analysis of chromosome 6 and direct sequencing of the HFE gene.Results: Of the 53 family members, 15 had abnormal serum ferritin levels, values for transferrin saturation that were higher than 50 percent, or both. Thirteen of the 15 had elevated body iron levels, diagnosed on the basis of the clinical evaluation and liver biopsy, and underwent iron-removal therapy. The other two, both children, did not undergo liver biopsy or iron-removal therapy. None of the 15 members had the C282Y mutation of the HFE gene; 5 of the 15 (as well as 5 healthy relatives) had another mutation of this gene, a substitution of aspartate for histidine at position 63, but none were homozygous for it. No other mutations were found after sequencing of the entire HFE gene for all family members. Microsatellite analysis showed no linkage of the hemochromatosis phenotype with the short arm of chromosome 6, the site of the HFE gene.Conclusions: Hereditary hemochromatosis can occur in adults who do not have pathogenic mutations in the hemochromatosis gene. [ABSTRACT FROM AUTHOR]

Objective: Referring to Leventhal's common-sense model, this observational cross-sectional study aimed at investigating the relationship between illness mental representations, coping mechanisms and psychological distress in a sample of women with gestational trophoblastic disease (GTD)., Methods: Thirty-eight women diagnosed with GTD (18 with hydatidiform mole; 20 with gestational trophoblastic neoplasia) were asked to complete the Illness Perception Questionnaire-Revised, the Coping Orientation to the Problems Experienced, the State-Trait Anxiety Inventory-Form Y and the Beck Depression Inventory-Short Form. Demographic and clinical information was collected through a self-report questionnaire., Results: The sample did not report significant symptomatic distress in relation to GTD. Correlation analysis showed that the Emotional representations subscale of the Illness Perception Questionnaire-Revised was significantly associated with both state anxiety and depression; avoidant coping significantly and positively correlated with anxiety and depression, as well as with illness emotional representations. Mediation analysis revealed significant indirect effects of avoidant coping on both anxiety and depression through the mediation of emotional representations., Conclusion: Avoidant coping could lead women to develop emotional representations of illness characterised by negative affects, which in turn enhance distress levels. Results underline the importance to promote adaptive coping strategies, along with accurate illness perceptions, to foster better psychological adjustment to GTD., (© 2021 John Wiley & Sons Ltd.)

Complex abdominal wall defects (CAWDs) can be difficult to repair and using a conventional synthetic mesh is often unsuitable. A biological mesh might offer a solution for CAWD repair, but the clinical outcomes are unclear. Here, we evaluated the efficacy of a cross-linked, acellular porcine dermal collagen matrix implant (Permacol) for CAWD repair in a cohort of 60 patients. Here, 58.3% patients presented with a grade 3 hernia (according to the Ventral Hernia Working Group grading system) and a contaminated surgical field. Permacol was implanted as a bridge in 46.7%, as an underlay (intraperitoneal position) in 38.3% and as a sublay (retromuscolar position) in 15% of patients. Fascia closure was achieved in 53.3% of patients. The surgical site occurrence rate was 35% and the defect size significantly influenced the probability of post-operative complications. The long-term (2 year) hernia recurrence rate was 36.2%. This study represents the first large multi-centre Italian case series on Permacol implants in patients with a CAWD. Our data suggest that Permacol is a feasible strategy to repair a CAWD, with acceptable early complications and long-term (2 year) recurrence rates.

Background: Among these diseases, congenital bleeding disorders (CBD) represent a significant societal burden in terms of high morbidity costs and health outcomes. In Italy, the organization and provision of health care is a regional responsibility and regions must assure equity and quality to all their residents. This is also true for CBD care which is provided by 54 multidisciplinary Hemophilia Treatment Centers (HTCs) distributed among the regions. With the present study, we intend to stimulate a debate on the effect that the decentralization process have in the delivery of services to CBD patients across Italy., Methods: The available comparable measures of caseloads per center and interregional patient mobility, as proxies of quality and responsiveness of the regional network of HTCs, were first analyzed for the using data from the Italian Hemophilia Centers Association for the year 2012., Results: Nine thousand one hundred and thirty four Italian residents with CBD received care in at least one of the Italian HTC in 2012. Preliminary findings suggested room for improvement in health care delivery for CBD patients. In 2012, 16 HTCs out of 51 (31.4%) treated a number of patients under the minimum requirement for treatment center accreditation (10 severe patients). Moreover, data on interregional patient mobility highlighted differences in the ability of each region to retain its own residents or to attract residents from other regions., Conclusions: Preliminary study results showed significant disparities among regions in terms of volumes and mobility of residents with CBDs that cannot be completely explained by the different geographical characteristics. Therefore, the central government should consider taking concrete measures to bridge the gap between regions to assure access to quality care for all individuals with CBD independently from where they live and therefore to move toward a more integrated and homogeneous national network of care centers. Typology of disease, patients' needs, and cost for outcomes, should have high priority on the political agenda. For CBD patients, even in a federal healthcare system, the national government should have the global responsibility to guaranteeing uniform levels of quality care over the country and overcome local institutions when necessary.

