Assessing the cost-effectiveness of capnography for end-tidal CO2 monitoring during in-hospital cardiac arrest: A middle-income country perspective analysis.

Study objective: To evaluate the cost-effectiveness of EtCO2 monitoring during in-hospital cardiorespiratory arrest (CA) care outside the intensive care unit (ICU) and emergency room department. Design: We performed a cost-effectiveness analysis based on a simple decision model cost analysis and reported the study using the CHEERS checklist. Model inputs were derived from a retrospective Brazilian cohort study, complemented by information obtained through a literature review. Cost inputs were gathered from both literature sources and contacts with hospital suppliers. Setting: The analysis was carried out from the perspective of a tertiary referral hospital in a middle-income country. Participants: The study population comprised individuals experiencing in-hospital CA who received cardiopulmonary resuscitation (CPR) by rapid response team (RRT) in a hospital ward, not in the ICU or emergency room department. Interventions: Two strategies were assumed for comparison: one with an RRT delivering care without capnography during CPR and the other guiding CPR according to the EtCO2 waveform. Main outcome measures: Incremental cost-effectiveness rate (ICER) to return of spontaneous circulation (ROSC), hospital discharge, and hospital discharge with good neurological outcomes. Results: The ICER for EtCO2 monitoring during CPR, resulting in an absolute increase of one more case with ROSC, hospital discharge, and hospital discharge with good neurological outcome, was calculated at Int$ 515.78 (361.57-1201.12), Int$ 165.74 (119.29-248.4), and Int$ 240.55, respectively. Conclusion: In managing in-hospital CA in the hospital ward, incorporating EtCO2 monitoring is likely a cost-effective measure within the context of a middle-income country hospital with an RRT.

Bacterial coinfections in COVID-19-hospitalized patients.

OBJECTIVE: The aim of this study was to assess the rate of bacterial infections in COVID-19-hospitalized patients and to analyze the most prevalent germs, sources, risk factors, and its impact on in-hospital mortality. METHODS: This observational retrospective study was conducted on 672 patients hospitalized between April and August 2020 in Nossa Senhora da Conceição Hospital, a public hospital located in Porto Alegre, Brazil. The inclusion criterion was adult patients hospitalized with confirmed COVID-19. Data were collected through chart review. Risk factors for bacterial infection and mortality were analyzed using both univariate and multivariate robust Poisson regression models. RESULTS: Bacterial coinfection was observed in 22.2% of patients. Risk factors for bacterial infections were dementia (RR=2.06 (1.18-3.60); p=0.011), cerebrovascular disease (RR=1.75 (1.15-2.67); p=0.009), active cancer (RR=1.52 (1.082-2.15); p=0.01), need for noninvasive ventilation (RR=2.320 (1.740-3.094); p<0.01), invasive mechanical ventilation (RR=4.63 (2.24-9.56); p<0.01), and renal replacement therapy (RR=1.68 (1.26-2.25); p<0.01). In the adjusted model, bacterial infections were not associated with mortality (0.96 (0.75-1.24); p=0.79). The most common source of infection was due to respiratory, blood, and central venous catheters, with 69 (29.36%), 61 (25.96%), and 59 (25.11%) positive cultures, respectively. CONCLUSION: We observed a high rate of bacterial infections in COVID-19-hospitalized patients, most commonly of respiratory source. Neurologic and oncologic morbidities and need for ventilation and renal replacement therapy was associated with risk factors for bacterial infections. Nevertheless, an association between bacterial infections and hospital mortality was not established.

Antioxidant, antimicrobial and healing properties of an extract from coffee pulp for the development of a phytocosmetic.

