Emergence of carbapenem-resistant Pseudomonas aeruginosa ST179 producing both IMP-16 and KPC-2: a case study of introduction from Peru to Spain.

We describe four cases of a novel carbapenem-resistant Pseudomonas aeruginosa ST179 clone carrying the blaKPC-2 or blaKPC-35 gene together with blaIMP-16, imported from Peru to Spain and isolated from leukemia patients. All isolates were multidrug-resistant but remained susceptible to fosfomycin, cefiderocol, and colistin. Whole-genome sequencing revealed that blaKPC-2 and blaKPC-35 were located in an IncP6 plasmid, whereas blaIMP-16 was in a chromosomal type 1 integron. This study highlights the global threat of multidrug-resistant P. aeruginosa clones and underscores the importance of monitoring and early detection of emerging resistance mechanisms to guide appropriate treatment strategies. The importation and spread of such clones emphasize the urgent need to implement strict infection control measures to prevent the dissemination of carbapenem-resistant bacteria. IMPORTANCE: This is the first documented case of a Pseudomonas aeruginosa ST179 strain carrying the blaKPC-35 gene, and it represents the first report of a P. aeruginosa co-harboring blaIMP-16 and either blaKPC-2 or blaKPC-35, which wre imported from Peru to Spain, highlighting a threat due to the capacity of spreading carbapenem-resistance via plasmid conjugation.

An 19F NMR fragment-based approach for the discovery and development of BRCA2-RAD51 inhibitors to pursuit synthetic lethality in combination with PARP inhibition in pancreatic cancer.

The BRCA2-RAD51 interaction remains an intriguing target for cancer drug discovery due to its vital role in DNA damage repair mechanisms, which cancer cells become particularly reliant on. Moreover, RAD51 has many synthetically lethal partners, including PARP1-2, which can be exploited to induce synthetic lethality in cancer. In this study, we established a 19F-NMR-fragment based approach to identify RAD51 binders, leading to two initial hits. A subsequent SAR program identified 46 as a low micromolar inhibitor of the BRCA2-RAD51 interaction. 46 was tested in different pancreatic cancer cell lines, to evaluate its ability to inhibit the homologous recombination DNA repair pathway, mediated by BRCA2-RAD51 and trigger synthetic lethality in combination with the PARP inhibitor talazoparib, through the induction of apoptosis. Moreover, we further analyzed the 46/talazoparib combination in 3D pancreatic cancer models. Overall, 46 showed its potential as a tool to evaluate the RAD51/PARP1-2 synthetic lethality mechanism, along with providing a prospect for further inhibitors development.

Risk factors and incidence of peripheral venous catheters-related phlebitis between 2017 and 2021: A multicentre study (Flebitis Zero Project).

BACKGROUND: The peripheral venous catheter is one of the most frequently used devices in inpatient units worldwide. The risk of complications arising from use of peripheral venous catheters is low, but phlebitis frequently develops. METHODS: A multicentre, prospective cohort study was conducted in 65 Spanish hospitals on 10,247 inpatients who had had a total of 38,430 peripheral venous catheters inserted. Data were collected for 15 consecutive days in 2017, 2018, 2019, 2020 and 2021. Central tendency and dispersion were measured, cumulative incidence and incidence density were determined and odds ratios (OR) were also calculated using binary logistic regression. RESULTS: The incidence density of phlebitis, during the period from 2017 to 2021, was 1.82 cases of phlebitis per 100 venous catheter-days. The difference between average cumulative incidence of phlebitis per year was statistically significant as determined by ANOVA test results (F = 10.51; df = 4; p < 0.000). Unequivocal risk factors for phlebitis were revealed to be hospitals with more than 500 beds (OR = 1.507; p < 0.001), patients suffering from neoplastic disease (OR = 1.234; p < 0.001) and the first 3-4 days after insertion (OR = 1.159; p < 0.001). CONCLUSIONS: A correct knowledge of insertion technique and venous catheter maintenance is likely to reduce the incidence of phlebitis and other complications, and hence continuing education of nurses is essential.

