Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

Lithium systematics in the Krafla volcanic system: comparison between surface rhyolites and felsic cuttings from the Iceland deep drilling project -1 (IDDP-1).

The unexpected discovery of felsic magma by the Iceland Deep Drilling Project-1 (IDDP-1) in the Krafla volcanic system (KVS) presents a unique opportunity to investigate pre-eruptive lithium (Li) dynamics and establish a more direct connection between magma reservoirs and volcanic deposits. Our study provides new insights into Li abundances and isotope compositions in bulk-rock, minerals, and groundmass glass from rhyolitic lavas at KVS, encompassing various stages of groundmass crystallisation. Additionally, we examined felsic cuttings retrieved from the IDDP-1 well, comprising crystal-poor obsidian and crystal-bearing to -rich 'felsite' particles. Groundmass glasses from surface lavas show limited variability in K/Na, indicating limited secondary hydration of the glasses and that their Li contents seem to not be affected by this post-eruptive process. Lithium inventories in groundmass glasses and minerals within lavas exhibit variations consistent with the cooling history of the deposit, resembling patterns seen in Snake River Plain ignimbrites. Lithium contents of glassy rhyolitic lavas, whether bulk-rock (avg. 27.2 ± 3.1 µg/g) or groundmass glass (average 28.4 ± 4.7 µg/g), and their bulk isotopic compositions (avg. δ7Li =+ 4.4 ± 0.2‰) overlap with those observed in IDDP-1 obsidian cuts (avg. 24.9 µg/g Li in bulk, 28.6 ± 1.5 µg/g in groundmass glass, and δ7Li = 4.5 ± 0.2‰). Glassy lavas lacking spherulites may potentially preserve pristine magmatic Li element and isotope compositions, while areas with extensive groundmass crystallisation reveal Li enrichments in phenocrysts. Plagioclases in slowly cooled parts of the deposit record a two-fold increase in Li contents compared to plagioclase found in glassy counterparts, along with evidence of open-system degassing marked by heavier bulk Li isotope compositions and lower bulk Li contents of the crystallised lava portions (avg. δ7Li = +7.2 ± 0.1‰ and 7 ± 0.8 µg/g Li) relative to bulk glassy lithologies (avg. δ7Li = +4.1 ± 0.1‰ and 28 ± 2 µg/g Li). Partition coefficients derived from IDDP-1 cuts successfully predict Li inventories in vitrophyres of rhyolites on the surface of the KVS. Lithium isotope compositions of the crystal-rich IDDP-1 cuts are significantly heavier (avg. δ7Li = +7.2 ± 0.2‰) than lavas and IDDP-1 obsidian cuts, casting doubt on the notion that the IDDP-1 rhyolitic magma could result from the melting of felsite lenses in the KVS. Lithium contents in groundmass glasses within IDDP-1 crystal-rich cuts show higher Li contents (avg. 55.1-60.7 µg/g), correlating with the higher crystal content and an increase in other incompatible elements (avg. 250 µg/g Rb) relative to obsidian cuttings (avg. 75 µg/g Rb). Supplementary Information: The online version contains supplementary material available at 10.1007/s00410-024-02119-y.

Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients.

INTRODUCTION: Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. METHODS: A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour¼ (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. RESULTS: The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). CONCLUSION: This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.

Effectiveness of clinical simulation on nursing student's improving critical care knowledge: a pretest-posttest study.

AIM: To evaluate the effectiveness of Human Patient Simulation method, as an additional method to theoretical lectures, on improving critical care knowledge of third course nursing students compared to only theoretical lectures. It was hypothesised that, the greater cognitive abilities used and trained around a specific subject, more strengthening of the subject contents is done by the students. METHODS: A non-experimental pretest-post test study was carried out with a questionnaire created ad hoc specifically for this study. Pretest questionnaire was administered after students received five weeks of theoretical lectures on critical care subjects. Post test was administered after students performed the theoretical classes and the simulation based learning activity on critical care subjects. RESULTS: 60 nursing students of the Campus Docent Sant Joan de Déu, attending to critical care subjects, were enrolled in the study. The statistical analyses performed showed a significance of the intervention in the post-test: p value 0.01 and the students improved on average by 1 point after the intervention, passing from 11.94 in the pre-test to 12.94 in the post-test. Results of this study suggest that use of Human Patient Simulation method of zone two made a positive difference in nursing students' ability to answer questions about critical care when there was need to apply their cognitives abilities. CONCLUSIONS: We evidenced that is crucial to direct cognitive resources appropriately toward each section of the simulation activity. Choosing the quantity and the kind of cognitive abilities that will be used by a specific group of students in a simulation activity, facilitators can upgrade the student knowledges and avoid impaired learning.

