Low vitamin D levels are linked with increased cardiovascular disease risk in young adults: a sub-study and secondary analyses from the ACTIBATE randomized controlled trial.

PURPOSE: Vitamin D deficiency is related to metabolic disturbances. Indeed, a poor vitamin D status has been usually detected in patients with cardiovascular disease (CVD). However, the relationship between vitamin D and CVD risk factors in young adults remains controversial at present. This study aimed to examine the association between circulating 25-hydroxivitamin D (25(OH)D) and CVD risk factors in young adults. METHODS: The present cross-sectional study included a cohort of 177 young adults aged 18-25 years old (65% women). 25(OH)D serum concentrations were assessed using a competitive chemiluminescence immunoassay. Fasting CVD risk factors (i.e., body composition, blood pressure, glucose metabolism, lipid profile, liver, and inflammatory markers) were determined by routine methods. A panel of 63 oxylipins and endocannabinoids (eCBs) was also analyzed by targeted metabolomics. RESULTS: Circulating 25(OH)D concentrations were inversely associated with a wide range of CVD risk factors including anthropometrical (all P ≤ 0.005), body composition (all P ≤ 0.038), glucose metabolism (all P ≤ 0.029), lipid profile (all P < 0.035), liver (all P ≤ 0.011), and pro-inflammatory biomarkers (all P ≤ 0.030). No associations of serum 25(OH)D concentrations were found with pro-inflammatory markers (all P ≥ 0.104), omega-6 and omega-3 oxylipins, nor eCBs concentrations or their analogs (all P ≥ 0.05). CONCLUSION: The present findings support the idea that 25(OH)D could be a useful predictor of CVD risk in young individuals.

Pharmacokinetics/pharmacodynamics and therapeutic drug monitoring of ceftazidime/avibactam administered by continuous infusion in patients with MDR Gram-negative bacterial infections.

BACKGROUND: Therapeutic drug monitoring (TDM) of ß-lactams in critically ill patients has been correlated with better clinical outcomes. Evidence on TDM of newer ß-lactams such as ceftazidime/avibactam administered by continuous infusion (CI) is very limited. OBJECTIVES: To describe our experience with TDM of ceftazidime/avibactam and pharmacokinetic/pharmacodynamic (PK/PD) target attainment in patients with MDR bacterial infections. Clinical outcomes of ceftazidime/avibactam administered by CI were also assessed. METHODS: Patients treated with ceftazidime/avibactam administered by CI and undergoing TDM of ceftazidime plasma concentrations were included. Blood samples were obtained as part of the TDM program. The PK/PD therapeutic target of ceftazidime/avibactam was defined as 100%fT > 4 × MIC of the causative pathogen, and 100%fT > 10 × MIC was considered overexposure. Dose changes were made according to the TDM results. RESULTS: Thirty-one patients were included. Ceftazidime/avibactam total daily doses ranged from 1 g/0.25 g to 6 g/1.5 g. Twenty-six patients (83.9%) achieved a 100%fT > 4 × MIC, 15 (48.4%) of which were overexposed (100%fT > 10 × MIC). Dose reduction was suggested in 16/28 (57.1%) patients and dose maintenance in 12/28 (42.9%). Overall clinical cure was observed in 21 (67.7%) patients, and 18 of these (85.7%) achieved a 100%fT > 4 × MIC. CONCLUSIONS: Administering ceftazidime/avibactam by CI enabled the desired PK/PD target to be achieved in a large proportion of patients, even at lower doses than those recommended for a 2 h extended infusion. We suggest that the use of CI with TDM may be a useful tool for reducing initial doses, which could help to reduce antimicrobial-related adverse effects and treatment costs.

Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Treatment of COVID-19 pneumonia with low-dose radiotherapy plus standard of care versus standard of care alone in frail patients : The SEOR-GICOR IPACOVID comparative cohort trial.

PURPOSE: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. MATERIALS AND METHODS: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. RESULTS: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1­month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed. CONCLUSION: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1­month mortality, and prolonged actuarial overall survival compared to SoC alone.

Impact of methods for data selection on the day-to-day reproducibility of resting metabolic rate assessed with four different metabolic carts.

