The Frequency of Germline BRCA and Non-BRCA HR-Gene-Variants in a Cohort of Pancreatic Cancer Patients.

Germline DNA alterations affecting homologous recombination pathway genes have been associated with pancreatic cancer (PC) risk. BRCA2 is the most studied gene and affects the management of PC patients and their families. Even though recent reports have suggested a similar role of germline ATM pathogenic variants (PV) in familial PC, there is still a disagreement between experts on how it could affect patient management given the lack of proper PC risk estimates. We retrospectively analyzed the germline data of 257 PC patients among whom nearly 50% were sporadic cases. We showed similar frequencies of BRCA2 (4.9%) and ATM (4.4%) PV or likely pathogenic variants, which were not related to familial history. Based on our findings and that of the literature, we suggest including ATM gene among the panel of genes analyzed in PC patients pending the publication of prospective studies.

Outcome of kidney transplant in primary, repeat, and kidney-after-nonrenal solid-organ transplantation: 15-year analysis of recent UNOS database.

The number of nonrenal solid-organ transplants increased substantially in the last few decades. Many of these patients develop renal failure and receive kidney transplantation. The aim of this study was to evaluate patient and kidney allograft survival in primary, repeat, and kidney-after-nonrenal organ transplantation using national data reported to United Network for Organ Sharing (UNOS) from January 2000 through December 2014. Survival time for each patient was stratified into the following: Group A (comparison group)-recipients of primary kidney transplant (178 947 patients), Group B-recipients of repeat kidney transplant (17 819 patients), and Group C-recipients of kidney transplant performed after either a liver, heart, or lung transplant (2365 patients). We compared survivals using log-rank test. Compared to primary or repeat kidney transplant, patient and renal allograft survival was significantly lower in those with previous nonrenal organ transplant. Renal allograft and patient survival after liver, heart, or lung transplants are comparable. Death was the main cause of graft loss in patients who had prior nonrenal organ transplant.

Insecticidal activity of a Moroccan strain of Streptomyces phaeochromogenes LD-37 on larvae, pupae and adults of the Mediterranean fruit fly, Ceratitis capitata (Diptera: Tephritidae).

The Mediterranean fruit fly (medfly), Ceratitis capitata, is considered the most important fruit pest worldwide. Its management is mainly based on the use of chemical insecticides. Although these conventional pesticides are effective at high doses, they cause considerable human health and environment problems. Thus, the aim of this study was to assess insecticidal activity of Moroccan actinobacteria against C. capitata. A total of 12 preselected actinobacteria isolated from various Moroccan habitats were screened for their insecticidal activity against larvae, pupae and adults of C. capitata. Four actinobacteria isolates were significantly active against the first-instar larvae, and nine were active against the medfly adult, while no significant mortality was obtained against the third-instar larval and pupal stages. Among the selected isolates, the biological screening revealed that strain Streptomyces LD-37, which showed 99.4% similarity with Streptomyces phaeochromogenes, exhibited the maximal corrected larval mortality of 98%. Moreover, the isolates AS1 and LD-37 showed the maximum significant corrected mortality against adults of 32.5 and 28.2%, respectively. The crude extract obtained from a fermented culture of strain S. phaeochromogenes LD-37 was separated into six fractions by thin layer chromatography. Fractions F3 and F4 caused a significant corrected larval mortality of 66.7 and 53.3%, respectively; whereas the maximum reduction in adult emergence was obtained with fraction F4. This finding could be useful for utilizing S. phaeochromogenes LD-37 as an alternative to chemical insecticides in pest management of C. capitata.

Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic PEEP in COPD?

INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume-time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied 19 patients (n=8 mild-moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV1 in the whole cohort (r=-0.71, p<0.001) and patients alone (r=-0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=-0.55, p=0.0015) and patients (r=-0.71, p<0.001) and peak exercise tidal volume (r=-0.58, p=0.0062 and r=-0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=-0.65, p<0.001) and patients considered alone (r=-0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=-0.69, p<0.001) and patients (r=-0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity.

Seminal androgens, oestradiol and progesterone in oligoasthenoteratozoospermic men with varicocele.

