Stem cells therapy in acute myocardial infarction: a new era?

Stem cells transplantation after acute myocardial infarction (AMI) has been claimed to restore cardiac function. However, this therapy is still restricted to experimental studies and clinical trials. Early un-blinded studies suggested a benefit from stem cell therapy following AMI. More recent blinded randomized trials have produced mixed results and, notably, the last largest pan-European clinical trial showed the inconclusive results. Furthermore, mechanisms of potential benefit remain uncertain. This review analytically evaluates 34 blinded and un-blinded clinical trials comprising 3142 patients and is aimed to: (1) identify the pros and cons of stem cell therapy up to a 6-month follow-up after AMI comparing benefit or no effectiveness reported in clinical trials; (2) provide useful information for planning future clinical programs of cardiac stem cell therapy.

New York Heart Association class associated with imaging is a prognostic mortality risk predictor in interstitial lung diseases.

OBJECTIVE: Mortality risk factors as forced vital capacity, diffuse lung capacity for carbon monoxide, and 6-minutes' walk test were studied in clinical trials monitoring patients affected by interstitial lung diseases (ILD). However, these parameters showed scarce accuracy. Our aim was to identify New York Heart Association (NHYA) class, in association with high resolution computed tomography (HRCT) and somatostatin receptor scintigraphy (Octreoscan), as a prognostic mortality risk factor in ILD patients. PATIENTS AND METHODS: Study population comprised 128 ILD patients (78 Males and 50 Females). Histological diagnosis was usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP) and granulomatous lung disease in 59, 19 and 50 patients, respectively. Patients were monitored by NYHA class, HRCT and Octreoscan at baseline and every 3 years up to a 10-year follow up. Overall survival was calculated from the date of diagnosis until death or last follow-up update. Statistical analysis was performed using Kaplan-Meier, log-rank test (LRT), multivariate analysis with Cox proportional hazard regression model, and log-likelihood ratio test. RESULTS: Overall median survival was 89.3 months (7.4 years) with the poorer survival rate observed in UIP patients. NYHA class came out as a reliable prognostic mortality risk factor in each group of patients and prognosis was progressively worse with NYHA class increase (LRT p<0.001). A strong correlation was found between NYHA class and age, CT-score, and Octreoscan in UIP patients (p<0.001). CONCLUSIONS: The determination of NYHA class can therefore be recommended as an additional prognostic mortality risk factor in ILD patients.

Role of Liver Transplantation in Bilio-Vascular Liver Injury After Cholecystectomy.

BACKGROUND: The aim of this study was to report 2 cases of liver transplantation (LT) for iatrogenic bile-vascular injury (BVI) sustained during cholecystectomy and to review the literature for LT after cholecystectomy. METHODS: Between March 2001 and July 2013, within our institution, 12 patients were treated after cholecystectomy, 3 of 12 received LT, 1 for acute de-compensation in a cirrhotic patient and 2 after iatrogenic lesions. RESULTS: The majority of iatrogenic injury occurred during video-laparocholecystectomy (63,6%; 7/11). Three patients of 12 (25%) received LT: the first patient developed acute de-compensation in chronic and after liver failure. The second patient developed recurrent cholangitis and secondary biliary cirrhosis. The third patient had undergone emergency hepatectomy because of bleeding and subsequent total hepatectomy with porto-caval shunt. Five of 12 (42%) patients were treated with bilio-digestive anastomosis: 1 patient with direct repair on T-tube; 2 patients (17%) with arterial vascular lesion requiring surgical treatment; and 1 patient treated with medical therapy. No deaths occurred. The post-operative morbidity included 1 re-intervention, 3 recurrent cholangitis, 1 anastomotic biliary stricture, 1 anastomotic bile leak, and cholestasis in 3 patients. The overall hospital stays were higher after LT. Median follow-up was 8.25 years (range, 2-14). CONCLUSIONS: The management of iatrogenic injury during cholecystectomy depends on the time of recognition, extent of injury, experience of the surgeon, and the patient's general condition. If safe repair is possible, BVI should be treated promptly, otherwise all patients should be treated in an experienced center.

Predictability and survival in liver replantransplantation: monocentric experience.

