Human health risk assessment associated with the consumption of mussels (Perna perna) and oysters (Crassostrea rhizophorae) contaminated with metals and arsenic in the estuarine channel of Vitória Bay (ES), Southeast Brazil.

The estuarine channel of Vitória Bay was evaluated regarding bioaccumulation of metals (Al, Ba, Mn, Fe, Zn, Cu, Cr, Pb, Ni, Cd, Hg) and As in mollusks. Mussels from an aquaculture farm and transplanted into the estuary, whereas oysters were collected in situ in the same area. Concentrations of Al, Mn, Fe, Cr and As were higher in P. perna, whereas C. rhizophorae bioaccumulated more Ba, Zn and Cu. Arsenic concentrations in P. perna exceeded the limit of the Brazilian legislation in the outer estuary. Salinity seemed to influence metal uptake differently for each bivalve, with P. perna absorbing more metal at higher salinities and C. rhizophorae in areas of lower salinity. Hazard index (HI) >1 revealed risk for both bivalves for high level consumers. Target Cancer Risk (TCR) for As revealed threat for human health associated with the consumption of mussels and oysters from the study area.

Evaluation of bioavailability of trace metals through bioindicators in a urbanized estuarine system in southeast Brazil.

The mussel Perna perna is one of the most used bioindicators of coastal areas and the most economically exploited species in Brazil through mariculture. In the present study, P. perna was used to investigate metal pollution in the estuarine area of Vitória Bay. Four sampling sites were located along an estuarine branch of Vitória Bay and stations were sampled during three campaigns. Trace metals in the tissues of P. perna were evaluated as well as dissolved trace metals and other ancillary variables in the water column. Dissolved Cd, Pb, Cu, Ni, and Fe concentrations surpassed the tolerance limits stablished by legislation in all the sampling campaigns. P. perna exhibited concentrations in disagreement with the Brazilian legislation for Cr and As. A general trend of higher concentrations in outer stations was observed for most metals, what suggested the occurrence of flocculation process in the lower estuary, reducing the concentrations of dissolved elements and increasing their bioavailability for the biota through the particulate form. Cd was highlighted with elevated concentrations in dissolved fraction but not detected in P. perna, probably due to chlor-complex formation under influence of more saline waters. Al, Ba, Mn, Fe, Cu, Zn, Ni, Cr, Pb, and As were considered bioavailable, once they were accumulated in the mussels' tissues. Hazard index (HI) and target cancer risk (TCR) showed that the consumption of mussels from the study area offers health risk issues, being iron and arsenic the main contributors for the high indexes.

Cancer Incidence in Heart Transplant Recipients With Previous Neoplasia History.

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post-Heart Transplant Tumor Registry) comparing the epidemiological data, immu-nosuppressive treatments and incidence of post-HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post-HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2-2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3-4.0, p < 0.004). OS during the 10-year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post-HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post-HT tumors and should be taken into account when considering a patient for HT.

Accuracy of noninvasive estimation of pulmonary wedge pressure by echocardiographic indices in heart transplant recipients.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) can be estimated from transmitral or color M-mode Doppler flow propagation velocities. However, it has been recommended to not use these indices in heart transplant recipients. Our aim was to compare the accuracy of color M-mode, Doppler, and Doppler tissue imaging (DTI)-derived indices to predict PCWP in heart transplant recipients. METHODS: We studied 50 consecutive heart transplant recipients scheduled for routine right-sided heart catheterization and endomyocardial biopsy. Their mean age was 49 ± 17 years and the mean time after heart transplantation was 29 ± 41 months. An echocardiogram was performed immediately after the invasive procedure. We analysed PCWP, transmitral flow velocity variables (peak velocity during early filling (E) and deceleration time [DT]), color M-mode Doppler flow propagation velocity (Vp), and mitral annulus peak early diastolic velocity (E') from DTI. Doppler estimated-PCWP (ePCWP) was calculated as follows: (5.27 × E/Vp) + 4.6. RESULTS: Mean ejection fraction was 66 ± 11%. The mean invasive measured PCWP was 11.14 ± 5.4 mm Hg and the mean noninvasive ePCWP was 11.13 ± 1.8 mm Hg (r = 0.66; P < .0001). A good correlation was present between invasive PCWP and mitral PW-Doppler and DTI parameters: peak E 91 ± 22 cm/s (r = 0.34; P = .02) and DT 143 ± 26 s (r = -0.436; P = .002), E/E' ratio medial mitral annulus 10 ± 4 cm/s (r = 0.353; P = .026) and E/E' ratio lateral mitral annulus 6 ± 2 cm/s (r = 0.462; P = .002). E/Vp was the most accurate index for predicting PCWP (r = 0.615; P < .0001). CONCLUSIONS: Compared with other indirect Doppler indices, E/Vp showed the best correlation to predict PCWP in heart transplant recipients. Despite previous recommendations, PCWP can be accurately estimated from color M-mode indices, giving useful information and avoiding the risks of invasive measurements.