Consumer demand for natural, chemical-free products has grown. Food industry residues, like coffee pulp, rich in caffeine, chlorogenic acid and phenolic compounds, offer potential for pharmaceutical and cosmetic applications due to their antioxidant, anti-inflammatory, and antibacterial properties. Therefore, the objective of this work was to develop a phytocosmetic only with natural products containing coffee pulp extract as active pharmaceutical ingredient with antioxidant, antimicrobial and healing activity. Eight samples from Coffea arabica and Coffea canephora Pierre were analyzed for caffeine, chlorogenic acid, phenolic compounds, tannins, flavonoids, cytotoxicity, antibacterial activity, and healing potential. The Robusta IAC-extract had the greatest prominence with 192.92 µg/mL of chlorogenic acid, 58.98 ± 2.88 mg GAE/g sample in the FRAP test, 79.53 ± 5.61 mg GAE/g sample in the test of total phenolics, was not cytotoxic, and MIC 3 mg/mL against Staphylococcus aureus. This extract was incorporated into a stable formulation and preferred by 88% of volunteers. At last, a scratch assay exhibited the formulation promoted cell migration after 24 h, therefore, increased scratch retraction. In this way, it was possible to develop a phytocosmetic with the coffee pulp that showed desirable antioxidant, antimicrobial and healing properties.

Unlocking the secrets of doxepin hydrochloride's crystal structure: Insights from high-quality powder diffraction analysis.

Doxepin hydrochloride, a versatile pharmaceutical compound, has been the subject of extensive research aimed at elucidating its crystal structure and solid-state characteristics. In this manuscript, we explore the significance of high-quality powder diffraction data in unveiling the intricate details of doxepin hydrochloride's crystal lattice. By examining the refined atom coordinates, density functional theory (DFT) optimization, and intermolecular interactions, we gain valuable insights into its structural conformation. This knowledge highlights the importance of precise crystallographic data in advancing our understanding of complex compounds and their pharmaceutical applications.

Bacterial coinfections in COVID-19-hospitalized patients

SUMMARY OBJECTIVE: The aim of this study was to assess the rate of bacterial infections in COVID-19-hospitalized patients and to analyze the most prevalent germs, sources, risk factors, and its impact on in-hospital mortality. METHODS: This observational retrospective study was conducted on 672 patients hospitalized between April and August 2020 in Nossa Senhora da Conceição Hospital, a public hospital located in Porto Alegre, Brazil. The inclusion criterion was adult patients hospitalized with confirmed COVID-19. Data were collected through chart review. Risk factors for bacterial infection and mortality were analyzed using both univariate and multivariate robust Poisson regression models. RESULTS: Bacterial coinfection was observed in 22.2% of patients. Risk factors for bacterial infections were dementia (RR=2.06 (1.18-3.60); p=0.011), cerebrovascular disease (RR=1.75 (1.15-2.67); p=0.009), active cancer (RR=1.52 (1.082-2.15); p=0.01), need for noninvasive ventilation (RR=2.320 (1.740-3.094); p<0.01), invasive mechanical ventilation (RR=4.63 (2.24-9.56); p<0.01), and renal replacement therapy (RR=1.68 (1.26-2.25); p<0.01). In the adjusted model, bacterial infections were not associated with mortality (0.96 (0.75-1.24); p=0.79). The most common source of infection was due to respiratory, blood, and central venous catheters, with 69 (29.36%), 61 (25.96%), and 59 (25.11%) positive cultures, respectively. CONCLUSION: We observed a high rate of bacterial infections in COVID-19-hospitalized patients, most commonly of respiratory source. Neurologic and oncologic morbidities and need for ventilation and renal replacement therapy was associated with risk factors for bacterial infections. Nevertheless, an association between bacterial infections and hospital mortality was not established.

Internal medicine consultation for high-risk surgical patients: reflection on hospital mortality and readmission rates in a low-income country.