BACKGROUND AND AIMS: Accomplishing a high day-to-day reproducibility is important to detect changes in resting metabolic rate (RMR) and respiratory exchange ratio (RER) that may be produced after an intervention or for monitoring patients' metabolism over time. We aimed to analyze: (i) the influence of different methods for selecting indirect calorimetry data on RMR and RER assessments; and, (ii) whether these methods influence RMR and RER day-to-day reproducibility. METHODS AND RESULTS: Twenty-eight young adults accomplished 4 consecutive RMR assessments (30-min each), using the Q-NRG (Cosmed, Rome, Italy), the Vyntus CPX (Jaeger-CareFusion, Höchberg, Germany), the Omnical (Maastricht Instruments, Maastricht, The Netherlands), and the Ultima CardiO2 (Medgraphics Corporation, St. Paul, Minnesota, USA) carts, on 2 consecutive mornings. Three types of methods were used: (i) short (periods of 5 consecutive minutes; 6-10, 11-15, 16-20, 21-25, and 26-30 min) and long time intervals (TI) methods (6-25 and 6-30 min); (ii) steady state (SSt methods); and, (iii) methods filtering the data by thresholding from the mean RMR (filtering methods). RMR and RER were similar when using different methods (except RMR for the Vyntus and RER for the Q-NRG). Conversely, using different methods impacted RMR (all P ≤ 0.037) and/or RER (P ≤ 0.009) day-to-day reproducibility in all carts. The 6-25 min and the 6-30 min long TI methods yielded more reproducible measurements for all metabolic carts. CONCLUSION: The 6-25 min and 6-30 min should be the preferred methods for selecting data, as they result in the highest day-to-day reproducibility of RMR and RER assessments.

Acute phase characteristics and long-term complications of pulmonary embolism in COVID-19 compared to non-COVID-19 cohort: a large single-centre study.

BACKGROUND: To compare the severity of pulmonary embolism (PE) and the long-term complications between patients with and without COVID-19, and to investigate whether the tools for risk stratification of death are valid in this population. METHODS: We retrospectively included hospitalized patients with PE from 1 January 2016 to 31 December 2022. Comparisons for acute episode characteristics, risk stratification of the PE, outcomes, and long-term complications were made between COVID and non-COVID patients. RESULTS: We analyzed 116 (27.5%) COVID patients and 305 (72.4%) non-COVID patients. In patients with COVID-19, the traditional risk factors for PE were absent, and the incidence of deep vein thrombosis was lower. COVID patients showed significantly higher lymphocyte count, lactate dehydrogenase, lactic acid, and D-dimer levels. COVID patients had PE of smaller size (12.3% vs. 25.5% main pulmonary artery, 29.8% vs. 37.1% lobar, 44.7% vs. 29.5% segmental and 13.2% vs. 7.9% subsegmental, respectively; p < 0.001), less right ventricular dysfunction (7.7% vs. 17.7%; p = 0.007) and higher sPESI score (1.66 vs. 1.11; p < 0.001). The need for mechanical ventilation was significantly higher in COVID patients (8.6% vs. 1.3%; p < 0.001); However, the in-hospital death was less (5.2% vs. 10.8%; p = 0.074). The incidence of long-term complications was lower in COVID cohort (p < 0.001). PE severity assessed by high sPESI and intermediate and high-risk categories were independently associated with in-hospital mortality in COVID patients. CONCLUSION: The risk of in-hospital mortality and the incidence of long-term complications were lower in COVID-19. The usual tools for risk stratification of PE are valid in COVID patients.

Cryopreservation of seeds of Neonotonia wightii Wight and Arn: a strategy for conservation, dormancy breaking and preservation of nutritional status.

BACKGROUND: N. wightii (Leguminosae) is valued as a cover crop and as a potential source of protein in food insecure countries. However, plantlet establishment is limited by physical dormancy. Our previous work has shown that exposure of N. wightii seeds to cryogenic temperatures is able to overcome physical dormancy. OBJECTIVE: The current study is an extension of that work where the field performance and nutritional composition of plants regenerated from N. wightii seeds was investigated. RESULTS: It was evident that plants regenerated from cryopreserved seeds displayed faster growth rates than those from control seeds. In addition, cryopreservation did not alter the nutritional profile of plants produced from cryo-stored seeds. CONCLUSION: Collectively, the results indicate that cryopreservation serves as a suitable strategy for the preservation of seeds of N. wightii with the added benefit of also serving as a dormancy breaking mechanism upon retrieval from cryogenic temperatures. Doi.org/10.54680/fr23510110712.

The genus Microcotyle in Mediterranean scorpaenoids (Teleostei), including the description of Microcotyle merche n. sp. from Helicolenus dactylopterus (Delaroche, 1809).

