Spectral Features Differentiate Aging-Induced Changes in Parchment-A Combined Approach of UV/VIS, µ-ATR/FTIR and µ-Raman Spectroscopy with Multivariate Data Analysis.

From the moment of production, artworks are constantly exposed to changing environmental factors potentially inducing degradation. Therefore, detailed knowledge of natural degradation phenomena is essential for proper damage assessment and preservation. With special focus on written cultural heritage, we present a study on the degradation of sheep parchment employing accelerated aging with light (295-3000 nm) for one month, 30/50/80% relative humidity (RH) and 50 ppm sulfur dioxide with 30/50/80%RH for one week. UV/VIS spectroscopy detected changes in the sample surface appearance, showing browning after light-aging and increased brightness after SO2-aging. Band deconvolution of ATR/FTIR and Raman spectra and factor analysis of mixed data (FAMD) revealed characteristic changes of the main parchment components. Spectral features for degradation-induced structural changes of collagen and lipids turned out to be different for the employed aging parameters. All aging conditions induced denaturation (of different degrees) indicated by changes in the secondary structure of collagen. Light treatment resulted in the most pronounced changes for collagen fibrils in addition to backbone cleavage and side chain oxidations. Additional increased disorder for lipids was observed. Despite shorter exposure times, SO2-aging led to a weakening of protein structures induced by transitions of stabilizing disulfide bonds and side chain oxidations.

Multi-Analytical Investigations of Andy Warhol's "Orange Car Crash": Polymeric Materials in Modern Paints.

This work presents strategic multi-analytical investigations performed on "Orange Car Crash" by Andy Warhol in order to make a well-informed conservation decision. For determining the type of binding medium used in the artwork, Pyrolysis-Gas Chromatography/Mass Spectrometry (Py-GC/MS) and Thermally Assisted Hydrolysis and Methylation of GC/MS (THM-GC/MS) were employed. The presence of a coating was investigated by Py-GC/MS. Moreover, the comprehension and elucidation of the paint stratigraphy were studied by examining cross-sections of samples taken from both canvases with Optical Microscopy (OM) under reflected visible (Vis) and ultraviolet light (UV) and by Scanning Electron Microscopy with Energy Dispersive X-ray spectroscopy (SEM-EDX). The investigation of possible synthetic organic pigments (SOPs) and extenders was performed by µ-Raman spectroscopy, while micro-Attenuated Total Reflection of Fourier-Transform Attenuated Total Reflection (µ-ATR-FTIR) allowed us to assign each component detected by Py-GC/MS or THM-GC/MS to a specific layer. The data collected from "Orange Car Crash" show mostly the application of acrylic-based paint as well as alkyd with rosin acids-based ink, thus providing fundamental information about the paint stratigraphy and chemical composition of each layer. In addition to the goal of informing an appropriate conservation-restoration strategy, this work represents a rare scientific study of a work by Andy Warhol.

Materials and techniques used for the "Vienna Moamin": multianalytical investigation of a book about hunting with falcons from the thirteenth century.

A multianalytical approach was used to characterize the materials in the "Vienna Moamin", an outstanding richly illustrated manuscript from the late thirteenth century, which was made in Italy and is now kept in the Kunsthistorisches Museum Wien. The investigations were carried out with a non-invasive approach by using complementary techniques, such as X-ray fluorescence (XRF), reflection Fourier transform infrared spectroscopy (rFTIR), Raman spectroscopy, and fiber optic reflectance spectroscopy (FORS). In addition, XRF scans were performed in two areas which yielded chemical maps showing the elemental distribution. The results revealed that typical materials from the medieval times were applied for the manuscript. Calcium carbonate on the parchment surface indicated a dehairing process with lime and/or whitening with chalk. Two different iron gall inks were detected in the main text and marginal notes, and vermilion was used for rubrication. The color palette included azurite, a green colorant composed of orpiment and indigo, yellow ochre, brown iron oxide pigments, minium, vermilion, brazilwood lake, and carbon black. Moreover, mosaic gold was detected in gold-beige hues. Lead white was identified for white areas and fine decoration lines, as well as in mixture with blue and red pigments for light color shades. No reliable information could be obtained concerning the binding media. Two differing application techniques for gold leaf were detected, which correspond with stylistic differences: either on gypsum or chalk preparation layers. Furthermore, calcium soap contents in certain colors were determined only on one folio with unique characteristics. The XRF scans of two historiated initials revealed that similar materials were applied in both cases and provided further valuable information about the painting technique. The results obtained enabled to gain insights into Italian thirteenth century manuscript production techniques and to characterize the used materials. The investigations showed the importance of scanning XRF for the elucidation of painting techniques, but also the demand of scanning devices utilizing compound specific analytical techniques such as rFTIR. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40494-021-00553-w.

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.

BACKGROUND: Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. METHODS: We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. FINDINGS: From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. INTERPRETATION: In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. FUNDING: Italian Medicine Agency.

Hypoventilation improvement in an adult non-invasively ventilated patient with Rapid-onset Obesity with Hypothalamic Dysfunction Hypoventilation and Autonomic Dysregulation (ROHHAD).