This study aimed to assess seminal androgens, oestradiol, progesterone levels in oligoasthenoteratozoospermic (OAT) men with varicocele (Vx). In all, 154 men with matched age and body mass index were investigated that were divided into healthy fertile controls (n = 35), OAT men with Vx (n = 55), OAT men without Vx (n = 64). They were subjected to assessment of semen parameters, seminal levels of testosterone (T), androstenedione (A), 5α-androstane-3 α,17 ß-diol (3 α-diol), oestradiol (E2 ), 17-hydroxyprogesterone (17-OHP) and progesterone (P). Seminal levels of T and A were significantly decreased where seminal levels of 3 α-diol, E2 , 17-OHP, P were significantly higher in OAT men with/without Vx compared with fertile controls. Sperm count, sperm motility and sperm normal forms percentage demonstrated significant positive correlation with seminal T and A and significant negative correlation with seminal 3 α-diol, E2 , P. It is concluded that in fertile men, seminal T and A are significantly increased and seminal 3 α-diol, E2 , 17-OHP, P are significantly decreased compared with infertile OAT men with/without Vx. Association of Vx demonstrated a nonsignificant influence on these hormonal levels in OAT cases. Sperm count, sperm motility and sperm normal forms demonstrated significant positive correlation with seminal T, A and significant negative correlation with seminal 3 α-diol, E2 , P.

The comfort perception in the critically ill patient from the Kolcaba theoretical model.

BACKGROUND: The stay in a critical care unit (CCU) has a serious impact on physical condition causing numerous discomfort factors such as pain or difficulty in communicating. All of these are associated with possible sequelae following discharge from the Intensive Care Unit (ICU) named post-ICU syndrome. The Kolcaba Comfort Theory allows, from a holistic approach, to identify care needs from the patient's perspective using instruments such as the General Comfort Questionnaire (GCQ). OBJECTIVES: To determine the comfort level of patients admitted to the CCU using the GCQ of Kolcaba and to identify the discomfort factors. METHODS: Cross-sectional descriptive observational prospective study. POPULATION: 580 patients admitted to adult CCU of two high complexity hospitals from June 2015 to March 2020 with stay ≥24 h were interviewed. Descriptive analysis, Student's t-test and ANOVA and multivariate analysis were performed using SPSS v26 and STATA v16. RESULTS: The mean age was 52,62 (16,21), 357 (61,6%) were male and 434 (74,8%) were believers. The type of admission was planned in 322 (55,5%) and the most prevalent reason for admission was surgical 486 (83,8%). The median pain score (NRS) was 3,00 [0-4] and severity score (APACHE II) was 13,26 (5,89), the median length of stay was 4,00 [2-7] days. The mean comfort level was 3,02 (0,31) showing the highest value Reanimation 3.02 (0.30) and the lowest Trauma and Emergency Unit 2.95 (0.38). Statistically significant differences were found between the units in the comfort level of patients >65 years of age (p = 0.029). The Relief comfort type obtained the lowest mean 2.81 (0.33) and the physical context 2.75 (0.41) in the three units. In the multivariate analysis, statistically significant differences were found between the comfort level and the pain level: no pain (p = 0,000) OR 4,361 CI [2,184-8,707], mild pain (p = 0,000) OR 4,007 CI [2,068-7,763], moderate pain (p = 0,007) OR 2,803 CI [1,328-5,913], and the APACHE II score equal to or greater than 10 (p = 0,000) OR 0,472 CI [0,316-0,705]. CONCLUSIONS: The comfort level showed high scores in all three units. The physical and environmental contexts and the relief comfort type negatively affected the perception of comfort. The variables that explained comfort were pain and severity of illness. The evaluation of comfort from the patient's perspective through the GCQ could be considered an indicator of quality of nursing interventions.

Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterised by myofibroblast proliferation leading to architectural destruction. Neither the origin nor the continued proliferation of myofibroblasts is well understood. Explanted human IPF lungs were stained by immunohistochemistry for calretinin, a marker of pleural mesothelial cells (PMCs). Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) lungs acted as controls. The number of PMCs per 100 nucleated cells and per photomicrograph was estimated along with the Ashcroft score of fibrosis. Mouse PMCs expressing green fluorescent protein (GFP) or labelled with nanoparticles were injected into the pleural space of mice given intranasal transforming growth factor (TGF)-ß1. Mouse lungs were lavaged and examined for the presence of GFP, smooth muscle α-actin (α-SMA) and calretinin. Calretinin-positive PMCs were found throughout IPF lungs, but not in COPD or CF lungs. The number of PMCs correlated with the Ashcroft score. In mice, nanoparticle-laden PMCs were recoverable by bronchoalveolar lavage, depending on the TGF-ß1 dose. Fluorescent staining showed α-SMA expression in GFP-expressing PMCs, with co-localisation of GFP and α-SMA. PMCs can traffic through the lung and show myofibroblast phenotypic markers. PMCs are present in IPF lungs, and their number correlates with IPF severity. Since IPF presumably begins subpleurally, PMCs could play a pathogenetic role via mesothelial-mesenchymal transition.

Calcium- and ROS-mediated defence responses in BY2 tobacco cells by nonpathogenic Streptomyces sp.

AIMS: The early molecular events underlying the elicitation of plant defence reactions by Gram-positive bacteria are relatively unknown. In plants, calcium and reactive oxygen species are commonly involved as cellular messengers of a wide range of biotic stimuli from pathogenic to symbiotic bacteria. In the present work, we checked whether nonpathogenic Streptomyces sp. strains could induce early signalling events leading to defence responses in BY2 tobacco cell suspensions. METHODS AND RESULTS: We have demonstrated that nonpathogenic Streptomyces sp. OE7 strain induced a cytosolic Ca(2+) increase and a biphasic oxidative burst in the upstream signalling events, leading to defence responses in BY2 tobacco cell suspensions. Streptomyces sp. OE7 also elicited delayed intracellular free scopoletin production and programmed cell death. In agreement with scopoletin production, OE7 induced accumulation of PAL transcripts and increased accumulation of transcripts of EREBP1 and AOX genes that are known to be regulated by the jasmonate/ethylene pathway. Transcript levels of PR1b and NIMIN2α, both salicylic acid pathway-linked genes, were not modified. Moreover, Streptomyces sp. OE7 culture filtrates could reduce Pectobacterium carotovorum- and Pectobacterium atrosepticum-induced death of BY2 cells and soft rot on potato slices. CONCLUSIONS: New insights are thus provided into the interaction mechanisms between Streptomyces sp. and plants; Streptomyces sp. could be sensed by plant cells, and through cytosolic Ca(2+) changes and the generation of reactive oxygen species, defence responses were induced. SIGNIFICANCE AND IMPACT OF THE STUDY: These induced defence responses appeared to participate in attenuating Pectobacterium-induced diseases in plants. Thus, Streptomyces sp. OE7 could be a biocontrol agent against Pectobacterium sp.

Control of potato soft rot caused by Pectobacterium carotovorum and Pectobacterium atrosepticum by Moroccan actinobacteria isolates.

Pectobacterium carotovorum and Pectobacterium atrosepticum are dreadful causal agents of potato soft rot. Actually, there are no efficient bactericides used to protect potato against Pectobacterium spp. Biological control using actinobacteria could be an interesting approach to manage this disease. Thus, two hundred actinobacteria isolated from Moroccan habitats were tested for their ability to inhibit in vitro 4 environmental Pectobacterium strains and the two reference strains (P. carotovorum CFBP 5890 and P. atrosepticum CFBP 5889). Eight percent of these isolates were active against at least one of the tested pathogens and only 2% exhibited an antimicrobial activity against all tested Pectobacterium strains. Four bioactive isolates having the greatest pathogen inhibitory capabilities and classified as belonging to the genus Streptomyces species through 16S rDNA analysis were subsequently tested for their ability to reduce in vivo soft rot symptoms on potato slices of Bintje, Yukon Gold, Russet and Norland cultivars caused by the two pathogens P. carotovorum and P. atrosepticum. This test was carried out by using biomass inoculums and culture filtrate of the isolates as treatment. Among these, strain Streptomyces sp. OE7, reduced by 65-94% symptom severity caused by the two pathogens on potato slices. Streptomyces OE7 showed a potential for controlling soft rot on potato slices and could be useful in an integrated control program against potato soft rot pathogens in the objective to reduce treatments with chemical compounds.