Innovative Strategy toward Mutant CFTR Rescue in Cystic Fibrosis: Design and Synthesis of Thiadiazole Inhibitors of the E3 Ligase RNF5.

In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) is associated to misfolding and defective gating of the mutant channel. One of the most promising CF drug targets is the ubiquitin ligase RNF5, which promotes F508del-CFTR degradation. Recently, the first ever reported inhibitor of RNF5 was discovered, i.e., the 1,2,4-thiadiazol-5-ylidene inh-2. Here, we designed and synthesized a series of new analogues to explore the structure-activity relationships (SAR) of this class of compounds. SAR efforts ultimately led to compound 16, which showed a greater F508del-CFTR corrector activity than inh-2, good tolerability, and no toxic side effects. Analogue 16 increased the basal level of autophagy similar to what has been described with RNF5 silencing. Furthermore, co-treatment with 16 significantly improved the F508del-CFTR rescue induced by the triple combination elexacaftor/tezacaftor/ivacaftor in CFBE41o- cells. These findings validate the 1,2,4-thiadiazolylidene scaffold for the discovery of novel RNF5 inhibitors and provide evidence to pursue this unprecedented strategy for the treatment of CF.

Influence of Genetics on the Response to Omalizumab in Patients with Severe Uncontrolled Asthma with an Allergic Phenotype.

Omalizumab is a monoclonal antibody indicated for the treatment of severe uncontrolled asthma with an allergic phenotype. Its effectiveness could be influenced by clinical variables and single nucleotide polymorphisms (SNPs) in one or more of the genes involved in the mechanism of action and process of response to omalizumab, and these could be used as predictive biomarkers of response. We conducted an observational retrospective cohort study that included patients with severe uncontrolled allergic asthma treated with omalizumab in a tertiary hospital. Satisfactory response after 12 months of treatment was defined as (1) Reduction ≥ 50% of exacerbations or no exacerbations, (2) Improvement of lung function ≥ 10% FEV1, and (3) Reduction ≥ 50% of OCS courses or no OCS. Polymorphisms in the FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs1054485, rs569108), C3 (rs2230199), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), IL1RL1 (rs1420101, rs17026974, rs1921622), and GATA2 (rs4857855) genes were analyzed by real-time polymerase chain reaction (PCR) using TaqMan probes. A total of 110 patients under treatment with omalizumab were recruited. After 12 months of treatment, the variables associated with a reduction in exacerbations were the absence of polyposis (odds ratio [OR] = 4.22; 95% confidence interval [CI] = 0.95-19.63), IL1RL1 rs17026974-AG (OR = 19.07; 95% CI = 1.27-547), and IL1RL1 rs17026974-GG (OR = 16.76; 95% CI = 1.22-438.76). Reduction in oral corticosteroids (OCS) was associated with age of starting omalizumab treatment (OR = 0.95; 95% CI = 0.91-0.99) and blood eosinophil levels > 300 cells/µL (OR = 2.93; 95% CI = 1.01-9.29). Improved lung function showed a relationship to the absence of chronic obstructive pulmonary disease (COPD) (OR = 12.16; 95% CI = 2.45-79.49), FCGR2B rs3219018-C (OR = 8.6; 95% CI = 1.12-117.15), GATA2 rs4857855-T (OR = 15.98; 95% CI = 1.52-519.57) and FCGR2A rs1801274-G (OR = 13.75; 95% CI = 2.14-142.68; AG vs. AA and OR = 7.46; 95% CI = 0.94-89.12; GG vs. AA). Meeting one response criterion was related to FCER1A rs2251746-TT (OR = 24; 95% CI = 0.77-804.57), meeting two to age of asthma diagnosis (OR = 0.93; 95% CI = 0.88-0.99), and meeting all three to body mass index (BMI) < 25 (OR = 14.23; 95% CI = 3.31-100.77) and C3 rs2230199-C (OR = 3; 95% CI = 1.01-9.92). The results of this study show the possible influence of the polymorphisms studied on the response to omalizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

Microwave-Assisted Hydrodistillation of Essential Oil from Plectranthus amboinicus: Evaluation of Its Antifungal Effect and Chemical Composition.

