Levels of IgE sensitization drive symptom thresholds in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common respiratory disease encompassing a variety of phenotypes. Patients can be sensitized to 1 or more allergens. There are indications that polysensitization is associated with more severe disease. However, the extent to which the level of sensitization is associated with clinical disease variability, underlying the distinct nature of AR from AR+ conjunctivitis or AR+ asthma, is not known. OBJECTIVE: To evaluate phenotypical differences between monosensitized and polysensitized patients with AR and to quantify their symptomatic variability. METHODS: A total of 565 patients with a confirmed diagnosis of AR were included in this cross-sectional study. Of those, 155 were monosensitized and 410 were polysensitized. Interactions between sensitization levels and the reporting of different symptoms of AR and co-morbidities, disease duration, and impact were assessed. Furthermore, patients were stratified into monosensitized, oligosensitized, and polysensitized to assess whether the effect of sensitization on the phenotype was ranked. RESULTS: Polysensitized patients reported itchy eyes significantly more often (P = .001) and had a higher number of ocular (P = .005), itch-related (P = .036), and total symptoms (P = .007) than monosensitized patients. In addition, polysensitized adults and children more often reported wheeze (P = .015) and throat-clearing (P = .04), respectively. Polysensitization was associated with more burdensome AR based on a visual analog scale (P = .005). Increased sensitization level was reflected in more itchy eyes, a higher number of ocular, itch-related, and total number of symptoms, and disease burden. CONCLUSION: With an increasing number of sensitizations, patients with AR experience an increased diversity of symptoms. Multimorbidity-related symptoms increase with sensitization rank, suggesting organ-specific thresholds.

Everolimus with or without mycophenolate mofetil in a liver transplantation setting: a single-center experience.

BACKGROUND: This study evaluated the efficacy, safety, and impact on renal function of everolimus in patients after liver transplantation (LT) with or without mycophenolate mofetil (MMF). METHODS: We evaluated LT recipients with calcineurin inhibitor (CNI)-related renal dysfunction after everolimus initiation. Laboratory data, including evaluation of renal function based on glomerular filtration rate (GFR) at baseline (i.e., everolimus initiation) and at the end of follow up, were analyzed. RESULTS: Fifty consecutive patients started taking everolimus at 30 months post-LT (range: 1-240), 6 as monotherapy and 44 in combination with MMF. After 30.5 months (range: 6-112), all patients were alive, without any biochemical evidence of a rejection episode or recurrence of hepatocellular carcinoma. The mean GFR, based on the Modification of Diet in Renal Disease equation, was 53±13 mL/min at baseline and 59±12 mL/min at the end of follow up (P=0.031). Eleven (22%) of the patients had GFR <60 mL/min at baseline but returned to GFR >60 mL/min by the end of follow up. In multivariate analysis, the time between the development of renal dysfunction and everolimus initiation was the only factor independently associated with GFR improvement (odds ratio [OR] 0.85, 95% confidence interval [95%CI] 0.76-0.96; P=0.007). Everolimus was stopped in 11 patients (22%) at the end of follow up because of adverse events. CONCLUSION: A CNI-free everolimus-based regimen was effective in LT recipients with renal dysfunction and was associated with an improvement in GFR.

Epidemiological surveillance of multidrug-resistant gram-negative bacteria in a solid organ transplantation department.

BACKGROUND: We assessed the impact of intensified infection control measures (ICM) on colonization and infection caused by carbapenem-resistant (CR) Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii in a solid organ transplantation (SOT) department. METHODS: A quasi-experimental methodology was followed. The study was divided into three periods: pre-intervention, intervention with implementation of an ICM bundle including active surveillance program (ASP) and gradually enhanced measures, and post-ASP without ASP. The bundle included active surveillance cultures, contact precautions, hand hygiene, education of health care workers (HCWs), monitoring of compliance, and environmental cleaning. Incidence of colonization and infection caused by CR gram-negative bacteria was recorded. Molecular analysis of CR bacteria was performed for a certain period. RESULTS: During the intervention, incidence of colonization reduced from 19% to 9% (P<.001). The compliance of HCWs with contact precautions and hand hygiene also improved. Monthly incidence of infections caused by these CR bacteria increased from 2.8 to 6.9/1000 bed-days (P<.001). However, this increase did not have such a strong trend after the intervention. Most K. pneumoniae isolates, the commonest pathogen, carried the blaKPC gene. Colonization and infection rates by CR K. pneumoniae, P. aeruginosa, and A. baumannii were high among SOT recipients. CONCLUSION: In settings where CR gram-negative bacteria are endemic, colonization and infection rates by these bacteria are high among SOT recipients. Implementation of enhanced ICM in all related units of a hospital, although challenging, reduces colonization rates by CR gram-negative bacteria.

