Procalcitonin in liver transplant patients – yet another stone turned

Liver transplantation has been reported to initiate increases in procalcitonin levels, in the absence of bacterial infection. The results of a study investigating the course of procalcitonin levels over several days after liver transplantation in noninfected patients were recently reported in Critical Care. This study shows that procalcitonin levels increase only transiently, immediately after surgery, and thereafter they rapidly decrease. This new information gives us hope that procalcitonin can be used as a marker of bacterial infection in these patients. Further studies of patients undergoing liver transplantation with and without bacterial infection are needed

Update on HIV in Western Europe

HIV infection in Western Europe is mainly concentrated among men who have sex with men, heterosexuals who acquired HIV from sub-Saharan African countries, and in people who inject drugs. The rate of newly diagnosed cases of HIV has remained roughly stable since 2004 whereas the number of people living with HIV has slowly increased due to new infections and the success of antiretroviral therapy in prolonging life. An ageing population is gradually emerging that will require additional care. There are large differences across countries in HIV testing rates, proportions of people who present to care with low CD4+ cell counts, accessibility to treatment and care, and rates of retention once in care. Improved collection of HIV surveillance data will benefit countries and help to understand their epidemic better. However, social inequalities experienced by people with HIV still remain in some regions and urgently need to be addressed

Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients

Background: Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods: Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results: During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions: An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications

A bioinformatic approach to identify new potential resistance relevant amino acid substitutions (AAS) in HIV-1 protease (H1P)

Background: Predicting potential drug resistance mutations are important when evaluating protein-drug interactions of potential new antiviral drugs. Here we used evolutionary data from the Retroviral Aspartyl Protease (RVP) family (PF00077, 54135 sequences) to estimate plausible PI resistant-associated AAS within the H1P. Methods: Using a Hidden Markov Model (HMM) of the RVP family probabilities were extracted for each possible AAS limited to the 38 positions reported in the IAS drug resistance listing for H1P (December 2008 version). The HMM is a dynamic Bayesian network, modeling sequences of amino acids. The HMM is based on curated and representative sequences from the RVP family. Results: Theoretically 760 AAS (20 × 38) are possible for the 38 evaluated positions within the H1P. Of these, the RVP-HMM detected a total of 229 AAS (30.1%) with a probability above 1/20 (0.05). Of the 229 AAS, 51 (70%) were among the 73 AAS included in the IAS listing as PI-resistant mutations, leaving 178 AAS with P > 0.05 as evolutionary plausible. Conclusion: Based on exploration of the RVP family by HMM, 70% of the established PI-resistant associated AAS could be predicted to occur. Additional 178 AAS was identified as evolutionary plausible and potentially could allow for drug-resistance. In conclusion, we provide a probability landscape of plausible/unfavorable AAS based on inherited structure through evolution and genetic distance, which could prove useful for future drug design

Regional differences in AIDS and non-AIDS related mortality in HIV-positive individuals across Europe and Argentina: the EuroSIDA study

BACKGROUND Differences in access to care and treatment have been reported in Eastern Europe, a region with one of the fastest growing HIV epidemics, compared to the rest of Europe. This analysis aimed to establish whether there are regional differences in the mortality rate of HIV-positive individuals across Europe, and Argentina. METHODS 13,310 individuals under follow-up were included in the analysis. Poisson regression investigated factors associated with the risk of death. FINDINGS During 82,212 person years of follow-up (PYFU) 1,147 individuals died (mortality rate 14.0 per 1,000 PYFU (95% confidence interval [CI] 13.1-14.8). Significant differences between regions were seen in the rate of all-cause, AIDS and non-AIDS related mortality (global p<0.0001 for all three endpoints). Compared to South Europe, after adjusting for baseline demographics, laboratory measurements and treatment, a higher rate of AIDS related mortality was observed in East Europe (IRR 2.90, 95%CI 1.97-4.28, p<.0001), and a higher rate of non-AIDS related mortality in North Europe (IRR 1.51, 95%CI 1.24-1.82, p<.0001). The differences observed in North Europe decreased over calendar-time, in 2009-2011, the higher rate of non-AIDS related mortality was no longer significantly different to South Europe (IRR 1.07, 95%CI 0.66-1.75, p = 0.77). However, in 2009-2011, there remained a higher rate of AIDS-related mortality (IRR 2.41, 95%CI 1.11-5.25, p = 0.02) in East Europe compared to South Europe in adjusted analysis. INTERPRETATIONS There are significant differences in the rate of all-cause mortality among HIV-positive individuals across different regions of Europe and Argentina. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes and individuals in North Europe had the highest rate of non-AIDS related mortality. These findings are important for understanding and reviewing HIV treatment strategies and policies across the European region

Trophic rewilding presents regionally specific opportunities for mitigating climate change

Large-bodied mammalian herbivores can influence processes that exacerbate or mitigate climate change. Herbivore impacts are, in turn, influenced by predators that place top-down forcing on prey species within a given body size range. Here, we explore how the functional composition of terrestrial large herbivore and carnivore guilds vary between three mammal distribution scenarios: Present-Natural, Current-Day, and Extant-Native Trophic (ENT) Rewilding. Considering the effects of herbivore species weakly influenced by top-down forcing, we quantify the relative influence keystone large herbivore guilds have on methane emissions, woody vegetation expansion, fire dynamics, large-seed dispersal, and nitrogen and phosphorous transport potential. We find strong regional differences in the number of herbivores under weak top-down regulation between our three scenarios with important implications for how they will influence climate change relevant processes. Under the Present-Natural non-ruminant, megaherbivore, browsers were a particularly important guild across much of the world. Megaherbivore extinction and range contraction and the arrival of livestock means large, ruminant, grazers have become more dominant. ENT Rewilding can restore the Afrotropics and Indo-Malay to the Present-Natural benchmark, but causes top-down forcing of the largest herbivores to become common place elsewhere. ENT Rewilding will reduce methane emissions, but does not maximise Natural Climate Solution potential

Vasoactive intestinal peptide in human nasal mucosa

Vasoactive intestinal peptide (VIP), which is present with acetylcholine in parasympathetic nerve fibers, may have important regulatory functions in mucous membranes. The potential roles for VIP in human nasal mucosa were studied using an integrated approach. The VIP content of human nasal mucosa was determined to be 2.84 +/- 0.47 pmol/g wet weight (n = 8) by RIA. VIP-immunoreactive nerve fibers were found to be most concentrated in submucosal glands adjacent to serous and mucous cells. 125I-VIP binding sites were located on submucosal glands, epithelial cells, and arterioles. In short-term explant culture, VIP stimulated lactoferrin release from serous cells but did not stimulate [3H]glucosamine-labeled respiratory glycoconjugate secretion. Methacholine was more potent than VIP, and methacholine stimulated both lactoferrin and respiratory glycoconjugate release. The addition of VIP plus methacholine to explants resulted in additive increases in lactoferrin release. Based upon the autoradiographic distribution of 125I-VIP binding sites and the effects on explants, VIP derived from parasympathetic nerve fibers may function in the regulation of serous cell secretion in human nasal mucosa. VIP may also participate in the regulation of vasomotor tone