Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers.

Hepatic ischemia reperfusion injury (IRI) is not only a pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. Hepatic IRI can seriously impair liver function, even producing irreversible damage, which causes a cascade of multiple organ dysfunction. Many factors, including anaerobic metabolism, mitochondrial damage, oxidative stress and secretion of ROS, intracellular Ca(2+) overload, cytokines and chemokines produced by KCs and neutrophils, and NO, are involved in the regulation of hepatic IRI processes. Matrix Metalloproteinases (MMPs) can be an important mediator of early leukocyte recruitment and target in acute and chronic liver injury associated to ischemia. MMPs and neutrophil gelatinase-associated lipocalin (NGAL) could be used as markers of I-R injury severity stages. This review explores the relationship between factors and inflammatory pathways that characterize hepatic IRI, MMPs and current pharmacological approaches to this disease.

Optimizing Patient Surgical Management Using WhatsApp Application in the Italian Healthcare System.

INTRODUCTION: Smartphones changed the method by which doctors communicate with each other, offer modern functionalities sensitive to the context of use, and can represent a valuable ally in the healthcare system. Studies have shown that WhatsApp™ application can facilitate communication within the healthcare team and provide the attending physician a constant oversight of activities performed by junior team members. The aim of the study was to use WhatsApp between two distant surgical teams involved in a program of elective surgery to verify if it facilitates communication, enhances learning, and improves patient care preserving their privacy. METHODS: We conducted a focused group of surgeons over a 28-month period (from March 2013 to July 2015), and from September 2014 to July 2015, a group of selected specialists communicated healthcare matters through the newly founded "WhatsApp Surgery Group." Each patient enrolled in the study signed a consent form to let the team communicate his/her clinical data using WhatsApp. Communication between team members, response times, and types of messages were evaluated. RESULTS: Forty six (n = 46) patients were enrolled in the study. A total of 1,053 images were used with an average of 78 images for each patient (range 41-143). 125 h of communication were recorded, generating 354 communication events. The expert surgeon had received the highest number of questions (P, 0.001), while the residents asked clinical questions (P, 0.001) and were the fastest responders to communications (P, 0.001). CONCLUSION: Our study investigated how two distant clinical teams may exploit such a communication system and quantifies both the direction and type of communication between surgeons. WhatsApp is a low cost, secure, and fast technology and it offers the opportunity to facilitate clinical and nonclinical communications, enhance learning, and improve patient care preserving their privacy.

Seven-year survival after pancreaticoduodenectomy for early recurrent renal cell carcinoma involving the duodenum A case report.

UNLABELLED: RCC has a range of clinical manifestations including vague abdominal symptoms, haematuria, flank pain and a palpable abdominal mass. Generally, 25-30% of patients are found to have metastases at diagnosis but a further 30-50% of patients with local disease will develop metastases during the course of their illness. Spread in RCC is lymphatic, haematogenous, transcoelomic or by direct invasion and the most common sites of metastasis in RCC are the lung, lymph nodes, bones and liver. Metastasis to the small intestine is rare and the duodenum is the segment least often affected. RCC metastasis to the duodenum occurs most commonly in the periampullary region, followed by the bulband usually manifest as gastrointestinal bleeding or obstruction. Bleeding may be the first symptom of metastatic disease in patients who have previously undergone nephrectomy for RCC. Survival is better for patients with localized disease compared with those with regional and distant metastases. This report describes a case of duodenal metastasis from RCC in which the patient presented with upper gastrointestinal bleeding and duodenal obstruction and was treated with pancreaticoduodenectomy with an excellent long-term outcome. Long-term survival was better than survival data reported in the current literature. . KEY WORDS: Duodenal metastasis, Gastrointestinal bleeding, Renal cell carcinoma, Pancreaticoduodenectomy.

"Of coronary arteries and men": the fight of a dialysis patient against his coronary arteries.