The decapeptide GnRH is known for its central role in the regulation of the hypothalamo-pituitary-gonadal axis. In addition, it is also known to have local effects within peripheral tissues. The zinc metalloendopeptidase, EC 3.4.24.15 (EP24.15), can cleave GnRH at the Tyr(5)-Gly(6) bond to form the pentapeptide, GnRH-(1-5). The central and peripheral effect of GnRH-(1-5) is different from its parent peptide, GnRH. In the current study, we examined the effect of GnRH-(1-5) on epidermal growth factor receptor (EGFR) phosphorylation and cellular migration. Using the Ishikawa cell line as a model of endometrial cancer, we demonstrate that GnRH-(1-5) stimulates epidermal growth factor release, increases the phosphorylation of EGFR (P < .05) at three tyrosine sites (992, 1045, 1068), and promotes cellular migration. In addition, we also demonstrate that these actions of GnRH-(1-5) are mediated by the orphan G protein-coupled receptor 101 (GPR101). Down-regulation of GPR101 expression blocked the GnRH-(1-5)-mediated release of epidermal growth factor and the subsequent phosphorylation of EGFR and cellular migration. These results suggest that GPR101 is a critical requirement for GnRH-(1-5) transactivation of EGFR in Ishikawa cells.

Background: Locoregional treatments represent a good option for patients suffering from hepatocellular carcinoma (HCC) not eligible for resection or transplantation. Locoregional approaches include a wide spectrum of therapeutic methods and hepatic intra-arterial drug infusion is also considered. Fotemustine is a chemotherapy drug usually administered intravenously according to standard administration schedules. Interferon alpha 2b (IFNα2b), a biological response modifier conventionally administered by a systemic route, has been employed in the treatment of both virus-related hepatitis and HCC. Nonetheless, both drugs can also be infused into the hepatic artery., Patients and Methods: We report on five patients with liver cancer, not suitable for conventional therapies, treated with hepatic intra-arterial administration of fotemustine in combination with IFNα2b. They received fotemustine at a dose of 30 mg/m(2) and IFNα2b at a starting dose of 2,000,000 IU (increasing up to 3,000,000 IU for subsequent administrations) weekly for three consecutive weeks, followed by two weeks of rest., Results: Among the patients suffering from HCC, the first patient showed a partial response, two patients had almost stable disease and one patient was not assessable. A patient with an intrahepatic biliary tract cancer experienced disease progression., Conclusion: The therapeutic regimen used showed acceptable tolerability profiles and lack of life-threatening side-effects. Further evaluation with a larger patient cohort will be required to clarify if fotemustine and IFNα2b administered into the hepatic artery could be beneficial in treating patients with HCC.

Background: Surgery (partial hepatic resection or orthotopic liver transplantation) remains the mainstay for treatment of hepatocellular carcinoma (HCC). Unfortunately, most patients have HCC that cannot be removed either as a result of its size, multiple tumors, location, proximity to major vessels or ducts within the liver, and comorbidity, such as a not well-compensated cirrhosis. For patients who cannot be treated surgically, systemic chemotherapy is frequently limited by unacceptable toxicity, poor response and low survival rates, so that locoregional approaches may be considered as alternatives., Patients and Methods: Nine patients with HCC, not eligible for conventional treatments, were treated with interferon alpha 2b-based locoregional, hepatic intra-arterial, immunotherapy and concomitant 5-fluorouracil (5-FU)-based systemic chemotherapy. Interferon was administered at a starting dose of 2,000,000 IU, which could be escalated to 9,000,000 IU, adding 1,000,000 IU weekly, depending on toxicity. 5-Fluorouracil was infused continuously over 28 days, administered as an endovenous protracted infusion weekly at a dose of 250 mg/m2/day for 4 weeks followed by a 2-week break. Eight out of nine patients were evaluable for response and toxicity. The median patient age was 68 years (range 51-77 years). All patients were suffering from cirrhosis., Results: A total of 29 cycles of treatment were administered with a median of 3.6 per patient (range 1-11 per patients). A partial response was observed in 3 out of 8 patients; 1 had stable and 4 progressive disease. The main toxicities were: grade 3 hepatic toxicity (1 patient), grade 3 flu-like syndrome (1 patient) and grade 3 abdominal pain (1 patient). Moreover, one patient developed fatal ischemic stroke and another a fatal central venous catheter infection., Conclusion: The preliminary data, show that an interferon-based hepatic intra-arterial immunotherapy combined with low doses of 5-fluorouracil (5-FU)-based systemic chemotherapy, can represent a tolerable combination to apply in the palliative treatment of patients with hepatocellular carcinoma.