Assessment of a sexual coercion prevention program for adolescents.

This study's focus is to evaluate a sexual coercion prevention program in adolescents. Using a before-and-after design with both a treatment group (n = 93) and a control group (n = 76), an intervention of seven sessions was completed. Said sessions included such content as conceptualizing sexual freedom, sexual coercion and voluntary consent, analyzing different sexual coercion tactics and the contexts in which they occur, empathy toward the victim, and developing abilities to avoid risky situations. Other risk factors for coercive behavior and sexual victimization are explored as well, such as alcohol use, sexist attitudes and inadequate communication, among others. The intervention's results include a decrease in stereotypical beliefs about the opposite sex and increased empathy toward victims of sexual coercion. These changes were maintained with the passage of time. Also, in the treatment group, a more acute decline was observed in the proportion of young people engaging in sexually coercive behaviors, This article emphasizes the importance, necessity and efficacy of such interventions, and discusses and analyzes possible improvements to the program for its future implementation.

The impact of insomnia disorder on adult attention-deficit/hyperactivity disorder severity: A six-month follow-up study.

BACKGROUND AND OBJECTIVES: The longitudinal relationship between insomnia disorder and adult attention-deficit/hyperactivity disorder (ADHD) has been scarcely investigated. This study aimed to evaluate the relationship between the remission of insomnia disorder and adult ADHD clinical severity, psychiatric and medical comorbidities, and the health-related quality of life (HRQoL) in a 6-month follow-up. METHODS: Ninety-two adult patients with ADHD and insomnia disorder (52.2% males; mean age 39.5 ± 11.0 years) were comprehensively assessed at baseline, 3 months, and 6 months of a follow-up period. The evaluation included semi-structured interviews (for ADHD and comorbidity assessment), the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale. The diagnosis of ADHD and insomnia disorder was performed according to DSM-5 criteria. At baseline and follow-up, psychoeducation/sleep hygiene and, if necessary, pharmacological were prescribed for insomnia. RESULTS: Eighty-seven patients completed the 6-month follow-up. Insomnia disorder remission was reported in 72.4% of cases and was related to a greater improvement in ADHD symptoms and severity throughout the follow-up period. Additionally, an improvement in psychiatric comorbidities and better HRQoL were associated with insomnia disorder remission. CONCLUSION: The current study highlights that the treatment of insomnia disorder in ADHD adult patients may have an important role in the outcome of ADHD therapeutic approaches by reducing their severity.

Clearance of Hepatitis C Virus Prior to Lung Transplantation: A Case Report.

Hepatitis C virus (HCV) continues to be considered a relative contraindication to lung transplantation due to concerns of progression of liver disease with the introduction of immunosuppression. Since the recent introduction of effective antiviral therapy for HCV, new approaches in the management of the HCV-positive recipient are being utilized in liver transplantation to clear HCV pre- and post-transplant. Herein, we report use of ledipasvir/sofosbuvir for HCV clearance prior to lung transplantation in a patient with usual interstitial pneumonia. Listing for transplant was delayed until completion of HCV treatment, and he subsequently required extracorporeal membrane oxygenation as a bridge to transplantation due to progressive hypoxia. With antiviral cure rates exceeding 90%, HCV should no longer be considered a relative contraindication to lung transplant, and timing of antiviral treatment should consider the progressive nature of the recipient's lung disease.

Primary hepatic carcinoid tumor: one Egyptian center experience.

BACKGROUND/AIMS: Carcinoid tumors of the liver are rare and pose both a diagnostic and therapeutic dilemma. Our aim was to study the diagnosis and treatment of primary hepatic carcinoid and to highlight its incidence in relation to hepatocellular carcinoma in our series and review of literature. METHODOLOGY: Between March 1992 and May 2005, we managed 5 patients (1 male, 4 females) with primary hepatic carcinoid in our center. RESULTS: The main presentation was upper abdominal pain with palpable mass, while in one patient tumor was discovered accidentally, none of them had carcinoid syndrome. The tumors were located in the left lobe in one patient, caudate lobe in two patients and right lobe in two patients. The diagnosis was confirmed histologically with light microscopy and immunohistochemistry. Four patients remain alive and disease free after follow-up of 72, 18, 16, and 4 months. One patient died after 11 years of follow-up with recurrence after 10 years, with mean follow-up of 45.2 +/- 53.1 months in May 2005. CONCLUSIONS: Primary hepatic carcinoid tumor is rare. It occurs on top of non-cirrhotic liver. Hepatic resection even in large-sized tumor is the treatment of choice.