Liver retransplantation is the only treatment for patients with hepatic graft failure. Due to the shortage of organs, it is essential to optimize its use. Between 1998-2010, our center performed retransplantations on 48 (12.8%) patients (re-OLT). The data are compared with those for a group of 374 patients who did not receive retransplantations (NO re-OLT). The re-OLT vs NO re-OLT groups did not significantly differ in mean age of recipients (47 vs 51 years), indications for transplantation (hepatitis C virus cirrhosis 54% vs 56%, alcoholic cirrhosis 25% vs 17%, hepatocellular carcinoma 14% vs 22%), mean Model for End-stage Liver Disease (25 vs 20), mean total cold ischemia time (385 vs 379 minutes), or mean age of donors (52 vs 49 years). The main causes of retransplantation were primary graft nonfunction (64%), arterial thrombosis (8%), biliary complications (6%), and hepatitis C virus recurrence (4%). The difference in overall patient survival was not statistically significant. The patient's survival at 1, 3, 5, and 10 years for RE-OLT vs NO-reOLT was 56% vs 63%, 53% vs 60%, 46% vs 57%, and 44% vs 53%, respectively. Multivariate analysis identified Model for End-stage Liver Disease≥23 as a predictor factor of retransplantation (P=.04). Other variables predicting outcome included age of donors (≥65 years vs younger group), age of recipients (≥50 years vs younger group), cold ischemia (≥600 vs <600 minutes), and transplantation indications (hepatitis C virus, hepatitis B virus, alcohol, and others). The retransplantation performed between 8-15 days appeared to have worse results than those in other periods (0-7 days, 16-30 days, 1-6 months, >6 months). The incidence of re-OLT in the series (12.8%) was comparable to that in the literature, and primary graft nonfunction in the study represents the main cause of retransplantation. Our analysis showed that the indication of the first transplant and the age of the donor were not risk factors for re-OLT. Liver retransplantation is a concrete alternative lifesaver for patients with graft failure.

Full-right-full-left split liver transplantation: the retrospective analysis of an early multicenter experience including graft sharing.

Full-right-full-left split liver transplantation divides a donor liver into two grafts to be transplanted in adult-size patients. Major technical and organizational difficulties have limited its application to few single center series. We retrospectively analyzed the long-term results of the first multicenter series of this procedure with graft sharing. Between November 1998 and January 2005, 43 transplants were performed by five centers from 23 full-right-full-left in situ split liver procedures; 65% of the grafts were shared. A total of 31 (72%) patients had complications above grade II; 3 (6.9%) were retransplanted. Hospital mortality was 23% with sepsis as the main cause. Six patients died in the long term, two of them for a road accident. A total of 27 patients are alive after a median follow-up of 3200 days (2035-4256). Actuarial survival at 1 and 10 years were 72.1%, 62.6% and 65.1%, 57.9%, respectively for patients and grafts. These figures are similar to those reported for adult living donor liver transplantation by the European Registry over a similar period. Multicenter collaboration in sharing of these grafts is feasible and can help facing the organizational limits, thus increasing diffusion of full-right-full-left split liver transplantation.

Predictors of survival in idiopathic interstitial pneumonia.

AIM: To evaluate the ability of newly identified clinical factors to predict prognosis and survival in idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP). METHODS: Seventy-eight patients referred to the University of Genoa and the Regional Hospital of Aosta between January 1995 and December 2006 were evaluated prospectively. Fifty-nine patients were diagnosed with IPF and 19 with NSIP on the basis of surgical lung biopsy specimens. Gender, age at diagnosis, smoking, New York Heart Association class (NYHA), systolic pulmonary artery pressure (sPAP), Octreoscan uptake index (UI), and therapy were the chosen variables. Primary end-point was survival. RESULTS: With the exception of gender and smoking history, all baseline patient characteristics correlated significantly with the diagnosis (IPF vs. NSIP). Median survival for the entire study group was 52.7 months. Univariate analysis showed poorer survival for the IPF group versus the NSIP group, and survival was significantly lower for older patients (p < 0.001). Multivariate analysis confirmed the negative prognostic effect of age (p < 0.001) on survival with a risk of death for older patients ( > OR =66 years old) being more than 4 times higher than that for younger patients (<58 yr.). NYHA class and pulmonary artery pressure were also significant predictors of survival, and all patients with a sPAP < OR = 35-mm Hg were alive at the end of the follow-up period. There was a good correlation between Octreoscan uptake index and the diagnosis. CONCLUSION: Diagnosis (IPF vs. NSIP), NYHA class, sPAP, and especially age appear to represent important prognostic indicators in the two most prevalent forms of idiopathic pulmonary fibrosis (IPF and NSIP). Lower Octreoscan uptake values were found in all patients with IPF, suggesting that this test may have a role as a new predictor of survival for differentiating IPF from NSIP.