The aim of this study is to identify the minimum safe amount of effective remnant liver volume (ERLV) in patients undergoing a major hepatectomy. Thirty-eight consecutive major hepatectomies (resection of > or = 3 Couinaud segments) performed between July 1999 and March 2004 in which a frozen section liver biopsy was obtained were included. No patient had chronic viral hepatitis, cirrhosis, or cholestasis. The total liver volume (TLV) was calculated using the Vauthey formula, and the postsurgical liver volume (PSLV) was derived by subtracting the estimated volume of liver resected from the TLV. The PSLV minus the percentage of macrovesicular steatosis as nonfunctional liver was defined as the effective remnant liver volume (ERLV). Three groups of ERLV/TLV ratios (<30%, between 30% and 60%, and >60%) were correlated with liver resection type, mortality, complications, intraoperative blood transfusions, operative time, length of hospitalization, and mean value of liver function tests in the first 5 postoperative days. Comparisons between clinical parameters were performed by Pearson chi2 test. There was significant correlation between ERLV/TLV ratios and surgical resection type (P < 0.001), early postoperative mortality (P < 0.01), and complications (P < 0.003). The ERLV/TLV ratio may be a useful predictor of surgical outcome after major hepatectomy.

Authors, believing that ileostomy is the cause of serious clinical, functional and psychological consequences, dwell upon principles of rehabilitation, which aim is the reinstatement of ileostomized patients into daily life. The most important aspect is to select the position of the stoma; it is necessary to consider some technical and functional aspects. The Authors examine local problems of the stoma, the unstable electrolytical balance, and report some therapeutical aspects. They expose early and late complications after surgical therapy and conclude underlining the advantages of a rapid social reinstatement of patients with an ileostomy.

Authors, after illustrating the pathogenesis of Pancreatic Pseudocysts (PPC) and classifying them into secondary to acute pancreatitis and arising in course of chronic pancreatitis, underline that the use of Ultrasound (US), CT-scan, Magnetic Resonance, Endoscopic Retrograde CholangioPancreatography and, above all, percutaneous drainage of the cysts has modified the therapeutic approach to this pathology. They describe indications and technique of US or CT-guided percutaneous drainage, and report their experience about 12 cases of PPC secondary to acute pancreatitis and 4 of PPC arising during chronic pancreatitis. They analyze the limits of this technique (risk of infections, recurrences, fistulas), and conclude that Percutaneous Drainage of Pancreatic Pseudocysts is a useful therapeutic approach in the treatment of PPC secondary to acute pancreatitis, while its use is complementary to surgery in the treatment of PPC due to chronic pancreatitis.

Seven-day-old rats (15 g body weight) were injected subcutaneously with iodo-[14C] antipyrine (5 microCi). After a variable period, each pup was decapitated and arterial blood collected for scintillation counting. Brains were immediately removed and either prepared for isotopic counting or frozen for autoradiography. The brain:blood partition coefficient was determined [0.944 +/- 0.006 ml/g (mean +/- SEM)]. Both cerebral blood flow (CBF) and regional CBF (RCBF) were calculated according to a formula derived from the Fick equation. CBF equaled 66 +/- 4 ml/100 g/min (mean +/- SEM), a value midway between reported 1-day-old rat CBF and adult rat CBF. Autoradiographs were of sufficient quality to permit microdensitimetric readings of a minimum of 11 structures. RCBF ranged from 20 ml/100 g/min in subcortical white matter to 71 ml/100 g/min in the brain stem. Immature rat RCBF, as a proportion of adult rat RCBF, was greatest in brain stem. Previously thought not feasible, this technique provides a reliable and relatively simple means of measuring both CBF and RCBF in the very small laboratory animal.

Unlike adult rats, glucose supplementation of immature rats does not lead to accentuated hypoxic-ischemic brain damage. To explore the reason for this age-specific paradox, we subjected 7-day postnatal rats to unilateral common carotid artery occlusion followed by a subcutaneous injection of either 0.1 ml 50% glucose or normal saline. They were then exposed to hypoxia with 8% oxygen, during which they received 2.5 microCi 2-[14C]-glucose or were quick-frozen for brain metabolite analysis. During hypoxia-ischemia, glucose transport into the ipsilateral cerebral hemisphere of the hyperglycemic rats was greater (+100-150%) than in normoglycemic animals. However, glucose consumption was similar in the two groups. Glucose concentrations in brain were lower during hypoxia-ischemia in the normoglycemic animals, whereas lactate increased to similar levels in the two groups. The high-energy phosphate reserves, ATP and phosphocreatine, were depleted to a similar extent. Thus, hyperglycemia combined with hypoxia-ischemia, although associated with increased glucose transport into brain, does not lead to enhanced glucose utilization or lactate accumulation by brain over that of hypoxia-ischemia alone.