Carbapenem-Resistant Klebsiella Pneumoniae Infections Early After Liver Transplantation: A Single-Center Experience.

The aims of this study were to define in a cohort of 310 liver transplant recipients, the incidence of post-liver transplantation (LT) non-carbapenem-resistant Klebsiella pneumoniae (CRKP) and CRKP infections, pre- and post-LT CRKP colonization, CRKP-associated mortality, and risk factors for non-CRKP and CRKP infections. Every patient was screened for CRKP immediately before and after LT. The 6-month survival rate was 95%. Fifty-two patients became infected (16.5%): 8 by CRKP (2.5%) and 44 (14%) by a non-CRKP micro-organism. Median onset of CRKP infections occurred at postoperative (POD) 12 (range, 4-70). CRKP colonization occurred in 20 patients (6%): 10 before LT (3 infected and died) and 10 after (5 infected, 3 died). CRKP- versus non-CRKP-infected patients had higher rates of intensive care unit (ICU) and hospital mortality (50% vs 20% and 62.5% vs 36%; P ≤ .001), septic shock (87% vs 34%; P = .0057; confidence interval [CI], 9.8-71.5), prolonged mechanical ventilation (100% vs 64%; P = .043, CI, 3.5-51.9), and renal replacement therapy (87% vs 41%; P = .0177; CI, 2.8-65). The small number of CRKP-infected patients did not allow the definition of specific risk factors for CRKP infection. At univariate analysis, pre- and post-LT colonization (odds ratio [OR], 10.76; CI, 2.6-44; OR, 14.99; CI, 3.83-58.66, respectively), relaparotomy (OR, 9.09; CI, 4.01-20.6), retransplantation (OR, 7.45; CI, 3.45-16), bile leakage (OR, 61.28; CI, 9.23-80), and early allograft dysfunction (EAD; OR, 5.7; CI, 3-10.7) were significantly associated with infections, making CRKP colonization (any time) and post-LT surgical and medical complications critical factors for post-LT CRKP infections.

Two cases of elevated tryptase in abdominal aortic aneurysm.

INTRODUCTION: From the literature, patients with a history of anaphylaxis to hymenoptera venom and positive specific IgE have shown a correlation between elevated tryptase levels and two clinical situations: systemic mastocytosis and an increased risk of reactions to venom immunotherapy or hymenoptera sting. Other clinical scenarios could explain elevated tryptase levels. MATERIAL AND METHODS: A 67 year old male (P1) and a 77 year old male (P2) were evaluated for previous severe anaphylaxis to hymenoptera sting. They underwent standard diagnostic work-up for hymenoptera venom allergy. Having found elevated tryptase levels, these were followed by a bone marrow biopsy to rule out systemic mastocytosis. RESULTS: P1: specific IgE and skin tests were positive for Vespula species; tryptase 52.8 ng/ml; P2: specific IgE and skin tests were positive for Vespa cabro and tryptase 153 ng/ml. Bone marrow biopsy results were negative for mastocytosis. We carried out magnetic resonance imaging, in P1 to better characterize the severe osteoporosis and in P2 because during physical examination a pulsating mass had been identified in the mesogastrium, and an aneurysm of the abdominal aorta which required surgical intervention in both patients was detected. Eight months after surgery, tryptase levels had diminished significantly (P1: 11.6 ng/ml and P2: 14.5 ng/ml). DISCUSSION: The elevated tryptase levels were correlated to abdominal aneurysm in both patients. In fact, post-surgery tryptase levels dramatically decreased. These two cases demonstrate that high tryptase levels in subjects with a history of hymenoptera venom anaphylaxis can be associated to undiagnosed aneurysmatic disease.

Italian guidelines for diagnosis, prevention, and treatment of invasive fungal infections in solid organ transplant recipients.

Use of various induction regimens, of novel immunosuppressive agents, and of newer prophylactic strategies continues to change the pattern of infections among solid organ transplant (SOT) recipients. Although invasive fungal infections (IFIs) occur at a lower incidence than bacterial and viral infections in this population, they remain a major cause of morbidity and mortality worldwide. In March 2008, a panel of Italian experts on fungal infections and organ transplantation convened in Castel Gandolfo (Rome) to develop consensus guidelines for the diagnosis, prevention, and treatment of IFIs among SOT recipients. We discussed the definitions, microbiological and radiological diagnoses, prophylaxis, empirical treatment, and therapy of established disease. Throughout the consensus document, recommendations as clinical guidelines were rated according to the standard scoring system of the Infectious Diseases Society of America and the United Stated Public Health Service.

