Pharmacology of boosted and unboosted integrase strand transfer inhibitors for two-dose event-driven HIV prevention regimens among men.

BACKGROUND: Event-driven HIV prevention strategies are a priority for users who do not require daily pre-exposure prophylaxis (PrEP). Regimens containing integrase strand transfer inhibitors (INSTIs) are under evaluation as alternatives to daily PrEP. To better understand INSTI distribution and inform dosing selection we compared the pharmacology of two-dose boosted elvitegravir and unboosted bictegravir regimens in MSM. MATERIALS AND METHODS: Blood, rectal and penile secretions and rectal biopsies were collected from 63 HIV-negative MSM aged 18-49 years. Specimens were collected up to 96 h after two oral doses of tenofovir alafenamide and emtricitabine with elvitegravir boosted by cobicistat or unboosted bictegravir given 24 h apart. Antiretroviral drugs were measured by LC-MS. RESULTS: Mean bictegravir plasma concentrations remained above the 95% protein-adjusted effective concentration 96 h after dosing [273 (95% CI: 164-456) ng/mL] whereas elvitegravir plasma concentrations became undetectable 48 h after the second dose. Bictegravir and elvitegravir reached rectal tissues within 2 h after the first dose, and elvitegravir tissue concentrations [1.07 (0.38-13.51) ng/mg] were greater than bictegravir concentrations [0.27 (0.15-0.70) ng/mg]. Both INSTIs became undetectable in tissues within 96 h. Elvitegravir and bictegravir were not consistently detected in penile secretions. CONCLUSIONS: Whereas bictegravir plasma concentrations persist at least 4 days after a two-oral-dose HIV prophylaxis regimen, elvitegravir accumulates in mucosal tissues. Differing elvitegravir and bictegravir distribution may result in variable mucosal and systemic antiviral activity and can inform dosing strategies for event-driven HIV prevention.

How useful is the machine perfusion in liver transplantation? An answer from a national survey.

Machine perfusion (MP) has been shown worldwide to offer many advantages in liver transplantation, but it still has some gray areas. The purpose of the study is to evaluate the donor risk factors of grafts, perfused with any MP, that might predict an ineffective MP setting and those would trigger post-transplant early allograft dysfunction (EAD). Data from donors of all MP-perfused grafts at six liver transplant centers have been analyzed, whether implanted or discarded after perfusion. The first endpoint was the negative events after perfusion (NegE), which is the number of grafts discarded plus those that were implanted but lost after the transplant. A risk factor analysis for NegE was performed and marginal grafts for MP were identified. Finally, the risk of EAD was analyzed, considering only implanted grafts. From 2015 to September 2019, 158 grafts were perfused with MP: 151 grafts were implanted and 7 were discarded after the MP phase because they did not reach viability criteria. Of 151, 15 grafts were lost after transplant, so the NegE group consisted of 22 donors. In univariate analysis, the donor risk index >1.7, the presence of hypertension in the medical history, static cold ischemia time, and the moderate or severe macrovesicular steatosis were the significant factors for NegE. Multivariate analysis confirmed that macrosteatosis >30% was an independent risk factor for NegE (odd ratio 5.643, p = 0.023, 95% confidence interval, 1.27-24.98). Of 151 transplanted patients, 34% experienced EAD and had worse 1- and 3-year-survival, compared with those who did not face EAD (NoEAD), 96% and 96% for EAD vs. 89% and 71% for NoEAD, respectively (p = 0.03). None of the donor/graft characteristics was associated with EAD even if the graft was moderately steatotic or fibrotic or from an aged donor. For the first time, this study shows that macrovesicular steatosis >30% might be a warning factor involved in the risk of graft loss or a cause of graft discard after the MP treatment. On the other hand, the MP seems to be useful in reducing the donor and graft weight in the development of EAD.

Antiretroviral drug exposure in urethral and glans surface sampling of the penis.