Fusarium wilt, a vascular syndrome in a wide range of plants, is caused by the pathogen Fusarium Oxysporum. The objective of this investigation was to evaluate the antifungal effect of four essential oils (EOs) (Plectranthus amboinicus, Syzygium aromaticum, Lippia alba, and Rosmarinus officinalis), which were obtained by using microwave-assisted hydrodistillation (MAH), against F. oxysporum. The yield obtained from P. amboinicus with the use of MAH was 0.2%, which was higher than that of a conventional extraction; its extraction time was also shorter. For concentrations of 100 and 300 µL/L, P. amboinicus caused an inhibition rate of 27.2 and 55.7%, respectively, while S. aromaticum caused an inhibition rate of 23.1 and 87.3%, respectively. It was observed that increasing the concentration also increased the % inhibition rate. The extracts of L. alba and R. officinalis caused an inhibition rate of 14.5 and 14.7% at 500 µL/L, respectively, at 10 days of incubation, while at this concentration, P. amboinicus and S. aromaticum achieved 100%. The major chemical compounds of P. amboinicus were carvacrol (41.20%), o-cymene (11.61%), caryophyllene (11.45%), α-bergamotene (7.71%), and caryophyllene oxide (4.62%), and these monoterpene hydrocarbons were responsible for the biological activity. The essential oil of P. amboinicus in appropriate concentrations is a potent antifungal agent that could be used for the control of F. oxysporum.

Pseudomonas aeruginosa Bloodstream Infection, Resistance, and Mortality: Do Solid Organ Transplant Recipients Do Better or Worse?

BACKGROUND: The prevalence of antimicrobial resistance of Pseudomonas aeruginosa (P. aeruginosa) in solid organ transplant (SOT) recipients is higher than that of the general population. However, the literature supporting this statement is scarce. Identifying patients at risk of carbapenem resistance (CR) is of great importance, as CR strains more often receive inappropriate empiric antibiotic therapy, which is independently associated with mortality in bloodstream infections (BSIs). METHODS: We prospectively recorded data from all consecutive BSIs from January 1991 to July 2019 using a routine purpose-designed surveillance database. The following variables were included: age, sex, type of transplant, use of vascular and urinary catheters, presence of neutropenia, period of diagnosis, treatment with steroids, origin of BSI, source of bacteremia, septic shock, ICU admission, mechanical ventilation, previous antibiotic treatment, treatment of bacteremia, and 30-day all-cause mortality. RESULTS: We identified 2057 episodes of P. aeruginosa BSI. Of these, 265 (13%) episodes corresponded to SOT recipients (130 kidney transplants, 105 liver, 9 hearts, and 21 kidney-pancreas). Hematologic malignancy [OR 2.71 (95% CI 1.33-5.51), p = 0.006] and prior carbapenem therapy [OR 2.37 (95% CI 1.46-3.86), p < 0.001] were associated with a higher risk of having a CR P. aeruginosa BSI. Age [OR 1.03 (95% CI 1.02-1.04) p < 0.001], urinary catheter [OR 2.05 (95% CI 0.37-3.06), p < 0.001], shock at onset [OR 6.57 (95% CI 4.54-9.51) p < 0.001], high-risk source [OR 4.96 (95% CI 3.32-7.43) p < 0.001], and bacteremia caused by CR strains [OR 1.53 (95% CI 1.01-2.29) p = 0.036] were associated with increased mortality. Correct empirical therapy was protective [OR 0.52 (95% CI 0.35-0.75) p = 0.001]. Mortality at 30 days was higher in non-SOT patients (21% vs. 13%, p = 0.002). SOT was not associated with a higher risk of having a CR P. aeruginosa BSI or higher mortality. CONCLUSIONS: In our cohort of 2057 patients with P. aeruginosa BSIs, hematologic malignancies and previous carbapenem therapy were independently associated with a risk of presenting CR P. aeruginosa BSI. Age, urinary catheter, high-risk source, bacteremia caused by carbapenem-resistant strains, and severity of the infection were independently associated with mortality, whereas correct empirical therapy was a protective factor. An increasing trend in the resistance of P. aeruginosa was found, with >30% of the isolates being resistant to carbapenems in the last period. SOT was not associated with a higher risk of carbapenem-resistant BSIs or higher mortality.