More than 65 species of the genus Microcotyle Van Beneden & Hesse, 1863, have been described to date, most of them infecting Perciformes. Among the scorpaenoids (Perciformes, formerly Scorpaeniformes) the species of the genus Microcotyle parasitize sebastids and scorpaenids worldwide. In this study, we provide new morphological and molecular data for Microcotyle spp. in sebastids and scorpaenids from the Western Mediterranean and north-east Atlantic. Specimens of Helicolenus dactylopterus (Delaroche, 1809) (n = 107) and Scorpaena spp. (n = 107) were examined and their microcotylid specimens morphologically and molecularly characterized. Microcotyle merche n. sp. ex H. dactylopterus and specimens of Microcotyle algeriensis Ayadi, Gey, Justine & Tazerouti, 2016 from a new host and locality (Scorpaena scrofa from the north-east Atlantic) are herein described. Both species are phylogenetically close, but their morphology is markedly different mostly because the anterior lobe of the haptor present in other Microcotyle species is almost absent in M. algeriensis. Findings of M. merche n. sp. in the Mediterranean also excludes the presence of Microcotyle sebastis in this sea, encouraging the review of the exceptionally large host range and geographical distribution of this species.

Evaluation of Expanded Criteria Donors Using the Kidney Donor Profile Index and the Preimplantation Renal Biopsy.

The increasing comorbidity of kidney transplant (KT) donors make it necessary to develop scores to correctly assess the quality of kidney grafts. This study analyzes the usefulness of the preimplantation biopsy and the Kidney Donor Profile Index (KDPI) as indicators of KT survival from expanded criteria donors (ECD). Retrospective study of KT in our center between January 2010 to June 2019 who received a kidney from an ECD and underwent a preimplantation biopsy. 266 KT were included. Graft survival was categorized by KDPI quartiles: Q1 = 86%, Q2 = 95%, Q3 = 99% and Q4 = 100%. KT from KDPI Q1 presented better survival (p = 0.003) and Q4 donors had worse renal function (p = 0.018) and poorer glomerular filtration rate (3rd month; p = 0.017, 1st year; p = 0.010). KT survival was analyzed according to KDPI quartile and preimplantation biopsy score simultaneously: Q1 donors with biopsy score ≤3 had the best survival, especially comparing against Q3 with a biopsy score >3 and Q4 donors (p = 0.014). In multivariable analysis, hyaline arteriopathy, glomerulosclerosis, and KDPI Q4 were predictors for graft survival. High KDPI and a greater histological injury in the preimplantation biopsy, especially glomerular and vascular lesions, were related to a higher rate of KT loss from ECD.

Cryopreservation of seeds of the highly valued tropical timber species Swietenia mahagoni.

BACKGROUND: Swietenia mahagoni wood is one of the most valuable in world trade and, as a result, natural populations have been decimated due to unsustainable harvesting. The decline in natural population levels is being exacerbated by climate change. In order to ensure the preservation of valuable genotypes, there is an urgent need to develop strategies to conserve the genetic diversity present within this species. At present, cryopreservation is the most viable option for the long-term storage of plant germplasm, particularly for long-lived species which are challenging to maintain in the field. OBJECTIVE: To cryopreserve intact seeds of S. mahagoni, with the dual goal of retaining the biosynthetic capacity of plants, which is critical since this species is highly valued for medicinal purposes. MATERIALS AND METHODS: Seeds at a moisture content of 6% were immersed in liquid nitrogen (LN) before warming and recovery. Plantlet establishment and growth were assessed over a period of 70 days and anthraquinone synthesis was determined in roots, stems and leaves. RESULTS: The results showed an initial lag in the germination rate of cryopreserved seeds compared with control seeds; however, this difference disappeared over time. The lag in seedling emergence observed in cryostored seeds was also evident in the plant characteristics measured following 30 days of culture when all plant parameters measured were significantly higher in plants produced from control than cryostored seeds. However, after 70 days of growth, these differences were no longer apparent. Anthraquinone levels were also initially lower (at 30 days) in plants regenerated from cryopreserved seeds than those from control seeds, however, this difference was substantially reduced by 70 days thereby indicating the ability of these plants to accumulate secondary metabolites, albeit at a reduced rate, during the early stages of development. CONCLUSION: In S. mahagoni, the delay in anthraquinone production in plants regenerated from cryostored seeds during the early stages of development may have occurred as a consequence of the preferential allocation of resources towards the initiation of recovery processes in response to the stresses imposed by cryopreservation. Once the stresses were overcome and plant growth resumed, resources could be directed to secondary processes such as anthraquinone synthesis. doi.org/10.54680/fr22610110412.

