A prospective, multicenter, three-cohort study evaluating contrast-induced acute kidney injury (CI-AKI) in patients with cirrhosis.

BACKGROUND & AIMS: Nephrotoxicity of intravenous iodinated contrast media (ICM) in cirrhosis is still a debated issue, due to scarce, low-quality and conflicting evidence. This study aims to evaluate the incidence and predisposing factors of acute kidney injury (AKI) in patients with cirrhosis undergoing contrast-enhanced computed tomography (CECT). METHODS: We performed a prospective, multicenter, cohort study including 444 inpatients, 148 with cirrhosis (cohort 1) and 163 without cirrhosis (cohort 3) undergoing CECT and 133 with cirrhosis (cohort 2) unexposed to ICM. Kidney function parameters were assessed at T0, 48-72 h (T1), 5 and 7 days after CECT/enrollment. Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) was measured in 50 consecutive patients from cohort 1 and 50 from cohort 2 as an early biomarker of tubular damage. RESULTS: AKI incidence was not significantly increased in patients with cirrhosis undergoing CECT (4.8%, 1.5%, 2.5% in cohorts 1, 2, 3 respectively, p = n.s.). Most AKI cases were mild and transient. The presence of concomitant infections was the only independent predictive factor of contrast-induced AKI (odds ratio 22.18; 95% CI 2.87-171.22; p = 0.003). No significant modifications of U-NGAL between T0 and T1 were detected, neither in cohort 1 nor in cohort 2 (median ΔU-NGAL: +0.2 [-7.6 to +5.5] ng/ml, +0.0 [-6.8 to +9.5] ng/ml, respectively [p = 0.682]). CONCLUSIONS: AKI risk after CECT in cirrhosis is low and not significantly different from that of the general population or of the cirrhotic population unexposed to ICM. It mostly consists of mild and rapidly resolving episodes of renal dysfunction and it is not associated with tubular kidney injury. Patients with ongoing infections appear to be the only ones at higher risk of AKI. IMPACT AND IMPLICATIONS: Nephrotoxicity due to intravenous iodinated contrast media (ICM) in patients with cirrhosis is still a debated issue, as the available evidence is limited and based on very heterogeneous studies, often conducted on small and retrospective cohorts. In this prospective three-cohort study we found that intravenous administration of ICM was associated with a low risk of AKI, similar to that of the general population and to that of patients with cirrhosis unexposed to ICM. Patients with ongoing infections were the only ones to have a significantly increased risk of contrast-induced AKI. Therefore, the actual recommendations of performing contrast imaging studies cautiously in cirrhosis do not seem to be reasonable anymore, with the exception of infected patients, who have a significantly higher risk of contrast-induced AKI.

Microangiopathic hemolytic anemia caused by a signet-ring cell carcinoma of the intrahepatic bile duct.

Microangiopathic hemolytic anemia (MAHA) originates from a mechanical injury of red cells, caused by vascular thrombosis or stenosis. Cancer is a cause of MAHA as a consequence of both chemotherapy and disseminated disease itself. Here we describe the case of a 60-year-old man who developed a signet-ring cell carcinoma originated from the intrahepatic bile ducts, complicated by bone marrow metastasis and MAHA.

Usefulness of thromboelastometry in predicting the risk of bleeding in cirrhotics who undergo invasive procedures.

OBJECTIVES: The management of patients with liver cirrhosis undergoing invasive procedures is controversial and haemostasis assessment using routine laboratory is inappropriate. We evaluated the following: (a) the ability of thromboelastometry to predict the risk of bleeding in cirrhotic patients undergoing invasive procedures and enable a decision on the prophylactic transfusional strategy; (b) the contribution of platelet adhesion and aggregation tests in the assessment of haemostasis. PATIENTS AND METHODS: Seventeen cirrhotic patients undergoing invasive procedures were analyzed retrospectively (training set). To obtain preliminary data, an observational study was carried out in 58 patients (test set). All 75 patients were evaluated by thromboelastometry. Platelet adhesion and aggregation were evaluated in 16 patients using Multiplate, PFA-100 and Light Transmission Aggregometry. Factor VIII was dosed in all patients of the test set. RESULTS: In the training set, thromboelastometry confirmed the haemostatic assessment shown by the conventional test only in 6/17 (35%) patients. In the test set, thromboelastometry identified all patients who had a bleeding event. In patients with a high risk of bleeding, the use of thromboelastometry was cost-effective, reducing the platelet infusions by 64%. Platelet adhesion/aggregation abnormalities were observed in 15/16 (94%) patients, but bleeding events occurred only in 2/15 (13%) patients. CONCLUSION: Thromboelastometry appears to be useful to screen cirrhotic patients undergoing invasive procedures to identify the risk of bleeding and to optimize the transfusional strategy. Adhesion/aggregation tests are not useful in identifying patients at risk of bleeding and their application is not cost-effective.