Presumed tuberculosis-related scleritis.

AIMS: To evaluate the clinical characteristics and therapeutic outcome of patients with recurrent scleritis of unknown demonstrable aetiology and positive QuantiFERON-TB Gold In-Tube test (QFT). METHODS: Retrospective chart review of the demographic, clinical, laboratory and therapeutic outcome data of 15 patients. Clinical characteristics as well as remission rate after standard antituberculous therapy (ATT) were assessed. RESULTS: There were 9 men and 6 women with a mean age of 48.9 years (range, 32-73). Scleritis was diffuse in 10 patients (66.6%) and nodular in 5 patients (33.3%), 1 of them with concomitant posterior scleritis. It was bilateral in 7 patients (46.6%) and recurrent in all of them. Scleritis appeared after prior uveitis (10 patients, 66.6%) and/or with concomitant uveitis (5 patients, 33.3%) or peripheral keratitis (5 patients, 33.3%). Previous ocular surgery was found in 7 patients (46.6%). Previous extraocular tuberculosis (TB) infection or previous TB contact was detected in 11 patients (73.3%). No radiologic findings of active extraocular TB were detected. ATT was used in 15 patients, sometimes with the addition of systemic corticosteroids (5 patients) and methotrexate (1 patient); 14 patients achieved complete remission (93.3%). CONCLUSION: Presumed TB-related scleritis may appear in recurrent scleritis of unknown origin and positive QFT. It may occur after prior uveitis and/or concomitantly with uveitis or peripheral keratitis, and it may be triggered by previous ocular surgery. No patients had evidence of concurrent active extraocular infection, although many had previous TB infection or TB contact. ATT was effective, sometimes with the addition of systemic corticosteroids and methotrexate.

Incidence and predictors of sternal surgical wound infection in cardiac surgery: A prospective study.

Sternal surgical wound infection (SSWI) in cardiac surgery is associated with increased morbidity. We investigated the incidence of SSWI, the main germs implicated and predictors of SSWI. Prospective study including patients undergoing full median sternotomy between January 2017 and December 2019. Patients were followed-up for 3 months after hospital discharge. All sternal wound infections up to 90 days after discharge were considered SSWI. 1004 patients were included. During follow-up, 68 (6.8%) patients presented SSWI. Patients with SSWI had a higher incidence of postoperative renal failure (29.4% vs 17.1%, P = .007), a higher incidence of early postoperative reoperation for non-infectious causes (42.6% vs 9.1%, P < .001), longer ICU stay (3 [2-9] days vs 2 [2-4] days, P = .006), and longer hospital stay (24.5 [14.8-38.3] days vs 10 [7-18] days, P < .001). Gram-positive germs were presented in 49% of the cultures, and gram-negative bacteria in 35%. Early reoperation for non-infectious causes (OR 4.90, 95% CI 1.03-23.7), and a longer ICU stay (OR 1.37 95% CI 1.10-1.72) were independent predictors of SSWI. SSWI is rare but leads to more postoperative complications. The need for early reoperation because of non-infectious cause and a longer ICU stay were independently associated with SSWI.

Prehabilitation and perioperative geriatric care in patients aged over 80 years with colorectal cancer: Results of a cross-speciality geriatrics program.