Alcohol abstinence and orthotopic liver transplantation in alcoholic liver cirrhosis.

Patients diagnosed with acute alcoholic hepatitis (AAH) are routinely managed medically and not considered suitable for orthotopic liver transplantation (OLT). The eligibility for OLT in these patients has been questioned due to the social stigma associated with alcohol abuse, based on the fact that AAH is "self-induced" with an unacceptably high recidivism rate. Many centers in Europe and the United States require abstinence periods between 6 and 12 months before OLT listing. AAH outcomes in the literature are poor, in particular due to patient noncompliance during the immediate 3 months preceeding OLT. Between January 1997 and December 2007, 246 patients were evaluated in our center for alcoholic liver disease: 133 (54%) were listed for OLT (I-OLT), including 110 (83%) who underwent transplantation and 8 (6%) still listed as well as 15 (11%) removed from consideration. One hundred thirteen (46%) patients had no indication for OLT (NO I-OLT), including 18 (16%) who died, 81 (71%) still monitored, and 14 (12%) lost to follow-up. Patient survival rates post-OLT were 79%, 74%, 68%, and 64% at 1, 3, 5, and 10 years, respectively. Explant (native liver) pathologic examination revealed AAH in 8 (7.2%) patients who underwent OLT. In this group, patient survival and the post-OLT recidivism rate were statistically identical to the overall group of transplant recipients.

A 20-year period of orthotopic liver transplantation activity in a single center: a time series analysis performed using the R Statistical Software.

In many Western countries a "minimum volume rule" policy has been adopted as a quality measure for complex surgical procedures. In Italy, the National Transplant Centre set the minimum number of orthotopic liver transplantation (OLT) procedures/y at 25/center. OLT procedures performed in a single center for a reasonably large period may be treated as a time series to evaluate trend, seasonal cycles, and nonsystematic fluctuations. Between January 1, 1987 and December 31, 2006, we performed 563 cadaveric donor OLTs to adult recipients. During 2007, there were another 28 procedures. The greatest numbers of OLTs/y were performed in 2001 (n = 51), 2005 (n = 50), and 2004 (n = 49). A time series analysis performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria), a free software environment for statistical computing and graphics, showed an incremental trend after exponential smoothing as well as after seasonal decomposition. The predicted OLT/mo for 2007 calculated with the Holt-Winters exponential smoothing applied to the previous period 1987-2006 helped to identify the months where there was a major difference between predicted and performed procedures. The time series approach may be helpful to establish a minimum volume/y at a single-center level.

Torque Teno Virus--cause of viral liver disease following liver transplantation: a case report.

Torque Teno Virus (TTV), a nonenveloped human virus of the Circoviridae family, is hepatotropic, causing liver damage, cirrhosis, and, rarely, fulminant hepatitis. It prevails in 10% to 75% of blood donors due to environmental differences, independent of chronic hepatitis B virus (HBV)/HCV hepatitis, cryptogenic cirrhosis, alcoholic cirrhosis, and in fulminant hepatitis non-A-G. Reports about the efficacy of clinical alpha interferon are rare. In July 2007, a 65-year-old man who was serologically negative for A-E viruses presented with acute liver failure due to a ruptured hepatic artery aneurysm and underwent orthotopic liver transplantation (OLT). Immunosuppression was based on cyclosporine and steroids. At postoperative day 20, there was persistent hypertransaminasemia with otherwise normal liver function. A percutaneous hepatic biopsy documented pattern suggestive of a viral etiology. Multiple tests for hepatotropic viruses in the donor and the recipient from the pre- and post-OLT periods remained negative. Only the TTV qualitative test, assessed by polymerase chain reaction (PCR) on patient sera, was positive. Immunosuppressive therapy was not changed; no antiviral therapy was undertaken. At 6 months posttransplantation, transaminase levels spontaneously normalized and the clinical situation was unchanged. No complications were observed; the patient is in good clinical condition. No graft rejection was observed. In histologically proven non-A-E viral hepatitis, it is important to consider TTV as an incidental pathogenic agent. It may be useful to extend virological tests to TTV among transplant recipients and donors and to gain further knowledge about this virus.