Proliferation signal inhibitors and post-transplant malignancies in heart transplantation: practical clinical management questions.

Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs.

Temporal trends in the use of proliferation signal inhibitors in maintenance heart transplantation: a Spanish multicenter study.

Proliferation signal inhibitors (PSI; sirolimus, everolimus) are being increasingly used in heart transplantation. We performed an observational, retrospective, multicenter study in 9 Spanish centers seeking to describe the clinical context in which a PSI was used among maintenance heart recipients and its evolution over time. We collected a cohort of 548 patients in whom a PSI was prescribed from October 2001 to March 2009. The group was divided into 3 time periods. The use of PSI steeply increased in the 2005-2006 period, remaining stable thereafter. There were no significant differences over time with regard to age, gender, or time from transplantation to the introduction of the PSI. Everolimus usage overtook sirolimus from 2005 on; currently, >90% of the subjects with PSI indications are prescribed everolimus. Compared with earlier periods, patients in the more recent period (October 2006-March 2009) showed less vascular graft disease and better basal renal function, irrespective of the primary indication for the PSI prescription. Also, skin cancer overtook solid cancer as the main type of neoplasm in patients for whom malignancy was the primary indication for the use of the PSI. The actuarial incidence of PSI withdrawal owing to adverse effects did not change significantly over time.

Incidence and risk factors for nonmelanoma skin cancer after heart transplantation.

INTRODUCTION: The incidence of skin cancer in heart transplant (HT) patients is higher than in the general population, reversing the proportion of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with a predominance of the former. The etiologic role of new immunosuppressants is not well known. We sought to ascertain the incidence of SCC and BCC in HT patients and the risk factors for its occurrence. PATIENTS AND METHODS: We report the incidence of all types of post-HT skin cancer, SCC, and BCC among adult HT patients in Spain (4089 subjects) as well as the influence of gender, age at heart transplant, immunosuppression, and sunlight exposure. RESULTS: The incidence rates of SCC and BCC, per 1000 persons/year, were 8.5 and 5.2, respectively. Males had a higher risk of SCC but not BCC. Induction therapy increased the risk of SCC and BCC. The relative risk of mycophenolate mofetil (MMF) was 0.3 (0.2-0.6; P<.0005) and azathioprine (AZA) 1.8 (1.2-2.7; P<.0032) for SCC, whereas tacrolimus and cyclosporine showed no difference. The relative risk of BCC was not affected by any immunosuppressant. CONCLUSION: Age at transplantation>45 years, induction therapy use, and high sunshine zone were risk factors for both SCC and BCC. Different immunosuppressive agents have different risks of nonmelanoma skin cancer, as AZA increases the risk of SCC and MMF is a protective factor. The relative risk of BCC was not affected by any immunosuppressor.

Malignancy after heart transplantation: incidence, prognosis and risk factors.

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

Impact of mild pulmonary hypertension on mortality and pulmonary artery pressure profile after heart transplantation.

BACKGROUND: Pulmonary hypertension is a risk factor for early mortality after transplantation, but the risk threshold is debated. Also, little is known about the evolution of pulmonary circulation after transplantation. The aim of this study was to determine the influence of current risk pulmonary pressure parameters on early post-operative mortality and to assess the time-related changes in pulmonary pressure after surgery. METHODS: One hundred twelve consecutive transplanted patients were studied retrospectively to determine the influence of trans-pulmonary gradient of >12 mm Hg and pulmonary vascular resistance of >2.5 Wood units, at baseline or after vasodilator test, on early mortality. A multivariate analysis was used to study the hemodynamic parameters associated with early mortality. The pulmonary pressures of all surviving patients were studied for up to 3 years after surgery. RESULTS: Early mortality in the groups with and without pulmonary hypertension were 24.4% and 5.6%, respectively (p =.009). The only variable that was independently associated with early mortality was the pulmonary vascular resistance index (odds ratio = 1.459). Mild pulmonary hypertension disappeared 1 year after heart transplantation. CONCLUSIONS: Mild pulmonary hypertension is a risk factor for early postoperative mortality. The hemodynamic parameter most closely associated with early mortality is pulmonary vascular resistance index. The hemodynamic profile of pulmonary circulation after heart transplantation is partially dependent on the level of pulmonary hypertension before transplantation, at least during the first year after surgery.