High frequency of chromosome 9p allelic loss and CDKN2 tumor suppressor gene alterations in squamous cell carcinoma of the bladder.

BACKGROUND: In the Western Hemisphere, 90% of bladder cancers are transitional cell carcinomas, while only 7% are classified as squamous cell carcinomas. In contrast, in Egypt and regions of the Middle East and Africa, where infection by the trematode Schistosoma haematobium is endemic, squamous cell carcinoma is the most common bladder cancer as well as the most common cancer in men. PURPOSE: We planned experiments to understand the genetic defects underlying the development of squamous cell carcinoma and to determine if the morphologically and clinically distinct squamous cell carcinoma and transitional cell carcinoma of the bladder evolve following different genetic alterations. METHODS: Squamous cell carcinoma specimens from high-risk (Egypt, n = 19) and low-risk (Sweden, n = 12) populations were examined for genetic defects known to be involved in transitional cell carcinoma tumorigenesis. Homozygous deletions of the CDKN2 tumor suppressor gene were detected by comparative multiplex polymerase chain reaction. Mutations in the CDKN2 and p53 (also known as TP53) genes were analyzed by single-strand conformation polymorphism and DNA sequencing. Immunohistochemical staining of p53 protein was also performed. Allelic losses in chromosome arms 9p, 9q, and 17p were determined by microsatellite analysis. RESULTS: Homozygous deletions and sequence mutations in the CDKN2 gene were found in 67% (eight of 12) of squamous cell carcinoma specimens, a frequency three times higher than that reported for uncultured transitional cell carcinomas (P = .009). Hemizygous and homozygous deletions in 9p, where CDKN2 resides, were found in 92% (11 of 12) of uncultured squamous cell carcinomas, while only about 39% (35 of 90) of transitional cell carcinomas showed these losses (P = .001). Deletions in 9p with no change in 9q were found in 92% (10 of 11) of squamous cell carcinomas compared with only 10% (11 of 110) of transitional cell carcinomas (P < .001) reported in the literature. The frequency of p53 mutations in squamous cell carcinomas was similar to that reported for invasive transitional cell carcinomas (60%), but the type and position of mutations differed between the two tumor types. Allelic losses in chromosome arm 17p, where the p53 gene resides, were found to be less frequent in squamous cell carcinomas (38%) than in invasive transitional cell carcinomas (60%). CONCLUSIONS: Our results suggest that a putative tumor suppressor gene on 9p, possibly CDKN2, may contribute to squamous cell carcinoma tumorigenesis. Our data on squamous cell carcinoma and previously reported data on transitional cell carcinoma indicate that these two bladder carcinomas differ in their genetic alterations, suggesting that distinct underlying genetic defects may explain, at least in part, the pathological differences between the two tumors of the bladder epithelium. IMPLICATIONS: Development of diagnostic and therapeutic strategies for squamous cell carcinoma of the bladder based on its distinct genetic alterations is warranted.

High-resolution NMR studies of transmembrane cation transport in uremic patients.

Cation transport in erythrocytes of some uremic patients is impaired. Most studies have focused on the defect of the erythrocyte Na+/K+ pump in these diseased states. Herein, this cation transport defect was studied by using nuclear magnetic resonance spectroscopy (NMR) which is a non-invasive method permitting study on living erythrocytes. Firstly, we verified that the Na+ transport defect in uremic erythrocytes was not due to non-specific causes such as membrane alteration or a modification of the intracellular metabolism. The proton relaxation data, determined using a paramagnetic doping method, are consistent with a lack of erythrocytic membrane damage in uremic patients. Also, 31P-NMR results showed that in our experimental conditions, uremic and normal erythrocytes exhibit similar variations of ATP level over time. Lastly, the use of anionic paramagnetic shift reagent in 23Na-NMR revealed a defect in the Na+/K+ pump of erythrocytes from uremic patients with high Nain concentration. This defect seems to be due to a reduced number of pump units and to the presence of an endogenous inhibitor in uremic plasma.