BACKGROUND: HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat. METHODS: Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography-mass spectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for plasma and urine. Concentrations are reported as median and range. RESULTS: Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for emtricitabine (36 ng/swab; 3-307 ng/swab) and 8 h for darunavir (25 ng/swab; 2-52 ng/swab). Glans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine 14 ng/swab,

Short Communication: Evaluation of Antiretroviral Drug Concentrations in Minimally Invasive Specimens for Potential Development of Point-of-Care Drug Assays.

Point-of-care (POC) tests for antiretroviral drugs (ARVs) could help improve individual adherence. This study sought to define the utility of urine, blood, and buccal swabs as minimally invasive specimens amenable to development of POC tests for ARVs. Urine, dried blood spots (DBS) and buccal swabs were collected from 35 HIV-negative men between 2 and 96 h after a single dose of tenofovir (TFV) alafenamide/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat and darunavir (DRV). ARV concentrations were measured by high-performance liquid chromatography-mass spectrometry. High concentrations of FTC, DRV, and TFV were detectable in urine at least 24 h after dosing. FTC, DRV, and EVG remained detectable in DBS at least 24 h postdose. FTC and DRV were detectable on buccal swabs up to 2 and 24 h postdose, respectively. TFV was not detectable in DBS or buccal swabs collected between 2 and 96 h after dosing. Variable distribution of ARVs in minimally invasive specimens highlights the challenge of developing POC assays for recent ARV exposure.

Healthcare-associated Clostridium difficile infection: role of correct hand hygiene in cross-infection control.

INTRODUCTION: Clostridium difficile (CD) is the most common cause of health-care-associated infectious diarrhea with increasing incidence and severity in recent years. The main cause of hospital's acquired cross infections can be attributed to incorrect hand hygiene. We described the epidemiology of CD infection (CDI) in a teaching hospital in Southern Italy during a two years surveillance period and evaluated the health-care workers compliance to hand hygiene. METHODS: CDI Incidence rates were calculated as the number of patients with positive C. difficile toxin assay per 10,000 patient-days. Compliance with hand hygiene was the ratio of the number of performed actions to the number of opportunities observed. Approximately 400 Hand Hygiene (HH) opportunities/year /ward were observed. We finally checked out if any correlation could be found. RESULTS: From January 2015 to December 2016 a total number of 854 CD determinations were performed in patients with clinical symptoms of diarrhea. The search for toxins A and B was positive in 175 cases (21,2%), confirming the diagnosis of CDI. Compliance to hand hygiene was significantly inversely associated with the number of CDIs: the lower the compliance of health-care workers with hand hygiene the higher was the number of cases of CDIs (p = 0.003). CONCLUSIONS: According to our results proper handwashing of health-care workers appears to be a key intervention in interrupting CD cross infections regardless of age and type of department in which the patient is admitted.

Evaluation of health status in patients with hepatitis c treated with and without interferon.

BACKGROUND: The evolution of technology in healthcare has increased the health care's costs and, the universal healthcare systems, in developed countries, need to ensure proper allocation of resources. Thus, the major issue is assessing the effectiveness of new medical technologies. The evaluation of quality of life in response to new treatments has become a key indicator in chronic conditions for which medical interventions are evaluated not only in terms of increasing the number of expected life years but also in terms of increasing quality of life. The aim of this observational study was to verify whether a simple instrument (EQ-5D-5 L) can capture variations in health-related quality of life (HRQoL) and allow us to evaluate the impact of different drug treatment protocols in patients with hepatitis C virus (HCV) on daily activities. METHODS: Sixty six patients with HCV were consecutively enrolled in the Hepatology Unit at the University Hospital of Catania "G. Rodolico". Sixteen patients received new direct-acting-antiviral agents (DAAs) plus pegylated alpha interferon (Peg-α-IFN) protocol (Group A) and 50 DAAs IFN free protocol (Group B). The EQ-5D-5 L® questionnaire and visual analog scale (VAS) were given to both groups to calculate coefficient's utility. We used the EQ-5D-5 L Crosswalk Index Value Calculator to obtain the utility EQIndex and both parametric and non parametric tests for the statistical analysis. RESULTS: The biopsy taken at the beginning of treatment showed comparable cell damage in both groups. The difference in the VAS results was negative for patients who received protocols containing IFN (indicating decreased quality of life),whereas it was positive in patients treated with IFN-free protocols. The baseline EQIndex did not reveal any differences between the two treatment groups. The post-treatment EQIndex was statistically better in the groups that received IFN-free therapy. CONCLUSIONS: When innovative treatments are introduced into clinical practice, assessing quality of life is mandatory to determine their benefits. The instruments used in the present study are effective in detecting the areas in which improvement has occurred. These instruments can be easily managed by general practitioners for follow up of progression of the disease and referred to the specialist.

Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential.

The female genital tract (FGT) provides a means of entry to pathogens, including HIV, yet immune cell populations at this barrier between host and environment are not well defined. We initiated a study of healthy women to characterize resident T cell populations in the lower FGT from lavage and patient-matched peripheral blood to investigate potential mechanisms of HIV sexual transmission. Surprisingly, we observed FGT CD4 T cell populations were primarily CCR7(hi), consistent with a central memory or recirculating memory T cell phenotype. In addition, roughly half of these CCR7(hi) CD4 T cells expressed CD69, consistent with resident memory T cells, whereas the remaining CCR7(hi) CD4 T cells lacked CD69 expression, consistent with recirculating memory CD4 T cells that traffic between peripheral tissues and lymphoid sites. HIV susceptibility markers CCR5 and CD38 were increased on FGT CCR7(hi) CD4 T cells compared with blood, yet migration to the lymphoid homing chemokines CCL19 and CCL21 was maintained. Infection with GFP-HIV showed that FGT CCR7(hi) memory CD4 T cells are susceptible HIV targets, and productive infection of CCR7(hi) memory T cells did not alter chemotaxis to CCL19 and CCL21. Variations of resident CCR7(hi) FGT CD4 T cell populations were detected during the luteal phase of the menstrual cycle, and longitudinal analysis showed the frequency of this population positively correlated to progesterone levels. These data provide evidence women may acquire HIV through local infection of migratory CCR7(hi) CD4 T cells, and progesterone levels predict opportunities for HIV to access these novel target cells.

Non-pegylated liposome-encapsulated doxorubicin citrate plus cyclophosphamide or vinorelbine in metastatic breast cancer not previously treated with chemotherapy:a multicenter phase III study.

We conducted a phase III multicenter randomized trial to compare the efficacy of the combination of liposome encapsulated doxorubicin (Myocet(©)) plus either cyclophosphamide (MC) or vinorelbine (MV). Since July 2006, 233 patients affected with metastatic breast cancer were randomized to receive the combination of Myocet (M) 60 mg/m(2) i.v. plus cyclophosphamide (C) 600 mg/m2 on Day 1 of a 21­day cycle (Arm A) or Myocet (M) at 50 mg/m2 plus vinorelbine (V) 25 mg/m2 i.v. on Day 1 and V 60 mg/m2 orally on Day 8 on a 21­day cycle (Arm B). The primary endpoints of the study was time to progression (TTP); secondary endpoints were RR, toxicity and OS. Response was observed in 53/116 (45.7%) evaluable patients of Arm A vs. 51/112 (45.5%) of Arm B, respectively (P=NS). Median TTP was 41 weeks (95% CI, 32­51) and 34 weeks (95% CI, 26­39), for M/C and M/V, respectively (P=0.0234). The difference in median OS was not statistically significant (131 vs. 122 weeks; P=0.107). With regard to toxicity, patients treated with MV showed a slight increase of neutropenia and constipation, as compared to those treated with MC. No clinical signs of cardiotoxicity were observed. The MC combination remains as an unbeaten 'standard' in first line treatment of MBC.

Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C.

BACKGROUND: The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients' survival. AIM: To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence. METHODS: 436 Liver transplant recipients (74.1% genotype 1) who underwent combined antiviral therapy for hepatitis C recurrence were retrospectively evaluated. RESULTS: The overall sustained virological response rate was 40% (173/436 patients), and the mean follow-up after liver transplantation was 11±3.5 years (range, 5-24). Patients with a sustained virological response demonstrated a 5-year survival rate of 97% and a 10-year survival rate of 93%; all but 6 (3%) patients remained hepatitis C virus RNA-negative during follow-up. Genotype non-1 (p=0.007), treatment duration >80% of the scheduled period (p=0.027), and early virological response (p=0.002), were associated with the maintenance of sustained virological response as indicated by univariate analysis. Early virological response was the only independent predictor of sustained virological response maintenance (p=0.008). CONCLUSIONS: Sustained virological response achieved after combined antiviral treatment is maintained in liver transplant patients with recurrent hepatitis C and is associated with an excellent 5-year survival.

