A Tale of Two Hospitals: Comparing CAPA Infections in Two ICUs During the Spanish Fourth Pandemic Wave.

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is a new clinical entity linked to SARS-CoV-2 infection that is causing a rise on the risk of complications and mortality, particularly in critical patients. METHODS: We compared diagnostic and clinical features in two cohorts of patients with severe COVID-19 admitted in the intensive care units (ICU) of two different hospitals in Madrid, Spain, between February and June 2021. Clinical and microbiological relevant aspects for CAPA diagnosis were collected for further classification. CAPA was classified as colonization, possible, probable, proven, and tracheobronchial aspergillosis according to the ECMM/ISHAM consensus, with some modifications to consider tracheobronchial aspirate as sample comparable to non-bronchoscopic lavages (NBL). RESULTS: 56 patients admitted in HULP (Hospital Universitario La Paz) ICU and 61 patients admitted in HEEIZ (Hospital de Emergencias Isabel Zendal) ICU had clinical suspicion of invasive fungal disease in the context of COVID-19 infection. Cultures were positive for Aspergillus spp. in 32 patients. According to 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus, 11 patients were diagnosed with possible CAPA and 10 patients with probable CAPA. Global incidence for CAPA was 6.3%. Global median days between ICU admission and diagnosis was 14 day. Aspergillus fumigatus complex was the main isolated species. Antifungal therapy was used in 75% of patients with CAPA suspicion, with inter-hospital differences in the administered antifungals. Global overall mortality rate for CAPA patients was 66.6% (14/21). All-cause mortality in non-CAPA cohorts were of 26.3% in HULP group (34/129) and 56.8% (104/183) in HEEIZ group. CONCLUSIONS: There were no significant differences in incidence between the two hospitals, and differences in antifungal therapy did not correlate with differences in mortality, reflecting that both first-line azoles and Amphotericin B could be effective in treating CAPA infections, according to the current guideline indications.

Endoplasmic Reticulum Protein TXNDC5 Interacts with PRDX6 and HSPA9 to Regulate Glutathione Metabolism and Lipid Peroxidation in the Hepatic AML12 Cell Line.

Non-alcoholic fatty liver disease or steatosis is an accumulation of fat in the liver. Increased amounts of non-esterified fatty acids, calcium deficiency, or insulin resistance may disturb endoplasmic reticulum (ER) homeostasis, which leads to the abnormal accumulation of misfolded proteins, activating the unfolded protein response. The ER is the primary location site for chaperones like thioredoxin domain-containing 5 (TXNDC5). Glutathione participates in cellular oxidative stress, and its interaction with TXNDC5 in the ER may decrease the disulfide bonds of this protein. In addition, glutathione is utilized by glutathione peroxidases to inactivate oxidized lipids. To characterize proteins interacting with TXNDC5, immunoprecipitation and liquid chromatography-mass spectrometry were used. Lipid peroxidation, reduced glutathione, inducible phospholipase A2 (iPLA2) and hepatic transcriptome were assessed in the AML12 and TXNDC5-deficient AML12 cell lines. The results showed that HSPA9 and PRDX6 interact with TXNDC5 in AML12 cells. In addition, TXNDC5 deficiency reduced the protein levels of PRDX6 and HSPA9 in AML12. Moreover, lipid peroxidation, glutathione and iPLA2 activities were significantly decreased in TXNDC5-deficient cells, and to find the cause of the PRDX6 protein reduction, proteasome suppression revealed no considerable effect on it. Finally, hepatic transcripts connected to PRDX6 and HSPA9 indicated an increase in the Dnaja3, Mfn2 and Prdx5 and a decrease in Npm1, Oplah, Gstp3, Gstm6, Gstt1, Serpina1a, Serpina1b, Serpina3m, Hsp90aa1 and Rps14 mRNA levels in AML12 KO cells. In conclusion, the lipid peroxidation system and glutathione mechanism in AML12 cells may be disrupted by the absence of TXNDC5, a novel protein-protein interacting partner of PRDX6 and HSPA9.

Differentially Expressed Genes in Response to a Squalene-Supplemented Diet Are Accurate Discriminants of Porcine Non-Alcoholic Steatohepatitis.

