The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0-2.5 µM) of OCA were added to culture media and, after 3-10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 µM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients.

Long-term Glomerular Filtration Rate and Kidney Disease: Improving Global Outcomes Stage Stability After Conversion to Once-Daily Tacrolimus in Kidney Transplant Recipients.

Close monitoring of estimated glomerular filtration rate (eGFR) is important for early recognition of worsening renal function to prevent further deterioration. Safe conversion from twice-daily tacrolimus (TD-Tac) to once-daily tacrolimus (OD-Tac) has been reported, but the effects on eGFR are contrasting. The aim of our study is to evaluate long-term stability of eGFR after 1:1 conversion from TD-Tac to OD-Tac and the effects on serum cytokine blood levels. Forty-six consecutive kidney transplant recipients treated with TD-Tac 3 to 5 years post-transplant, with stable renal function, were enrolled in the study (2009-2011). Clinical and biochemical parameters were evaluated for 12 months before conversion up to 6 years after conversion. The patients served as their own controls. A panel of cytokines was evaluated repeatedly during the first year after conversion. Mean values of eGFR were not different long-term after conversion (P = .11) compared with baseline, and the majority of patients remained stable on Kidney Disease: Improving Global Outcomes stage during the study period; eGFR was stable in 30.0% after 5 years, decreased > 1 mL/min/1.73 m2/y in 13.3%, and improved > 1 mL/min/1.73 m2/y in 56.7%. Cytokine levels and C-reactive protein did not show any significant deterioration. Metabolic parameters were stable during the 6 years of follow-up. OD-Tac therapy can preserve an effective immunosuppressive state together with a safe profile of eGFR.

Surgical Technique Notes of Arterial Vascular Reconstruction During Kidney Transplantation: Personal Experience and Literature Review.

BACKGROUND: Arterial vascular anomalies in patients undergoing kidney transplantation (KT) are correlated with a higher incidence of early surgical complications, potentially causing graft loss. Arterial reconstruction allows patients to overcome these surgical challenges, thus minimizing the risk of poor outcomes. The aim of the present study is to retrospectively investigate the safety and effectiveness of the multiple arterial reconstruction technique with a Teflon patch in case of an unavailable aortic patch: to do so, surgical complications, graft function, and patient survival were evaluated. METHODS: During the period January 2009 to August 2016, 202 adult deceased-donor KTs were performed at our center. Group A (n = 27; reconstruction of multiple arteries) and Group B (n = 175; control group) were compared. RESULTS: No differences were observed between the 2 groups in terms of early postoperative course, with no vascular complication observed in Group A. No vascular patch infections were reported, nor longer cold ischemia time rates. Similarly, long-term survival rates were similar between the 2 groups. CONCLUSIONS: The Teflon-patch arterial reconstruction technique appears to be safe and effective, with an acceptable balance of benefits and potential risks of using a prosthetic material. Studies based on larger series are needed to further validate this approach.

Automated Intelligent Microscopy for the Recognition of Decoy Cells in Urine Samples of Kidney Transplant Patients.

BACKGROUND: BK virus (BKV)-associated nephropathy is definitely involved in allograft failure after kidney transplant. Thus, the need for an early control of viral reactivation in immunocompromised patients is well established. Determination of urinary release of decoy cells (DC) and BK viral load in plasma and urine by polymerase chain reaction (PCR) usually precedes renal biopsy. The aim of the study is to assess viral reactivation by BKV-DNA PCR and DC detection in urinary sediment using automated intelligent microscopy. METHODS: Seventy-eight kidney transplant patients were analyzed for the presence of plasma BKV-DNA by quantitative TaqMan real-time PCR. Additionally, automated intelligent microscopy was used for urine sediment analysis, allowing to count cells with decoy feature, confirmed by phase contrast microscopic review. RESULTS: Plasma BKV-DNA PCR was detected in 14 (17.9%) patients. DC were identified in 19 (24.3%) urine sediments by automated analyzers and confirmed by microscopic observation. Two patients were BKV-DNA-positive/DC-negative; conversely, 7 subjects were DC-positive/BKV-DNA-negative. CONCLUSIONS: Plasma quantification of BK viral load is currently the best noninvasive method for the detection of viral reactivation. Nevertheless, automated methods to screen for the presence of DC in urine could facilitate early BK virus replication diagnosis and patient follow-up by quantitative and visual results.