OBJECTIVE: The objective of this study was to assess the impact of internal medicine consultation on mortality, 30-day readmission, and length of stay in surgical patients. METHODS: This is a retrospective descriptive study developed in a public Brazilian teaching hospital with 850 beds. RESULTS: A total of 70,245 patients were admitted from 2010 to 2018 to the surgery departments. The main outcomes measured were patients' mortality, 30-day readmission, and length of stay. Mortality of high-risk patients was lower when followed by internal medicine consultation: patients with ASA≥3 (RR 0.89 [95% confidence interval (95%CI) 0.80-0.99], p=0.02), patients with ASA≥3 plus≥65 years (RR 0.88 [95%CI 0.78-0.99], p=0.04), patients with ASA≥3 plus high-risk surgery (RR 0.86 [95%CI 0.77-0.97], p=0.01), and patients with ASA≥4 plus age ≥65 years (RR 0.83 [95%CI 0.72-0.96], p=0.01). The 30-day readmission of high-risk patients was lower when followed by internal medicine consultation: patients with ≥65 years (RR 0.57 [95%CI 0.37-0.89], p=0.01) and patients with high-risk surgery (RR 0.63 [95%CI 0.46-0.57], p=0.005). The Poisson multivariate regression with adjustment in variances showed that all the variables (namely, age, ASA, morbidity index, surgery risk, and internal medicine consultation) were associated with higher mortality of patients; however, internal medicine consultation was associated with a reduction of mortality in high-risk patients (RR 0.72 [95%CI 0.65-0.84], p=0.02) and an increase of mortality in low-risk patients (RR 1.55 [95%CI 1.31-1.67], p=0.01). CONCLUSION: High-risk surgical patients may benefit from perioperative internal medicine consultations, which probably decrease hospital mortality and 30-day hospital readmission.

Extraction, identification and antitumor activity in cell cultures of cubebin isolated from dry seeds Piper cubeba (Piperaceae).

The Pipercubeba, it is one spice, widely consumed in Europe, which has several bioactive molecules, between those a lignan named cubebin. Cubebin has several known biological activities, such as analgesic activity and anti-inflammatory, trypanocidal activity, leishmanicidal and antitumor activity. The objective of this study was to evaluate the antiproliferative activity "in vitro" cubebin in eight different human tumor cell lines. It was fully characterized by IR analysis, NMR, mass spectrometry, DSC, TGA, residual solvent and elemental analysis. The antitumor activity of cubebin was evaluated "in vitro" on eight different human tumor cell lineages. Cubebin showed GI50≤30µg/mL for lineage cell U251 (glioma CNS), 786-0 (kidney), PC-3 (prostate), HT-29 (colon rectum). For K562 cells (leukemia), cubebin presented GI50≤to 4.0mg/mL. For the other lineages cells, MCF-7 (breast) and NCI-H460 to cubebin can be considered inactive because of GI50>250mg/mL. Analyzing the selectivity index for cubebin, it can be observed that high selectivity of cubebin to K562 lineage cells (leukemia). Analyzing the cytotoxic potential of cubebin was observed that probably acts cubebin altering metabolism, inhibiting cell growth - a cytostatic effect, showing no cytocidal effect on any lineage cell.

Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line.

Rubus rosifolius, popularly known as "red mulberry", is a common medicinal plant in southern Brazil and is used as an antidiarrheal, analgesic, antimicrobial and antihypertensive, and to treat stomach diseases. The aim of this study was to analyze the R. rosifolius stem extract (RrSE) for possible in vitro cytotoxic and genotoxic effects, using the comet assay and the micronucleus test to assess genotoxicity, and flow cytometry to assess the impact on the cell cycle and apoptosis in HepG2/C3A cells, in addition to evaluating the expression of genes linked to the induction of DNA damage, cell cycle, apoptosis and metabolism of xenobiotics. The MTT assay observed no cytotoxic effects at concentrations between 0.01 and 100 µg/mL of the extract. However, genotoxic effects occurred in treatments with the extract from a 1 µg/mL concentration. Flow cytometry analysis revealed a significant increase in cells in the G2/M phase after treatment with 10 µg/mL, a decrease in cells in the G0/G1 phase in the treatment with 100 µg/mL, and a significant increase in total apoptotic cells. In the gene expression analysis, an increase in the CYP1A2 xenobiotics metabolizing gene expression was observed. Despite the promising pharmacological effects of R. rosifolius, the results revealed that the RrSE has genotoxic effect and induces apoptosis in HepG2/C3A cells, indicating danger in using this plant extract by humans.