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare disease of unknown etiology, characterized by rapid-onset obesity in young children, hypoventilation, hypothalamic and autonomic dysfunction. Patients between the ages of 2 and 4 present with hyperphagia and weight gain, followed by neuro-hormonal dysfunction and central hypoventilation months or years later. Cardiac arrest may represent the fatal complication of alveolar hypoventilation and early mechanical ventilation is essential for the patient's life. In this paper, we describe a 22-year-old patient with ROHHAD syndrome who had an acute respiratory failure during nocturnal non-invasive ventilation (NIV).

Pulmonary scintigraphy as a method to investigate gastrobronchial communication in tracheostomized patients.

Amyotrophic Lateral Sclerosis (ALS) is a degeneration of somatic motor neurons extending from upper motor cortical pyramidal neurons to lower motor neurons of the brainstem and cord. During the course of the disease patients require invasive procedures for nutrition and ventilation. Percutaneous Endoscopic Gastrostomy (PEG), performed in patients with impaired swallowing, is a safe procedure for the administration of Enteral Nutrition (EN). In the advanced stages of the disease patients develop a ventilatory failure due to muscolar weakness in these case they need a permanent tracheal tube with mechanical ventilation. Here we reported a case of a patient with Amyotrophic Lateral Sclerosis (ASL) who developed an increased gastric endocavitary pressure after a Percutaneous Endoscopic Gastrostomy (PEG).

How albumin administration for cirrhosis impacts on hospital albumin consumption and expenditure.

AIM: To assess the impact of guidelines for albumin prescription in an academic hospital, which is a referral center for liver diseases. METHODS: Although randomized trials and guidelines support albumin administration for some complications of cirrhosis, the high cost of albumin greatly limits its use in clinical practice. In 2003, a multidisciplinary panel at Sant'Orsola-Malpighi University Hospital (Bologna, Italy) used a literature-based consensus method to list all the acute and chronic conditions for which albumin is indicated as first- or second-line treatment. Indications in hepatology included prevention of post-paracentesis circulatory dysfunction and renal failure induced by spontaneous bacterial peritonitis, and treatment of hepatorenal syndrome and refractory ascites. Although still debated, albumin administration in refractory ascites is accepted by the Italian health care system. We analyzed albumin prescription and related costs before and after implementation of the new guidelines. RESULTS: While albumin consumption and costs doubled from 1998 to 2002, they dropped 20% after 2003, and remained stable for the following 6 years. Complications of cirrhosis, namely refractory ascites and paracentesis, represented the predominant indications, followed by major surgery, shock, enteric diseases, and plasmapheresis. Albumin consumption increased significantly after guideline implementation in the liver units, whereas it declined elsewhere in the hospital. Lastly, extra-protocol albumin prescription was estimated as < 10%. CONCLUSION: Albumin administration in cirrhosis according to international guidelines does not increase total hospital albumin consumption if its use in settings without evidence of efficacy is avoided.

Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival.

BACKGROUND & AIMS: The current guidelines recommend the surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on liver ultrasonography repetition at either 6 or 12 month intervals, since there is no compelling evidence of superiority of the more stringent program. This study aimed at comparing cancer stage, treatment applicability, and survival between patients on semiannual or annual surveillance. METHODS: We analyzed the clinical records of 649 HCC patients in Child-Pugh class A or B, observed in ITA.LI.CA centers. HCC was detected in 510 patients submitted to semiannual surveillance (Group 1) and in 139 submitted to annual surveillance (Group 2). In Group 1 the survival was presented as observed and corrected for the lead time. RESULTS: The cancer stage was less severe in Group 1 than in Group 2 (p<0.001), with more single tiny (2 cm) and less advanced tumors. Treatment applicability was improved by the semiannual program (p=0.020). The median observed survival was 45 months (95% CI 40.0-50.0) in Group 1 and 30 months (95% CI 24.0-36.0) in Group 2 (p=0.001). The median corrected survival of Group 1 was 40.3 months (95% CI 34.9-45.7) (p=0.028 with respect to the observed survival of Group 2). Age, platelet count, alpha-fetoprotein, Child-Pugh class, cancer stage, and hepatocellular carcinoma treatment were independent prognostic factors. CONCLUSIONS: Semiannual surveillance increases the detection rate of very early hepatocellular carcinomas and reduces the number of advanced tumors as compared to the annual program. This translates into a greater applicability of effective treatments and into a better prognosis.

Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience.