Open and endovascular treatment by covered and multilayer stents in the therapy of renal artery aneurysms: mid and long term outcomes in a single center experience.

AIM: The purpose of this paper is to evaluate the mid and long terms outcomes of open and endovascular surgical treatment, as well as multilayer stent, in patients affected by Renal Artery Aneurysm (RAA). PATIENTS AND METHODS: Twenty five patients with RAA (24 monolateral and 1 bilateral aneurysm, 26 aneurysms) were observed between 2000 and 2015: 4 were not treated due to the small size of the aneurysm (< 2.5 cm); out of the remaining, 16 underwent endovascular treatment, 2 were treated by open surgery consisting in aneurysmectomy and graft reconstruction and 5 (in 1 patient bilateral) were treated by ex vivo repair and autotransplantation. RESULTS: Out of the 22 patients treated for RAA, one patient operated upon open surgery presented an early thrombosis of a PTFE graft, followed by nephrectomy (4.7%); one patient underwent autotransplantation showed an ureteral kinking without functional consequences. In a follow-up ranging from 1 and 11 years (mean 5 years), no deaths were observed; all the renal arteries repaired were patents and 16 out of 21 patients had a significative reduction of systemic blood pressure. DISCUSSION: The choice of the best treatment is based on aneurysm's morphology according to Rundback's classification. The type I, involving the main renal artery, is always treated by endovascular approach; type II, involving renal artery bifurcations may be treated by open surgery or multilayer stents; type III (hilar or intraparenchymal aneurysms) needs only an open surgical treatment as autotransplantation. CONCLUSION: Based on our experience it seems that most of RAAs may be treated by endovascular technique. The ex vivo autotransplantation represents the first-line treatment in hilar and intraparenchymal aneurysms. Multilayer stents seem to have good outcome in the treatment of aneurysms involving arterial bifurcations. Mid and long term results, related to kidney preservation and to normalization of blood pressure, seems satisfying.

Pre-Emptive Therapy for the Treatment of Cytomegalovirus After Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) represents the leading cause of viral infection in kidney transplantation patients. The aim of the present study was to evaluate the efficacy and safety of pre-emptive anti-CMV therapy. MATERIALS AND METHODS: We performed a retrospective analysis based on data from 227 consecutive patients transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor, considering: incidence of rejection, CMV organ localization, and graft and patient survival. All patients underwent induction immunosuppressive therapy followed by maintenance therapy consisting of corticosteroids, antimetabolites, and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of plasma CMV-DNA in the post-transplantation period was: weekly (first month), quarterly (second through twelfth month), and then half-yearly. RESULTS: CMV viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482 copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity after a median period of 2.5 months from kidney transplantation (range: 0.2 months to 43 months). A total of 49 of 227 (21.5%) patients were treated with antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%) patients died (noninfectious CMV-related complications = 8, cardiovascular causes = 6, bleeding complications = 1). CONCLUSION: Our experience confirms the validity of the pre-emptive anti-CMV therapy in renal transplantation patients.

Kidney Transplantation in Alström Syndrome: Case Report.

The Alström syndrome is a rare genetic disorder, inherited in an autosomal recessive manner. It has recently been classified as a ciliopathic disorder. Alström syndrome is a multiorgan pathology characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, short stature in adulthood, hypothyroidism, hypogonadism, dilated or restrictive cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. End-stage renal disease can occur as early as the late teens and is the leading cause of death. More than 900 people with Alström syndrome have been reported worldwide. We present a case of a 42-year-old man affected by this syndrome with end-stage renal disease, type 2 diabetes mellitus, and loss of visual function and hearing who received a kidney transplant from a cadaveric donor. Basiliximab and steroid were used as induction therapy. Tacrolimus, mycophenolate mofetil, and steroid were used as maintenance therapy. No complications were reported during the recovery. In selected patients affected by Alström syndrome, renal transplantation can be a successful treatment for chronic kidney disease.