The influence of hospital antimicrobial use on carbapenem-non-susceptible Enterobacterales incidence rates according to their mechanism of resistance: a time-series analysis.

BACKGROUND: Carbapenem non-susceptible Enterobacterales (CNSE) can be broadly divided into those that produce carbapenemases (carbapenemase-producing Enterobacterales (CPE)), and those that harbour other mechanisms of resistance (non-carbapenemase-producing CNSE (NCP-CNSE)). AIM: To determine the predictors of CNSE nosocomial incidence rates according to their mechanism of resistance. METHODS: A time-series analysis was conducted (July 2013 to December 2018) to evaluate the relationship in time between hospital antibiotic use and the percentage of adherence to hand hygiene with the CNSE rates. FINDINGS: In all, 20,641 non-duplicated Enterobacterales isolates were identified; 2.2% were CNSE. Of these, 48.1% and 51.9% were CPE and NCP-CNSE, respectively. Of the CPE, 78.3% possessed a blaOXA-232 gene. A transfer function model was identified for CNSE, CPE, and OXA-232 CPE that explained 20.8%, 19.3%, and 24.2% of their variation, respectively. According to the CNSE and CPE models, an increase in piperacillin-tazobactam (TZP) use of 1 defined daily dose (DDD) per 100 hospital patient-days (HPD) would lead to an increase of 0.69 and 0.49 CNSE and CPE cases per 10,000 HPD, respectively. The OXA-232 CPE model estimates that an increase of 1 DDD per 100 HPD of TZP use would lead to an increase of 0.43 OXA-232 CPE cases per 10,000 HPD. A transfer function model was not identified for NCP-CNSE, nor was there an association between the adherence to handhygiene and the CNSE rates. CONCLUSION: The use of TZP is related in time with the CPE nosocomial rates, mostly explained by its effect on OXA-232 CPE.

Adequacy and prognostic impact of treatment for severe exacerbation of chronic obstructive pulmonary disease. / Adecuación e impacto pronóstico del tratamiento de las exacerbaciones graves de la enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To define the clinical characteristics of patients hospitalised in pneumology and internal medicine departments for chronic obstructive pulmonary disease (COPD) exacerbation, to assess the compliance with the recommendations of the clinical practice guidelines and to determine the impact on the patients' prognosis. METHODOLOGY: We conducted a retrospective longitudinal study that randomly included patients hospitalised for COPD exacerbation in a tertiary hospital. We collected demographic and clinical variables (degree of dyspnoea and obstruction, previous exacerbations, comorbidities), readmission and mortality data and criteria for compliance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and the Spanish COPD guidelines (GesEPOC). We performed a univariate, multivariate and survival analysis. RESULTS: The study included 108 patients, and the mean age was 71.48±11.65 years. The readmission rate was 26.4% at 3 months and 43.4% at 1 year. The hospital mortality rate was 3.9%, the mortality rate at 3 months was 21.9%, and the mortality rate at 1 year was 27.4%. The patients hospitalised in the internal medicine department had higher mortality during hospitalisation (p=.043), at 3 months (p=.028) and at 1 year (p=.007) compared with the rates for the pneumology department. Overall compliance with the clinical guidelines was 63% for the clinical evaluation (less for the patients in internal medicine: 56.1% vs. 73.8%, p=.063). For the treatment, the compliance was 26.9% for GOLD and 28.7% for GesEPOC. Compliance with the GOLD guidelines in the use of corticosteroids was associated with a lower rate of long-term readmissions (p=.041) and hospital mortality (p=.007) and 3-month mortality (p=.05). CONCLUSIONS: The clinical profile of the patients is currently similar to that previously reported, but their clinical progression was poorer. Overall compliance with the clinical guidelines for drug treatment was low, and only appropriate use of systemic steroids was associated with a reduction in early mortality and in medium-term readmissions.

Anticoagulant treatment of medical patients with complex clinical conditions. / Tratamiento anticoagulante en pacientes médicos con situaciones clínicas complejas.