OBJECTIVES: To describe a perioperative cross-speciality geriatrics program for patients aged >80 years with colorectal cancer (CRC), aimed to detect and manage frailty and to understand its influence on clinical outcomes. MATERIALS AND METHODS: Patients aged >80 years with CRC and proposed for surgery were included from October 2018 to March 2020. Comprehensive geriatric assessments (CGA) were performed. Patients were classified according to the estimated physiological reserve, from fit, frail patients and even the disabled: CGA-1, CGA-2, CGA-3, and CGA-4. Individualised treatment was adapted to each patient's situation. Patients who underwent surgery were followed up by a geriatrician. The presence of complications, length of stay, hospital readmissions at 30 days, and short- and long-term mortality were recorded. RESULTS: Seventy-four patients were included. The mean age was 84.5 ± 4.5 years. 55.4% patients were classified as CGA-1, 24.3% as CGA-2, 16.2% as CGA-3, and 4.1% as CGA-4. No CGA-4 patient was operated on. Frail (CGA-2 and CGA-3) patients had higher medical complications (50% vs 21.2%, p < 0.05) and delirium (30% vs 9.1%, p < 0.05) than fit patients (CGA-1). They also had higher rates of surgical complications (20% vs 15.2%), longer hospital stay (10 ± 6.2 vs 8.4 ± 4.2 days), 30-day readmissions (15% vs 6.3%), and mortality at six (10% vs 3%) and twelve months (20% vs 6.1%), although it was not statistically significant. CONCLUSION: CGA and prehabilitation can classify patients according to their frailty status, support clinicians in decision-making to achieve tailored treatment, and detect clinical conditions for intervention in multiple domains of health in the perioperative period.

Bacterial co-infection at hospital admission in patients with COVID-19.

OBJECTIVES: We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19. METHODS: Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020-February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included. RESULTS: A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p<0.001, and p<0.001, respectively). In multivariate analysis, oxygen saturation ≤94% (OR 2.47, CI 1.57-3.86), ferritin levels <338 ng/mL (OR 2.63, CI 1.69-4.07), and PCT higher than 0.2 ng/mL (OR 1.74, CI 1.11-2.72) were independent risk factors for co-infection at hospital admission owing to COVID-19. CONCLUSIONS: Bacterial co-infection in patients hospitalized for COVID-19 is relatively common. However, clinicians could spare antibiotics in patients with PCT values <0.2, especially with high ferritin values and oxygen saturation >94%.

Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.

INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis. METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis. RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04). CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.

Current Status of Metabolic/Bariatric Surgery in Type 1 Diabetes Mellitus: an Updated Systematic Review and Meta-analysis.

This systematic review and meta-analysis intend to evaluate the efficacy of metabolic/bariatric surgeries (MBS) in patients with type-1 diabetes mellitus. A systematic literature search and meta-analysis were performed in electronic databases up to July 2021. In total, 27 primary studies comprising 648 subjects were included in this systematic review and meta-analysis. Patients had a mean age of 38.0 ± 7.3 years. Preoperative mean BMI was 42.6 ± 4.7 kg/m2 and 29.4 ± 4.7 kg/m2 after surgery, respectively. Following bariatric surgeries in patients with type 1 diabetes mellitus, insulin (unit/day) decreased by a weighted mean difference (WMD) of - 10.59. Also, insulin (unit/kg/day) decreased by a WMD of - 0.2, and HbA1C decreased by a WMD of - 0.71, showing MBS acceptable and durable effects of bariatric surgical procedures.

Socio-demographic and psychological features associated with smoking in pregnancy.

