Gilda Pepe

Bacterial Bloodstream Infections in Liver Transplantation: Etiologic Agents and Antimicrobial Susceptibility Profiles

Liver transplantation (OLT) is a lifesaving procedure for the treatment of many end-stage liver diseases, but infection and acute rejection episodes still remain the main causes of morbidity and mortality. Bloodstream infections (BSIs), particularly, are the major cause of mortality among these patients. BSIs in OLT, are from intra-abdominal, biliary, respiratory, urinary, wound and/or central venous catheter sources. A certain percentage are of unknown origin. Using the computerized database of our microbiology laboratory, we analyzed all BSIs in 75 consecutive adult liver transplant patients in a single center between January 2008 and July 2011. BSIs occurred in 21/75 (28%) patients. Thirteen subjects had a single; two, two episodes, and the other six patients each >4 episodes. All episodes occurred in the first 60 days following OLT; the majority (74%), in the first month. Among 44 microorganisms recovered, 52.3% were gram-negative, the most frequent being Pseudomonas aeruginosa and Klebsiella pneumoniae; 47.7% were gram-positive, the most frequent being coagulase-negative staphylococci, particularly Staphylococcus epidermidis. Overall 65.9% of the isolates were resistant to several antibiotics: 40.9% displayed the multiding-resistant and 25% the panding-resistant phenotype. There was a high incidence of gram-negative and most importantly, resistant bacteria, which required appropriate therapy. These data showed that it is imperative to promote strategies to prevention and contain antimicrobial resistance.

Quantification of degree of steatosis in extended criteria donor grafts with standardized histologic techniques: implications for graft survival

The gap between the availability of livers from organ donors and the increased demand has led many centers to apply strategies to reduce this deficit. Splitting of cadaveric organs for use in 2 recipients; domino transplantation; and organs from living donors, non-heart-beating donors, and extended-criteria donors (ECDs) are all currently used in orthotopic liver transplantation (OLT). Fatty changes in the donor liver are a risk factor for poor function after OLT; however, the presence of steatosis, frequently present in livers from ECDs, does not exclude the use of these organs. Since January 2000 at our institution, we observed 39 steatotic grafts that were stratified istologically as follows: low steatosis, 5% to 15%; mild steatosis, 16% to 30%; moderate steatosis, 31% to 60%; and severe steatosis (>60%). Histologic techniques can enable identification of the type of fatty change as macrovesicular and microvesicular. These alterations have different effects on primary nonfunction and primary dysfunction. Fifteen grafts, all with severe or moderate, macrovesicular changes were discarded. Twenty-four fatty grafts with low to moderate steatosis were utilized for transplant. Sections from 2 liver biopsies (1 wedge in the left lobe and 1 needle in the right lobe) were stained with hematoxylin-eosin, Masson trichrome, Gomori reticulin, and oil red O. The OLT was performed only in patients with a MELD (Model for End-Stage Liver Disease) score lower than 27. The rate of primary dysfunction was 12.5%, and of primary nonfunction 8.4%. The 6-month graft survival for all fatty livers was 80%. We encourage the careful use of grafts with low to moderate steatosis in recipients without additional risks.

Fatigue Is Associated with Increased Risk of Mortality in Patients on Chronic Hemodialysis

Background: Little is known about the correlation between fatigue and survival in patients on chronic hemodialysis and whether fatigue is an independent predictor of outcome above and beyond the effects of depression. The aim of the present study was to determine if fatigue is a predictor of mortality in patients on chronic hemodialysis (CHP) and if this occurs independently of the symptoms of depression. Methods: CHP referring to the Hemodialysis Service of the Università Cattolica of Rome, Italy between November 2007 and January 2015 were studied. Demographic, clinical, and laboratory data were recorded for each patient at the moment of the inclusion in the study. Fatigue levels were assessed in patients using the Vitality Scale of SF-36 (SF-36 VS), functional ability by the activities of daily living (ADL) and instrumental activities of daily living (IADL), depressive symptoms through the Geriatric Depression Scale (GDS), cognitive function using the Mini Mental State Examination (MMSE), and comorbidity through the Charlson Comorbidity Index (CCI). Patients were grouped into four groups (quartiles): Quartile 1 (Q1), >65; Q2, ≥50 to <65; Q3, ≥35 to <50; Q4, <35. Results: We studied 126 patients: 11 were transplanted and 53 died. Patients who later died were older and had a worse cognitive performance, higher CCI and GDS scores, lower ADL, IADL and SF-36 VS scores, lower serum creatinine and albumin levels. Kaplan-Meier survival was significantly lower in Q4 than in Q1 (p = 0.0001). According to Cox regression analysis, higher fatigue (Q4) was associated with a higher risk of mortality (HR, 95% CI: 5.29, 2.2-12.73). Conclusion: Fatigue is associated with an increased risk of mortality in CHP, with the relationship independent of symptoms of depression. Fatigue should be assessed routinely and may be a potential target of interventions that aim to reduce mortality in CHP.