There is scarce available information on the treatment or prophylaxis with anticoagulant drugs of outpatients with medical diseases and complex clinical conditions. There are no clinical practice guidelines and/or specific recommendations for this patient subgroup, which are frequently treated by internists. Complex clinical conditions are those in which, due to comorbidity, age, vital prognosis or multiple treatment with drugs, a clinical situation arises of disease-disease, disease-drug or drug-drug interactions that is not included within the scenarios that commonly generate the scientific evidence. The objective of this narrative review is collecting and adapting of the clinical guidelines recommendations and systematic reviews to complex clinical conditions, in which the direct application of recommendations based on studies that do not include patients with this complexity and comorbidity could be problematic.

Pneumocystis jirovecii infection in patients with acute interstitial pneumonia. / Infección por Pneumocystis jirovecii en pacientes con neumonía intersticial aguda.

OBJECTIVE: Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP. SUBJECTS AND METHODS: The presence of P. jirovecii in bronchoalveolar lavage fluid in the four confirmed cases of AIP identified in a tertiary-care hospital over a period of nine years was studied using a 2-step nested-PCR protocol assay. RESULTS: P. jirovecii was identified in the four cases. None of them had HIV infection. Two of the patients were treated empirically with trimethoprim-sulfamethoxazole, the only survivor was being one of them. CONCLUSIONS: Our data suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to evaluate the role of the pathogen in the physiopathology of this disease.

Delphi-RAND consensus of the Spanish Society of Internal Medicine on the controversies in anticoagulant therapy and prophylaxis in medical diseases. INTROMBIN Project (Uncertainty in thromboprophylaxis in internal medicine). / Consenso Delphi-RAND de la Sociedad Española de Medicina Interna sobre controversias en terapia y profilaxis anticoagulante en enfermedades médicas. Proyecto INTROMBIN (INcertidumbre en TROMBoprofilaxis en Medicina INterna).

The aim of this study was to determine the opinion of internists on the management of anticoagulation and thromboembolism prophylaxis in complex clinical scenarios in which the risk-benefit ratio of surgery is narrow and to develop a consensus document on the use of drugs anticoagulant therapy in this patient group. To this end, we identified by consensus the clinical areas of greatest uncertainty, a survey was created with 20 scenarios laid out in 40 clinical questions, and we reviewed the specific literature. The survey was distributed among the internists of the Spanish Society of Internal Medicine (SEMI) and was completed by 290 of its members. The consensus process was implemented by changing the Delphi-RAND appropriateness method in an anonymous, double-round process that enabled an expert panel to identify the areas of agreement and uncertainty. In our case, we also added the survey results to the panel, a methodological innovation that helps provide additional information on the standard clinical practice. The result of the process is a set of 19 recommendations formulated by SEMI experts, which helps establish guidelines for action on anticoagulant therapy in complex scenarios (high risk or active haemorrhage, short life expectancy, coexistence of antiplatelet therapy or comorbidities such as kidney disease and liver disease), which are not uncommon in standard clinical practice.

Monte Carlo calculations of the cellular S-values for α-particle-emitting radionuclides incorporated into the nuclei of cancer cells of the MDA-MB231, MCF7 and PC3 lines.

S-values (dose per unit of cumulated activity) for alpha particle-emitting radionuclides and monoenergetic alpha sources placed in the nuclei of three cancer cell models (MCF7, MDA-MB231 breast cancer cells and PC3 prostate cancer cells) were obtained by Monte Carlo simulation. The MCNPX code was used to calculate the fraction of energy deposited in the subcellular compartments due to the alpha sources in order to obtain the S-values. A comparison with internationally accepted S-values reported by the MIRD Cellular Committee for alpha sources in three sizes of spherical cells was also performed leading to an agreement within 4% when an alpha extended source uniformly distributed in the nucleus is simulated. This result allowed to apply the Monte Carlo Methodology to evaluate S-values for alpha particles in cancer cells. The calculation of S-values for nucleus, cytoplasm and membrane of cancer cells considering their particular geometry, distribution of the radionuclide source and chemical composition by means of Monte Carlo simulation provides a good approach for dosimetry assessment of alpha emitters inside cancer cells. Results from this work provide information and tools that may help researchers in the selection of appropriate radiopharmaceuticals in alpha-targeted cancer therapy and improve its dosimetry evaluation.

Assessment of cell death mechanisms triggered by 177Lu-anti-CD20 in lymphoma cells.

