Inferior vena cava diameters and collapsibility index reveal early volume depletion in a blood donor model.

BACKGROUND: Changes of volume status can be readily inferred from variations in diameter of the inferior vena cava (IVC) measured by ultrasound. However the effect of IVC changes following acute blood loss are not fully established. In this study, three different approaches to measuring IVC variables were compared in healthy blood donors, as a model of acute volume depletion, in order to establish their relative ability to detect acute blood loss. METHODS: Inspiratory and expiratory IVC diameters were measured before and after blood donation in hepatic long axis, hepatic short axis and renal short axis views using a 2-5 MHz curvilinear probe. All measurements were recorded and examined in real-time and post-processing sessions. RESULTS: All windows performed satisfactorily but the renal window approach was feasible in only 30 out of 47 subjects. After blood donation, IVC diameters decreased in hepatic long axis, hepatic short axis and renal short axis (expiratory: -19.9, -18.0, -26.5 %; CI 95 %: 14.5-24.1; 13.1-22.9; 16.0-35.9, respectively) (inspiratory: -31.1, -31.6, -36.5 %; CI 95 %: 21.3-40.1; 18.8-45.2; 23.4-46.0, respectively), whereas the IVC collapsibility index increased by 21.6, 22.6 and 19.3 % (CI 95 %: 11.6-42.9; 18.5-39.5; 7.7-30.0). IVC diameters appeared to return to pre-donation values within 20 min but this was only detected by the hepatic long axis view. CONCLUSIONS: IVC diameter and collapsibility index variations, as measured in M mode, consistently detect volume changes after blood donation. The longitudinal mid-hepatic approach performed better by allowing a panoramic view, avoiding anatomical aberrancies at fixed points and permitting to identify the best possible perpendicular plane to the IVC. In addition, it was able to detect time-dependent physiological volume replacement. In contrast, in our hands, the renal window could not be visualized consistently well.

Caspofungin benefit on phagocytes from patients with renal dysfunction infected with multidrug-resistant Candida glabrata.

AIM: We evaluated the potential impact of caspofungin (CAS) on the functional activities of polymorphonuclear leukocytes (PMNs) from hemodialyzed patients (HDs) and renal transplant recipients (RTRs) against a multidrug-resistant clinical strain of Candida glabrata compared with those of PMNs from healthy subjects (HSs). MATERIALS & METHODS: Effects of CAS on PMN phagocytosis and intracellular killing towards multidrug-resistant C. glabrata were evaluated in 66 HDs, 54 RTRs and 30 HSs in the absence and presence of CAS at MIC and sub-MICs. RESULTS: When HD PMNs and RTR PMNs were exposed to both MICs and sub-MICs of CAS, their fungicidal activity against the multidrug-resistant C. glabrata strain was significantly higher than that of drug-free controls, with survival index values that overlapped with those achieved by HS PMNs. CONCLUSION: The obtained results underline the role of CAS in the restoration of the impaired PMN functions in HDs and RTRs. CAS might still constitute an effective therapeutic option for the treatment of invasive fungal infections caused by multidrug-resistant C. glabrata in patients with altered phagocyte-dependent innate immunity.

Synergy of caspofungin with human polymorphonuclear granulocytes for killing Candida albicans.

The influence of caspofungin on polymorphonuclear leukocyte (PMN) phagocytosis and intracellular killing of Candida albicans was investigated. Caspofungin, at all of the concentrations tested (2, 3.2, and 8 microg/ml), significantly increased intracellular killing by PMNs through its direct action on both yeast cells and PMNs, indicating the potential ability of caspofungin to synergize with phagocytes for candidal killing. Caspofungin may therefore constitute an effective therapeutic option for the treatment of invasive fungal infections, including those refractory to conventional treatment with azole agents.

Italian blood donors with anti-HBc and occult hepatitis B virus infection.

BACKGROUND AND OBJECTIVES: Occult hepatitis B virus (HBV) infection might allow the release of viremic units into the blood supply network if blood is tested only for hepatitis B surface antigen (HBsAg). The aim of our study was to evaluate the actual prevalence, viral load and genotype of occult HBV infections among first-time blood donors in north-western Italy and to suggest a way to minimize risks of transmission of this infection. DESIGN AND METHODS: We assayed 6313 consecutive blood donors for antibodies to HBV core antigen (anti-HBc) in addition to mandatory screening. HBsAg-negative/anti-HBc-positive donors were assayed for antibodies to HBsAg (anti-HBs) and for HBV-DNA using COBAS Ampliscreen HBV (Roche) on individual donations. All HBV-DNA-positive samples underwent confirmatory testing with additional polymerase chain reaction-based assays. RESULTS: The prevalence of anti-HBc positive subjects was 4.85%. Fourteen out of 288 blood donors (4.86%) were confirmed to have circulating HBV-DNA at a low level (range 8-108 IU/mL). All viremic donors were also anti-HBs-positive. INTERPRETATION AND CONCLUSIONS: We estimate that in north-western Italy up to 2298 units per million donated units from first-time donors may contain HBV-DNA. The risk of an HBV-DNA positive unit from an occult carrier being released into the blood supply is more than 100 times higher than the estimated residual risk related to the window phase of HBV infection in our country. The potential infectivity of these units is debated, but their use cannot be considered safe at least in immunocompromised patients.