Squalene is the major unsaponifiable component of virgin olive oil, the fat source of the Mediterranean diet. To evaluate its effect on the hepatic transcriptome, RNA sequencing was carried out in two groups of male Large White x Landrace pigs developing nonalcoholic steatohepatitis by feeding them a high fat/cholesterol/fructose and methionine and choline-deficient steatotic diet or the same diet with 0.5% squalene. Hepatic lipids, squalene content, steatosis, activity (ballooning + inflammation), and SAF (steatosis + activity + fibrosis) scores were analyzed. Pigs receiving the latter diet showed hepatic squalene accumulation and twelve significantly differentially expressed hepatic genes (log2 fold change < 1.5 or <1.5) correlating in a gene network. These pigs also had lower hepatic triglycerides and lipid droplet areas and higher cellular ballooning. Glutamyl aminopeptidase (ENPEP) was correlated with triglyceride content, while alpha-fetoprotein (AFP), neutralized E3 ubiquitin protein ligase 3 (NEURL3), 2'-5'-oligoadenylate synthase-like protein (OASL), and protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) were correlated with activity reflecting inflammation and ballooning, and NEURL3 with the SAF score. AFP, ENPEP, and PPP1R1B exhibited a remarkably strong discriminant power compared to those pathological parameters in both experimental groups. Moreover, the expression of PPP1R1B, TMEM45B, AFP, and ENPEP followed the same pattern in vitro using human hepatoma (HEPG2) and mouse liver 12 (AML12) cell lines incubated with squalene, indicating a direct effect of squalene on these expressions. These findings suggest that squalene accumulated in the liver is able to modulate gene expression changes that may influence the progression of non-alcoholic steatohepatitis.

Duplex Ultrasound Screening for Deep and Superficial Vein Thrombosis in COVID-19 Patients.

BACKGROUND: There is growing evidence regarding the venous thromboembolic (VTE) pathophysiology of coronavirus disease 2019 (COVID-19). Several studies have reported varying incidences of this disease. OBJECTIVES: The main purpose of this study was to determine the real incidence of deep or superficial vein thrombosis in COVID-19. The study also aimed to identify risk and protective factors for VTE. METHODS: Patients were consecutively enrolled and assessed with a bilateral Duplex ultrasonography of lower limbs during hospitalization. The exam was repeated weekly until discharge, and then follow-up for 1 month. RESULTS: Two-hundred and thirty-three patients were enrolled. Mean age was 54.4 years (SD 12.7) and 47.8% were female. About 127 patients (54.5%) had comorbidities. At enrollment, patients were normotensive and had normal saturation (95.6%-SD 1.6, with a respiratory rate of 19.1 rpm-SD 4.0), with 130 needing at least supplementary oxygen therapy (55.8%). About 147 patients (63.1%) had at least 1 Duplex ultrasonography study performed and 1.7% had 5 or more studies. One patient had a distal posterior tibial vein thrombosis, which showed signs of chronicity and was congruent with the patient history. Therefore, the incidence of thrombotic events was nearly zero. DISCUSSION: Our study results suggest that performing a Duplex Ultrasonography screening protocol in stable COVID-19 patient populations, who may need hospitalization but are without symptoms of vein thrombosis, is not founded. We presumably emphasize the advantage of using intermediate LMWH doses as well as early walking in COVID-19 patients.

Squalene through Its Post-Squalene Metabolites Is a Modulator of Hepatic Transcriptome in Rabbits.

