Pretransplant survival is shorter in HIV-positive than HIV-negative subjects with end-stage liver disease.

Despite improved survival after liver transplantation (OLTX) in HIV-positive individuals treated with highly active antiretroviral therapy (HAART), some transplant candidates do not survive to OLTX. To determine if pretransplant outcome is related to severity of liver disease and/or HIV infection, we prospectively evaluated 58 consecutive HIV-positive candidates seen at a single center from 1997-2002. Of the 58, 15 (25.9%) were transplanted, whereas 21 (36.2%) died before OLTX, a median one month of evaluation, with more than half of those (12 of 21, 57.1%) dying from infection. By contrast, of 1,359 HIV-negative candidates, 860 (63.3%) were transplanted, whereas 211 (15.5%) died before OLTX (P < 0.001). The cumulative survival following initial evaluation was significantly shorter among HIV-positive than HIV-negative candidates (880 vs. 1,427 days, P = 0.035, Breslow) but was not related to the initial pretransplant MELD score (16 vs. 15), INR (1.5 vs. 1.5), creatinine (1.3 vs. 1.3 mg/dL), or total bilirubin (6.6 vs. 5.7 mg/dL), respectively, all P > 0.05. Among untransplanted HIV-positive candidates, the 21 who died did not differ from the 22 surviving in initial MELD (15 vs. 13), CD4 (230 vs. 327/microL), HIV load (both < 400 copies/mL), HAART intolerance (10/21, 47.6% vs. 10/22, 45.4%), or HCV infection (16/21, 76.2% vs. 16/22, 72.3%), all P > 0.05. Further, the 21 did not differ from the 15 transplanted in pre-OLTX CD4, HIV load, or MELD score, all P > 0.05. In conclusion, pretransplant survival appears shorter in HIV-positive OLTX candidates and is unrelated to severity of liver or HIV disease. Further study is warranted to determine risk factors for poorer pretransplant outcomes.     

Immunosuppression in liver transplantation: beyond calcineurin inhibitors.

Although calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression in liver transplantation (LTX), their long-term toxicity significantly contributes to morbidity and mortality. The elucidation of mechanisms of alloimmunity and leukocyte migration have provided novel targets for immunosuppression development. The toxicities of these agents differ from that of the CNI and act additively or synergistically. CNI avoidance protocols in LTX have not been achieved routinely; however, pilot trials have begun to delineate the limitations and promises of such approaches. CNI-sparing protocols appear to be much more promising in balancing the early need for minimizing rejection while tapering doses and minimizing long-term toxicity.     

Four-color flow cytometric analysis of peripheral blood donor cell chimerism

Passenger leukocytes have been demonstrated to play significant roles in initiating and also regulating immune reactions after organ transplantation. Reliable techniques to detect donor leukocytes in recipients after organ transplantation are essential to analyze the role, function, and behavior of these leukocytes. In this report we describe a simple, reliable method to detect donor cells with low frequencies using peripheral blood samples. Detection of small numbers of major histocompatibility complex (MHC) mismatched cells was first studied using four-color flow cytometry in artificially created cell mixtures. By selecting the CD45(+) population and simultaneous staining with several leukocyte lineage markers (CD3, CD4, CD8, CD56, and CD19), MHC-mismatched leukocytes were consistently detected in cell suspensions prepared from directly stained whole blood samples with a threshold sensitivity as low as 0.1%-0.2%. When the fresh peripheral blood mononuclear cells were separated by conventional Ficoll gradient purification, similar, but slightly lower levels of donor cells were detected. Blood samples obtained 1-5 months after liver, kidney, and intestine transplants revealed that the kind of organ allograft influenced levels and lineage pattern of the circulating donor cells. This procedure provided a simple and reliable method in determining early chimerism in transplant recipients. However, the detection of MHC-mismatched leukocytes of all lineages was much lower when frozen peripheral blood mononuclear cells were used.     

Expression of MHC class I heavy chain and beta2-microglobulin in rat brainstem motoneurons and nigral dopaminergic neurons

We demonstrate here that motoneurons and nigral dopaminergic neurons in the brainstem of the adult rat, with the exception of motoneurons innervating ocular muscles, display high levels of both MHC class I heavy chain and beta2-microglobulin mRNAs. These neurons also display interferon-gamma receptor mRNA. We find it striking that these particular neurons are those which are vulnerable to neurodegeneration in diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).     

Pancreatitis after liver transplantation in children: a single-center experience

BACKGROUND AND METHOD: Posttransplantation acute pancreatitis (PTAP) is a rare but serious complication after pediatric liver transplantation (LTx). We performed a retrospective review in a large cohort of pediatric liver transplant recipients at a single institution to define the impact of this problem in children. RESULTS: Between January 1986 and December 1999, 634 pediatric LTx were performed. Twenty-six patients developed serious acute pancreatitis. The mean age at transplantation was 7.7 years (9 months to 19 years), and the indications for transplantation were biliary atresia in seven, fulminant hepatic failure in six, chronic rejection in seven, and other etiologies in six patients. PTAP was more likely to occur early after LTx (61% within the first week), was associated with the presence of an infrarenal aortic graft in 14 (54%) of 26 patients, was more likely to occur after retransplantation (11/26 patients), and was associated with blood loss and prolonged surgery in four cases. Acute renal failure occurred in 15 (58%) of 26 patients. Mortality was 42% (11/26); causes of death were sepsis or multiple organ failure in nine and hemorrhage in two patients. Management of PTAP included antibiotics, sphincterotomy, debridement with drainage, hepatic arterial revascularization, and arterial ligation. Of the 14 patients with complicated pancreatitis, 5 were treated conservatively and died. Nine patients had extensive operative interventions and four survived (45%). CONCLUSIONS: Several risk factors such as retransplantation, extensive dissection at the time of LTx, and use of infrarenal arterial graft contribute to development of PTAP in children. Early exploration and debridement in patients with complicated pancreatitis may result in a better outcome. Retransplantation in the presence of clinical pancreatitis has a high failure rate.     