Clinical and bacteriological efficacy of 5-day telithromycin in acute maxillary sinusitis: a pooled analysis.

OBJECTIVES: To compare the efficacy and tolerability of a 5-day course of telithromycin (800 mg once daily) with a 10-day course of telithromycin or standard comparators (amoxicillin-clavulanate 500/125 mg three times daily or cefuroxime axetil 250 mg twice daily) in patients with acute maxillary sinusitis (AMS). METHODS: Data from three randomised double blind studies were pooled. The studies included patients with clinical symptoms of AMS and sinus X-ray findings of total opacity, air-fluid levels or mucosal thickening. RESULTS: Pooled analysis of results for 5-day telithromycin revealed overall clinical cure rates of 83.6% (383/458 patients) at post-therapy (days 17-24) and 78.9% (330/418 patients) at late post-therapy (days 31-45) in the per-protocol population. Clinical cure rates at post-therapy were equivalent to those observed with 10-day telithromycin (82.5% vs 81.7%) or comparator treatment (80.9% vs 77.4%). Moreover, clinical cure rates exceeded 80% in subgroups of patients of interest, including those with severe infection and those fulfilling more stringent criteria for bacterial AMS. A satisfactory bacteriological outcome was achieved in 87.6% of patients. The 5-day telithromycin regimen was well tolerated. CONCLUSIONS: Telithromycin once daily for 5 days offers effective treatment for AMS and is comparable to 10-day courses of standard treatments.

[Epidemiology of hepatocellular carcinoma in a rural area. Role of hepatotrophic viruses on survival]. / Epidemiología del carcinoma hepatocelular en un área rural. Papel de los virus hepatotropos en la supervivencia.

BACKGROUND: Chronic hepatitis C and B are the main causes of hepatocellular carcinoma (HCC) worldwide. It is not clear whether chronic hepatitis C or B virus (HCV or HBV) infection is a prognostic factor for HCC. This study aimed to asses epidemiology of HCC in a rural area and to determine if chronic HCV or HBV infection had any impact on survival after the diagnosis of HCC. MATERIAL AND METHODS: Fifty-one consecutive patients were retrospectively studied. All of them were diagnosed of HCC between january 1994 and december 2002 in a First Level Hospital. The following variables were analysed: age, sex, HCV and HBV infection, chronic alcohol abuse (daily intake upper 80 g), clinical presentation, Child stage, number ol liver nodules, therapeutic options and survival. RESULTS: The mean age at diagnosis of HCC was 68,5 years old (age range 45-90) and 45 patients (88,6%) were male. Heavy alcohol intake (66%) and chronic HCV infection (42,8%) were the most prevalent etiologic factors. Chronic HBV was found in 11,9%. Chronic HCV or HBV infection was present in 48,9%. Twenty-five percent were asymptomatic and 66% were in Child stage A. The rate single lesion / multilobular HCC was 52/48. Only 6% of all patients could be treated with a curative intention. The mean survival was 10,9 +/- 9,1 months, and there were no differences in age, sex, Child stage and number of nodules. There was a significantly higher survival in patients with chronic HCV or HBV infection (16,7 +/- 13,1 months versus 4,75 +/- 5,3 months in seronegative patients; p=0.02). On multivariate analysis, only chronic HCV or HBV infection was associated with survival longer than 10 months (OR 22,3; CI 95% 1,8-277,9). CONCLUSIONS: In our area, heavy alcohol abuse and HCV infection were the most prevalent etiologic factors of HCC. Chronic HCV or HBV infection was associated with longer survival in patients with HCC.

Fungal infections in lung and heart-lung transplant recipients. Report of 9 cases and review of the literature.