Acute liver failure: managing coagulopathy and the bleeding diathesis.

Acute liver failure (ALF) is defined as a severe, sudden liver dysfunction that induces encephalopathy and coagulopathy (prothrombin time [PT/INR] > 1.5) within 26 weeks of the onset of symptoms (usually jaundice) in patients without previous liver disease. Quantitative and qualitative platelet dysfunction, reduced synthesis of clotting factors, increased consumption of factors (mainly II, V, VII, X), reduced clearance of both activated factors, and/or factor inhibitor complexes are among the most important proposed pathogenetic factors. A possible role might be also played by the diminished degradation of anticoagulants. Plasminogen activator inhibitor 1 (PAI-1) is increased, shifting the balance toward hypofibrinolysis, despite the elevated levels of tissue plasminogen activator (tPA). Although changes in coagulation parameters provide crucial information for the management of the patient with ALF, the optimal management of the hemostatic defects is far from being defined. Because spontaneous bleeding occurs rarely during ALF, measures to improve the bleeding diathesis (fresh frozen plasma, cryoprecipitate, platelet transfusion) are recommended only in patients with clinically significant bleeding or before placement of invasive devices. Antifibrinolytic drugs are used in some cases, but often empirically. The role of rFVIIa, even if promising, is still under debate.

Prevalence of primary headaches and cranial neuralgias in men and women aged 55-94 years (Bruneck Study).

The aim of the current study was to estimate the prevalence of all primary headaches and cranial neuralgias in the general community. As part of the population-based Bruneck Study, 574 men and women aged 55-94 years underwent extensive neurological and laboratory examinations involving a standardized headache interview. In the Bruneck Study population the lifetime prevalence of all primary headaches combined and of cranial neuralgias was 51.7 and 1.6%, respectively. Tension-type headache (40.9%) and migraine (19.3%) emerged as the most common types of headache. In men and women aged 55-94 years the 1-year prevalence of primary headaches was high at 40.5%. In this age range headaches caused significant impairment of health-related quality of life. The Bruneck Study has confirmed the high lifetime prevalence of primary headaches and cranial neuralgias in the general population and provided first valid prevalence data for all primary headaches based on International Classification of Headache Disorders, 2nd edition criteria.

Burden of atherosclerosis and risk of venous thromboembolism in patients with migraine.

BACKGROUND: Previous studies have yielded evidence of an enhanced risk of cardiovascular disease, especially stroke, among patients with migraine. Our understanding of the underlying mechanisms is far from complete. The aims of the present study were to investigate the potential association between migraine and atherosclerosis and to assess the risk of venous thromboembolism as a clinical surrogate for a procoagulant state in patients with migraine. METHODS: The examination was part of the population-based Bruneck Study. During the 2005 evaluation, 574 participants aged 55-94 years underwent neurologic and laboratory examinations involving a standardized headache interview and scanning of the carotid and femoral arteries to evaluate presence, severity, and progression (2000-2005) of atherosclerosis. RESULTS: A large number of well-founded and putative cardiovascular risk factors have emerged as being unrelated to migraine status. Prevalence, severity, and 5-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs. In fact, there was even a tendency for atherosclerosis to be less pronounced among patients with migraine, and for the intima-media thickness to be lower (p = 0.029). As a novel finding migraineurs faced a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs, age/sex-adjusted p = 0.031). CONCLUSION: This study is the first to compare the burden of atherosclerosis as quantified by high-resolution duplex ultrasound between migraineurs and nonmigraineurs in the general community, and provides solid evidence against the view that migraine predisposes to atherosclerosis. The higher risk for venous thromboembolism among migraineurs (prothrombotic state) awaits confirmation and elaboration in future research.

Renal grafts from elderly donors: histological studies and long-term results.