Delayed Introduction of Everolimus in De Novo Renal Transplanted Patients: A Single-Center Experience.

INTRODUCTION: Immunosuppressive protocols containing everolimus (EVR) preserve good renal function in kidney transplantation (KT), although they are often complicated by several adverse events. We have evaluated the efficacy and safety of a protocol with late (1 month after KT) EVR introduction. MATERIAL AND METHODS: This study randomized 49 de novo patients undergoing KT between September 2012 and June 2014 into 2 groups: group A (n = 24) with late EVR introduction and tacrolimus reduction, and group B (control group; n = 25) with a standard immunosuppressive regimen. Primary aims were 1-year patient and graft survivals and acute rejection rates. Secondary aims were related to wound, metabolic, and hematologic complications. RESULTS: Patient and graft survivals were similar in both groups. One year after KT, median serum creatinine was inferior in group A (1.4 vs 1.8 mg/dL; P = .004). Late acute rejection (8.3 vs 12.0%; P = 1.0) and wound complication (4.2 vs 4.0%; P = 1.0) rates were similar. Higher cholesterol and triglycerides and lower platelets and hemoglobin levels were observed in group A. CONCLUSIONS: In our experience, delayed introduction of EVR shows similar results with respect to its early introduction, contemporaneously presenting fewer wound complications and lymphoceles. A higher rate of metabolic and hematologic complications are, however, observed in patients under EVR therapy. Further multicenter studies should be performed to confirm these preliminary results.

Adacolumn Granulocyte-Apheresis for Alcoholic Hepatitis: Preliminary Study.

INTRODUCTION: Alcoholic hepatitis (AH) is an acute-on-chronic inflammatory response affecting the liver. It has been recognized that white blood cells (WBCs) are involved in the pathogenesis and in the prognosis of AH. The aim of study was to use Adacolumn, which can selectively adsorb myeloid linage leucocytes (granulocytes and monocytes/macrophages) from the blood in the column and improve the clinical status of patients. MATERIALS: Six patients with a diagnosis of AH were treated with Adacolumn granulocyte-apheresis therapy. INCLUSION CRITERIA: patients not responders to corticosteroids therapy with Maddrey Discriminant Function (MDF) >32 and MELD score 20-26. The patients underwent five 1-hour sessions for 5 consecutive days with a follow-up at 28 days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. Liver parameters, WBC count, proinflammatory cytokines, coagulation, and predictive scores were valued before and after the cycle of apheresis treatment. RESULTS: After 5 days, the findings showed a significant improvement of WBC count (P < .014) and cytokines such as interleukin (IL)-6 (P < .019), tumor necrosis factor α (TNFα) (P < .02), and IL-8 (P < .029). The results probably determined a reduction of aspartate transaminase (AST; P < .02) and alanine transaminase (ALT; P < .011), although we did not observe a significant improve in bilirubin, prothrombin time (PT), and Maddrey score. The improvement of MELD score, depending on an improvement of international normalized ratio for administration of plasma, was not considered. At day 28 of follow-up, PT, IL-6, TNFα, AST and ALT results significantly improved. CONCLUSIONS: The Adacolumn apheresis was safe and was able to determine an improvement of clinical status of patients with reduction of inflammatory markers. More patients are needed to validate these results.

Multiple Organ Failure Associated With Coxsackie Virus in a Kidney Transplant Patient: Case Report.