Phytocosmetic Containing Pink Pepper Extracts Obtained by Sustainable Extraction.

Pink pepper (Schinus terebinthifolius Raddi) has high potential for commercial use because of its biological activities (anti-inflammatory, antitumor, and antioxidant activities, among others). Herein, the antioxidant activity of a topical formulation containing pink pepper extract obtained by supercritical carbon dioxide extraction is reported. The effects of extraction pressure (100-300 bar) and temperature (40-60 °C) on its antioxidant activity were investigated. The extracts obtained at 50-60 °C showed a higher inhibition percentage in the α,α-diphenyl-ß-picrylhydrazyl (DPPH) assay (80.16-91.27 %), regardless of pressure. The extract obtained under optimized conditions (200 bar and 50 °C) was incorporated into an oil-in-water emulsion containing 2 % (m/m) pink pepper extract. The product presented a creamy texture, light rose color, mild spicy odor, and desirable pH for a topical formulation. Furthermore, the product was stable and remained effective when stored and protected from heat and light, showing 35.38 % inhibition of DPPH.

Development and Evaluation of an Antimicrobial Formulation Containing Rosmarinus officinalis.

Rosmarinus officinalis belongs to the Lamiaceae family, and its constituents show antioxidant, anti-inflammatory, antidepressant, antinociceptive, and antibacterial properties. The aim of this study was to develop a topical formulation with R. officinalis extract that had antimicrobial and antioxidant activity. Maceration, infusion, Soxhlet, and ultrasound were used to produce rosemary extracts, which were submitted to antioxidant, compound quantification, cell viability, and antimicrobial assays. Infusion and Soxhlet showed better results in the DPPH assay. During compound quantification, infusion showed promising metabolite extraction in phenolic compounds and tannins, although maceration was able to extract more flavonoids. The infusion and ultrasound extracts affected more strains of skin bacteria in the disk diffusion assays. In the minimum inhibitory concentration assay, the infusion extract showed results against S. aureus, S. oralis, and P. aeruginosa, while ultrasound showed effects against those three bacteria and E. coli. The infusion extract was chosen to be incorporated into a green emulsion. The infusion extract promoted lower spreadability and appropriated the texture, and the blank formulation showed high levels of acceptance among the volunteers. According to the results, the rosemary extract showed promising antioxidant and antimicrobial activity, and the developed formulations containing this extract were stable for over 90 days and had acceptable characteristics, suggesting its potential use as a phytocosmetic. This paper reports the first attempt to produce an oil-in-water emulsion using only natural excipients and rosemary extract, which is a promising novelty, as similar products cannot be found on the market or in the scientific literature.

Stability of vancomycin hydrochloride employed in antimicrobial seal solutions of central intravenous catheters. / Estabilidade do cloridrato de vancomicina empregado em soluções de selo antimicrobiano de cateteres intravenosos centrais.

OBJECTIVE: to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and association time. METHOD: an experimental study designed for the analysis of hydrogenionic potential and concentration by means of high-efficiency liquid chromatography of vancomycin hydrochloride (n=06) and vancomycin hydrochloride and heparin sodium (n=06). The solutions studied were submitted to absence of light, as well as to 22°C and 37°C. Analyses in triplicate (n=192) were performed at the initial moment (T0) and three (T3), eight (T8) and 24 hours (T24) after preparation. The data were submitted to analysis of variance (p≤0.05). RESULTS: concentration of the antimicrobial at 22°C presented a reduction (T0-T8) and a subsequent increase (T24); hydrogenionic potential decreased significantly over time. At 37°C, the concentration increased up to T3 and decreased at T24, with a reduction of hydrogenionic potential up to 24 hours. Concentration of the vancomycin hydrochloride and heparin sodium solutions varied with a reduction at 22°C, accompanied by increased hydrogenionic potential. Precipitate formation was observed by visual inspection of the vancomycin hydrochloride-heparin sodium association (T3). CONCLUSION: pharmacological stability of vancomycin hydrochloride (5 mg/mL) and physical incompatibility with heparin sodium (100 IU/mL) were evidenced after three hours of association in the antimicrobial seal solutions studied.