Squalene is a natural bioactive triterpene and an important intermediate in the biosynthesis of sterols. To assess the effect of this compound on the hepatic transcriptome, RNA-sequencing was carried out in two groups of male New Zealand rabbits fed either a diet enriched with 1% sunflower oil or the same diet with 0.5% squalene for 4 weeks. Hepatic lipids, lipid droplet area, squalene, and sterols were also monitored. The Squalene administration downregulated 9 transcripts and upregulated 13 transcripts. The gene ontology of transcripts fitted into the following main categories: transporter of proteins and sterols, lipid metabolism, lipogenesis, anti-inflammatory and anti-cancer properties. When the results were confirmed by RT-qPCR, rabbits receiving squalene displayed significant hepatic expression changes of LOC100344884 (PNPLA3), GCK, TFCP2L1, ASCL1, ACSS2, OST4, FAM91A1, MYH6, LRRC39, LOC108176846, GLT1D1 and TREH. A squalene-enriched diet increased hepatic levels of squalene, lanosterol, dihydrolanosterol, lathosterol, zymostenol and desmosterol. Strong correlations were found among specific sterols and some squalene-changed transcripts. Incubation of the murine AML12 hepatic cell line in the presence of lanosterol, dihydrolanosterol, zymostenol and desmosterol reproduced the observed changes in the expressions of Acss2, Fam91a1 and Pnpla3. In conclusion, these findings indicate that the squalene and post-squalene metabolites play important roles in hepatic transcriptional changes required to protect the liver against malfunction.

Orthopedic Surgical Treatment and Perioperative Complications in Multiple Myeloma Bone Disease: Analysis of a Series (2009-2018).

BACKGROUND: More than 90% of patients with multiple myeloma (MM) develop lytic bone lesions that can be surgically treated for symptomatic relief and functional improvement. METHODS: This was a retrospective observational analytic study conducted between 2009 and 2018, including 58 patients with MM bone disease who underwent 77 orthopedic surgical procedures and were co-managed by internal medicine. Analysis of data related to MM bone disease, different modalities of surgical treatment, perioperative complications, and survival was performed. RESULTS: Median age was 72 years (66.5-77 years) and 56.9% of patients were males; 54.43% of injuries were located in the spine, 27.85% in the pelvis or lower limbs, 15.19% in the upper limbs, and 75.32% of patients had pathologic fractures. In 29.31% of the cases, the bone lesion was the debut of MM. Surgical procedures performed were mainly kyphoplasty (48.05%) and intramedullary nailing (29.87%). The overall complication rate following surgery was 74.03%. Only 20.78% of cases had a surgical complication. Among medical complications, we registered 28.57% transfusion requirements, 25.97% acute renal failures, 24.68% developed an infection, and 10.39% developed hypercalcemia. Patients were followed-up for a mean of 6.13 years and 37.93% suffered a new fracture. The median overall survival time for patients after surgery was 32.9 months (11.6-49). The estimated overall survival at 1, 3, and 5 years after surgery was 81.17%, 57%, and 34.11%, respectively. CONCLUSIONS: The orthopedic surgical treatment of MM bone disease aims to improve symptomatology and patient quality of life; however, these patients have a high risk of perioperative complications and considerable early mortality, making multidisciplinary management with medical specialties essential.

Comparing demographics of organ donor referrals from the intensive care unit and outside units.

The Spanish organ donation system is a world leader in organ recovery. One of Spain's strategies is the identification of organ donor referrals outside of the intensive care unit (ICU) for intensive care to facilitate organ donation (ICOD). There are limited data comparing the profiles of ICU-based and non-ICU ICOD referrals. This single-center retrospective chart review analyzed organ donor referrals of ICU and non-ICU patients to better understand the demographic and clinical differences between cohorts. The primary outcome was to understand if organ donation conversion rates were similar between ICU and non-ICU referrals. We collected data from 745 organ donor referral candidates, 235 (32%) of whom entered ICOD protocols. Out of this cohort, 144 (61%) became actual organ donors, 37 of whom (26%) were referred from non-ICU units. The ICU had the highest organ donor conversion rate (66% of ICU ICOD patients became actual organ donors) whereas non-ICU referrals had a 51% conversion rate. Non-ICU unit donors contributed to 21% and 26% of all kidney and liver donations, respectively. Though organ referral candidates from non-ICU units contribute to a small proportion of actual donors, their donated organs are important to sustaining organ donation and transplant activity.

Extracorporeal photopheresis vs standard therapies for steroid-refractory chronic graft-vs-host disease: Pharmacoeconomic assessment of hospital resource use in Spain.