HIV-1 genital shedding is suppressed in the setting of high genital antiretroviral drug concentrations throughout the menstrual cycle.

BACKGROUND: It is not known if fluctuations in genital tract antiretroviral drug concentrations correlate with genital virus shedding in human immunodeficiency virus (HIV)-infected women on antiretroviral therapy (ART). METHODS: Among 20 HIV-infected women on ART (tenofovir [TFV], emtricitabine [FTC], and ritonavir-boosted atazanavir [ATV]) with suppressed plasma virus loads, blood and cervicovaginal samples collected twice weekly for 3 weeks were tested for antiretroviral concentrations, HIV-1 RNA, and proviral DNA. RESULTS: Cervicovaginal:plasma antiretroviral concentration ratios were highest for FTC (11.9, 95% confidence interval [CI], 8.66-16.3), then TFV (3.52, 95% CI, 2.27-5.48), and ATV (2.39, 95% CI, 1.69-3.38). Within- and between-person variations in plasma and genital antiretroviral concentrations were observed. Low amounts of genital HIV-1 RNA (<50 copies/mL) were detected in 45% of women at 16% of visits. Genital HIV-1 DNA was detected in 70% of women at 35% of visits. Genital virus detection was associated with higher concentrations of mucosal leukocytes but not with genital antiretroviral concentrations, menstrual cycle phase, bacterial vaginosis, genital bleeding, or plasma virus detection. CONCLUSIONS: Standard doses of ART achieved higher genital than plasma concentrations across the menstrual cycle. Therapeutic ART suppresses genital virus shedding throughout the menstrual cycle, even in the presence of factors reported to increase virus shedding.

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery.

OBJECTIVES: To investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-ß1 (TGF-ß1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics. DESIGN AND METHODS: Prospective, observational study. BDNF, TGF-ß1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 -174 G/C polymorphism was genotyped. RESULTS: Serum BDNF concentrations decreased (P=0.048), correlated with TGF-ß1 (r=0.610 at T1, r=0.493 at T2, r=0.554 at T3). Plasma BDNF concentrations raised (P=0.049), correlated with IL-6 and TNF-α at T1 (r=0.495 and r=0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 -174 G/C genotype. CONCLUSION: Serum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.

Balancing donor and recipient risk factors in liver transplantation: the value of D-MELD with particular reference to HCV recipients.

Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

Randomized clinical trial of radiofrequency-assisted versus clamp-crushing liver resection.

BACKGROUND: Surgical resection remains the treatment of choice for primary and secondary liver cancer. Complications are mainly related to blood loss. Radiofrequency-assisted liver resection (RF-R) has been proposed for parenchymal division as an alternative to clamp crushing in order to reduce blood loss. METHODS: Fifty patients (median age 62 (range 30-82) years) undergoing hepatectomy were randomized to RF-R (24 patients) or the clamp-crushing method (26). In the RF-R group the resection plane was precoagulated by multiple insertion of a planar triple-cooled radiofrequency ablation needle, and then the parenchyma was sectioned using a scalpel. RESULTS: The two groups were well matched in terms of age, sex, liver disease and type of resection. There were no deaths. Eight in the RF-R group developed complications (abscess in six, biliary fistula in three and biliary stenosis in one) compared with none of those who had resection by the crush method (P < 0.001). Two patients with cirrhosis in each group developed decompensation. Blood transfusion was required in eight of 24 patients in the RF-R group and 13 of 26 in the clamp-crushing group (P = 0.079). CONCLUSION: RF-R allows parenchymal resection in a clean surgical field but is associated with a higher rate of postoperative complications than the clamp-crushing technique.