Acute myocardial infarction (AMI) in dialysis patients is associated with high mortality rate. Large randomized controlled trials documenting the benefits of revascularization in the general population have excluded chronic dialysis patients. Few observational data suggest that revascularization may provide a survival benefit compared with medical treatment alone also in these patients. We report a case of a dialysis patient who survived five documented AMIs, underwent five coronary angiographies in 11 years, had several episodes of angina pectoris and underwent percutaneous transluminal coronary angioplasty (PTCA) with stenting and heart surgery for coronary bypassing. It represents a highly unusual therapeutic approach and might contribute to support also in dialysis patients the use of revascularization to improve survival.

A very unusual case of hypokalaemia.

Cystic fibrosis (CF) is diagnosed in the first years of life. There are only two reports in the literature of adult patients with unusual presentation of newly diagnosed CF. We report here an adult patient apparently in a good health, who presented with serious hypokalaemia and metabolic alkalosis as the only abnormalities, who, through a fortuitous event, was tested by additional means for seemingly unrelated conditions that led to evidence of signs typical of CF, which was then confirmed by genetic analyses. This is the first adult patient in Italy with newly diagnosed CF. As unexplained hypokalaemia in an apparently healthy adult is very rare and has now been shown to represent an uncommon presentation of CF, physicians must take these facts into account when determining an appropriate imaging, biochemical work-up and genetic analyses to arrive at a diagnosis.

Treatment with calcimimetic (cinacalcet) alters epoetin dosage requirements in dialysis patients: preliminary report.

BACKGROUND: Secondary hyperparathyroidism (SHPT), known complication of chronic renal failure, in addition to effects on bone and cardiovascular systems, is associated with reduced response to erythropoietin (EPO). Calcimimetics such as cinacalcet are the latest generation of drugs used in the treatment of SHPT. Few studies have evaluated the effect of cinacalcet on anemia associated with SHPT in dialysis patients, while no study has compared this cinacalcet effect with that of vitamin D analogs such as paricalcitol. PATIENTS AND METHODS: Using a retrospective chart-based review of dialysis patients' records to identify patients being treated with either cinacalcet or paricalcitol alone, matched for the same EPO treatment, which had been followed for 1 year, we have evaluated the effect of cinacalcet on anemia compared to that of paricalcitol. RESULTS: Ten patient records were found that fit the criteria, five treated with cinacalcet (Group 1) and five treated with paricalcitol (Group 2), all treated with the same dose of darbepoetin. Darbepoetin dosage was the only parameter that significantly changed between groups, decreasing in Group 1 (-33%, p = 0.009) while remaining unchanged in Group 2. PTH-level reduction, which was significant versus baseline in both groups, although not statistically different between groups, was higher with cinacalcet. CONCLUSION: The combination of lower EPO dose in cinacalcet-treated patients compared with paricalcitol-treated patients, along with good SHPT control is a novel information and might have considerable benefits in dialysis patients not only preventing bone (fractures) and cardiovascular system (calcifications) damages but also in terms of cost savings via a reduction of EPO dosage.

The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis.

BACKGROUND: This prospective, randomized, controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone. METHODS: Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone (PTH) > 300 pg/mL or PTH 150-300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2) while receiving vitamin D. All subjects received calcium-based phosphate binders. Coronary artery calcification (CAC) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography. Subjects with Agatston CAC scores ≥ 30 were randomized to cinacalcet (30- 180 mg/day) plus low-dose calcitriol or vitamin D analog (≤ 2 µg paricalcitol equivalent/dialysis), or flexible vitamin D therapy. The primary end point was percentage change in Agatston CAC score from baseline to Week 52. RESULTS: Median (P10, P90) Agatston CAC scores increased 24% (-22%, 119%) in the cinacalcet group and 31% (-9%, 179%) in the flexible vitamin D group (P = 0.073). Corresponding changes in volume CAC scores were 22% (-12%, 105%) and 30% (-6%, 133%; P = 0.009). Increases in calcification scores were consistently less in the aorta, aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols, and the differences between groups were significant at the aortic valve. CONCLUSIONS: In hemodialysis patients with moderate to severe secondary hyperparathyroidism, cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification.