BACKGROUND: This study assessed pharmacoeconomic costs associated with extracorporeal photopheresis (ECP) compared with other available second-line therapies for chronic graft-vs-host disease (cGvHD) in a tertiary Spanish institution. METHODS: Patients (≥18 years) diagnosed with steroid-refractory cGvHD were eligible. Data were collected retrospectively from index date until 1 year or relapse. Patients were distributed in two cohorts (ECP vs non-ECP), matched by age (≤ or > 40), hematopoietic stem cell transplant (HLA-identical sibling donor or other) and number of previous immunosuppressive lines (1, 2, or ≥ 3). Costs were assigned using the 2016 diagnosis-related group (DRG) system: DRG 579 (€22 383) overnight stay due to major complication (ie, sepsis, pneumonia, parenteral nutrition, or respiratory failure), and DRG 875 (€5154) if no major complication. The primary endpoint was healthcare resource utilization per patient. RESULTS: Forty patients (n = 20 per cohort) were included. Median age was 49, and 37.5% were female. Mean total cost per patient was €25 319 (95% CI: €17 049-€33 590) across the two cohorts, with a slightly lower mean cost per ECP-treated patient (€23 120) compared with the non-ECP cohort (€27 519; P = .597). Twenty-seven inpatient hospitalizations occurred among ECP-treated patients, vs 33 in the non-ECP cohort. Day hospital and external consultations were more frequent in the ECP cohort. However, fewer inpatient admissions included DRG 579 compared with the non-ECP cohort (44% vs 58%). Inpatient length of stay was slightly shorter in the ECP cohort (30 vs 49 days; P = .298). CONCLUSIONS: ECP treatment may yield economic savings in Spain through resource savings and moving costs toward outpatient care.

Gorgan (Turkmen in Iran) HLA genetics: transplantation, pharmacogenomics and anthropology.

HLA class I and II alleles have been studied in a population from Gorgan (North East Iranian city bordering Turkmenistan). This population is composed of mainly Turkmen who speak Oghuz Turkish language. Comparison of Gorgan people HLA profile has been carried out with about 7984 HLA chromosomes from other worldwide populations; extended haplotypes and three dimension genetic distances have been calculated by using neighbor-joining and correspondence relatedness analyses. Most frequent extended HLA haplotypes show a Siberian/Mediterranean admixture and closest populations are Chuvashians (North Caspian Sea, Russia) and other geographically close populations like Siberian Mansi, Buryats and other Iranians. New extended HLA haplotypes have been found, such as: A*31:01-B*35:01-DRB1*15:01-DQB1*03:01, A*01:01-B*35:01-DRB1*03:01-DQB1*02:01. Relationships of Turkmen with Kurgan (Gorgan) archaeological mounds, Scythians and Sarmatians are discussed. This study is also useful for a future transplantation Gorgan waiting list, Gorgan HLA and disease epidemiology and HLA pharmacogenomics.

The obesity paradox in stroke: impact on mortality and short-term readmission.

BACKGROUND: The aim of the present study was to assess the association of obesity with the mortality of hospitalized patients with acute stroke and the risk of readmission in less than 30 days. METHODS: A retrospective chart review of a cohort of consecutive patients admitted with stroke as the primary reason for discharge in Spain between January 1, 2005, and December 31, 2011, was performed. Patients with a diagnosis of obesity were identified. The mortality and readmittance indexes of obese patients were compared against the subpopulation without theses diagnosis. RESULTS: A total of 201,272 stroke admittances were analyzed, and 14,047 (7.0%) diagnosis of obesity were identified. In-hospital global mortality reached 14.9%, and readmittance risk was 5.9%. Obese patients showed a lower in-hospital mortality risk (odds ratio [OR], .71; 95% confidence interval [CI], .67-.76) and early readmittance risk (OR, .89; 95% CI, .82-.96) than the nonobese even after adjusting for possible confounding factors. CONCLUSIONS: Obesity in those hospitalized for stroke is associated with reduced in-hospital mortality risk and early readmittance.

Mixtec Mexican Amerindians: an HLA alleles study for America peopling, pharmacogenomics and transplantation.