Model for End-Stage Liver Disease (MELD) score and organ allocation from cadaveric donors for 198 liver transplantation procedures performed in a single center.

Since February 2002, the United Network for Organ Sharing (UNOS) proposed to adopt a modified version of the Model for End-Stage Liver Disease (MELD) to assign priority on the waiting list for orthotopic liver transplantation (OLT). In this study, we evaluated the impact of MELD score on liver allocation in a single center series of 198 liver recipients (mean age of patients, 52.21+/-8.92 years), considering the relationship between clinical urgency derived from MELD score (overall MELD, 18.7+/-6.83; MELD <15 in 69 patients, MELD >or=15 in 129 patients) and geographical distribution of cadaveric donors (inside/outside Liguria Region, 125/73). The waiting time for OLT was 230+/-248 days, whereas the 3-month and 1-year patient survivals were 87.37% and 79.79%, respectively. No difference was observed for MELD score retrospectively calculated for patients who underwent OLT before February 2002 (n=71) compared with MELD score calculated for patients who received a liver thereafter (18.26+/-6.68 vs 18.94+/-6.92; P= .504). No significant difference was found in waiting time before and after adoption of MELD score (213+/-183 vs 238+/-278 days; P= .500), or by stratifying patients for MELD <15/>or=15 (225+/-234 vs 232+/-256 days; P= .851). Using the geographical distribution of donors as a grouping variable (outside vs inside Liguria Region), no significance occurred for MELD score (19.68+/-7.42 vs 18.17+/-6.42; P= .135) or waiting time (211+/-226 vs 242+/-261 days; P= .394). In our series, more OLTs were performed among sicker patients and no differences were found in the management of livers procured from cadaveric donors outside or inside Liguria Region. However, further efforts are needed to reduce the waiting time among patients with higher MELD scores.

Sirolimus therapy in liver transplant patients: an initial experience at a single center.

Sirolimus (SRL) is an mTOR inhibitor that has been shown, in contrast to calcineurin inhibitors (CNI), to inhibit cancers in experimental models. Since February 2005, we introduced SRL in liver transplant patients in group a, in whom the primary disease was hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic or autoimmune liver cirrhosis, and group b, HCC-negative patients who developed posttransplantation cancers de novo. Of 18 patients in group a, 11 received SRL ab initio (subgroup a1), starting for 10 patients at 66.1+/-29.2 days after surgical healing and after 10 days in 1 case; the remaining 7 patients (subgroup a2) received SRL at 31.2+/-24.2 months. Three patients in group b, included 1 with Kaposi's sarcoma, 1 with bladder cancer, and 1 with thyroid cancer. In this group, SRL was introduced at 80.8+/-40.4 months. In all patients but one, who received a single 5 mg loading dose, SRL was started at 2 mg/d and adjusted to 6 to 8 ng/mL blood levels. CNI drugs, present as primary therapy, were gradually tapered to low levels and eventually stopped. The following observations were drawn from this initial experience: (1) 4/21 (19.0%) patients had to discontinue SRL because of early and late side effects: thrombocytopenia (n=2) and headache with leukopenia and leg edema associated with knee joint arthralgia (n=2); (2) 14 patients (11 in group a and 3 in group b) are still on SRL monotherapy; (3) 1 HCC recurrence and 1 de novo pancreatic adenocarcinoma were observed at 14 and 16 months, respectively (at the time of transplantation, both patients were beyond the MIlan HCC criteria), and (4) 1 patient, from subgroup a1, died after 99 days due to pneumonitis and possible relation to SRL lung toxicity. In conclusion, SRL appeared to be an effective immunosuppressant that could be used as monotherapy in liver transplant patients. Any conclusion on SRL anticancer effects can only come from randomized large studies after long follow-up.