Effect of a dialysis session on the prognostic values of NT-proBNP, troponins, endothelial damage and inflammation biomarkers.

BACKGROUND: In hemodialysis, the relationship between the increased concentration of natriuretic peptides and volume overload, inflammatory activity, endothelial dysfunction, left ventricular function and mass, and silent ischemic events is not clear. To investigate the relationship, a 3-year prospective cohort study was conducted in 50 adult hemodialysis patients in NYHA class I-II who were free from diabetes and ischemic heart events. METHODS: Doppler echocardiogram, plasma NT-proBNP, troponin T and I, CRP, TNF alpha, big-endothelin 1, and cystatin-C, were determined both before and after a dialysis session. The outcome was all-cause death. RESULTS: 13 out of 50 patients died. Survival curves significantly differed by age (above vs. below the median 68 yrs), NT-proBNP (9719 pg/mL), troponin T (0.03 ng/mL), C-reactive protein (4.8 mg/L), left atrial volume index (51 mL/sqm), ejection fraction (61%), and diastolic pattern. In the Cox model only NT-proBNP (cutoff 10000 pg/mL) had a significant hazard ratio (4.1). Post-HD measurements of NT-proBNP, troponin T, and CRP maintained their prognostic value. The high correlation between pre and post values of NT-proBNP, and the lack of correlation with ultrafiltration volume excluded a role for acute fluid removal on its regulation. CONCLUSIONS: The increased level of NT-proBNP is the most important prognostic factor even in the absence of severe heart dysfunction and myocardial ischemic events, without any relationship with endothelial dysfunction, inflammatory biomarkers, or with acute fluid removal. A cutoff value of NT-proBNP of 10000 pg/mL could be used to identify hemodialysis patients with a higher risk of death.

Diagnosis of iron deficiency in patients undergoing hemodialysis.

To diagnose iron deficiency in patients undergoing hemodialysis, the percentage of hypochromic RBCs (with cellular hemoglobin concentration <280 g/L [HYPO%]) and mean reticulocyte hemoglobin content (CHret) provided by the Siemens ADVIA 120 and 2120 analyzers (Siemens Diagnostic Solutions, Tarrytown, NY) were proposed as alternatives to biochemical tests. Sysmex, with its XE-5000 analyzer (Sysmex, Kobe, Japan), also proposed the percentage of erythrocytes with cellular hemoglobin content lower than 17 pg (%Hypo-He) and equivalent of the mean reticulocyte hemoglobin content (Ret-He) with similar clinical applications. Our aim was to verify the clinical usefulness of the biochemical and cellular parameters as predictors of iron deficiency in patients undergoing long-term hemodialysis. We studied 69 patients undergoing hemodialysis 3 times weekly. The baseline values of serum ferritin and percentage of transferrin saturation were poor predictors of iron responsiveness. Better ability was demonstrated by reticulocyte indices (area under the curve [AUC], 0.74 for CHret and 0.72 for Ret-He; best cutoff values, 31.2 and 30.6 pg, respectively) and erythrocyte parameters (AUC, 0.72 for HYPO% and 0.68 for %Hypo-He; best cutoff values, 5.8 and 2.7, respectively). The newly proposed Ret-He and %Hypo-He can provide clinicians with information equivalent to CHret and HYPO%.

Study design and subject baseline characteristics in the ADVANCE Study: effects of cinacalcet on vascular calcification in haemodialysis patients.