OBJECTIVES: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. We compared the presenting features and outcome of HCC in elderly (>or=70 years) and younger patients (<70 years). DESIGN: Multicentre retrospective cohort study and nested case-control study. Patients 614 elderly and 1104 younger patients from the ITA.LI.CA database, including 1834 HCC cases consecutively diagnosed from January 1987 to December 2004. Both groups were stratified according to treatment: hepatic resection, percutaneous procedures, transarterial chemoembolisation (TACE). Survival was assessed in the whole population and in each treatment subgroup. Age, sex, aetiology, cirrhosis, comorbidities and cancer stage (CLIP score) were tested as predictors of survival. In each subgroup, differences in patient survival were also assessed after adjustment and matching by propensity score. RESULTS: Ageing was associated with a higher prevalence of comorbidities, better liver function and CLIP score. Regardless of age, two-thirds of patients underwent radical treatments or TACE. Elderly patients underwent more ablative procedures and fewer resections or TACE sessions. The survival of elderly and younger patients was comparable in each treatment subset, and was predicted by CLIP score. This result was confirmed by the propensity analysis. CONCLUSIONS: The overall applicability of radical or effective HCC treatments was unaffected by old age. However, treatment distribution differed, elderly individuals being more frequently treated with percutaneous procedures and less frequently with resection or TACE. Survival was unaffected by age and primarily predicted by cancer stage, assessed by the CLIP system, both in the overall population and in treatment subgroups.

Telangiectasia as a presenting sign of Graves' disease.

Acquired nevoid telangiectasia (ANT) is observed in several conditions including primary cutaneous disorders, systemic autoimmune disease and hyperestrogenism occurring in puberty, pregnancy and chronic liver disease. We describe a patient in whom ANT was a presenting sign of autoimmune hyperthyroidism, which improved after thyroidectomy. A 43-year-old Caucasian woman experienced an asymptomatic development of multiple widespread red skin lesions, diagnosed to be ANT. Blood tests revealed increased serum levels of free tri-iodothyronine and thyroxine and suppressed thyroid-stimulating hormone. Other causes of ANT were excluded. ANT improved but did not disappear after thyroidectomy. The possible pathogenetic factors linking ANT and Graves' disease, such as an immune-mediated process, altered estrogen metabolism or vasodilatation associated with hyperdynamic circulation, are discussed.

Daily profile of circulating C-type natriuretic peptide in pre-ascitic cirrhosis and in normal subjects: relationship with renal function.

OBJECTIVE: To investigate whether the C-type natriuretic peptide (CNP) has a role in the regulation of fluid and sodium homeostasis in normal subjects and in pre-ascitic cirrhotic patients. MATERIAL AND METHODS: The daily profile of CNP plasma levels was assessed by serial measurements (0700 h, 0900 h, 1800 h, 2300 h) in 10 pre-ascitic cirrhotic outpatients (age 56+/-4 years) and in 10 age-matched healthy controls (54+/-2 years) on a normal sodium diet (150 mmol/day) while carrying on their usual activities (mobile from 0700 h to 2200 h), after an equilibration period of 5 days. Daily diuresis and natriuresis were also monitored. RESULTS: Mean daily CNP was comparable in cirrhotic and healthy subjects (3.64+/-0.32 versus 3.20+/-0.20 pg/ml; p=0.139); CNP concentration showed a tendency towards a circadian fluctuation in healthy subjects (p=0.053) but not in patients (p=0.171). Mean daily CNP concentration significantly correlated with 24-h natriuresis (r=0.709; p=0.022) and urine volume (r=0.745; p=0.013) in patients but not in healthy subjects. CONCLUSIONS: CNP plasma levels appear to play a role in the water-sodium balance regulation in patients with pre-ascitic cirrhosis.

Effect of liver transplantation on tuftsin activity and phagocytic activity of neutrophil granulocytes in patients with liver cirrhosis.

BACKGROUND: Tuftsin activity (TA) is reduced in cirrhosis. This contributes to the defective phagocytic activity (PA) of neutrophil granulocytes and is related to the impairment of splenic function. Orthotopic liver transplantation (OLT) cures cirrhosis and might restore TA. This study was aimed at determining if OLT restores TA and PA. METHODS: We measured in 9 cirrhotic patients, before and after successful OLT, TA by a bioassay and PA by chemiluminescence in which neutrophils of the patient were tested with both autologous (PA1) and pooled sera from healthy subjects (PA2). Splenic function was assayed by the pitted red cell count. RESULTS: Before OLT, TA was reduced in 7 patients, and PA1 in all the patients. Pitted cell count was elevated in all the patients. After OLT (median 39 months; range 21-49), TA improved in all cases [median: from 8% (5-16%) to 20% (9-22%), p < 0.008], normalizing in 5 out of the 7 patients with low values. PA1 improved in all the patients [from 102 cpm (65-128 cpm) to 235 cpm (78-280 cpm), p < 0.008], normalizing in 5. Pitted red count decreased in 7 patients and normalized in 3 [from 3.3% (2.1-6.0%) to 2.4% (1.4-2.8%), p < 0.021]. Platelet count [from 55 x 10(3) (30-100) to 185 x 10(3) (93-286), p < 0.008] and leucocyte count [from 3.60 x 10(3) (1.81-5.23) to 5.53 x 10(3) (3.31-6.71), p < 0.008] also improved. CONCLUSIONS: OLT improves TA and PA of cirrhotic patients. This effect is associated with an improvement of both functional hyposplenism and haematological hypersplenism. The restoration of natural defences against infections may mitigate the adverse effect of immunosuppressive treatment.