Preliminary results of liver transplantation for hepatocellular carcinoma among allocation organ policy strategies, neoadjuvant treatments, and intention-to-treat analysis.

We retrospectively evaluated the impact of our strategy for patients with hepatocellular carcinoma (HCC) according to an intention-to-treat analysis and drop-out probability. We evaluated only patients within the Milan criteria. We analyzed the outcomes of neoadjuvant strategies for HCC, organ allocation policy, and systematic application of strategies to increase the deceased donor pool as the current tendency to expand transplantability criteria for those patients. Kaplan-Meier survival probability rates at 1, 3, and 5 years according to an intention-to-treat analysis were 87.02%, 74.53%, and 65.93% for transplanted patients (n=108), and 50%, 14.29%, and 14.29% for the excluded or waiting list group (n=13), respectively (P< .0001). Drop-out risk at 3, 6, and 12 months was 2.40%, 8.59%, and 16.54%, respectively. During the same period, the mortality probability rates at 3, 6, and 12 months among patients without HCC awaiting orthotopic liver transplantation (OLT) were 3.60%, 9.50%, and 18.34%, respectively. Drop-out rate was lower among patients treated before OLT (P< .0001). On the basis of the neoadjuvant treatment results to reduce drop-out risk, we suggest avoiding the high priority for the HCC cohort, particularly within the first 6 months from entrance on the waiting list, because this approach can reduce the chances of patients with end-stage liver disease (ESLD) alone.

Predictors of mortality of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF), a disease with histological features corresponding to usual interstitial pneumonia (UIP), is a disorder of unknown cause. Not only it is the most common subtype of idiopathic interstitial pneumonias but it is also associated with the highest mortality rate. Despite a good number of studies investigating the mortality of patients with UIP the prognostic factors that have been studied have several limitations. To date it is unclear when in the course of the disease and with what modality these patients should be treated. According to the literature we subcategorized predictors of mortality into (a) baseline predictors; (b) dynamic predictors. IPF perspectives in therapy have been also analyzed. Moreover, the principal aims of this review were: (1) to analyze and to clarify the clinical utility of different prognostic factors for IPF; (2) to enable clinicians to better evaluate the eligibility criteria for lung transplantation in the clinical practice.

Medical report type in liver transplantation as a quality system document: new prospects for computerization.

The usage of a computerized system to organize data and ease the activity procedures of liver transplantation is useful in clinical transplantation. Preliminary cognitive research on systems of clinical transplantation database concerning medical reports was performed to verify their development level. The survey highlighted that, so far, there has been no experimentation that can be applied to a medical report type devoted to liver transplantation. Regulations in force substantially point out that the medical report ought to contain all items that have to be taken into account in handling the patient from pretransplantation to follow-up. The Department of Transplantation of Genoa chose its medical report model for liver transplantation. The medical report model included the following items: personal data; case history; diagnosis; initial examination for prelisting; fitness for transplantation; assistance context; clinical data including subjective, objective, and instrumental parameters; pharmacological therapies; informed consent, evaluation of fitness; nursing data; counseling and clinical evaluations according to protocols and guidelines of the national transplantation centers. If the computing is well trained, it is supposed to help maintain a whole data view provided it is supplied information in an adequate way. Immediate clinical procedural advantages and useful scientific observations may be obtained from a high-quality database. In fact, all functions have to be applied to specific clinical, administrative needs to be remotely shared and conveniently integrated with each other to make the liver transplantation medical report an easy and handy instrument for inputting and handling data. It must be a precise, complete instrument that may be accessible in real time from any site connected with the intranet network, be unchangeable, and be protected to ensure certification and forensic medicine value.

Split liver transplantation for acute Wilson's disease: new option for urgent recipient?