BACKGROUND: The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics. METHODS: ADVANCE is a multinational, multicentre, randomized, open-label study. Adult haemodialysis patients with moderate to severe secondary hyperparathyroidism (intact parathyroid hormone [iPTH] >300 pg/mL or bio-intact PTH >160 pg/mL) and baseline CAC score >or=30 were stratified by CAC score (>or=30-399, >or=400-999, >or=1000) and randomized in a 1:1 ratio to cinacalcet (30-180 mg/day) plus low-dose active vitamin D (cinacalcet group) or flexible dosing of active vitamin D alone (control). The study had three phases: screening, 20-week dose titration and 32-week follow-up. CAC scores obtained by cardiac computed tomography were determined at screening and weeks 28 and 52. The primary end point was percentage change in CAC score from baseline to Week 52. RESULTS: Subjects (n = 360) were randomized to cinacalcet or control. Mean age was 61.5 years, 43% were women, and median dialysis vintage was 36.7 months (range, 2.7-351.5 months). The baseline geometric mean CAC score by the Agatston method was 548.7 (95% confidence interval, 480.5-626.6). Baseline CAC score was independently associated with age, sex, dialysis vintage, diabetes and iPTH. Subjects also had extensive aortic and valvular calcification at baseline. CONCLUSIONS: Subjects enrolled in ADVANCE have extensive CAC at baseline. The ADVANCE Study should help determine whether cinacalcet attenuates progression of vascular calcification.

Carnitine-mediated improved response to erythropoietin involves induction of haem oxygenase-1: studies in humans and in an animal model.

BACKGROUND: Carnitine improves erythropoetin (EPO) response and anaemia in haemodialysis patients (HD); however, the mechanism(s) responsible remain unidentified. We have reported that carnitine induces haem oxygenase (HO)-1, which is an antioxidant and antiapoptotic that acts via pathways shared with EPO. Therefore carnitine's effect on these pathways may account for the improved EPO response. This study evaluates carnitine's effect on protein expression of HO-1 in unexplained EPO resistant HD. Carnitine's effect was assessed by HO-1 expression in patients and compared to its antiapoptotic effect via HO-1 induction in a rat model of carnitine-treated heart failure. METHODS: Unexplained EPO resistant HD mononuclear cell HO-1 and rat gastrocnemious muscle HO-1 and Bcl-2 protein expression were evaluated by western blot. RESULTS: HD's haemoglobin (Hb) and haematocrit (Ht) were not different before carnitine treatment: 8.8 +/- 0.4 mg/dl versus 8.98 +/- 0.13 and 30.20% +/- 0.84 versus 30.72 +/- 1.14, respectively. Carnitine increased HO-1, Hb and Ht compared with patients not treated with carnitine: 2.40 +/- 0.58 versus 1.49 +/- 0.41, P = 0.02; 11.22 +/- 0.54 versus 8.90 +/- 0.15, P < 0.0001; 32.72 +/- 1.77 versus 30.66 +/- 0.43, P = 0.035, respectively. Carnitine-treated HD's HO-1 significantly correlated with haemoglobin. HO-1 and Bcl-2 protein levels in untreated heart failure rat's gastrocnemious muscle were reduced when compared with controls: 3.41 +/- 0.49 versus 5.32 +/- 0.38 and 0.69 +/- 0.11 versus 1.65 +/- 0.37, respectively, but were higher in carnitine-treated heart failure rats: 4.8 +/- 0.32 versus 3.41 +/- 0.49, P < 0.0002 and 1.09 +/- 0.08 versus 0.69 +/- 0.11, P = 0.0007, respectively. CONCLUSIONS: These results are consistent with an involvement of HO-1 in carnitine's effect on erythropoiesis. The initial signals or effectors responsible for carnitine's effect remain to be identified.

Cytokines and liver failure: modification of TNF- and IL-6 in patients with acute on chronic liver decompensation treated with Molecular Adsorbent Recycling System (MARS).

Liver transplantation, considered today as the most effective treatment for end-stage liver diseases, can not always be performed on every patient affected with a liver disease. Patients with end-stage liver diseases, usually have high bilirubin, encephalopathy and renal failure. In these situations cytokines play an important role in different processes, from apoptosis to regeneration. The aim of this clinical study has been to analyse the action of new artificial liver system, called Molecular Adsorbent Recycling System (MARS) on cytokines metabolism in patients affected with acute on chronic liver failure. The results are intriguing because an increase of IL-6 and a decrease of TNF-alpha observed during MARS treatment. The study confirms the efficacy of MARS therapy in terms of homeostasis of the cytokines network and suggests an usefulness of monitoring their level during liver failure.