Is there relationship between serum uric acid levels and lower urinary tract symptoms,prostate volume,and PSA in men without cancer? A prospective population-based study

There are conflicting results about uric acid (UA) effect on the prostate. We investigated the relationship between UA and PSA, free PSA, prostate volume and international prostate symptoms score (IPSS) in benign prostate hyperplasia (BPH). This study was conducted in BPH men without cancer who were referred for annual health workup (N = 910) from 2017 to 2020. The mean ages were 67.28 ± 9.2 years. UA was positively related to IPSS and PSA (r = 0.210, p = .023 and r = 0.156, p = .041 respectively) and also negatively related to free/total PSA ratio (r = −0.332, p = .01) but not related to prostate volume (r = 0.036, p = .696). After adjustment for age, BMI and prostate volume, there were significant relationships between hyperuricaemia and PSA, free/total PSA ratio, and IPSS (95% CI: 0.254–1.645, OR = 0.647, p = .039; 95% CI: 0.076–0.899, OR = 0.270, p = .033 and 95% CI: 1.011–3.386, OR = 1.851, p = .038 respectively). These results should be considered during the general assessment of the patients with BPH. The findings raise the possible hypothesis of relationship between serum UA with IPSS and PSA which should be investigated by future studies.     

Association between donor-recipient serum sodium differences and orthotopic liver transplant graft function.

Previous studies have shown that donor hypernatremia and possibly recipient hyponatremia negatively impact graft function after orthotopic liver transplant (OLT). The purpose of this retrospective investigation was to determine whether measured differences in serum sodium values between cadaveric donors and OLT recipients (DeltaNa(+)) influence immediate postoperative allograft function and short-term patient outcomes. Two hundred and fifty patients that underwent OLT from January 2001 to December 2005 were included in this study. The DeltaNa(+) for each donor recipient pair was correlated with standard postoperative liver function tests as well as recipient length of intensive care unit stay (LOICUS), length of hospital stay (LOHS) and recipient survival. The relationship between donor hypernatremia (serum sodium >or= 155 mEq/mL), recipient hyponatremia (serum sodium level 相似文献   

Assessment of the Thrombogenic Effect of Fibrin Sealant Dressing in a Vascular Surgery Model in Rabbits

This study's objective was to investigate the potential thrombogenic effects of thrombin-containing fibrin sealant dressings (FSD) in a vascular repair model. Oval-shaped pieces of the rabbit abdominal aorta and vena cava were excised, the injuries were repaired with FSD, and animals were allowed to recover. Thrombus formation was examined by (1) an infusion of indium-labeled platelets into the rabbits following FSD application and estimation of total number of platelets attached to the wounds at 2, 4, and 6 h later (short-term effect, n = 12); and by (2) morphological and histological examinations of the vessels and dressings on days 1, 3, and 7 after repair operation in another group of rabbits (long-term effect, n = 12). Application of FSD sealed the vascular injures and produced immediate hemostasis that was stable up to 1 week. The highest numbers of platelets (both native and labeled) adhered to the arterial and venous repair sites were 6.5 × 10⁶ and 4.4 × 10⁷, respectively, 6 h after operation. The adhered platelets, however, did not form a visible and clinically significant thrombus. In long-term experiments, no evidence of thrombus was found in the lumens of the repaired vessels or on the dressings, and no microthrombi were detected histologically in other tissues at any time point. Although vena caval injuries showed signs of healing at day 7 postoperatively, the aortic wounds expanded progressively (pseudoaneurysm) and were prone to rupture at later times. Thus, direct exposure of FSD does not cause intravascular thrombosis or thrombotic events in rabbits. The dressing appears to be safe and effective for short-term repair of vascular injuries. It may also allow healing of minor venous defects, but cannot replace conventional surgical techniques (suturing) for permanent repair of arterial damages.     

Serum Isoform [−2]proPSA Derivatives Significantly Improve Prediction of Prostate Cancer at Initial Biopsy in a Total PSA Range of 2–10 ng/ml: A Multicentric European Study

Background

Strategies to reduce prostate-specific antigen (PSA)–driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary.

Objective

To test the accuracy of serum isoform [−2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)—called index tests—in discriminating between patients with and without PCa.

Design, setting, and participants

This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2–10 ng/ml who were subjected to initial prostate biopsy for suspected PCa.

Outcome measurements and statistical analysis

The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis.

Results and limitations

Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p = 0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p < 0.001), %fPSA (0.14 vs 0.17; p < 0.001), %p2PSA (2.1 vs 1.6; p < 0.001), and PHI (48.2 vs 38; p < 0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p < 0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values.

Conclusions

In patients with a tPSA range of 2–10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA.

Trial registration

The study is registered at http://www.controlled-trials.com, ref. ISRCTN04707454.