HLA-A, -B and -DRB1 alleles have been studied in a Mixtec Mexican Amerindian population by indirect DNA sequencing. HLA relatedness has been tested by comparing results with other Amerindians and worldwide populations; a total of 15,681 chromosomes have been used. Genetic distances between populations, Neighbour Joining (NJ) dendrograms and correspondence analyses have been carried out. Conclusions are: 1) Our Mixtec sample from Oaxaca Coastal Mexican area shows an HLA profile different to that of Oaxaca Central Mountains area showing that genes and languages do not correlate which is inferred both by plane genetic distances and NJ dendrograms and correspondence analyses. 2) Genetic distances and NJ dendrograms join together Mazatecan Mexican Amerindians with our studied Coastal Mixtec group; it fits with the historical relationship between Mixtec and Mazatecans. 3) A*24:02-B*35:14-DRB1*04:11, A*02:01-B*15:15-DRB1*04:11 and A*68:03-B*39:08-DRB1*08:02 extended HLA haplotypes have been "de novo" found in our Mixtec Coastal sample. 4) Shared HLA alleles are found between our Pacific Coast Mixtec Amerindians and Pacific Islanders. 5) These results are useful for establishing a future area transplantation waiting list, for the study of HLA linked diseases epidemiology and for pharmacogenomics in certain drug therapy.

Frequency of hypoglycemia and its impact on length of stay, mortality, and short-term readmission in patients with diabetes hospitalized in internal medicine wards.

OBJECTIVE: To evaluate whether hypoglycemia is associated with increases in length of stay (LOS), inpatient mortality, and readmission among patients with diabetes hospitalized in internal medicine wards. METHODS: A retrospective cohort study was carried out using the Basic Minimum Data Set registry of the Spanish National Health System, which contains clinical and administrative information for every patient discharged from system hospitals. The analysis included patients discharged between January 2005 and December 2010 and had a primary (i.e., reason for the admission) or secondary diagnosis of diabetes and a secondary diagnosis of hypoglycemia. The associations between hypoglycemia and the study outcomes (mortality, readmission, and LOS) were evaluated using multivariate and multilinear regression models that included age, sex, and the Charlson index as covariates. RESULTS: During the study period, 3,361,104 patients were admitted to internal medicine wards in the National Health System. Of these, 921,306 (27.4%) had diagnoses of diabetes, and among these patients, 46,408 (5%) had secondary hypoglycemia. A total of 4,754 (10.2%) patients with secondary hypoglycemia died during their hospital stays, compared with 83,508 (9.5%) patients without hypoglycemia. The multivariate/multilinear regression models demonstrated significant associations between the presence of secondary hypoglycemia and greater inpatient mortality (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.20-1.28), a greater likelihood of readmission (OR 1.20, 95% CI 1.17-1.23), and an increased LOS (ß 1.24, 95% CI 1.15-1.35). CONCLUSION: Hypoglycemia in patients with diabetes hospitalized in internal medicine wards is associated with increases in the LOS, inpatient mortality, and early readmission.

Thioredoxin domain containing 5 is involved in the hepatic storage of squalene into lipid droplets in a sex-specific way.

Hepatic thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family found associated with anti-steatotic properties of squalene and located in the endoplasmic reticulum and in lipid droplets. Considering that the latter are involved in hepatic squalene accumulation, the present research was aimed to investigate the role of TXNDC5 on hepatic squalene management in mice and in the AML12 hepatic cell line. Wild-type and TXNDC5-deficient (KO) mice were fed Western diets with or without 1% squalene supplementation for 6 weeks. In males, but not in females, absence of TXNDC5 blocked hepatic, but not duodenal, squalene accumulation. Hepatic lipid droplets were isolated and characterized using label-free LC-MS/MS analysis. TXNDC5 accumulated in this subcellular compartment of mice receiving squalene and was absent in TXNDC5-KO male mice. The latter mice were unable to store squalene in lipid droplets. CALR and APMAP were some of the proteins that responded to the squalene administration in all studied conditions. CALR and APMAP were positively associated with lipid droplets in the presence of squalene and they were decreased by the absence of TXNDC5. The increased squalene content was reproduced in vitro using AML12 cells incubated with squalene-loaded nanoparticles and this effect was not observed in an engineered cell line lacking TXNDC5. The phenomenon was also present when incubated in the presence of a squalene epoxidase inhibitor, suggesting a mechanism of squalene exocytosis involving CALR and APMAP. In conclusion, squalene accumulation in hepatic lipid droplets is sex-dependent on TXNDC5 that blocks its secretion.