Factors predicting ischemic-type biliary lesions (ITBLs) after liver transplantation

Among biliary complications, ischemic-type biliary lesions (ITBLs) remain a major cause of morbidity in liver transplant recipients, significantly affecting the chance of survival of both patients and grafts. We retrospectively reviewed 10 years of prospectively collected donor and recipient data from April 2001 to April 2011. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, including donor and recipient data. Two hundred fifty-one grafts were harvested: 222 of them were transplanted at our institution, the remaining 29 (11.6%) discarded by our donor team as showing >40% macrovesicular steatosis. Mild-moderate (20%-40%) macrovesicular steatosis (P < .001) and cold ischemia time (P = .048) significantly increased the risk of ITBL, also as an independent risk factor after multivariate analysis.

Enteric-Coated Mycophenolate Sodium: One-Way Conversion From Mycophenolate Mofetil and De Novo Use in Stable Liver Transplant Recipients

Enteric-coated mycophenolate sodium (EC-MPS) is a formulation of mycophenolic acid (MPA) that releases the active molecule in the intestine reducing drug-related gastrointestinal (GI) side effects. The aim of present work was to summarize the use of EC-MPS for one-way conversion from mycophenolate mofetil (MMF) due to GI side effects and for de novo administration in a stable liver transplant population. In 10 patients on MMF and low-dose calcineurin inhibitors (CNI), significant GI side effects suggested drug conversion to ameliorate subjective symptoms. In 5 patients, EC-MPS was initiated de novo together with reduction of CNI for prevention of long-term renal failure. Conversion was carried out at equivalent MMF/EC-MPS dosages. Reevaluation at 2 months after conversion showed that no episode of rejection or infection occurred, and white blood cell count, CNI levels and doses, and creatinine clearance did not vary significantly. In 70% of converted patients there was a reduction of GI symptoms, especially diarrhea. Eighty percent suspended proton pump inhibitors. The de novo-treated patients showed no significant GI side effects. In conclusion, conversion from MMF to EC-MPS demonstrated significant GI symptom relief and de novo drug administration was well tolerated.

Fatigue in kidney transplant recipients.

Fatigue is still present in approximately 40%‐50% of kidney transplant recipients (KTR), rates comparable to that of the hemodialysis population. Correlates of fatigue include inflammation, symptoms of depression, sleep disorders, and obesity. Fatigue in KTR determines a significant severe functional impairment, either when globally considered or when analyzed at the level of the single domains such as sleep and rest, homemaking, mobility, social interaction, ambulation, leisure activities, alertness behavior, and work limitations. In addition, fatigue in KTR is significantly associated with a severe deterioration of quality of life. Fatigue is very common among KTR poorly adherent to immunosuppressive therapy. Unfortunately, there is no evidence of studies about the treatments of this symptom in KTR. Efforts to detect and treat fatigue should be a priority in order to improve quality of life of KTR.

Vacuum-assisted wound care (v.a.C.®) for enteric fistula closure: how we do it

Enterocutaneous fistulas (ECFs) are a surgical problem that is difficult to manage and they have a mortality rate between 6 and 33 % [1]. Many fistulas show a natural tendency to heal; however, the main problem in fistula care usually is adequate drainage of secretions from the wound. Vacuum-assisted wound care (V.A.C. , Kinetic Concept, Inc., San Antonio, TX, USA) therapy can be used to treat intestinal fistulas [2–4]. We successfully treated some cases of ECFs and enteroatmospheric fistulas (EAFs; an EAF is an ECF that opens into the base of a largely disrupted wound with exposed bowel) with the device (Table 1). In our experience, the results we obtained with V.A.C. therapy are strictly related to some tricks used with the black sponge and negative pressure.