To satisfy the increasing requests for renal grafts, elderly donors are increasingly accepted for kidney transplant at many centers. The main unresolved question is the long-term effect on graft survival of potential histological lesions due to donor age. We present a prospective histological study performed from January 1997 to December 2001 on 184 consecutively transplanted renal grafts in which the only criterion for graft acceptance was a normal value of serum creatinine upon admission to the intensive care unit independent of donor age. At the end of the study, 57 recipients (31%) of mean age 55 years (range 39 to 67 years) received a renal graft from donors aged more than 60 years (mean age 66 years; range 60 to 75 years), this cohort denoted as older donor kidney transplant group (ODKTG) and 127 recipients (69%) with a mean age of 49 years (range 21 to 63 years) received a renal graft from donors whose age was lower than 60 years (mean age 49 years; range 16 to 59 years), a cohort denoted as the younger donor kidney transplant group (YDKTG). The two groups were comparable for time of dialysis, cold ischemia time, immunosuppression therapy, grading of histological damage. At the end of the study with a mean follow-up of 5.6 years (range 3.5 to 7.5 years), primary graft nonfunction and delayed graft function were significantly more represented in the ODKTG than the YDKTG. Cumulative patient and graft survival was 84.3% and 79.4% in the ODKTG, respectively, and 93.8% and 85.9% in the YDKTG, respectively (P = NS). Cumulative serum creatinine values were 1.98 mg/100 mL in ODKTG and 1.65 mg/100 mL in YDKTG (P = NS). In conclusion, renal grafts from older donors presented histological damage comparable to that seen among renal grafts from younger donors.

[Fulminant liver failure: intensive care, extracorporeal treatment and liver transplantation]. / Il trattamento dell'patite acuta fulminante: trattamento intensivo, sostituzione artificiale, trapianto epatico.

Fulminant liver failure is characterized by massive acute Hepatocyte dysfunction associated with severe coagulopathy, acute hyperdynamic circulatory failure and hepatic encephalopathy. According to the more recent classification, which takes into account the interval between the onset of jaundice and the hepatic encephalopathy, three are the main forms of ALF hyperacute, acute or subacute. Despite recent and relevant advances in intensive care management and organ support techniques (both artificial and bioartificial), mortality remains extremely high, early deaths being related to cerebral oedema and circulatory failure, whereas late deaths are associated with sepsis and multiple organ failure. Orthotopic liver transplantation has proven to be the only treatment modality able to change radically the ALF natural course. he experiences with artificial and bioartificial devices, in spite of being interesting and sometimes very promising, are far from giving a real impact on survival and remain, so far, important interim measures for patients eventually candidate to liver transplantation.

Perioperative fluid management in kidney transplantation: is volume overload still mandatory for graft function?

Kidney transplantation is now recognized as the treatment of choice for patients with chronic renal failure. Despite the extension of indications to patients suffering severe hypertension, ischemic heart disease, and chronic heart failure, the worldwide results are superb. However, perioperative cardiac complications occur in 6% to 10% of transplanted patients. Aggressive intraoperative volume expansion is still recommended to maximize graft functional recovery (up to 30 mL/kg/h, central venous pressure [CVP] > 15 mm Hg), but patients with preexistent cardiac disease or poor myocardial function are exposed to the risk of fluid overload, acute respiratory failure, and prolonged ventilation. Among the last 90 cases performed at our institution, good functional recovery of the graft was present in 94% of the patients within 2 weeks, despite a much more conservative intraoperative hydration policy (crystalloids 2400 +/- 1000 mL, 15 mL/kg/h, CVP 7-9 mm Hg). Graft failure which occurred in 5 patients was significantly correlated only with donor age, while perioperative cardiovascular complications had been present in 9 cases (10%) who were coronary artery disease patients (55%). Age above 50 years was the only significant risk factor. Supranormal volume loading is probably not always warranted in kidney transplantation.

Intraoperative use of recombinant activated factor VII (rFVIIa).