The aim of this research was to evaluate the cell cycle redistribution and activation of early and late apoptotic pathways in lymphoma cells after treatment with 177Lu-anti-CD20. Experimental and computer models were used to calculate the radiation absorbed dose to cancer cell nuclei. The computer model (Monte Carlo, PENELOPE) consisted of twenty spheres representing cells with an inner sphere (cell nucleus) embedded in culture media. Radiation emissions of the radiopharmaceutical located in cell membranes and in culture media were considered for nuclei dose calculations. Flow cytometric analyses demonstrated that doses as low as 4.8Gy are enough to induce cell cycle arrest and activate late apoptotic pathways.

Expression of a symbiosis-specific gene in Symbiodinium type A1 associated with coral, nudibranch and giant clam larvae.

Symbiodinium are responsible for the majority of primary production in coral reefs and found in a mutualistic symbiosis with multiple animal phyla. However, little is known about the molecular signals involved in the establishment of this symbiosis and whether it initiates during host larval development. To address this question, we monitored the expression of a putative symbiosis-specific gene (H+-ATPase) in Symbiodinium A1 ex hospite and in association with larvae of a scleractinian coral (Mussismilia hispida), a nudibranch (Berghia stephanieae) and a giant clam (Tridacna crocea). We acquired broodstock for each host, induced spawning and cultured the larvae. Symbiodinium cells were offered and larval samples taken for each host during the first 72 h after symbiont addition. In addition, control samples including free-living Symbiodinium and broodstock tissue containing symbionts for each host were collected. RNA extraction and RT-PCR were performed and amplified products cloned and sequenced. Our results show that H+-ATPase was expressed in Symbiodinium associated with coral and giant clam larvae, but not with nudibranch larvae, which digested the symbionts. Broodstock tissue for coral and giant clam also expressed H+-ATPase, but not the nudibranch tissue sample. Our results of the expression of H+-ATPase as a marker gene suggest that symbiosis between Symbiodinium and M. hispida and T. crocea is established during host larval development. Conversely, in the case of B. stephanieae larvae, evidence does not support a mutualistic relationship. Our study supports the utilization of H+-ATPase expression as a marker for assessing Symbiodinium-invertebrate relationships with applications for the differentiation of symbiotic and non-symbiotic associations. At the same time, insights from a single marker gene approach are limited and future studies should direct the identification of additional symbiosis-specific genes, ideally from both symbiont and host.

Importance of tissue sampling, laboratory methods, and patient characteristics for detection of Pneumocystis in autopsied lungs of non-immunosuppressed individuals.

To understand the epidemiological significance of Pneumocystis detection in a lung tissue sample of non-immunosuppressed individuals, we examined sampling procedures, laboratory methodology, and patient characteristics of autopsy series reported in the literature. Number of tissue specimens, DNA-extraction procedures, age and underlying diagnosis highly influence yield and are critical to understand yield differences of Pneumocystis among reports of pulmonary colonization in immunocompetent individuals.

Relationship between lymphocyte DNA fragmentation and dose of iron oxide (Fe2O3) and silicon oxide (SiO2) nanoparticles.

At present, the use of nanoparticles is a controversial topic, especially when analyzing their effects in human tissues. Nanoparticles (NPs) can cause oxidative stress by increasing membrane lipids peroxidation and reactive oxygen species, and decreasing intracellular glutathione. Oxidative stress plays an important role in cell signaling and inflammatory responses. It can result in genotoxicity, affect cell proliferation, and induce DNA damage. The objective of this study is to evaluate the genotoxic potential of NPs in lymphocyte DNA. Wistar female rats (N = 45) were sorted in three randomized groups as follows: Group 1 (N = 20); Group 2 (N = 20) and a control group (N = 5). A single dose of iron oxide (Fe2O3) and silicon oxide (SiO2) NPs dissolved in saline solution were administered orally to the rats. Cardiac puncture was performed to extract peripheral blood for genotoxic analysis. DNA fragmentation for lymphocytes was performed. Control rats showed a fragmentation percentage of 11.20 ± 2.16%. Rats exposed to SiO2 and Fe2O3 NPs for 24 h showed statistically significant differences in DNA fragmentation percentages as compared with that of the control group. A lineal dose-response correlation between genotoxic damage and exposure to SiO2 and Fe2O3 NPs was found (r2 = 0.99 and 0.98 for SiO2 and Fe2O3, respectively). In conclusion, we found that exposure to Fe2O3 and SiO2 NPs can cause DNA fragmentation in lymphocytes in a dose-dependent manner.