INTRODUCTION: Viral myocarditis can emerge with various symptoms, including fatal arrhythmia and cardiogenic shock, potentially evolving in chronic myocarditis or dilatative cardiomyopathy. We report a case of a kidney transplant patient affected by coxsackie viral myocarditis. METHODS: A 49-year-old man was admitted to our hospital with dyspnea and fever in August 2014. He underwent living donor kidney transplantation in 1986 and polar graft resection for papillary carcinoma in 2012. RESULTS: The initial investigation showed pulmonary congestion, pancreatitis, increased serum troponin I, and increased liver enzyme levels. Echocardiogram revealed an ejection fraction (EF) of 20% and PAPS 45 mm Hg. He underwent coronary stent implantation, started hemodialysis, and continued on low-dose steroid immunosuppressive therapy. The clinical course improved rapidly, but endomyocardial biopsy showed acute myocarditis. Further investigation revealed a high antibody titer against coxsackievirus B4 and B5. Pancreatic enzyme levels normalized 2 months after patient admission; his cardiac condition improved after 6 months. The patient has been followed for 1 year, and his left ventricular EF is stable (45%). CONCLUSIONS: Viral myocarditis represents a serious clinical condition requiring a fast therapeutic intervention. This patient's clinical course suggests that changes in his immunosuppressive therapy were associated with progressive amelioration of his viral myocarditis.

Plasmapheresis, Photopheresis, and Endovenous Immunoglobulin in Acute Antibody-mediated Rejection in Kidney Transplantation.

INTRODUCTION: Acute antibody-mediated rejection (AAMR) is the subject of much research. It is diagnosed by C4d staining at biopsy and circulating donor-specific antibodies (DSA). The combination of intensive plasmapheresis and intravenous immunoglobulin (IVIG) has been recognized as an effective treatment for AAMR. We report our single-center experience on AAMR treatment. MATERIALS AND METHODS: We treated 23 transplanted patients (group A) with protein-A immunoadsorption (IA) and 7 patients (group B) with double-filtration plasmapheresis. All patients were treated with IVIG (400 mg/kg/d). Basic immunosuppression included cyclosporine, steroids, azathioprine, and antilymphocyte globulin or monoclonal antibodies (OKT3). A subgroup of 3 patients (3/7; group B1) was treated with photopheresis. RESULTS: In both groups, the mean number of extracorporeal procedures was 7.3 ± 4.5 and 5.5, respectively; the mean duration of treatment was 12.3 ± 10.2 and 14.5 days, respectively. In group A, we observed negative cross-matching in 96% after mean of 18 days; 1 patient died from sepsis, and 6 lost their grafts. In group B, negative circulating DSA were observed in all patients after a mean of 25 days, and 1 patient lost their allograft. CONCLUSIONS: In our observation, the 2 extracorporeal procedures had similar effects in terms of graft survival, DSA removal, and cross-match negativity (group A 74% vs 86%; 95.6% vs 100%). IA was faster for DSA removal. In our opinion, the higher costs of IA suggests its use just in high-risk cases, such as in hyperimmune or sensitized patients. Further studies are necessary to improve our knowledge.

Diaphragmatic hernia as a spontaneous sequela of a surgically-treated left infiltrating renal tumor: a case report.

A diaphragmatic hernia is a protrusion of abdominal structures within the thoracic cavity through a defect in the diaphragm, which can be either congenital or acquired. Diaphragmatic rupture, as a sequela following abdominal surgery, is rarely documented. Approximately 80% of the reported cases, the injury occurred on the left side. We discuss a case of a 37 year-old male who underwent a left nephrectomy with ipsilateral adrenalectomy and diaphragmatic resection, by direct reconstruction that developed the sequela of a diaphragmatic hernia. We chose a surgical transthoracic approach for herniation repair.

Early right hepatectomy for severe liver trauma: a case report.

Liver is frequently involved and injured in blunt abdominal trauma. Although over the last three decades the management of blunt hepatic trauma has gradually shifted toward nonoperative approach whit a significant reduction in overall mortality, surgery remains the main option for hemodinamically unstable patients whit severe liver injuries. A 16-yr-old male in good health suffered a blunt abdominal trauma from a sport accident falling while playing football resulting in a grade V liver injury according to the American Association for the Surgery of Trauma Organ Injury Score. He underwent first to liver packing and next to an early right hepatectomy to arrest the clinical condition impairment In high grade liver injuries, liver resection makes possible to effectively control bleeding, remove necrotic tissue and prevent complications as bile leak. Nevertheless when patient's clinical condition continue to deteriorate despite optimal management a quickly and experienced hands performed hepatectomy may solve the situation.