Recombinant activated factor VII (rFVIIa, Novoseven, Novo Nordisk, Denmark) was introduced as a prohemostatic agent in the early 80s: the only indication approved in USA by Food and Drug Administration (FDA) is the spontaneous bleeding in congenital hemophilia patients who developed inhibitors to FVIII and FIX. Recently, EMEA approved the use of rFVIIa in congenital hemophilia patients with inhibitors undergoing surgery, in subjects with congenital FVII deficiency undergoing surgical or invasive procedures, in patients with acquired hemophilia and in case of Glanzmann's thromboasthenia. Out of these approved indications, the off label use of rFVIIa is rapidly expanding, particularly in surgical patients with acquired coagulation disorders in order to manage severe, uncontrolled bleeding nonresponsive to conventional therapeutic measures or to reduce blood loss and transfusion requirements in potentially bleeding surgical procedures (major liver surgery, liver transplantation, major abdominal or obstetric surgery, trauma surgery). This paper reviews the more recent data coming from retrospective or prospective studies performed in different surgical settings: so far, the major point to be addressed is the place for rFVIIa as an adjunctive but sometimes lifesaving treatment to control haemostasis and critical bleeding in surgery and critically ill patients.

Restless legs syndrome: a community-based study of prevalence, severity, and risk factors.

OBJECTIVE: To assess the prevalence and severity of restless legs syndrome (RLS) in the general community and to investigate its potential relationship with iron metabolism and other potential risk factors. METHODS: This was a cross-sectional study of a sex- and age-stratified random sample of the general population (50 to 89 years; n = 701). The diagnosis of RLS was established by face-to-face interviews; severity was graded on the RLS severity scale. Each subject underwent a thorough clinical examination and extensive laboratory testing. RESULTS: The prevalence of RLS was 10.6% (14.2% in women, 6.6% in men); 33.8% of all patients with RLS had mild, 44.6% had moderate, and 21.6% had severe disease expression. None had been previously diagnosed or was on dopaminergic therapy. Free serum iron, transferrin, and ferritin concentrations were similar in subjects with and without RLS. However, soluble transferrin receptor (sTR) concentrations were different in subjects with and without RLS (1.48 vs 1.34 mg/L; p < 0.001). Female sex and high sTR independently predicted the risk of RLS. CONCLUSION: This large survey confirms the high prevalence, female preponderance, and underrecognition of restless legs syndrome in the general community. Although two-thirds of patients had moderate to severe disease, none was on current dopaminergic therapy.

Right hemiliver transplant: results from living and cadaveric donors.

UNLABELLED: Although right hemiliver transplant from living donors (LD) is gaining acceptance as a way to overcome the critical organ shortage, splitting a liver for two adults from cadaveric donor (CD) is still controversial. METHODS: From May 1999 to August 2004 we performed nine right hemiliver transplants using segments 5-6-7-8 from CD and 18 from LD. RESULTS: We compared the two procedures to evaluate both the technical aspects and the patients' outcomes. In the CD group, three recipients died (33%), two of whom were UNOS Status 2A. Patient and graft survivals were 67% (median follow-up: 23 months). Among the LD group, three recipients died (17%) and two were retransplanted; one because of arterial thrombosis and the other as a consequence of small-for-size syndrome. Patient and graft survivals were 83% and 72%, respectively (median follow-up: 8 months). There were five early complications in the CD group (55%) and five (27%) in the LD group. Two patients in the LD group experienced a late stenosis of the biliary anastomosis. DISCUSSION: Data from our early experience show that better results are achieved by right hemiliver transplants from LD; the morbidity and mortality are higher among the CD group. We believe that this finding is probably a consequence of better preoperative donor evaluation, shorter ischemia time, better logistics, and learning curve. Recipient selection is crucial; this kind of graft is at high risk of poor function, technical complications, and infections. Further experience will help to clarify the reliability of right hemiliver transplants from CD.

Number processing in temporal lobe epilepsy.

BACKGROUND: Specific cognitive impairments have been found in association with mesial temporal lobe epilepsy (TLE), such as deficits in declarative memory or verbal abilities. No attention has been paid so far to possible deficits in number processing. OBJECTIVE: To investigate deficits in number processing in patients with TLE. METHODS: Numerical abilities were assessed in 28 right handed patients with medically intractable unilateral TLE and in a control group. RESULTS: No differences between patients and controls were found in analogue number processing with Arabic input, in a comparison task, or in simple addition and simple subtraction; however, there were significant group differences in tasks with verbal input, in simple division, in complex mental calculation, in a semantic knowledge task, and in conceptual tasks. Only minor differences were found between patients with right and left TLE. CONCLUSIONS: While numerical deficits may be expected in patients with left sided TLE, it is open for discussion why patients with right sided TLE also show numerical deficits.