Multicentre study highlighting clinical relevance of new high-throughput methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia.

Pneumocystis jirovecii causes severe interstitial pneumonia (PcP) in immunosuppressed patients. This multicentre study assessed the distribution frequencies of epidemiologically relevant genetic markers of P. jirovecii in different geographic populations from Portugal, the USA, Spain, Cuba and Mozambique, and the relationship between the molecular data and the geographical and clinical information, based on a multifactorial approach. The high-throughput typing strategy for P. jirovecii characterization consisted of DNA pooling using quantitative real-time PCR followed by multiplex-PCR/single base extension. The frequencies of relevant P. jirovecii single nucleotide polymorphisms (mt85, SOD110, SOD215, DHFR312, DHPS165 and DHPS171) encoded at four loci were estimated in ten DNA pooled samples representing a total of 182 individual samples. Putative multilocus genotypes of P. jirovecii were shown to be clustered due to geographic differences but were also dependent on clinical characteristics of the populations studied. The haplotype DHFR312T/SOD110C/SOD215T was associated with severe AIDS-related PcP and high P. jirovecii burdens. The frequencies of this genetic variant of P. jirovecii were significantly higher in patients with AIDS-related PcP from Portugal and the USA than in the colonized patients from Portugal, and Spain, and children infected with P. jirovecii from Cuba or Mozambique, highlighting the importance of this haplotype, apparently associated with the severity of the disease and specific clinical groups. Patients from the USA and Mozambique showed higher rates of DHPS mutants, which may suggest the circulation of P. jirovecii organisms potentially related with trimethoprim-sulfamethoxazole resistance in those geographical regions. This report assessed the worldwide distribution of P. jirovecii haplotypes and their epidemiological impact in distinct geographic and clinical populations.

High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia.

We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2%, p 0.021, and 11.5% vs. 3.6%, p 0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (odds ratio (OR) 6.34, 95% confidence interval (CI) 1.86-21.65), HIV infection (OR 2.99, 95% CI 1.16-7.70), grunting (OR 2.64, 95% CI 1.04-6.73) and digital clubbing (OR 10.75, 95% CI 1.21-95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed.

Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers.

The diagnosis of Pneumocystis pneumonia (PCP) relies on microscopic visualization of Pneumocystis jirovecii organisms or DNA detection in pulmonary specimens. This study aimed to assess the usefulness of (1-3)-ß-d-glucan (BG), Krebs von den Lungen-6 antigen (KL-6), lactate dehydrogenase (LDH) and S-adenosyl methionine (SAM) as serologic biomarkers in the diagnosis of PCP. Serum levels of BG, KL-6, LDH and SAM were investigated in 145 Portuguese patients, 50 patients from the Netherlands, 25 Spanish patients and 40 Portuguese blood donors. Data on clinical presentation, chest imaging and gasometry tests were available. PCP cases were confirmed by microscopy and PCR techniques. A cost-effectiveness analysis was performed. BG was found to be the most reliable serologic biomarker for PCP diagnosis, followed by KL-6, LDH and SAM. The BG/KL-6 combination test was the most accurate serologic approach for PCP diagnosis, with 94.3% sensitivity and 89.6% specificity. Although less sensitive/specific than the reference standard classic methods based on bronchoalveolar lavage followed by microscopic or molecular detection of P. jirovecii organisms, the BG/KL-6 test may provide a less onerous procedure for PCP diagnosis, as it uses a minimally invasive and inexpensive specimen (blood), which may be also a major benefit for the patient's care. The BG/KL-6 combination test should be interpreted within the clinical context, and it may be used as a preliminary screening test in patients with primary suspicion of PCP, or as an alternative diagnostic procedure in patients with respiratory failure or in children, avoiding the associated risk of complications by the use of bronchoscopy.

Preparation and preclinical evaluation of (66)Ga-DOTA-E(c(RGDfK))2 as a potential theranostic radiopharmaceutical.