Wilson's disease is a rare metabolic disorder that may lead to fulminant hepatitis and subsequent liver failure. Herein, we present a case of split liver transplantation performed on a patient with acute Wilson's disease. A 27-year-old female with acute presentation of Wilson's disease and advanced neurological impairment, received a Right Split liver Graft (Segments: IV, V, VI, VII and VIII) transplant. The graft was obtained by an in situ splitting technique. The graft implantation was performed in a standard fashion. No acute rejection episodes of the organ occurred. The postoperative course was uneventful. The graft function, ceruloplasmine level and copper levels progressively normalized. The patient totally recovered from neurological symptoms and the Kayser-Fleischer rings disappeared within one month. At 13 months of follow-up, the patient presented with no symptoms and in good condition. The current literature reports high preoperative mortality rate in patients that underwent partial liver graft for acute hepatic failure. However, our experience indicates that in situ split technique of liver may be a feasible and effective alternative to whole graft transplantation in urgent cases. Moreover, to our knowledge, this is the first successfully case of in situ split liver transplantation for acute Wilson's disease described in literature.

Impact of different cadaveric donor age cut-offs on adult recipient survival after liver transplantation: a single-center analysis.

The increase in the number of patients awaiting liver transplantation (OLT) has forced the use of cadaveric donors (CD) with suboptimal characteristics. Of these, donor age is perhaps the most investigated parameter. Although excellent outcomes were observed for OLT using CD aged over 60 years, the European Liver Transplant Registry (ELTR) Group found an increased risk by using CD of more than 55 years. The Italian National Transplant Center has recently assumed that CD age more than 60 years is a potential risk factor for OLT. In this study, a single-center analysis was performed by stratifying CD by three age cut-offs (< or =55 or >55, < or =60 or >60, and < or =65 or >65 years) to evaluate effects on OLT outcome. Although no significant difference in 6-month and 1-year patient or graft survival occurred after stratification for each donor age cut-off, a better survival was observed with OLT performed using livers procured from CD >55 years. A significant increase in cold ischemia time (CIT) was observed among OLT performed with grafts procured from CD < or =55 and < or =65 years (P = .007), and there was an inverse correlation between overall CIT and donor age (R = -0.300; P = .0022). However, no impact on 1-year patient survival was observed by introducing CIT in univariate logistic regression models as well as donor age, recipient age, donor/recipient age ratio, donor/recipient sex mismatch, ELTR diagnostic categories, and UNOS status. The results of this study suggest the suitability of CD of more than 55 years for OLT and the need to further investigate the cut-off value for CIT-related risk.

Bronchial hyperresponsiveness in asthmatic adults--a long-term correlation study.

BACKGROUND: Bronchial hyper responsiveness (BHR), is a risk factor for asthma. It is a state in which excessive narrowing of the airways occurs in response to varying stimuli. BHR seems to be due to the interaction of multiple factors and its relation to asthma is complex. Asthma without BHR is unusual. Indeed, patients who show a higher degree of symptoms have higher levels of BHR. To date no study has investigated the correlation between BHR in mild persistent asthmatic adults and a long-term therapy of five years. The aim of this study is to evaluate (i) the role of BHR in the clinical evaluation of asthma, (ii) the correlation between BHR and therapy in asthma. METHODS: Seventy patients (were recruited 34 men, age 21-55 years) suffering from: (a) mild seasonal allergic asthma (17/70), (b) mild perennial allergic asthma (34/70) and (c) mild non-allergic [corrected] asthma (19/70). 14 patients from group (a) and 28 patients from group (b) were treated with inhaled beta2-agonists, beclomethasone, disodiumcromoglycate and immunotherapy. 14 patients from group (c) underwent the same treatment regimen without immunotherapy. All patients were evaluated with a metacholine challenge test. The BHR (PD20 FEV1) was calculated at baseline and after a two-year symptom free period. Fifteen pts were followed-up for five years with an evaluation every year. All other patients did not receive any treatment. The results (expressed as mean +/- SE) were evaluated. RESULTS: Fourteen pts and three pts from group (a) showed a mean BHR value of 984 +/- 3.66 and 674 +/- 2.06; 343 +/- 7.60 and 208 +/- 7.70 respectively. The results were not statistically significant Twenty-eight and six pts from group (b) showed mean values of 685 +/- 1.45 and 1405 +/- 5.65; 856 +/- 7.09 and 435 +/- 2.20 with apparent improvement for the former. Five pts and fourteen pts from group (c) showed mean value of 2682 +/- 7.85 and 2099 +/- 6.82; 816 +/- 2.53 and 877 +/- 4.78 respectively. As for the 5-yr follow up ten pts and five pts from group (b) showed mean values of 705 +/- 1.6 and 861 +/- 7.15; 911 +/- 7.3 and 457 +/- 2.3 respectively. CONCLUSIONS: Although the clinical picture improved with therapy, BHR was not significantly affected in any patient group, at two and five years of follow-up. Furthermore, no correlation was found between the clinical picture and PD20 FEV1 values. BHR seems to result from the interaction of multiple factors that are worth further investigating. BHR cannot be considered a marker of disease activity in asthma and therefore is not a useful tool for guiding asthma therapy.