Digestive endoscopy is not a major risk factor for transmitting hepatitis C virus.

BACKGROUND: The potential role of digestive endoscopy as a mode for transmission of hepatitis C virus (HCV) is controversial. OBJECTIVE: To evaluate the role of digestive endoscopy in transmitting HCV by comparing the incidence of HCV infection in a cohort of patients undergoing endoscopy and in a cohort of blood donors. DESIGN: Prospective cohort study. SETTING: 3 endoscopic units and 2 blood banks in northwestern Italy. PATIENTS: The potentially exposed cohort consisted of 9188 outpatients consecutively recruited from 3 endoscopic units. Of 9008 patients negative for antibody to HCV (anti-HCV), 8260 (92%) were retested for anti-HCV 6 months after endoscopy. The unexposed cohort consisted of 51,230 healthy, anti-HCV-negative persons who donated blood at 2 blood banks in the same area and during the same time period; 38,280 of them (75%) were tested again for anti-HCV 6 to 48 months after the first blood donation (95,317 person-years of observation). MEASUREMENTS: Differences in the anti-HCV seroconversion rate between the exposed cohort (patients undergoing endoscopy) and the unexposed cohort (blood donors). Seroconversion was evaluated by a third-generation enzyme immunoassay for anti-HCV; persons positive for anti-HCV were tested for HCV RNA by polymerase chain reaction. RESULTS: All 8260 persons undergoing endoscopy remained negative for anti-HCV 6 months after the procedure (risk per 1000 persons, 0 [95% CI, 0 to 0.465]); in particular, none of the 912 patients who underwent endoscopy with the same instrument previously used on HCV carriers showed anti-HCV seroconversion (risk per 1000 persons, 0 [CI, 0 to 4.195]). Four blood donors became positive for anti-HCV and HCV RNA (mean follow-up, 2.49 years; 0.042 case per 1000 person-years [CI, 0.011 to 0.107 case per 1000 person-years]); each had undergone minor surgery before the second test. LIMITATIONS: In the endoscopy cohort, 8.3% of patients were lost to follow-up. CONCLUSIONS: These findings support the hypothesis that properly performed digestive endoscopy is not a major risk factor for the transmission of HCV.

Screening selected blood donors with biochemical iron overload for hemochromatosis: a regional experience.

BACKGROUND AND OBJECTIVES: Hemochromatosis is a genetic disorder characterized by progressive iron overload which leads to early abnormalities of iron parameters (increased transferrin saturation =TS and serum ferritin=SF) and late clinical complications. The disease is prevalently due to C282Y and H63D mutations in the HFE gene, but additional molecular defects are present in a minority of patients. DESIGN AND METHODS: From January to December 2002 we screened first time blood donors of Piedmont, a region of North-western Italy, for TS>45%. Individuals with TS>45% underwent a second fasting check, SF assessment and molecular tests, investigating 12 hemochromatosis-associated molecular defects. RESULTS: A total of 13,998 subjects were screened; 868 (6.2%) had TS>45% and were recalled. Four hundred and eight-six underwent molecular testing. In this selected population allele frequencies of C282Y, H63D and S65C were 6.8%, 22.4% and 1.0%, respectively. No rare mutations were detected, except E168Q in HFE. When measured during fasting, TS was significantly higher in C282Y homozygotes and H63D/C282Y heterozygotes (p<0.05) than in wild type subjects, but not in H63D homozygotes. Hyperferritinemia was documented in 32 cases, 9 with wild type genotype. Mean age, body mass index (BMI) and alcohol intake were higher in this group than in individuals with normal SF. INTERPRETATION AND CONCLUSIONS: This study is an example of a large, two-step hemochromatosis screening with moderate effort and low cost, that enriches basal C282Y allele frequency by about three-fold. Screening based on genotyping only subjects found to have a TS>45% is feasible but, in order to be cost effective should be based on the identification of the two prevalent mutations even in an area where several forms of hemochromatosis have been reported.