Femoral neck phantom imaging using time-domain topological energy method.

Ultrasonic bone imaging is a complex task, primarily because of the low energy contained in the signals reflected from the internal bone structures. In this study, the reconstruction of a bone-mimicking phantom echographic image using time-domain topological energy (TDTE) is proposed. A TDTE image results from a combination of forward and adjoint fields. The first is a solution of a numerical model that reproduces the setup of the experimental data acquisition to the best extent possible. The second has similar characteristics, but the source term is the time-reversed residue between the forward field and signals obtained from the experiment. The acquisition-reconstruction system used a linear phased-array transducer with a 5 MHz center frequency to acquire the signals and was coupled with a k-wave toolbox to implement the numerical models and perform the image reconstruction. The results showed good agreement between the geometry of the real phantom and the ultrasonic images. However, thickness evaluation errors were observed, which may be due to incorrect assumptions about the velocity models throughout the medium, a priori assumed to be known. Thus, this method has shown promising results and should be applied to the real femoral neck as a long-term objective.

Symptom-based clusters of hospitalized patients with severe acute respiratory illness by SARS-CoV-2 in Brazil.

BACKGROUND: COVID-19 has shown a broad clinical spectrum, ranging from asymptomatic to mild, moderate, and severe infections. Many symptoms have already been identified as typical of COVID-19, but few studies show how they can be useful in identifying clusters of patients with different severity of illness. This interpretation may help to recognize the different profiles of symptoms of COVID-19 expressed in a population at certain time. The aim of this study was to identify symptom-based clusters of hospitalized patients with severe acute respiratory illness by SARS-CoV-2 in Brazil. The clusters were evaluated based on sociodemographic characteristics, admission to the Intensive Care Unit (ICU), use of respiratory support, and outcome. METHODS: The Multiple Correspondence Analysis (MCA)-based cluster analysis was applied to symptoms presented before admission. Pearson's chi-square test was used to compare the proportions of symptoms between the clusters and to examine differences in the calculated rates for the following variables: sex, age group, race, Brazilian region, use of respiratory support, admission to the ICU and outcome. RESULTS: Three COVID-19 clusters with distinct symptom profiles were identified by MCA-based cluster analysis. Cluster 1 had the mildest severity profile, with the lowest frequencies for most symptoms investigated. Cluster 2 had a severe respiratory profile, with the highest frequencies of patients with dyspnea, respiratory discomfort and O2 saturation< 95%. Cluster 2 was also the most prevalent in all Brazilian regions and had the highest percentages of patients who used invasive respiratory support (27.4%) (p-value<0.001), were admitted to the ICU (42.6%) (p -value<0.001) and died (39.0%) (p-value<0.001). Cluster 3 had a prominent profile of gastrointestinal symptoms. CONCLUSIONS: The study identified three distinct COVID-19 clusters based on the symptoms presented by patients with severe acute respiratory illness by SARS-CoV-2, but without distinction in their prevalence in the Brazilian regions.

The influence of prorenin/(pro)renin receptor on progesterone secretion by the bovine corpus luteum.