INTRODUCTION: Integrin αvß3 plays an important role in angiogenesis and is over-expressed in tumoral endothelial cells and some other tumor cells. RGD (Arg-Gly-Asn) peptides labeled with (68)Ga (t1/2=68min) have showed good characteristics for imaging of αvß3 expression using positron emission tomography (PET). Gallium-66 has been proposed as a PET imaging alternative to (68)Ga and given the unique high energy of its emitted positrons (Emax 4.15MeV) it may also be useful for therapy. The aim of this research is to prepare [(66)Ga]DOTA-E-[c(RGDfK)]2 and evaluate in mice its potential as a new theranostic radiopharmaceutical. METHODS: High specific activity (66)Ga was produced via the (66)Zn(p,n) reaction, and the labelling method of DOTA-E-[c(RGDfK)]2 with (66)Ga was optimized. Radiochemical purity was determined by TLC, and in vitro stability and protein binding were determined. Serial microPET imaging and biodistribution studies were carried out in nude mice bearing C6 xenografts. Radiation absorbed dose estimates were based on the biodistribution studies, where tumor and organs of interest were collected at 0.5, 1, 3, 5 and 24h post-injection of [(66)Ga]DOTA-E-[c(RGDfK)]2. RESULTS: Our results have shown that [(66)Ga]DOTA-E-[c(RGDfK)]2 can be prepared with high radiochemical purity (>97%), specific activity (36-67GBq/µmol), in vitro stability, and moderate protein binding. MicroPET imaging up to 24 post-injection showed contrasting tumors reflecting αvß3-targeted tracer accumulation. Biodistribution studies and dosimetry estimations showed a stable tumor uptake, rapid blood clearance, and favorable tumor-to-tissue ratios. CONCLUSIONS: The peptide conjugated DOTA-E-[c(RGDfK)]2 labeled with (66)Ga may be attractive as a theranostic agent for tumors over-expressing αvß3 integrins.

Tumoral fibrosis effect on the radiation absorbed dose of (177)Lu-Tyr(3)-octreotate and (177)Lu-Tyr(3)-octreotate conjugated to gold nanoparticles.

The aim of this work was to evaluate the tumoral fibrosis effect on the radiation absorbed dose of the radiopharmaceuticals (177)Lu-Tyr(3)-octreotate (monomeric) and (177)Lu-Tyr(3)-octreotate-gold nanoparticles (multimeric) using an experimental HeLa cells tumoral model and the Monte Carlo PENELOPE code. Experimental and computer micro-environment models with or without fibrosis were constructed. Results showed that fibrosis increases up to 33% the tumor radiation absorbed dose, although the major effect on the dose was produced by the type of radiopharmaceutical (112Gy-multimeric vs. 43Gy-monomeric).

Serum and bal beta-D-glucan for the diagnosis of Pneumocystis pneumonia in HIV positive patients.

BACKGROUND/PURPOSE: The diagnosis of patients with pulmonary infiltrates and human immunodeficiency virus (HIV) infection remains a challenge. In current clinical practice the gold standard for Pneumocystis jirovecii pneumonia (PCP) diagnosis remains the identification of the organism in bronco alveolar lavage (BAL) using microscopy (e.g., silver stain). (1->3)-ß -d-glucan (BG) is a polysaccharide that is present within the cell wall of Pneumocystis and other fungi. METHODS: We analyzed serum and BAL lavage fluid from a cohort of 119 patients that did have HIV, a diagnosis of pneumonia and underwent bronchoscopy (FOB) for diagnosis of PCP. RESULTS: The discriminative power of serum BG for the diagnosis of PCP in this group of patients was very high. Using a cutoff of 300 pg/mL, the sensitivity, specificity, positive predictive value(PPV) and negative predictive value (NPV) were 91%, 92%, 89% and 93% respectively. A model for ROC with just serum BG (N = 108) had an AUC of 0.95. Serum procalcitonin (PCT) and BAL BG were not as accurate for the diagnosis of PCP. For BAL BG using a cutoff of 783 pg/mL, the sensitivity,specificity, positive predictive value (PPV) and negative predictive value (NPV) were 72%, 79%,72% and 79% respectively. The differences between the medians for serum PCT between the group with a without PCP did not reach statistical significance (p = 0.6137). CONCLUSION: The measurement of serum BG should be incorporated in the diagnostic work up of HIV positive patients with dyspnea and infiltrates on chest X X-ray. Our study confirms the diagnostic value of serum BG previously reported by others but we add a cutoff value that we believe is more accurate for patients with AIDS and suspicion of PCP.