OBJECTIVE: To investigate how social and psychological characteristics differ between pregnant women who smoke and do not smoke. To explore associations between social and psychological features with changes of smoking habits by the end of pregnancy. METHODS: A case-control study was set up. Smokers cases were never-smokers and ex-smokers controls. Pregnant women (n=328) from public prenatal services were interviewed. Socio-demographic data and psychological variables - personality traits, anxiety, depression, perceived stress, maternal fetal-attachment - were measured. Saliva samples were collected to measure cotinine and to check self-informed smoking status. In addition, 66 smokers were also assessed regarding smoking habits by late pregnancy. Smoking status was defined as a dependent variable. Exposure factors were analyzed through odds ratios. Logistic models and contingency tables were employed according to the nature of variables. "Qualitative change in smoking" was defined as a dependent variable for the last evaluation, and a logistic regression model was built. RESULTS: Lower schooling, higher age, use of alcohol and drugs, living without a partner, and passive smoking showed associations with smoking. Anxiety, depression and perceived stress also exhibited positive association with smoking. Among personality traits, only Neuroticism was associated with smoking. None of the variables were associated with qualitative change in smoking by the end of pregnancy. CONCLUSION: Smoking during pregnancy is associated with more unfavorable social conditions. Pregnant women who smoke exhibit more negative psychological states than nonsmokers, including a profile of accentuated Neuroticism. None of the investigated variables could predict changes in smoking during pregnancy.

Impact of remdesivir according to the pre-admission symptom duration in patients with COVID-19.

BACKGROUND: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. METHODS: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days). CONCLUSIONS: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.

Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension.

Idiopathic pulmonary artery hypertension (IPAH), chronic thromboembolic pulmonary hypertension (CTEPH), and acute pulmonary embolism (APTE) are life-threatening cardiopulmonary diseases without specific surgical or medical treatment. Although APTE, CTEPH and IPAH are different pulmonary vascular diseases in terms of clinical presentation, prevalence, pathophysiology and prognosis, the identification of their circulating microRNA (miRNAs) might help in recognizing differences in their outcome evolution and clinical forms. The aim of this study was to describe the APTE, CTEPH, and IPAH-associated miRNAs and to predict their target genes. The target genes of the key differentially expressed miRNAs were analyzed, and functional enrichment analyses were carried out. The miRNAs were detected using RT-PCR. Finally, we incorporated plasma circulating miRNAs in baseline and clinical characteristics of the patients to detect differences between APTE and CTEPH in time of evolution, and differences between CTEPH and IPAH in diseases form. We found five top circulating plasma miRNAs in common with APTE, CTEPH and IPAH assembled in one conglomerate. Among them, miR-let-7i-5p expression was upregulated in APTE and IPAH, while miRNA-320a was upregulated in CTEP and IPAH. The network construction for target genes showed 11 genes regulated by let-7i-5p and 20 genes regulated by miR-320a, all of them regulators of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell, and pulmonary artery smooth muscle cells. AR (androgen receptor), a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in pathways in cancer, whereas PRKCA (Protein Kinase C Alpha), also a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in KEGG pathways, such as pathways in cancer, glioma, and PI3K-Akt signaling pathway. We inferred that CTEPH might be the consequence of abnormal remodeling in APTE, while unbalance between the hyperproliferative and apoptosis-resistant phenotype of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell and pulmonary artery smooth muscle cells in pulmonary artery confer differences in IPAH and CTEPH diseases form. We concluded that the incorporation of plasma circulating let-7i-5p and miRNA-320a in baseline and clinical characteristics of the patients reinforces differences between APTE and CTEPH in outcome evolution, as well as differences between CTEPH and IPAH in diseases form.

Impact of Inflammatory Response Modifiers on the Incidence of Hospital-Acquired Infections in Patients with COVID-19.