Spontaneous Bilateral Adrenal Haemorrhage after Duodenopancreatectomy: a case report.

it is difficult to diagnose because of its nonspecific presentation. This condition frequently occurs in association with an extreme physical stress and may lead to acute adrenal insufficiency or death if not promptly and properly treated. We report a rare case of acute bilateral adrenal hemorrhage with adrenal insufficiency following duodenopancreatectomy for ampulloma in absence of surgical complications. Early diagnosis and corticosteroid replacement with aggressive management of the precipitating pathology are essential to enable a successful outcome.

Adult Wilms tumor: Case report.

Wilms tumor (WT) occurs infrequently in adults. Even rarer is adult WT with extension by direct intravascular spread into the right side of the heart. The present report describes a WT with intracaval and intracardiac extension in a 38-year-young man. In addition, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable hemorrhages and tumor fragmentation. We report the results of a surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. The morphologic and immune-histochemical findings confirmed the diagnosis.

Adaptive support ventilation versus synchronized intermittent mandatory ventilation with pressure support in weaning patients after orthotopic liver transplantation.

BACKGROUND: The extubation phase is an extremely critical moment in patients who have undergone orthotopic liver transplantation, who do not always have the advantage of long-lasting positive-pressure ventilation and positive expiratory end pressure; these factors can lead to splanchnic venous congestion, and this is why a rapid extubation can represent a great benefit for the graft. METHODS: The aim of this study was to compare the adaptive support ventilation (ASV) mode with the standard mode of weaning in our intensive care unit, synchronized intermittent mandatory ventilation with pressure support (P-SIMV), in patients who received orthotopic liver transplantation. ASV is a positive-pressure mode, in which pressure level and respiratory rate are automatically adjusted according to measured lung dynamics at each breath. Eligible patients were assigned to either ASV or P-SIMV group. The weaning protocol was based on the individual respiratory activity and structured in 4 different phases. RESULTS: The average length of intubation was significantly shorter in the ASV group than in the P-SIMV group (90±13 vs 153±22 minutes, P=.05). The total modifications to the ventilator settings were significantly larger in the P-SIMV group (1.5±1 vs 6±2; P=.003). CONCLUSIONS: Our results suggest that although both procedures are safe and easy to apply, ASV is superior in terms of weaning times, and it simplifies respiratory management. The better patient-machine interaction in ASV has been highlighted by other authors for different clusters of patients.

Is HE4 serum level a valid screening test in women candidates for kidney transplant? A case report and a review of literature.

While studying a candidate for kidney transplant it is essential to exclude active malignant diseases. Serum biomarkers help to exclude specific cancers. Tumor markers are proteins secreted by neoplastic cells that can mark their activities. HE4 is a new tumor marker used in ovarian cancer. It is an epithelium protein that appears overexpressed in ovarian cancer, but it is also present in other normal human tissues. Often in patients with kidney failure serum biomarkers are increased compared to healthy people. We report a case of a Caucasian woman suffering from kidney failure examined by our team to be included on the kidney transplantation list. Patient had a known pelvic mass. Determination of serum biomarkers, CA125 and HE4, was performed to exclude pelvic tumor, and we found high levels of HE4 with normal levels of CA125. A new transvaginal ultrasound was performed on the patient and it showed a pelvic mass near the left ovary. This mass resulted bigger than in the previous ultrasound, performed about a month before. We decided to perform a pelvic CT for improved diagnostic accuracy. The reports of this exam showed that the mass was a hematoma correlated with a previous knee prosthetic surgery. Even tough many serum biomarkers are higher in patients with renal failure, there is no study to demonstrate that HE4 blood levels are modified in these patients. This case report shows how HE4 can be elevated in people in hemodialysis in a benign situation, also in a pelvic mass not from the genital tract. There is no similar case described in literature.