Secondary pulmonary hypertension--diagnosis and management.

Secondary pulmonary hypertension (SPHtn) is generally attributable to abnormalities in structure or function of the heart or lung parenchyma. While often defined as a physiologic parameter, pulmonary hypertension (PHtn) can be a major contributor to death and disability in cardiopulmonary diseases. Both detection and management are a challenge. We will review the pathophysiology, diagnostic tools, and treatment strategies in SPHtn with an emphasis on cor pulmonale associated with chronic obstructive pulmonary disease (COPD), pulmonary vasculopathies, and pulmonary embolus. The pathophysiology and common etiologies of SPHtn can be divided into three major categories: (1) elevated pulmonary venous pressure (LV failure and mitral valve disease), (2) pulmonary vascular occlusive disease with or without pulmonary parenchymal disease (pulmonary emboli, COPD, connective tissue diseases), and (3) hypoxemia (sleep apnea). The echo-Doppler is a simple cost-effective tool for detecting PHtn, evaluating right ventricular function, and distinguishing common etiologies such as abnormal systolic and diastolic left ventricular function and mitral valve disease. The ventilation-perfusion radionuclide scan can be used to exclude thromboembolic PHtn, but a helical computer tomography with contrast or pulmonary angiography are necessary to distinguish patients that may benefit from a pulmonary thromboendarterectomy. The six minute walk oxygen saturation test is useful as a quantitative measure of functional capacity, prognosis, response to therapy, and oxygen requirement. Treatment strategies in cor pulmonale are tailored to the specific diagnosis, but generally include proper nutrition, exercise, oxygen supplementation, medications such as digoxin, diuretics, anti-coagulation, and pulmonary vasodilator therapy in selected patients.

Simultaneous liver-kidney transplantation for glycogen storage disease type IA (von Gierke's disease).

INTRODUCTION: Glycogen storage disease type Ia (GSDIa) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney, and intestine. Although significant progress has been achieved in the management of patients with GSDIa, complications still emerge. The potential for development of liver adenomatosis and kidney failure makes these patients candidates for simultaneous liver-kidney transplantation (SLKT). Herein, we describe such a transplantation in a patient affected by this rare storage disease. METHODS: A 25-year-old female patient with GSDIa developed hepatic adenoma and kidney failure despite dietary therapy. The patient underwent an SLKT from a cadaveric donor. RESULTS: The operative time was 8 hours without hemotransfusion. Only a transitory lactic acidosis was observed. Laboratory results normalized on postoperative day 7. The patient was discharged on postoperative day 9. After 4 months, the patient is in good condition with well-functioning kidney and liver allografts. CONCLUSION: Patients with end-stage renal disease secondary to GSDIa should be considered for SLKT, especially when the disease is in an early stage.

Split liver transplantation in Italy.

The role of split liver transplantation has been well established. The limitation to this technique is the number of potential recipients for a left lateral segment graft. The optimal use of the donor pool is to split the liver to provide 2 grafts suitable for adults obtaining right or left lobe. We explored the potential increase in the number of liver grafts gained from systematically using the technique of splitting on national basis. The crucial factor appeared to be creation of guidelines for the use of optimal livers to optimize organ allocation while minimizing pretransplantation mortality and maximizing post-orthotopic liver transplantation outcome.