Incidence of sepsis in central venous catheter-bearing patients with hematologic malignancies: preliminary results.

BACKGROUND: Indwelling central venous catheters (CVCs) are essential devices in the management of patients with hematological disorders treated with chemotherapy. However, their nature predisposes patients to unwanted complications. METHODS: CVC-related complications were retrospectively analyzed in 227 hematologic patients who were consecutively admitted to our hematology department between May 2002 and April 2004. Patients' diagnoses comprised acute myeloid leukemia (36.8%), acute lymphoid leukemia (7.3%), lymphoproliferative disorders (28.3%), multiple myeloma (19.5%), myeloproliferative syndromes (5%) and others (3.1%). The CVCs used were polyurethane three lumen 7-Fr (111 patients) for chemotherapy and 12-Fr (114 patients) for chemotherapy and peripheral blood stem cell apheresis, plus two tunneled catheters. RESULTS: The pathological events were: bacteriaemias (n=46); occlusions (n=10); exit tunnel infections (n=8); thrombosis (n=6); lung emboli (n=2). Among febrile patients the bacteriemia frequency was 20%, of which 13.6% were CVC-related (with a higher incidence in leukemia patients (p=0.027). Among the isolates, gram-positive bacteria were found in 29 cases (23 CVC-related cases), and gram-negative bacteria in 16 cases (8 CVC-related cases). Only one patient had Candida albicans sepsis. At univariate and multivariate analysis significant risk factors for infection (p<0.0001) were only the number of days/catheters and neutropenia duration. CONCLUSIONS: In our hematologic patients, the CVC complications were mainly septic, with only 10.1% of CVC-related bacteriemias, despite prolonged catheterization duration. Acute leukemia patients were at major risk for sepsis, probably due to a more severe neutropenia and prolonged catheterization duration.

The prevalence of primary dystonia in the general community.

The prevalence of primary dystonia was assessed in a random population sample of individuals aged 50 and over in Bruneck, South Tyrol. The diagnosis of primary dystonia was confirmed by videotaped review. Primary dystonia was present in 6 of 707 cases resulting in a prevalence rate of 732 per 100,000 (95% CI 319-1,564) in the general population aged 50 and over. Only two cases (33%) had been previously diagnosed. These results indicate that the true prevalence of primary dystonia is significantly higher than published rates.

Novel three-stage ascertainment method: prevalence of PD and parkinsonism in South Tyrol, Italy.

BACKGROUND: A number of community-based studies on the prevalence of PD have been conducted worldwide, but they are often extremely costly and time consuming. OBJECTIVE: To assess the prevalence of PD and parkinsonism for the population aged between 60 and 85 years in South Tyrol, Northern Italy, using a novel population-based three-stage ascertainment method. METHODS: Seven hundred fifty persons aged 60 to 85 years from South Tyrol received a validated screening mail questionnaire for parkinsonism. In the second stage of the ascertainment method, trained primary care physicians (PCP) identified all persons with possible parkinsonism among those screened positive. In the third stage, movement disorders specialists excluded or confirmed the diagnosis in all identified people. RESULTS: The response rate was 87.6%. The prevalence rate per 100 population over 65 years of age was 1.5 (95% CI 0.6 to 2.3) for PD and 2.2 (95% CI 1.2 to 3.3) for parkinsonism after having been adjusted to the 1991 European standard population. Overall, 78% (95% CI 59 to 96%) of patients with parkinsonism were newly detected through the survey. CONCLUSIONS: The prevalence of PD and parkinsonism in people aged over 65 in South Tyrol was similar to that observed in door-to-door surveys in other European countries. The novel three-stage case ascertainment method employed proved a useful tool to substitute for expensive door-to-door surveys for prevalence studies of parkinsonism, detecting a high number of undiagnosed cases, particularly in geographically remote areas.