Medication related to pigmentation of oral mucosa.

BACKGROUND: The diagnosis of oral melanotic lesions is, more often than not, challenging in the clinical practice due to the fact that there are several reasons which may cause an increase in pigmentation on localized or generalized areas. Among these, medication stands out. MATERIAL AND METHODS: In this work, we have carried out a review in the reference pharma database: Micromedex® followed by a review of the scientific published literature to analyse coincidences and possible discrepancies. RESULTS: Our findings show that there are several prescription drugs that can cause pigmented lesions in the oral mucosa. This must be known by clinicians in order to properly diagnose pigmented lesions. We have identified a set of 21 medicaments which cause these lesions, some of which are used frequently in the clinic, such as Metronidazole, Amitriptyline, conjugated oestrogens and Chlorhexidine gluconate. We also found discrepancies with the data published in specialized literature, some of which wasn't reflected in the Summary of Product Characteristics. CONCLUSIONS: Our work highlights the importance of the proper communication of adverse drug reactions (ADR) by health professionals in order to provide thorough and accurate information and diagnosis.

Protocol for assessing mortality reduction with the early use of noninvasive ventilation in prehospital emergency services: A multicentre, observational cohort study in Madrid, Spain.

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.

Pulmonary mixed squamous and glandular papilloma: diagnostic challenges of a rare lesion when the clock is ticking. How to avoid interpretation mistakes.

Pulmonary mixed squamous and glandular papillomas (MSCGPs) are rare, benign neoplasms with peculiar clinical and histological features. However, on occasion, they can present certain characteristics that overlap with other neoplasms including carcinomas. Recognising these features is hence important for treatment purposes. Molecular studies can sometimes help in further characterisation, although they should not guide the diagnosis which ultimately relies on morphology.We report a challenging case of MSCGP with unusual features, received during intraoperative consultation. We highlight the subtle morphological features to help avoid overcalling a benign lesion as malignant.

Clinicopathological significance of the expression of PD-L1 in non-small cell lung cancer.

INTRODUCTION: PD1/PD-L1 pathway targeting therapies are nowadays an established treatment option for patients with NSCLC. We assessed whether PD-L1 expression in NSCLC tumor cells was associated with specific clinical features or overall survival using four different clones. METHODS AND RESULTS: A retrospective study included formalin-fixed paraffin embedded (FFPE) surgical tumors from 482 patients. PD-L1 status was assessed with immunohistochemistry in tumor cells on tissue microarrays using clones 28-8, 22C3, SP263 and SP142. Associations with OS were assessed by Kaplan-Meier and multivariate Cox's regression analysis. Patients' median age: 68 years (39-86); histology: adenocarcinoma (AdCa) 61%, squamous-cell carcinoma (SqCC) 33%, and large cell carcinoma (LCC) 6%; p-stage: IA (46%), IB (30%), IIA (10%), IIB (11,4%), IIIA (1,2%), IIIB - IV (0,4%). PD-L1 positivity (≥1%) in NSCLC for clones 28-8, 22C3, SP263, SP142 was 41.5%, 34.2%, 42.7%, 10.4%, respectively (Pearson Chi-square p < 0.0001). PD-L1 expression was correlated with histology, tumor size and grading. Statistically significant association between PD-L1 expression and OS in NSCLC and Non-AdCa was observed with clone SP142 (log-rank p = 0.045 and p = 0.05, respectively). Statistically significant association between PD-L1 expression and OS in LCC was observed with clones 22C3 (log-rank p = 0.009) and SP263 (log-rank p = 0.050). CONCLUSIONS: Overexpression of the PD-L1 clone SP142 was associated with poor overall survival in NSCLC and Non-AdCa. Clones 22C3 and SP263 were associated with poor prognosis in LCC. PD-L1 status might serve as a prognostic marker in NSCLC.

Exposure of Teramnus labialis (L.F.) Spreng Seeds to Liquid Nitrogen Does Not Affect Nutritional Status of Field Grown Adult Plants.