Long-term outcome of pediatric kidney transplantation: A single-center experience from Greece.

Pediatric kidney Tx has critically altered the outcome in ESRD pediatric patients. The aims of this study were to determine long-term graft and patient survival in a homogeneous ethnic population. We reviewed the medical charts of pediatric kidney Tx performed between 1990 and 2012 in Greece. Seventy-five kidney Txs were performed from LRD and 62 from DD. The 10- and 20-yr graft survival was higher in LRD Tx compared with DD Tx. Both patient and graft survival at 10 and 20 yr after Tx were similar in LRD Tx from grandparents compared with parents (92.9% vs. 93.4% 20-yr patient survival, 71.4% vs. 78.7% and 57.1% vs. 72.1%, 10- and 20-yr graft survival, respectively). However, there was a decreasing tendency in LRD Tx rates in period 2001-2012 compared with period 1990-2000 (47.1% vs. 62.7%). Risk factors for poor five-yr graft survival were DD Tx, and induction treatment with ALG compared with basiliximab, but their effect attenuated at 10 yr after Tx. In conclusion, Tx from LRD may offer efficient survival outcomes irrespective of donor age, suggesting that even older LRD could be an excellent option for the 1st kidney Tx in children and adolescents.

Interleukin 18 binding protein ameliorates ischemia/reperfusion-induced hepatic injury in mice.

Inflammation-associated oxidative stress contributes to hepatic ischemia/reperfusion injury (IRI). Detrimental inflammatory event cascades largely depend on activated Kupffer cells (KCs) and neutrophils, as well as proinflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL) 18. The aim of our study was to evaluate the effects of IL 18 binding protein (IL 18Bp) in hepatic IRI of mice. Thirty C57BL/6 mice were allocated into 3 groups: sham operation, ischemia/reperfusion (I/R), and I/R with intravenous administration of IL 18Bp. Hepatic ischemia was induced for 30 minutes by Pringle's maneuver. After 120 minutes of reperfusion, mice were euthanized, and the liver and blood samples were collected for histological, immunohistochemical, molecular, and biochemical analyses. I/R injury induced the typical liver pathology and upregulated IL-18 expression in the liver of mice. Binding of IL 18 with IL 18Bp significantly reduced the histopathological indices of I/R liver injury and KC apoptosis. The I/R-induced increase of TNF-α, malondialdehyde, aspartate aminotransferase, and alanine aminotransferase levels was prevented in statistically significant levels because of the pretreatment with IL 18Bp. Likewise, blocking of IL 18 ablated the I/R-associated elevation of nuclear factor kappa B, c-Jun, myeloperoxidase, and IL 32 and the up-regulation of neutrophils and T-helper lymphocytes. Administration of IL 18Bp protects the mice liver from I/R injury by intervening in critical inflammation-associated pathways and KC apoptosis.

New nucleos(t)ide analogue monoprophylaxis after cessation of hepatitis B immunoglobulin is effective against hepatitis B recurrence.

New nucleos(t)ide agents (NAs) [entecavir (ETV) and tenofovir (TDF)] have made hepatitis B immunoglobulin (HBIG)-sparing protocols an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). Twenty-eight patients transplanted for HBV cirrhosis in our centre were prospectively evaluated. After LT, each patient received HBIG (1000 IU IM/day for 7 days and then monthly for 6 months) plus ETV or TDF and then continued with ETV or TDF monoprophylaxis. All patients had undetectable HBV DNA at the time of LT, and they were followed up with laboratory tests including glomerular filtration rate (GFR) after LT. All patients (11 under ETV and 17 under TDF) remained HBsAg/HBV DNA negative during the follow-up period [median: 21 (range 9-43) months]. GFR was not different between TDF and ETV groups of patients at 6 and 12 months and last follow-up (P value >0.05 for all comparisons). The two groups of patients were similar regarding their ratio of maximum rate of tubular phosphate reabsorption to the GFR (TmP/GFR). In conclusion, in this prospective study, we showed for the first time that maintenance therapy with ETV or TDF monoprophylaxis after 6 months of low-dose HBIG plus ETV or TDF after LT is highly effective and safe.