From listing to transplant: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

Nephrologic monitoring of end-stage liver disease (ESLD) patients is part of evaluation for orthotopic liver transplantation (OLT). The numerous causes of renal dysfunction in ESLD patients sometimes relate to the extent of liver damage or sometimes more closely to organic nephropathy. The aim of this study was to evaluate renal function through a specific nephrologic form applied in our outpatient clinic to optimize nephrologic monitoring in ESLD patients awaiting OLT. We enrolled 69 cirrhotic patients (56 men, 13 women) awaiting OLT from April 2008 to January 2012. All patients were evaluated at listing and every 3 months until OLT. The most interesting result was the stable values of serum creatinine from listing to transplantation. We think that dedicated liver transplant nephrologic evaluation is important in the follow-up of ESLD patients awaiting OLT, because the presence of renal dysfunction may represent an important criterion for specific therapeutic interventions to minimize pre-OLT renal injuries that limit the effect of impaired renal function on patient outcomes.

Resistive index and MELD-Na: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

Renal dysfunction in cirrhotic patients is primarily related to disturbances in circulatory function. In decompensated cirrhosis, ascites and water retention are associated with development of dilutional hyponatremia. The arterial resistive index (RI) is a measure of resistance to arterial flow within the renal vascular bed. Hyponatremia is an independent predictor of mortality in patients with ascites. The aim of this study was to evaluate intrarenal RI in end-stage liver disease (ESLD) patients awaiting liver transplantation (LT) and its association with renal and hepatic function as assessed by Model for End-Stage Liver Disease (MELD) and MELD-Na scores. We evaluated 40 cirrhotic patients (23 males, 17 females) awaiting LT from January 2009 to January 2012. Twenty-six of the 40 patients (65%) showed a renal RI ≥ 0.70, the normal value according to standard reported evaluations. Patients with RI ≥ 0.70 showed significantly higher MELD and MELD-Na scores as well as greater higher serum creatinine and lower serum sodium concentrations compared with subject displaying RI <0.70. The most relevant result of our study was the strong association between elevated renal RI in ESLD patients and advanced liver dysfunction, as demonstrated by MELD and MELD-Na scores, hyponatremia, ascites, and acute renal failure episodes. In conclusion, this study suggested that intrarenal RI assessment should be considered in the clinical and nephrologic monitoring of cirrhotic patients awaiting LT.

Pathfast presepsin assay for early diagnosis of bacterial infections in surgical patients: preliminary study.

BACKGROUND: Various biomarkers have been studied for diagnosing bacterial infections, seeking to stop the sepsis cascade. Presepsin, which is ∼13 kDa in size, has been identified to increase specifically in the blood of sepsis patients. Additionally, measurement of presepsin is useful to evaluate the severity of infection and monitor clinical responses. We evaluated the analytical and clinical performance of the Pathfast presepsin (PFP) assay system for early diagnosis of infection. MATERIALS AND METHODS: From November 2011 to June 2012 we studied 70 adult patients, including 35 cadaveric organ transplant recipients and 35 abdominal surgery patients. The 32 female and 38 male subjects had a mean age of 56.1 years (range, 19-70). Heparinized whole blood for PFP assay was tested at 48 hours after surgery together with blood cultures. RESULTS: The mean presepsin level (PL) in the 50 positive patients was 3,957.45 pg/mL (range 255-20,000). For transplant patients, PL was 3,034.43 ± 2,880.791 pg/mL, with 30 positive results. Microbiologic findings confirmed the presence of bacterial infections within 69 ± 2.5 hours from enrollment despite that when the test was performed, 70% showed no sign or symptom of infection. In 15 abdominal surgery patients, the PFP test was negative with negative blood cultures. The positive PFP test in 20 other abdominal surgery patients showed PL of 2,363 ± 7,988.47 pg/mL in the absence of signs or symptoms of infection in 25% of them. The 20 positive patients showed positive blood cultures within 67 ± 1.8 hours from enrollment. CONCLUSIONS: The PFP test had a (100%) sensitivity to show the presence of infection in a short time (15 min), confirmed by positive blood cultures.