BACKGROUND: Teramnus labialis (L.f.) Spreng is a potentially important legume species, and can be used as an animal feed and to enhance soil physicochemical characteristics. Despite the biological and agricultural importance, the low availability of seeds, their small size and the low percentage germination limit their large-scale use by farmers. We previously reported a method to cryopreserve seeds of T. labialis which also allowed for the breaking of seed dormancy. OBJECTIVE: The current study reports on the nutritional status of 5 month old field grown plants regenerated from cryostored and control seeds. MATERIALS AND METHODS: Biomass (fresh and dry mass of leaves and stems) and contents of ash, neutral detergent fiber, acid detergent fiber, lignin, cellulose, crude protein, P, Ca, Mg and K were measured. RESULTS: Seeds germinated and emerged faster following immersion in liquid nitrogen (LN) which was supported by quantitative evaluations of fresh and dry weights per m2. However, the ratio of leaf:stem mass were not altered by seed exposure to LN. CONCLUSION: The results showed that exposure of seeds to cryogenic temperatures did not alter the nutritional composition of regenerated plants.

Consensus on improving the comprehensive care of patients with acute heart failure. / Consenso para la mejora de la atención integral de los pacientes con insuficiencia cardíaca aguda.

The latest acute heart failure consensus document from the Spanish Society of Cardiology, Spanish Society of Internal Medicine, and Spanish Society of Emergency Medicine was published in 2015, which made an update covering the main novelties regarding acute heart failure from the last few years necessary. These include publication of updated European guidelines on heart failure in 2016, new studies on the pharmacological treatment of patients during hospitalization, and other recent developments regarding acute heart failure such as early treatment, intermittent treatment, advanced heart failure, and refractory congestion. This consensus document was drafted with the aim of updating all aspects related to acute heart failure and to create a document that comprehensively describes the diagnosis, treatment, and management of this disease.

Corrected Super-Resolution Microscopy Enables Nanoscale Imaging of Autofluorescent Lung Macrophages.

Observing the cell surface and underlying cytoskeleton at nanoscale resolution using super-resolution microscopy has enabled many insights into cell signaling and function. However, the nanoscale dynamics of tissue-specific immune cells have been relatively little studied. Tissue macrophages, for example, are highly autofluorescent, severely limiting the utility of light microscopy. Here, we report a correction technique to remove autofluorescent noise from stochastic optical reconstruction microscopy (STORM) data sets. Simulations and analysis of experimental data identified a moving median filter as an accurate and robust correction technique, which is widely applicable across challenging biological samples. Here, we used this method to visualize lung macrophages activated through Fc receptors by antibody-coated glass slides. Accurate, nanoscale quantification of macrophage morphology revealed that activation induced the formation of cellular protrusions tipped with MHC class I protein. These data are consistent with a role for lung macrophage protrusions in antigen presentation. Moreover, the tetraspanin protein CD81, known to mark extracellular vesicles, appeared in ring-shaped structures (mean diameter 93 ± 50 nm) at the surface of activated lung macrophages. Thus, a moving median filter correction technique allowed us to quantitatively analyze extracellular secretions and membrane structure in tissue-derived immune cells.

Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Neosaxitoxin Inhibits the Expression of Inflammation Markers of the M1 Phenotype in Macrophages.

(1) Background: Neosaxitoxin (NeoSTX) has been used as a local anesthetic, but its anti-inflammatory effects have not been well defined. In the present study, we investigate the effects of NeoSTX on lipopolysaccharide (LPS)-activated macrophages. (2) Methods: Raw 264.7 and equine PBMC cells were incubated with or without 100 ng/mL LPS in the presence or absence of NeoSTX (1µM). The expression of inflammatory mediators was assessed: nitric oxide (NO) content using the Griess assay, TNF-α content using the ELISA assay, and mRNA of inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) using a real-time polymerase chain reaction. (3) Results: NeoSTX (1 µM) significantly inhibited the release of NO, TNF-α, and expression of iNOS, IL-1ß, and TNF-α in LPS-activated macrophages of both species studied. Furthermore, our study shows that the LPS-induced release of inflammatory mediators was suppressed by NeoSTX. Additionally, NeoSTX deactivated polarized macrophages to M1 by LPS without compromising its polarization towards M2. (4) Conclusions: NeoSTX inhibits LPS-induced release of inflammatory mediators from macrophages, and these effects may be mediated by the blockade of voltage-gated sodium channels (VGSC).

Population Pharmacokinetics of Anidulafungin in Critically Ill Patients.

A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of Candida albicans and Candida glabrata infections.