Everolimus-based immunosuppression in liver transplant recipients: a single-centre experience.

PURPOSE: Everolimus, a mammalian target of rapamycin inhibitor, has been shown to reduce growth factor-mediated cell proliferation, but data regarding its effectiveness and impact on renal function and recurrence of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients are limited. METHODS: We evaluated LT recipients with a calcineurin inhibitor (CNI)-based immunosuppression regimen in whom everolimus treatment was initiated. The changes in laboratory data, including glomerular filtration rate (GFR), compared to the baseline (i.e. the day of everolimus conversion), were assessed. RESULTS: Totally, 44 consecutive patients (32 men, age 55 ± 7 years) were commenced on everolimus [indications: renal dysfunction post-LT (16 patients, group 1); prevention of HCC recurrence (21 patients) or others (7 patients), group 2] at 6 months (range 1-206) post-LT. After 48 (range 12-76) months, all patients were alive without any rejection episodes. Compared to group 2 patients, group 1 patients had significantly greater improvement in renal function (DGFR: 12 ± 5 vs. -0.4 ± 0.2 ml/min, p = 0.02). GFR at baseline (OR 0.08, p = 0.002) and the combination of everolimus + MMF (OR 0.14, p = 0.024) were the factors independently associated with improvement in renal function. Finally, HCC recurrence was observed less frequently in the everolimus group of patients (n = 21) compared to the CNI-historical control group (n = 22) with HCC before LT [0/21 (0 %) vs. 4/22 (18.5 %), log rank p = 0.055), although the two groups of recipients had similar baseline characteristics and follow-up. CONCLUSIONS: Everolimus is effective and is associated with low rates of HCC recurrence and improvement of renal function in LT recipients.

HCC influence on patient survival after liver transplantation for HDV cirrhosis.

BACKGROUND/AIMS: The effect of hepatocellular cancer (HCC) in patients transplanted for hepatitis B and D virus (HB/DV) cirrhosis is not well studied. Our aim was to study the long-term survival outcomes of patients who underwent liver transplantation for HB/DV cirrhosis with and without HCC. METHODOLOGY: A total of 231 primary, adult, single- organ liver transplants were performed from 1990 to 2007. HB/DV was the cause of cirrhosis in 36 patients. Nine patients died during the first 3 postoperative months from surgical complications. The study group comprised the remaining 27 patients. The median follow-up was 1515 days. RESULTS: The mean patient survival was 3760 days (95% CI: 3013-4507). Six patients were diagnosed with HCC. The mean patient survival was 3011 days (95% CI: 2344-3679) and 4036 days (95% CI: 3002-5070) for recipients without and with HCC, respectively. For the same groups, the incidence of microbial infections was 61.9% and 33.3%, respectively (p=0.219). HCC has not recurred in any of the six patients. CONCLUSIONS: The mean long-term survival after liver transplantation for HB/DV and HCC surpassed 11 years. The superior survival of HCC patients is difficult to explain. The increased number (almost double) of microbial infections in the non- HCC population might be held accountable.

Successful, combined long-term treatment of cerebral aspergillosis in a liver transplant patient.

Invasive aspergillosis has long been recognized as one of the most significant and often fatal opportunistic fungal infections in liver transplant recipients. We report a case of a liver transplant recipient who developed an Aspergillus fumigatus brain abscess that produced significant neurologic symptoms. The patient was managed successfully with a combination of surgery and medical treatment with Voriconazole. To our knowledge, this is the second such case reported in the literature.

Attenuation of liver ischemia/reperfusion induced apoptosis by epigallocatechin-3-gallate via down-regulation of NF-kappaB and c-Jun expression.

INTRODUCTION: Hepatic ischemia/reperfusion (I/R) activates Kupffer cells and initiates severe oxidative stress with enhanced production of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha). ROS and TNF-alpha mediate the expression of nuclear factors and kinases, activating the signal transduction pathway, and triggering apoptosis. The aim of our study was to evaluate the potential protective effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kappaB, c-Jun, and caspase-3 in a model of severe hepatic I/R. MATERIALS AND METHODS: Thirty Wistar rats were allocated into three groups. Sham operation, I/R, and I/R-EGCG 50mg/kg. Hepatic ischemia was induced for 60min by Pringle's maneuver. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, scanning electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry for NF-kappaB, c-Jun, caspase-3, analysis on liver specimens and aspartate (AST), and alanine (ALT) transferases analysis in serum, were performed 120min after reperfusion. RESULTS: Apoptosis as indicated by TUNEL and caspase-3 was widely expressed in the I/R group but very limited in the EGCG treated group. Liver was stained positive for NF-kappaB and c-Jun in the I/R group but failed to be stained positive in the EGCG treated group. MDA, MPO, AST, and ALT showed marked increase in the I/R group and significant decrease in EGCG treated group. Significant alterations of liver specimens were observed by light histology and transmission electron microscopy whilst pretreatment with EGCG resulted in parenchymal preservation. CONCLUSIONS: Administration of EGCG is likely to inhibit I/R-induced apoptosis and protect liver by down-regulating NF-kappaB and c-Jun signal transduction pathways.