We reviewed the pattern and incidence of fungal infections in patients undergoing lung and heart-lung transplantation at Duke University Medical Center from September 1992 until August 1995, and present here 9 illustrative cases. Of the 73 lung and heart-lung transplant recipients studied, 59 (81%) had positive fungal cultures at some point after transplantation. The cases presented here illustrate that lung transplant recipients are predisposed to a wide variety of fungal infections. The clinical pattern of these infections ranges from asymptomatic to rapidly progressive fatal disease. In addition to the reactivation of previous fungal infections and recent exposure to new environmental sources, the donor lung itself can be the source of fungal infection, as we showed by using molecular epidemiology techniques. Because of the associated morbidity and mortality, efforts should be directed at investigating prophylactic antifungal regimens in lung transplant recipients. Preliminary reports on the use of itraconazole and aerosolized amphotericin B have been encouraging. Prospective randomized studies are needed to assess the safety and cost effectiveness of different regimens. Fungal infections in patients after lung transplantation can significantly impede recovery and lead to substantial mortality.

Susceptibility of lung transplants to preformed donor-specific HLA antibodies as detected by flow cytometry.

BACKGROUND: Preformed anti-HLA antibodies are known to have the potential to induce early graft damage in organ transplant recipients. However, in lung transplant recipients, little information exists about the significance of preformed antibodies directed to either class I or class II HLA antigens. METHODS: A two-color flow cytometry cross-match was performed in 92 consecutive lung transplant recipients using serum obtained immediately before transplantation. The presence of preformed antibodies was correlated with the incidence of severe graft dysfunction manifested as pulmonary infiltrates and severe hypoxemia with onset in the first few hours after transplantation. RESULTS: Six patients (6.5%) had low-level anti-donor IgG antibodies detected by flow cytometry, four against T and two against B lymphocytes. Three patients (50%) developed severe graft dysfunction with pulmonary infiltrates and hypoxemia. Two patients responded to treatment, but the third, who had an antibody highly specific for HLA-DR11, died at 48 hr after transplant. Results of histopathologic studies in this patient are consistent with hyperacute rejection and support a pathogenic role of these antibodies. In contrast, of 86 (93.5%) cases with a negative flow cytometry cross-match, only 4 (5%) had severe but reversible early graft dysfunction with pulmonary infiltrates and hypoxemia, attributed to ischemia-reperfusion injury (P<0.005). CONCLUSIONS: Class II, and perhaps class I HLA antibodies at relatively low concentrations represent a risk factor for severe early pulmonary graft dysfunction, with the potential to progress to hyperacute rejection and death.

Results of a randomized, prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection.

BACKGROUND: Although the use of mycophenolate mofetil (MMF) has reduced the incidence of acute rejection in heart and kidney allograft recipients, its role in lung transplantation remains controversial. Therefore, we conducted a randomized, prospective, open-label, multicenter study in lung transplant recipients to determine whether MMF decreases episodes of acute allograft rejection when compared with azathioprine (AZA). METHODS: Between March of 1997 and January of 1999, 81 consecutive lung transplant recipients from two centers were prospectively randomized to receive cyclosporine, corticosteroids, and either 2 mg/kg per day of AZA or 1 g twice daily of MMF. The primary study endpoint was biopsy-proven acute allograft rejection over the first 6 months posttransplant. Secondary endpoints included clinical rejection, cytomegalovirus (CMV) infection, adverse events, and survival. Surveillance bronchoscopies were performed at 1, 3, and 6 months, or if clinically indicated. Pathologists interpreting the biopsy results were blinded to the randomization. Results were analyzed according to intention-to-treat. Between group comparisons of means and proportions were made by using two sample t tests and Fisher's exact tests, respectively. Six-month survival was calculated by the Kaplan-Meier method and compared by the log rank test. RESULTS: Thirty-eight patients were prospectively randomized to receive AZA, and 43 MMF. The incidence of biopsy proven grade II or greater acute allograft rejection at 6 months was 58% in the AZA group and 63% in the MMF group (P=0.82). The 6-month survival rates in the MMF and AZA groups were 86% and 82%, respectively (P=0.57). Rates of CMV infection and adverse events were not significantly different between the two groups. CONCLUSIONS: Acute rejection rates and overall survival at 6 months are similar in lung transplant recipients treated with either MMF- or AZA-based immunosuppression.