Nummular headache and epicrania fugax: possible association of epicranias in eight patients.

OBJECTIVES: Epicrania fugax (EF) is a novel syndrome presenting with brief pain paroxysms that always start in a particular area of the head to spread immediately either forward or backward. Paroxysms stem from a focal area, in which a well-shaped continuous pain reminiscent of the symptomatic area described in nummular headache (NH) can be present. We aimed to analyze the association of these two epicranial headaches in eight patients. METHODS: We prospectively assessed all patients with EF attending an outpatient headache office from March 2008, when EF was first described, to June 2012. Among them, we selected those patients with a well-circumscribed continuous pain at the stemming point fulfilling the research diagnostic criteria for NH of the International Classification of Headache Disorders II Edition (ICHD-II) appendix. We considered the demographic and clinical features of the selected patients. RESULTS: Eight patients (five females, three males) were diagnosed with both EF and NH. Mean age of onset was 44.2 ± 12 (range: 23-60). Regarding NH, the diameter of the painful area was 4.4 ± 1 centimeters (range: 3-6) and pain intensity was 4.2 ± 0.7 (range: 3-5) on a 10-point verbal analogical scale (VAS). As for the EF, the radiating paroxysms always started in the NH painful area and lasted 6.6 ± 4.5 seconds (range: 2-15), with a pain intensity of 7.9 ± 1.6 (range 5-10) on the VAS. Five cases had forward radiation, while three cases had backward EF. Four cases had ipsilateral autonomic accompaniments. Six patients required a preventive, and lamotrigine achieved complete response in three of them. CONCLUSION: Although the etiology of NH and EF remains uncertain, both syndromes seem to share a peripheral source. Their association in a number of patients is probably reflecting a pathophysiological connection. Lamotrigine might be a good therapeutic option for those patients presenting with both disorders.

Hip fracture in hospitalized medical patients.

BACKGROUND: The aim of the present study is to analyze the incidence of hip fracture as a complication of admissions to internal medicine units in Spain. METHODS: We analyzed the clinical data of 2,134,363 adults who had been admitted to internal medicine wards. The main outcome was a diagnosis of hip fracture during hospitalization.Outcome measures included rates of in-hospital fractures, length of stay and cost. RESULTS: A total of 1127 (0.057%) admittances were coded with an in-hospital hip fracture. In hospital mortality rate was 27.9% vs 9.4%; p < 0.001, and the mean length of stay was significantly longer for patients with a hip fracture (20.7 days vs 9.8 days; p < 0.001). Cost were higher in hip-fracture patients (6927€ per hospitalization vs 3730€ in non fracture patients). Risk factors related to fracture were: increasing age by 10 years increments (OR 2.32 95% CI 2.11-2.56), female gender (OR 1.22 95% CI 1.08-1.37), admission from nursing home (OR 1.65 95% CI 1.27-2.12), dementia (1.55 OR 95% CI1.30-1.84), malnutrition (OR 2.50 95% CI 1.88-3.32), delirium (OR 1.57 95% CI 1.16-2.14), and anemia (OR 1.30 95%CI 1.12-1.49). CONCLUSIONS: In-hospital hip fracture notably increased mortality during hospitalization, doubling the mean length of stay and mean cost of admission. These are reasons enough to stress the importance of designing and applying multidisciplinary plans focused on reducing the incidence of hip fractures in hospitalized patients.

Dietary proteins modulate high-density lipoprotein characteristics in a sex-specific way in Apoe-deficient mice.