The natural history of vascular access for hemodialysis: a single center study of 2,422 patients.

BACKGROUND: Our objective is to provide provision of primary and secondary patency rates data and incidence of complications. Despite the publication of some review articles and small prospective trials about vascular accesses, controversy still exists regarding the choice of the outflow conduit and especially the choice of the fistula to be formed in secondary and tertiary access procedures. METHODS: This is a retrospective study of 2,422 consecutive patients who underwent 3,685 vascular access procedures in a tertiary care hospital, including radial-cephalic (RCAVF), brachial-cephalic (BCAVF), brachial-basilic (BBAVF), and prosthetic graft (PTFE) fistulas. Maximum follow-up period was 20 years. Actuarial patency rates were obtained by Kaplan-Meier analysis. RESULTS: The median primary patency (days) of the most common 1st choices for vascular access were 712 (95% CI: 606, 818), 1,009 (95% CI: 823, 1,195), and 384 (95% CI: 273, 945) days for RCAVF, BCAVF, and PTFE, respectively. The median secondary patency was 1809 days (95% CI: 1,692, 1,926) for the RCAVF. The median primary patency of BBAVF (2nd or 3rd choice for vascular access) was 1,582 days (95% CI: 415, 2,749). The cumulative incidence of clinically important complications for the patients who received a RCAVF, BCAVF, BBAVF, and u-PTFE was 0.25, 0.57, 0.33, and 0.61 per patient-year, respectively. CONCLUSION: We advocate maximal use of autogenous conduits, except probably the case of the older diabetic patient, in whom access at the antecubital fossa should be the first choice. BBAVF is an excellent fistula and should probably be constructed before prosthetic graft placement.

Inhibition of intestinal ischemia/repurfusion induced apoptosis and necrosis via down-regulation of the NF-kB, c-Jun and caspace-3 expression by epigallocatechin-3-gallate administration.

Intestinal ischemia/reperfusion (I/R) produces reactive oxygen species (ROS) activating signal transduction and apoptosis. The aim of this study was to evaluate the effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kB, c-Jun and caspace-3 in intestinal I/R. Thirty male wistar rats were used. Group A sham operation, B I/R, C I/R-EGCG 50 mg/kg ip. Intestinal ischemia was induced for 60 min by clamping the superior mesenteric artery. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, Fragment End Labelling of DNA (TUNEL), immunocytochemistry for NF-kB, c-Jun and caspace-3 analysis in intestinal specimens were performed 120 min after reperfusion. Apoptosis as indicated by TUNEL and Caspace-3, NF-kB and c-Jun was widely expressed in I/R group but only slightly expressed in EGCG treated groups. MDA and MPO showed a marked increase in the I/R group and a significant decrease in the EGCG treated group. Light histology showed preservation of architecture in the EGCG treated group. In conclusion, EGCG pre-treatment is likely to inhibit intestinal I/R-induced apoptosis by down-regulating the expression of NF-kB, c-Jun and caspase-3.

Papillomatosis of intra- and extrahepatic biliary tree: Successful treatment with liver transplantation.

Approximately 60 cases of biliary papillomatosis have been reported in the world literature, while only 6 cases have been reported to be treated with liver transplantation. This rare disease, which is characterized by relapsing episodes of obstructive jaundice and cholangitis that lead to secondary cirrhosis and death from sepsis or liver failure, it is also considered premalignant because of its frequent malignant transformation (25-50%). We present a case of a 43-year-old white man with papillomatosis of intra- and extrahepatic biliary tree who sought care for repeated episodes of obstructive jaundice and cholangitis. The diagnosis was suspected after endoscopic retrograde cholangiopancreatography and confirmed by liver and common bile duct biopsies. The patient underwent orthotopic liver transplantation with Roux-en-Y hepatico-jejunostomy to treat end-stage liver cirrhosis. Fifteen months' follow-up revealed a patient with normal graft function and with no clinically or laboratory findings of disease recurrence or cancer development.