Dynamic variation in the cellular origin of HIV type 1 during treatment of tuberculosis in dually infected subjects.

HIV-1 replication remains elevated in dually infected HIV-1/TB subjects at completion of antituberculosis therapy. A viral immunocapture assay was used to examine the cellular origin of HIV-1 within plasma from HIV-1/TB subjects at time of diagnosis of pulmonary TB, at end of TB treatment, and 6 months after completion of treatment. Asymptomatic HIV-1-infected subjects without TB (HIV-1/C) served as controls. Both activated immature macrophage (CD36(+)) and CD4 T cell (CD26(+)) compartments contributed to viral load. Changes in the activation status of either cellular compartment paralleled their contribution to viral load. Levels of HIV-1 originating from activated (HLA-DR(+)) cells and from CD36(+) and CD26(+) mononuclear cells resolved to levels observed in HIV-1/C by the end of treatment. HIV-1 isolated by anti-CD3 immunocapture from HIV-1/TB patients remained significantly higher than from HIV-1/C patients at the end of TB treatment and at 12 months follow-up. Therefore, viral production by lymphocytes extends well beyond the completion of TB treatment.

Single hepatocellular carcinoma ranging from 3 to 5 cm: radiofrequency ablation or resection?

BACKGROUND: The optimal therapy for hepatocellular carcinoma (HCC) is transplantation. For all those patients not eligible for transplantation (or on the waiting list) among the treatments of choice used more frequently in recent years are resection (RES) and radiofrequency ablation (RFA). RFA is less efficacious for HCC ranging over 3 cm. The aim of this study was to compare RFA to RES in a restricted cohort of patients with a single naive HCC ranging from 3 to 5 cm in size and without end-stage liver disease. PATIENTS AND METHODS. A total of 102 patients who had never been treated before were enrolled. Those patients whose HCC position would have required too much parenchymal loss at RES (central or close to main vascular structures) were treated with RFA (n=60), and the others underwent RES (n=42). The two groups were similar for HCC size and liver disease status. The outcome was considered in terms of overall survival (OS) and disease-free survival (DFS) calculated by the Kaplan-Meier method. Differences among groups were validated by log-rank test. RESULTS: The RES group seemed to present a better long-term OS (91%, 57%, and 43% vs 96%, 53%, and 32% at 1, 3, and 5 years, respectively) and DFS (74%, 35%, and 14% vs 68%, 18%, and 0%, respectively) but there was no statistical significance. Age, gender, virus etiology, HCC size and alpha-fetoprotein levels did not correlate with survival. Patients with recurrence within the first 12 months after treatment showed a worse long-term survival (p=0.011). Patients in Child-Pugh class B had poor prognoses compared with those in class A (p=0.047). CONCLUSION: Even if RES seemed to promise better long-term results, in the medium term this difference had no statistical significance. Survival in this series was more closely related to the stage of the underlying liver disease than to treatment (RES/RFA).

[Smoking habits in health care workers: experience in two general hospitals of Eastern Sicily]. / Abitudine al fumo di tabacco in operatori della Sanità: esperienza in Aziende Ospedaliere della Sicilia Orientale.

PURPOSE: The aim of our study was to assess the smoking habits in health care workers. MATERIALS AND METHODS: In concomitance with a medical examination for Health Care Surveillance requested by the Italian Laws (D. Lgs. 626/94), our operative units interviewed 2,000 persons (47.9% males, 52.1% females, mean age = 45 yrs (SD+/-9.41 yrs) working in two General Hospitals of Eastern Sicily. RESULTS: The prevalence of smokers was found to be higher in men (34.5%) than in women (33.6%), in Health Care Operators (36.4%) and professional nurses (36.2%) than in medical doctors (27.7%), in night-time workers (34,5%) then in day-time-workers (28,7%). The compliance with smoking restriction was found to be poor; in fact, 60% out of smokers declared to smoke during the working hours. CONCLUSIONS: This investigation has revealed the significant prevalence of tobacco smoking among the health care workers in general. We think that the inclusion of an anonymous questionnaire on smoking habits within the Services of Sanitary Surveillance may help in the national campaign against cigarette smoking.