INTRODUCTION: The study aim was to assess the influence of inflammatory response modifiers, including anti-interleukin-6 (IL-6) biologics and corticosteroids, on the incidence of hospital-acquired infections in patients with coronavirus disease 2019 (COVID-19). METHODS: Case-control study performed at a university hospital from February 26 to May 26, 2020. Cases were defined as patients with COVID-19 who developed hospital-acquired infections. For each case, two controls were selected among patients without infections. Cases and controls were matched obeying three criteria in a hierarchical sequence: length of hospital stay up until the first infection; comorbidity; and need for Intensive care unit (ICU) admission. Conditional logistic regression analysis was used to estimate the association of exposures with being a case. RESULTS: A total of 71 cases and 142 controls were included. Independent predictors for acquiring a hospital infection were chronic liver disease [odds ratio (OR) 16.56, 95% CI 1.87-146.5, p = 0.012], morbid obesity (OR 6.11, 95% CI 1.06-35.4, p = 0.043), current or past smoking (OR 4.15, 95% CI 1.45-11.88, p = 0.008), exposure to hydroxychloroquine (OR 0.2, 95% CI 0.041-1, p = 0.053), and invasive mechanical ventilation (OR 61.5, 95% CI 11.08-341, p ≤ 0.0001). CONCLUSIONS: Inflammatory response modifiers had no influence on acquisition of nosocomial infections in admitted patients with COVID-19. Hospital-acquired infections primarily occurred in the critically ill and invasive mechanical ventilation was the main exposure conferring risk.

Evaluación de una intervención para mejora en la administración segura de medicación en el turno de noche / An Intervention to Improve Safe Administration of Medication in the Night Shift

Introducción: Uno de cada siete pacientes hospitalizados experimenta un evento adverso relacionado con la administración de medicación. Los errores de medicación son una de las causas más importantes de mortalidad y morbilidad prevenible. Objetivo: Evaluar la eficacia de una intervención formativa sobre la población de enfermeras de turno de noche de un hospital de agudos para mejorar el cumplimiento del protocolo de administración segura de medicación. Métodos: Ensayo experimental, pre-post intervención formativa, realizado en Hospital Clínic de Barcelona, durante 2015-2016. Población: 268 enfermeras en dos turnos de noche, muestra: 177 participantes (88 Grupo Control y 89 Grupo Experimental). La intervención consistió en sesiones informativas y acceso a Procedimiento escrito. El instrumento de medida fue el Procedimiento Normalizado de Trabajo de la institución mediante check-list de cumplimiento. Se realzó estudio uni-bivariable, mediante Chi2 y test de Fisher con significancia para p < 0,05. Resultados: Se realizaron 219 observaciones en Grupo Control y 207 en Grupo Experimental. De 17 variables analizadas, solo tres mostraron diferencias significativas: en Grupo Experimental mejoró el conocimiento del Procedimiento; se incrementó el uso del agua y jabón sobre la solución hidroalcohólica; y empeoró la identificación normalizada de fármacos pendientes de administrar. Ninguna de las 14 variables restantes mostró diferencias significativas. De 426 observaciones, solo se produjeron 3 errores de medicación en Grupo control, subsanados antes de su administración, y 0 en Grupo Experimental. Conclusiones: Las intervenciones formativas clásicas con receptores pasivos pueden no ser eficaces para mejorar la práctica enfermera en administración segura de medicación(AU)

Introduction: One in seven hospitalized patients experiences an adverse event related to administration of medication. Medication errors are one of the most important causes of preventable mortality and morbidity. Objective: To assess the efficacy of a training intervention with the population of night shift nurses in an acute care hospital, in order to improve compliance with the protocol for the safe administration of medication. Methods: Experimental trial, pre-post training intervention, carried out at Hospital Clínic of Barcelona, during 2015-2016. The population consisted of 268 nurses in two night shifts. The sample consisted of 177 participants (88 from the control group and 89 from the experimental group). The intervention consisted in information sessions and access to a written procedure. The measurement instrument was the Institution's Standard Work Procedure by means of a compliance check-list. Uni-bivariate study was performed, using chi-square and Fisher's test with a significance of P < 0.05. Results: 219 observations were carried out in the control group and 207, in the experimental group. Of seventeen variables analyzed, only three showed significant differences: in the experimental group, knowledge of the procedure improved, increase in the use of soap and water over hydroalcoholic solution, and worsening of standardized identification of drugs pending from being administered. None of the fourteen remaining variables showed significant differences. Of 426 observations, only three medication errors occurred in the control group, corrected before its administration, and zero occurred in the experimental group. Conclusions: Classic training interventions with passive receptors may not be effective to improve nursing practice in safe administration of medication(AU)