OBJECTIVES: The type and amount of dietary protein have become a topic of renewed interest, considering their involvement in several diseases. However, little attention has been devoted to the effect of avian proteins despite their wide human consumption. In a previous study, we saw that compared with soybean protein, the consumption of avian proteins, depending on sex, resulted in similar or lower atherosclerosis with a higher paraoxonase 1 activity, an antioxidant enzyme carried by high-density lipoproteins (HDL). This suggests that under these conditions, the HDL lipoproteins may undergo important changes. The aim of this research was to study the influence of soybean, chicken, and turkey proteins on the characteristics of HDL. METHODS: Male and female Apoe-deficient mice were fed purified Western diets based on the AIN-93 diet, differing only in the protein source, for 12 wk. After this period, blood and liver samples were taken for analysis of HDL composition and hepatic expression of genes related to HDL metabolism (Abca1, Lcat, Pltp, Pon1, and Scarb1). Depending on sex, these genes define a different network of interactions. Females consuming the turkey protein-containing diet showed decreased atherosclerotic foci, which can be due to larger very-low-density lipoproteins (VLDLs) calculated by molar ratio triacylglycerols/VLDL cholesterol and higher expression of Lcat. In contrast, in males, a higher ratio of paraoxonase1 to apolipoprotein A1 decreased the oxidative status of the different lipoproteins, and augmented Abca1 expression was observed. CONCLUSIONS: The source of protein has an effect on the development of atherosclerosis depending on sex by modifying HDL characteristics and the expression of genes involved in their properties.

Pharmacist care in hospital emergency departments: a consensus paper from the Spanish hospital pharmacy and emergency medicine associations. / Atención farmacéutica en los servicios de urgencias: documento de posicionamiento de la Sociedad Española de Farmacia Hospitalaria (SEFH) y la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES).

OBJECTIVES: To draft a list of actions and quality indicators for pharmacist care in hospital emergency departments, based on consensus among a panel of experts regarding which actions to prioritize in this setting. MATERIAL AND METHODS: A panel of experts from the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Emergency Medicine (SEMES) evaluated a preliminary list of potential actions and quality of care indicators. The experts used a questionnaire to assess the proposals on the basis of available evidence. In the first round, each expert individually assessed the importance of each proposed action based on 4 dimensions: evidence base, impact on clinical response and patient safety, ease of implementation, and priority. In the second round the experts attended a virtual meeting to reach consensus on a revised list of proposals; suggestions and comments that had been made anonymously in the first round were included. The group then prioritized each action as basic, intermediate, or advanced. RESULTS: The experts evaluated a total of 26 potential actions and associated quality indicators. No items were eliminated in the analysis of scores and comments from the first round. After the second round, 25 actions survived. Nine were considered basic, 10 intermediate, and 6 advanced. CONCLUSION: The expert panel's list of pharmacist actions and care quality indicators provides a basis for developing a pharmacist care program in Spanish emergency departments on 3 levels of priority. The list can serve as a guide to pharmacists, managers, physicians, and nurses involved in the effort to improve drug therapy in this hospital setting.

OBJETIVO: Desarrollar un conjunto de actividades e indicadores de atención farmacéutica en los servicios de urgencias hospitalarios mediante un consenso colectivo de un panel de expertos que permita priorizar las actividades a realizar por los farmacéuticos en estas unidades. METODO: Un comité formado por miembros de la Sociedad Española de Farmacia Hospitalaria (SEFH) y de la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) evaluó una propuesta inicial de actividades e indicadores potenciales, basados en la evidencia científica disponible, en formato de cuestionario. En una primera ronda, cada uno de los expertos del panel clasificó de forma individual la relevancia de cada una de las actividades propuestas en cuatro dimensiones: evidencia científica, impacto en la respuesta clínica y seguridad para el paciente, facilidad de implementación y grado de prioridad. La segunda ronda se realizó mediante una reunión grupal de forma virtual, a partir del cuestionario modificado de acuerdo con las sugerencias planteadas, así como los comentarios vertidos por los participantes del panel de forma anónima. En esta ronda, cada actividad fue clasificada por consenso como básica, intermedia o avanzada en función del grado de prioridad de implantación considerado por el grupo de expertos. RESULTADOS: Se propusieron un total de 26 potenciales actividades a los expertos, con indicadores asociados. Tras el análisis de las puntuaciones y los comentarios realizados en la primera ronda, no se eliminó ninguna de las actividades propuestas. Tras la segunda ronda, se mantuvieron 25 actividades, de las cuales se puntuaron 9 como actividades básicas, 10 actividades como intermedias y 6 actividades como avanzadas. CONCLUSIONES: El desarrollo del conjunto de actividades e indicadores de atención farmacéutica en urgencias, priorizados por grado de relevancia para la unidad, es la base para el desarrollo de esta cartera de servicios en los hospitales españoles, y sirve como guía tanto para farmacéuticos como para gestores, médicos y enfermeros de la unidad a fin de mejorar la farmacoterapia los pacientes atendidos en los servicios de urgencias.