The aim of this study was to evaluate the role of prorenin/(pro)renin receptor activation on luteal progesterone (P4) secretion. Our hypothesis was that the nonproteolytic activation of (pro)renin receptor [P(RR)] is part of the regulatory mechanism responsible for corpus luteum (CL) function. In the first three experiments, prorenin was found to stimulate the production of P4, which is not inhibited by an angiotensin receptor antagonist (saralasin), but rather by a renin/prorenin inhibitor (aliskiren), a MAPK1/3 inhibitor (PD325901) or an EGFR inhibitor (AG1478), which are evidence of nonproteolytic activation of prorenin. Moreover, prorenin induced phosphorylation of MAPK1/3 in luteal cells. Following these in vitro experiments, a sequence of in vivo experiments was performed demonstrating that the intrafollicular injection of aliskiren in preovulatory follicles impaired P4 secretion in cows that ovulated. Furthermore, all profibrotic genes studied were present in the CL and TGFB1 and FN1 mRNA were upregulated from day 5-10 post-ovulation. During luteolysis, REN was downregulated at 48 h, whereas TGFB1 and SERPINE1 were dramatically upregulated in luteal tissue at 12 h after PGF. In summary, these data are evidence that nonproteolytic activation of (P)RR is involved in luteal function.

Pracaxi oil affects xenobiotic metabolisms, cellular proliferation, and oxidative stress without cytotogenotoxic effects in HepG2/C3A cells.

Pentaclethra macroloba (Willd.) Kuntze seeds oil has been used as a topical healing agent, applied mainly to parturients and snake bites. The objective was to investigate the effects of pracaxi oil (POP) on HepG2/C3A cells under cytogenotoxicity, cell cycle and apoptosis influence, and expression of metabolism and other related cell types proliferation genes. Cytotoxicity was analyzed by MTT test and apoptosis and cell cycle interferences by flow cytometry. To identify genotoxicity were used comet and micronucleus tests. RT-qPCR investigated gene expression. PO chemical characterization has shown two significant triterpenes, identified as oleanolic acid and hederagenin. The results showed that the PO did not reduce cell viability at concentrations ranging from 31 to 500 µg/ml. Comet and micronucleus assays revealed the absence of genotoxic effects, and flow cytometry showed no cell cycle or apoptosis disturbance. RT-qPCR indicated that PO up-regulated genes related to metabolism (CYP3A4, CYP1A2, CYP1A1), cell proliferation (mTOR), and oxidative stress (GPX1). The data indicate that PO has no cytogenotoxic effects and suggest that it activated the PI3/AKT/mTOR cascade of cell growth and proliferation. Inside the cells, the PO activated xenobiotic metabolizing genes, responsible for reactive oxygen species (ROS) generation, can neutralize ROS with increased GPX1 gene expression without genetic damage, interruption of the cell cycle, or induction of apoptosis.

Biomechanical and Anthropometric Factors That Differentiate National- and Regional-Level Judo Players.

PURPOSE: The study aimed to identify the variables that differentiate judo athletes at national and regional levels. Multivariable analysis was applied to biomechanical, anthropometric, and Special Judo Fitness Test (SJFT) data. METHOD: Forty-two male judo athletes from 2 competitive groups (14 national and 28 state levels) performed the following measurements and tests: (1) skinfold thickness, (2) circumference, (3) bone width, (4) longitudinal length, (5) stabilometric tests, (6) dynamometric tests, and (7) SJFT. The variables with significant differences in the Wilcoxon rank-sum test were used in stepwise logistic regression to select those that better separate the groups. The authors considered models with a maximum of 3 variables to avoid overfitting. They used 7-fold cross validation to calculate optimism-corrected measures of model performance. RESULTS: The 3 variables that best differentiated the groups were the epicondylar humerus width, the total number of throws on the SJFT, and the stabilometric mean velocity of the center of pressure in the mediolateral direction. The area under the receiver-operating-characteristic curve for the model (based on 7-fold cross validation) was 0.95. CONCLUSION: This study suggests that a reduced set of anthropometric, biomechanical, and SJFT variables can differentiate judo athlete's levels.

Continuous wave milipulse yellow laser treatment for perifoveal exudative vascular anomalous complex-like lesion: A case report.