Living-related transplantation of an ectopic pelvic kidney.

Ectopic kidneys are usually contraindicated for transplantation as a result of anomalous vascular and drainage system. Graft shortage increases the need of expanding the donor pool and the use of ectopic pelvic kidneys might provide a small but useful source. Transplantation of an ectopic pelvic kidney is a technically demanding procedure and very few cases have been published. We present a case of a living-related kidney transplantation of an ectopic pelvic kidney. The donor was a healthy 65-year-old lady and preoperative work-up had showed a left ectopic pelvic kidney. The recipient was a 34-year-old male with a history of end-stage renal disease secondary to chronic glomerulonephritis. After the transplantation, there was an immediate function of the allograft and the donor's postoperative course was uneventful. The donor was discharged on the fifth postoperative day.

The protective effect of alpha-tocopherol and GdCl3 against hepatic ischemia/reperfusion injury.

PURPOSE: To evaluate the combined effect of alpha-tocopherol and gadolinium chloride (GdCl3) in reducing lipid peroxidation after severe hepatic ischemia/reperfusion (IR) injury. METHODS: Sixty male Wistar rats, 200-250 g, were randomly divided into six equal groups. There were two sham operation (SHAM) groups, two untreated IR groups, and two IR groups treated with GdCl3 and alpha-tocopherol (IRGT). After 60 min of total hepatic ischemia and 120 min reperfusion, one of each group was killed, liver samples were taken for malondialdehyde (MDA) and myeloperoxidase (MPO) analysis and light microscopy examination, and blood samples were analyzed for aspartate (AST) and alanine (ALT) transaminase, lactate dehydrogenase (LDH), and alpha-tocopherol content. The remaining groups were monitored for survival rate determination. RESULTS: The mean MDA and MPO values in the SHAM, IR, and IRGT groups, respectively, were 1.117, 1.476, and 0.978 nmol/g wet tissue and 1.49, 6.26, and 1.78 (U/g). The mean alpha-tocopherol values in the SHAM, IR, and IRGT groups, respectively, were 10.4, 1.9, and 12 micromol/l. The mean serum AST, ALT, and LDH values were significantly higher in the IR group than in the SHAM group (P < 0.001), and significantly lower in the IRGT group than in the IR group (P < 0.001). Light microscopy examination revealed more severe congestion and vacuolization in the IR group than in the SHAM group, and minimal congestion and vacuolization in the IRGT group. Survival was significantly higher in the IRGT group than in the IR group. CONCLUSION: The administration of GdCl3 and alpha-tocopherol is likely to protect the liver against lipid peroxidation by suppressing Kupffer cell and polymorphonuclear leukocyte activation and enhancing endogenous antioxidant activity.

Mycophenolate mofetil impairs the integrity of colonic anastomosis.

BACKGROUND: The aim of this experimental study was to investigate the effect of mycophenolate mofetil (MMF) during the three phases of colonic anastomosis healing and specifically to check the effect of MMF on the expression of transforming growth factor-beta1 (TGF-beta1), one of the most important growth factors contributing to mechanical stability of colonic anastomosis. MATERIALS AND METHODS: Sixty male Wistar rats underwent colonic resection and end-to-end anastomosis. The animals were divided into two groups, a study group given MMF 40 mg/kg, intraduodenally and a control group given vehicle. The rats were sacrificed at 3, 7, and 14 days (10 animals in each group). The anastomoses were tested by measuring bursting pressure and hydroxyproline content. Histological examination and immunohistochemical expression of TGF-beta1 also were assessed. RESULTS: The mean bursting pressure in the study group was significantly lower on day 3 and 7, but there was no statistical significance on day 14. The mean hydroxyproline content was lower in the study group on days 3, 7, and 14. Histology showed decreased number of macrophages and fibroblasts on days 3 and 7 but no difference on day 14. The expression of TGF-beta1 was significantly reduced in the study group, with the difference being more pronounced on days 3 and 7. CONCLUSION: MMF weakens the integrity of colonic anastomosis, and this effect is more significant during the inflammatory phase of healing. MMF has a negative effect on macrophages and TGF-beta1 expression, resulting in decreased collagen accumulation at the anastomosis.