Background & AimsEnvironmental and genetic factors contribute to alcoholic cirrhosis onset. In particular, age at exposure to liver stressors has been shown to be important in progression to fibrosis in hepatitis C individuals. However, no definite data on the role of age at onset of at-risk alcohol consumption are available. Moreover, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis, but only in cross-sectional studies. The aim of this study was to investigate the role of age at onset of at-risk alcohol consumption and PNPLA3 I148M variant on alcoholic cirrhosis incidence.MethodsA total of 384 at-risk alcohol drinkers were retrospectively examined. The association among age at onset of at-risk alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested.ResultsA higher incidence of alcoholic cirrhosis was observed in individuals with an older (≥24 years) compared with a younger (<24) age at onset of at-risk alcohol consumption (P-value < 0.001). Moreover, PNPLA3 148M allele carriers showed an increased incidence of cirrhosis (P-value < 0.001). Both age at onset of at-risk alcohol consumption and PNPLA3 148M allele were independent risk factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18–3.50), P-value < 0.001; 1.53(1.07–2.19), P-value = 0.021 respectively). The 148M allele was associated with a two-fold increased risk of cirrhosis in individuals with a younger compared with an older age at onset of at-risk alcohol consumption (H.R. (95% C.I.): 3.03(1.53–6.00) vs. 1.61(1.09–2.38).ConclusionsAge at onset of at-risk alcohol consumption and PNPLA3 I148M genetic variant are independently associated with alcoholic cirrhosis incidence.

Background. There is increasing interest in the development of vessel substitutes, and many studies are currently focusing on the development of biodegradable scaffolds capable of fostering vascular regeneration. We tested a new biocompatible and biodegradable material with mechanical properties similar to those of blood vessels.Methods. The material used comprises a mixture of a,b-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and polylactic acid (PLA), combined with polycaprolactone (PCL) by means of electrospinning technique. Low-molecular-weight heparin was also linked to the copolymer. A tubular PHEA-PLA/PCL sample was used to create an arteriovenous fistula in a pig model with the use of the external iliac vessels. The flow was assessed by means of Doppler ultrasound examination weekly, and 1 month after the implantation we removed the scaffold for histopathologic evaluation. Results. The implants showed a perfect leak-proof seal and adequate elastic tension to blood pressure. About w3 weeks after the implantation, Doppler examination revealed thrombosis of the graft, so we proceeded to its removal. Histologic examination showed chronic inflammation, with the presence of foreign body cells and marked neovascularization. The material had been largely absorbed, leaving some isolated spot residues. Conclusions. The biocompatibility of PHEA-PLA/PCL and its physical properties make it suitable for the replacement of vessels. In the future, the possibility of functionalizing the material with a variety of molecules, to modulate the inflammatory and coagulative responses, will allow obtaining devices suitable for the replacement of native vessels.

BackgroundAlcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and results from the combination of environmental and genetic factors. Among all the genetic determinants of alcoholic cirrhosis, the patatin-like phospholipase domain protein 3 (PNPLA3) rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 (TM6SF2) rs58542926, membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, and cluster of differentiation 14 (CD14) rs2569190 as new genetic risk factors for alcoholic cirrhosis. We aimed to develop a gene-based risk score to predict the incidence of alcoholic cirrhosis in males with at-risk alcohol consumption.Materials and methodsA total of 416 male at-risk alcohol drinkers were retrospectively examined. The association between alcoholic cirrhosis incidence and PNPLA3, CD14, TM6SF2, and MBOAT7 variants was tested. Age at onset of at-risk alcohol consumption, age, and body mass index (BMI) were included as covariates to determine the prediction score for alcoholic cirrhosis incidence by evaluating time-dependent receiver operating characteristic curves.ResultsWe found that PNPLA3, CD14, and TM6SF2 were associated with alcoholic cirrhosis prevalence. PNPLA3 and CD14 were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption × 0.1) + (number of CD14 allele T) + (number of PNPLA3 allele M) + (BMI × 0.1). A threshold of 7.27 was identified as cutoff for the predictive risk of alcoholic cirrhosis development in 36 years from the onset of at-risk alcohol consumption with 70.1% sensitivity and 78.7% specificity.ConclusionWe developed the first score for alcoholic cirrhosis prediction that combines clinical and genetic factors.

Renal allograft compartment syndrome (RACS) is a complication characterized by increased pressure over 15 to 20 mm Hg of the iliac fossa site of transplanted kidney that can lead to a reduction of the blood supply to the graft, resulting in organ ischemia. This study aims to evaluate, through a review of the literature, the incidence, detection, treatment, and possible prevention of RACS. The incidence of this complication, which appears generally in the immediate post-transplantation period, is currently approximately 1% to 2% and is underestimated because of poor nosography for the presence of symptoms common to other post-transplantation complications. Doppler ultrasound is indispensable to evaluate the graft function in the immediate postoperative period and in the following days. The onset of RACS involves a surgical decompression of the graft and the subsequent closure of the abdominal wall with tension-free technique. Several authors agree that only the immediate surgical decompression following an early diagnosis can ensure a recovery of the graft. Early detection of the RACS is the key to preventing the loss of the graft. It is desirable to prevent this syndrome by reducing the discrepancy in weight between donor and recipient by 17%. However the shortage of organs makes such a selection not easy; therefore, in cases at risk for RACS, a close instrumental and clinical monitoring of the patient during post-transplantation recovery is recommended, so a prompt surgical decompression can be performed if RACS is suspected.

Background. The rapid intraoperative parathormone (PTH) and at central laboratory PTH dosage gives similar results. The central laboratory provides results in longer times and higher costs. Intraoperative measurement can reduce time and costs during parathyroidectomy. Methods. Twelve patients undergoing parathyroidectomy for hyperparathyroidism renal transplant candidates were included. Diagnosis was made by laboratory tests (serum calcium, PTH) and imaging techniques (ultrasonography and scintigraphy). All patients presented PTH levels of >400 pg/mL (the limit value to be maintained in list for kidney transplantation) and resistant to medical therapy. For each patient, 2 blood samples were collected before surgery at anesthesia induction for PTH testing intraoperative (rapid assay) and central laboratory, and 10 minutes after the removal of each gland. The times from collectioneprocessing to communication to the surgeon of the results were compared for both the methods. It was considered successful the abatement of PTH of !70% at rapid intraoperative testing and consequently surgical intervention stopped before communication of central laboratory PTH testing. Results. The average time of reporting the test results of the central laboratory was 41.5 minutes (SD AE 9), whereas with the rapid intraoperative PTH (ioPTH) testing the average time was 9.9 minutes (SD AE 2.02). An average of 33.6 minutes of the duration per intervention (SD AE 10.27) were virtually saved with the use of ioPTH testing. The 2 values of the Pearson correlation (r) of 0.99 obtained (for baseline) and 0.975 (for the 10-minute) lead us to conclude that there is an excellent correlation between the series of data. Conclusions. Rapid ioPTH testing, owing to its accuracy, permits a dramatic reduction of operating time for patients with secondary hyperparathyroidism that need to be treated before inclusion on the waiting list.