Anidulafungin--a new therapeutic option for Candida infections in liver transplantation.

INTRODUCTION In the last years, the incidence of Candida infections in liver transplant recipients has increased with still higher morbidity and mortality. Anidulafungin, a new echinocandin that does not interfere with cytochrome p450, shows no need for dosage adjustment based upon renal or hepatic function or weight. AIM To analyze tolerance to and microbiologic and clinical efficacy of Anidulafungin to treat Candida infections in liver transplant patients. MATERIALS AND METHODS This phase 3b, prospective, open-label, single-center study focused on liver transplant patients with a suspected and/or diagnosed Candida infection. The patients received Anidulafungin intravenously, optionally followed by oral therapy with azoles. The primary endpoint was the global response at the end of therapy; secondary endpoints were the efficacy of intravenous therapy, 90-day survival, as well as tolerance for and interaction with immunosuppresants. RESULTS We considered 42 consecutive liver recipients transplanted between 2009 and 2010 among whom 13 (31%) were recruited for the study and four patients were treated with Anidulafungin as empirical therapy, six as preemptive therapy, and three as targeted treatment for documented candidemia (7.1%). The immunosuppressive regimen consisted of tacrolimus and low dose of steroids. The Candida species were: C albicans (50%), C glabrata (12.5%), C parapsilosis (12.5%), C krusei (12.5%), C lusitaniae (6.2%), C tropicalis (6.2%), and multiple others (25%). The principle site of isolation was the bile (53.8%), followed by the bloodstream (23.1%), central venous catheters (15.4%), bronchoalveolar lavage (15.4%), peritoneum (7.7%), and other locations (7.7%). Two patients (15.4%) died of severe sepsis with multiple organ failure. There was no alteration of hepatic enzymes, indices of cholestasis or changes in immunosuppressant drug levels. CONCLUSION Anidulafungin was an effective, safe, and well-tolerated drug. There were neither toxic effects to the grafts or adverse interactions with immunosuppresants.

Intra-operative parathyroid hormone monitoring through central laboratory is accurate in renal secondary hyperparathyroidism.

OBJECTIVE The usefulness, the methods and the criteria of intra-operative monitoring of the parathyroid hormone (ioPTH) during parathyroidectomy (PTX) for renal secondary hyperparathyroidism (rSHPT) in patients on chronic hemodialysis remain still matter of debate. The present study aimed to evaluate the ability of a low cost central-laboratory second generation PTH assay to predict an incomplete resection of parathyroid glands (PTG). METHODS The ioPTH decay was determined In 42 consecutive patients undergoing PTX (15 subtotal and 27 total without auto-transplant of PTG) for rSHPT. The ioPTH monitoring included five samples: pre-intubation, post-manipulation of PTG and at 10, 20 and 30min post-PTG excision. The patients with PTH exceeding the normal value (65pg/ml) at the first postoperative week, 6 and 12months were classified as persistent rSHPT. RESULTS The concentrations of ioPTH declined significantly over time in patients who received total or subtotal PTX; however, no difference was found between the two types of PTX. Irrespective of the type of PTX and the number of PTG removed, combining the absolute and percentage of ioPTH decay at 30min after PTG excision, we found high sensitivity (100%), specificity (92%), negative predictive value (100%) and accuracy (93%) in predicting the persistence of rSHPT. CONCLUSIONS The monitoring of the ioPTH decline by a low cost central-laboratory second generation assay is extremely accurate in predicting the persistence of disease in patients on maintenance hemodialysis undergoing surgery for rSHPT.

The Frustrating Attempt to Limit the Interdialytic Weight Gain in Patients on Chronic Hemodialysis: New Insights Into an Old Problem

A significant percentage of patients on chronic hemodialysis have an interdialytic weight gain (IDWG) above the recommended values. High IDWG has detrimental effects on survival, cardiovascular outcomes, and quality of life. High IDWG is secondary to poor adherence to fluid restriction and to excessive intake of fluids, due to thirst and xerostomia. Various strategies have been proposed to limit IDWG such as the reduction of dietary salt intake, behavioral interventions aimed at improving the adherence to fluid restriction, the improvement of xerostomia, and the use of lower dialysate sodium concentration. The present narrative review aims to evaluate the efficacy of each of such strategies.