Role of PTHrp and PTHrp-engaged pathways in MCF-7 cells migration/invasion.

In this paper the effect of N-terminal parathyroid hormone-related protein (PTHrp) and PTHrp-engaged pathways on MCF-7 breast cancer cell migration/invasivity and matrix metalloproteinases (MMPs) production were investigated. We found that: a) migration is not affected by PTHrp and Forskolin (FK)-activated PKA, while Phorbol Myristate Acetate (PMA)-activated PKC strongly stimulates MCF-7 cells motility. b) MMPs production was unaffected by PTHrp, but FK reduced membrane-type (MT)-1 MMP expression. Conversely, PMA induced a marked increase of MT1-MMP and MMP-9. c) Chemical activation of PKC is not sufficient, by itself, to confer invasive ability to MCF-7 cells, unless they were provided with additional factors, supplied by fibroblasts. d) Matrix invasion likely occurs through an activation cascade, involving at least three components: pro-MMP-9 and MT-1 MMP (supplied by PMA-stimulated MCF-7 cells) and pro MMP-2 (supplied by fibroblasts). e) The selective chemical inhibition of the adenylylciclase (AC)/PKA and phospholipase C (PLC)/PKC pathways confirmed that MCF-7 cells invasivity is not affected by exogenous PTHrp, which can only modulate their growth. However, the PTHrp responsibility in breast cancer invasion cannot be completely excluded. Indeed, fibroblasts are known to respond to PTHrp (which is a normal product of MCF-7 as well as other breast cancer cells) with enhanced release of MMP-2. On the basis of the documented requirement of fibroblast-derived MMP-2 for MCF-7 cell invasivity, a novel humoral fibroblast-breast cancer cell interaction, mediated by PTHrp, can be recognised.

Omental milky spots and peritoneal dialysis--review and personal experience.

BACKGROUND: Little research has been dedicated to milky spots (MS), except for their role in oncology. In the field of peritoneal dialysis (PD), studying MS could help in understanding peritoneal defenses. METHODS: We reviewed the methods for detecting and counting omental MS and studied modifications induced by chemical and inflammatory stimuli. The reactions of MS to peritoneal catheters, PD solutions, and infection were studied in 32 rabbits. We also evaluated changes in MS in 39 serial omental biopsies from 16 patients with different histories of PD, and examined peritoneal biopsies from 38 patients with sclerosing peritonitis. RESULTS: The catheter provoked an immediate increase in the number and size of MS in rabbits. Intraperitoneal infusion of commercial PD solution containing 1.38% or 3.86% glucose for 30 days led to a slight but significant increase in the number and size of MS, without differences between the two glucose concentrations. Peritonitis caused a sharp increase in the number of MS in rabbits and humans, and a particular transformation. In patients with simple sclerosis, we observed normal MS having the same number and size as in patients without simple sclerosis. A few MS were found in only 2 patients with sclerosing peritonitis. CONCLUSIONS: Peritoneal dialysis activates omental MS. Peritoneal infection leads to a marked increase in the activity of MS, some of which undergo a singular transformation, casting doubt on previous theories about differentiation of MS from other lymphatic organs. Comparison with oncological studies indicates certain contact points. The presence of MS in PD patients with simple sclerosis is in contradiction to other morphological studies sustaining that MS act only when in contact with a fenestrated mesothelial basement membrane. Finally, the shortage of MS in patients with sclerosing peritonitis raises certain questions about etiopathogenesis.