The value of combined hemodynamic, respiratory and intra-abdominal pressure monitoring in predicting acute kidney injury after major intraabdominal surgeries

Background: The incidence of postoperative acute kidney injury (AKI) is predominantly determined by renal hemodynamics. Beside arterial blood pressure, the role of factors causing a deterioration of venous congestion (intraabdominal pressure, central venous pressure, mechanical ventilation) has emerged. The value of combined hemodynamic, respiratory and intra-abdominal pressure (IAP) monitoring in predicting postoperative acute kidney injury has received only limited exploration to date. Methods: Data were collected for adult patients admitted after major abdominal surgery at nine Hungarian ICUs. Hemodynamic parameters were compared in AKI vs. no-AKI patients at the time of admission and 48 h thereafter. Regarding ventilatory support, we tested mean airway pressures (Pmean). Effective renal perfusion pressure (RPP) was calculated as MAP−(IAP + CVP + Pmean). The Mann–Whitney U and the chi-square tests were carried out for statistical analysis with forward stepwise logistic regression for AKI as a dependent outcome. Results: A total of 84 patients (34 ventilated) were enrolled in our multicenter observational study. The median values of MAP were above 70 mmHg, IAP not higher than 12 mmHg and CVP not higher than 8 mmHg at all time-points. When we combined those parameters, even those belonging to the ‘normal’ range with Pmean, we found significant differences between no-AKI and AKI groups only at 12 h after ICU admission (median and IQR: 57 (42–64) vs. 40 (36–52); p < .05). Below it’s median (40.7 mmHg) on admission, AKI developed in all patients. If above 40.7 mmHg on admission, they were protected against AKI, but only if it did not decrease within the first 12 h. Conclusions: Calculated effective RPP with the novel formula MAP−(IAP + CVP + Pmean) may predict the onset of AKI in the surgical ICU with a great sensitivity and specificity. Maintaining effective RPP appears important not only at ICU admission but during the next 12 h, as well. Additional, larger studies are needed to explore therapeutic interventions targeting this parameter

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Effect of Dexrazoxane and Amifostine on the Vertebral Bone Quality of Doxorubicin Treated Male Rats

Doxorubicin (DOX) is widely used in combination cocktails for treatment of childhood hematological cancers and solid tumors. A major factor limiting DOX usage is DOX-induced cardiotoxicity. However, it is not known whether protectants like dexrazoxane (DXR) and amifostine (AMF) can prevent DOX-mediated bone damage. The present study investigated whether administration of AMF alone or in combination with DXR would prevent any DOX-mediated bone damage. Male rat pups were treated with DOX, DXR, AMF, and their combinations. On neonate day 38, the bone mineral density (BMD), bone mineral content (BMC) and the micro-architecture of the lumbar vertebrae were analyzed. We have shown that when male rats are treated with DOX, DXR, DOX+DXR, AMF, DOX+AMF or DOX+DXR+AMF, there is a decrease in lumbar vertebral BMD (p<0.05). Furthermore, the relative bone volume (BV/TV) was decreased by DXR, DOX+DXR, and DOX+AMF treatments. Interestingly, DOX+AMF significantly increased BV/TV when compared to DXR treatment (p<0.04). The trabecular number (Tb.N) decreased with DXR and DOX+DXR and increased with DOX+AMF treatments. This information will be useful in designing better cancer combination therapies that do not lead to vertebrae deterioration

Exposure to HIV-1 Directly Impairs Mucosal Epithelial Barrier Integrity Allowing Microbial Translocation

While several clinical studies have shown that HIV-1 infection is associated with increased permeability of the intestinal tract, there is very little understanding of the mechanisms underlying HIV-induced impairment of mucosal barriers. Here we demonstrate that exposure to HIV-1 can directly breach the integrity of mucosal epithelial barrier, allowing translocation of virus and bacteria. Purified primary epithelial cells (EC) isolated from female genital tract and T84 intestinal cell line were grown to form polarized, confluent monolayers and exposed to HIV-1. HIV-1 X4 and R5 tropic laboratory strains and clinical isolates were seen to reduce transepithelial resistance (TER), a measure of monolayer integrity, by 30–60% following exposure for 24 hours, without affecting viability of cells. The decrease in TER correlated with disruption of tight junction proteins (claudin 1, 2, 4, occludin and ZO-1) and increased permeability. Treatment of ECs with HIV envelope protein gp120, but not HIV tat, also resulted in impairment of barrier function. Neutralization of gp120 significantly abrogated the effect of HIV. No changes to the barrier function were observed when ECs were exposed to Env defective mutant of HIV. Significant upregulation of inflammatory cytokines, including TNF-α, were seen in both intestinal and genital epithelial cells following exposure to HIV-1. Neutralization of TNF-α reversed the reduction in TERs. The disruption in barrier functions was associated with viral and bacterial translocation across the epithelial monolayers. Collectively, our data shows that mucosal epithelial cells respond directly to envelope glycoprotein of HIV-1 by upregulating inflammatory cytokines that lead to impairment of barrier functions. The increased permeability could be responsible for small but significant crossing of mucosal epithelium by virus and bacteria present in the lumen of mucosa. This mechanism could be particularly relevant to mucosal transmission of HIV-1 as well as immune activation seen in HIV-1 infected individuals

Comparative quantification of health risks: Conceptual framework and methodological issues

Reliable and comparable analysis of risks to health is key for preventing disease and injury. Causal attribution of morbidity and mortality to risk factors has traditionally been conducted in the context of methodological traditions of individual risk factors, often in a limited number of settings, restricting comparability. In this paper, we discuss the conceptual and methodological issues for quantifying the population health effects of individual or groups of risk factors in various levels of causality using knowledge from different scientific disciplines. The issues include: comparing the burden of disease due to the observed exposure distribution in a population with the burden from a hypothetical distribution or series of distributions, rather than a single reference level such as non-exposed; considering the multiple stages in the causal network of interactions among risk factor(s) and disease outcome to allow making inferences about some combinations of risk factors for which epidemiological studies have not been conducted, including the joint effects of multiple risk factors; calculating the health loss due to risk factor(s) as a time-indexed "stream" of disease burden due to a time-indexed "stream" of exposure, including consideration of discounting; and the sources of uncertainty