Lipoprotein(a), lipids and proinflammatory cytokines in patients undergoing major abdominal surgery.

BACKGROUND: The aims were to investigate whether surgical stress can induce a positive or negative lipoprotein(a) acute response, to determine any association with apolipoprotein(a) phenotypes, and to establish whether any such response is dependent on changes in lipids and proinflammatory cytokines. In addition, the impact of interleukin (IL) 6 genetic variability on the cytokine response to surgery was examined. METHODS: This prospective, observational study included 41 patients with cancer referred for abdominal surgery. Preoperative (T0) plasma concentrations of lipoprotein(a), IL-6, tumour necrosis factor alpha, and serum concentrations of transforming growth factor beta1 and lipids, were compared with values obtained 5 h (T1), 24 h (T2) and 5 days (T3) after surgery. Apolipoprotein(a) Kringle IV (KIV)-VNTR (variable-number tandem repeat) and IL-6 - 174 G/C polymorphisms were analysed. RESULTS: Lipoprotein(a) was found to act as a negative acute-phase reactant (30.0 per cent reduction at T2) (P = 0.009). Surgery had a more profound impact on subjects with low KIV-VNTR. After surgery, lipoprotein(a) correlated significantly with corrected low-density lipoprotein (LDL)-cholesterol (r = 0.408 at T2). IL-6 inversely correlated with lipoprotein(a) (r = -0.321 at T1) and LDL-cholesterol (r = -0.418 at T1). The IL-6 response could be predicted from a combination of the surgical severity and -174 G/C genotype. CONCLUSION: Although temporal associations did not indicate causality, these data provide a hypothesis to explain the inverse relationship between lipoprotein(a) and IL-6.

[Essential levels of care and mode of admission: a trial of cost-volume contracts]. / LEA e riconversione dei ricoveri: sperimentazione di contratti per costo e volume.

Within a research project funded by the Ministry of Health, the purpose of this work was to define the procedures of a contract for the provision of health services (hospital admissions), between the regional health administration (the "buyer") and the University teaching hospital (the "provider"), with the aim of improving efficiency. The contract concerned a few DRGs, among those identified as being "at risk of inappropriateness", in the national decree on "essential levels of care" (LEA). The contract defined production levels (number and percentage of admissions in day hospital), financing rules and methods for evaluation of results and improvement of performance within the hospital. This trial, even if run for a limited time and for demonstration purposes, showed that some results can be attained, provided some organizational adjustments are made.

Solutions for organ perfusion and storage: haemorheologic aspects.

BACKGROUND: The hydroxyethyl starch (HES) contained in University of Wisconsin (UW) solution causes erythrocyte aggregation. The effect of UW on red blood cell (RBC) deformability is still unclear. HES-free preservation solutions, Celsior (CS) and Custodiol (CU) are available. In this study we evaluated whether they really showed a reduced aggregating and stiffening effect on RBCs when compared with UW. We was also evaluated the effect of these solutions on cellular membranes by measuring acetylcholinesterase (AChE), which is a marker of RBC membrane integrity. METHODS: The determination of RBC aggregation and deformability was performed by a laser-assisted optical rotation cell analyzer (LORCA). AChE measurement was performed with a spectrophotometric technique. RESULTS: The mean RBC aggregation index (AI) measured in pure blood control samples was 28.00 +/- 0.73%. The AI measured samples containing UW was 38.82 +/- 1.58%. In samples with CS, it was 13.307 +/- 0.64% and in samples with CU the mean AI was 12.47 +/- 0.42%. Also the RBC aggregating time was quicker in presence of UW compared with controls. AChE concentration in blood was 3.043 +/- 0.4 nmol. CS and UW did not produce any significant change; a significant reduction was found when CU was added to blood, namely 1.975 +/- 0.1 nmol (P < .05). The use of UW or CS or CU did not result in any significant change in RBC deformability. DISCUSSION: CS and CU solutions do not aggregate erythrocytes, whereas Wisconsin does massively. CU causes an alteration of RBC cellular membrane as demonstrated by depletion of AChE.