Venous thromboembolism in COPD hospitalized patients.

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for venous thromboembolism (VTE). We analyzed a large Spanish database to determine the incidence of VTE in these patients during hospitalization. A retrospective chart review of cohort of consecutive patients admitted with COPD as the primary reason for discharge in Spain between January 1st 2006 and December 31st 2007 was performed. For each patient, demographic data, risk factors for VTE and the diagnosis of VTE during hospitalization was recorded. We analyzed the clinical data of 313,233 adults with acute exacerbations of COPD admitted to the hospital at any public centre in Spain, in 2006 and 2007. We identify 3,562 new diagnosed VTE events among 270,840 COPD patients hospitalized more than two days (incidence 1.32%). Hospitalized-acquired VTE risk factors were male gender (odds ratio [OR] 1.77; CI95% 1.66-1.90), neoplasic disease (OR 2.93 CI95% 2.69-3.16, systemic arterial disease (OR 1.17 CI95% 1.10-1.36), decubitus ulcer (OR 1.19 CI95% 1.01-1.43), diabetes (OR 0.74 IC95% 0.69-0.81), and atrial fibrillation (OR 0.79 CI95% 0.72-0.87). VTE appears as a major threat to patients admitted for acute exacerbation of COPD, and pharmacologic prophylaxis should be considered in all high risk situations.

Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins.

Thioredoxin domain containing 5 (TXNDC5) is a protein disulfide isomerase involved in several diseases related to oxidative stress, energy metabolism and cellular inflammation. In a previous manuscript, a negative association between fatty liver development and hepatic Txndc5 expression was observed. To study the role of TXNDC5 in the liver, we generated Txndc5-deficient mice. The absence of the protein caused an increased metabolic need to gain weight along with a bigger and fatter liver. RNAseq was performed to elucidate the putative mechanisms, showing a substantial liver overexpression of serum amyloid genes (Saa1, Saa2) with no changes in hepatic protein, but discrete plasma augmentation by the gene inactivation. Higher levels of malonyldialdehyde, apolipoprotein A1 and platelet activating factor-aryl esterase activity were also found in serum from Txndc5-deficient mice. However, no difference in the distribution of high-density lipoproteins (HDL)-mayor components and SAA was found between groups, and even the reactive oxygen species decreased in HDL coming from Txndc5-deficient mice. These results confirm the relation of this gene with hepatic steatosis and with a fasting metabolic derive remedying an acute phase response. Likewise, they pose a new role in modulating the nature of HDL particles, and SAA-containing HDL particles are not particularly oxidized.

Squalene Loaded Nanoparticles Effectively Protect Hepatic AML12 Cell Lines against Oxidative and Endoplasmic Reticulum Stress in a TXNDC5-Dependent Way.

Virgin olive oil, the main source of fat in the Mediterranean diet, contains a substantial amount of squalene which possesses natural antioxidant properties. Due to its highly hydrophobic nature, its bioavailability is reduced. In order to increase its delivery and potentiate its actions, squalene has been loaded into PLGA nanoparticles (NPs). The characterization of the resulting nanoparticles was assessed by electron microscopy, dynamic light scattering, zeta potential and high-performance liquid chromatography. Reactive oxygen species (ROS) generation and cell viability assays were carried out in AML12 (alpha mouse liver cell line) and a TXNDC5-deficient AML12 cell line (KO), which was generated by CRISPR/cas9 technology. According to the results, squalene was successfully encapsulated in PLGA NPs, and had rapid and efficient cellular uptake at 30 µM squalene concentration. Squalene reduced ROS in AML12, whereas ROS levels increased in KO cells and improved cell viability in both when subjected to oxidative stress by significant induction of Gpx4. Squalene enhanced cell viability in ER-induced stress by decreasing Ern1 or Eif2ak3 expressions. In conclusion, TXNDC5 shows a crucial role in regulating ER-induced stress through different signaling pathways, and squalene protects mouse hepatocytes from oxidative and endoplasmic reticulum stresses by several molecular mechanisms depending on TXNDC5.