INTRODUCTION: Perifoveal exudative vascular anomalous complex (PEVAC) is an underdiagnosed macular entity. A striking feature of this entity is the unresponsiveness to anti-VEGF treatment. Continuous wave milipulse yellow laser 577 nm (CWMYL-577) has a high absorption peak for oxyhaemoglobin, which allows for low power density use. PURPOSE: To report a case of a PEVAC-like lesion unresponsive to anti-VEGF and corticosteroids, successfully treated with a single session of minimally invasive focal laser, using CWMYL-577. METHODS: A diabetic patient with a symptomatic PEVAC-like lesion in the right eye, presented with decreased vision (20/100) and cystoid edema that had persisted for the last 18 months, despite multiple intraocular injections of anti-VEGF and long acting corticosteroids. Three spots of low power density CWMYL-577 (100 mW, 25 ms and 100 µm, using lens with no amplification factor) over the lesion were successfully performed in one laser session. One month and three months after the laser procedure, a gradual decrease of edema and lipid exudates was observed and at a 6-month follow-up, the retina had recovered its normal anatomy with visual acuity of 20/20 that have persisted for 4 years after treatment. CONCLUSIONS: Minimal invasive focal laser using the CWMYL-577 can be considered an effective therapeutic strategy for symptomatic nonresponding PEVAC-like lesion in patients with DM without DR.

Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial.

IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. METHODS: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). RESULTS: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.

In vivo toxicogenic potential of Salix alba (Salicaceae) bark extract.

Salix alba (white willow) bark extract is widely used for conditions associated with inflammation, fever, microbial infection or pain. Exposure of human cultured leukocytes to S. alba in vitro noted a genotoxic response. However, data regarding the influence of this bark extract on DNA damage in vivo are lacking. The main goal of this study was to examine the potential of S.alba bark extract to induce DNA damage and chromosome aberrations in an in vivo model using cells obtained from male Swiss albino mice administered the compound orally. The extract was administered by oral gavage daily for 7 days at doses of 500, 1000, or 2000 mg/kg b.w. Genotoxicity analysis was performed using the comet assay on peripheral blood leukocytes, as well as liver, bone marrow, heart, and testicular cells collected 4 hr after the last treatment and the micronucleus (MN) test on bone marrow cells. In essence cells were collected 28 hr after the penultimate treatment Data demonstrated that S. alba bark extract did not induce significant DNA damage in any cell types examined, or clastogenic/aneugenic effects as detected by the MN test at the three tested doses. Under these experimental conditions, evidence indicates that S.alba bark extract did not initiate genotoxic or chromosome aberrations in various mouse cells investigated.

Estabilidade do cloridrato de vancomicina empregado em soluções de selo antimicrobiano de cateteres intravenosos centrais / Stability of vancomycin hydrochloride employed in antimicrobial seal solutions of central intravenous catheters / Estabilidad del clorhidrato de vancomicina utilizado en soluciones de sellado antimicrobiano para catéteres intravenosos centrales

Resumo Objetivo: verificar a estabilidade do cloridrato de vancomicina em soluções de selo antimicrobiano sem e com associação de heparina sódica segundo a temperatura e tempo de associação. Método: estudo experimental delineado para análise de potencial hidrogeniônico e concentração por cromatografia líquida de alta eficiência de soluções de cloridrato de vancomicina (n=06) e cloridrato de vancomicina e heparina sódica (n=06). Submeteram-se as soluções estudadas à ausência de luz, 22°C e 37°C. Análises em triplicadas (n=192) ocorreram no momento inicial (T0), três (T3), oito (T8) e 24 horas (T24) após preparo. Os dados foram submetidos à análise de variância (p≤0,05). Resultados: a concentração do antimicrobiano a 22°C apresentou redução (T0-T8) e posterior elevação (T24); o potencial hidrogeniônico diminuiu significativamente ao longo do tempo. Em 37°C a concentração aumentou em até T3 e reduziu em T24, com redução de potencial hidrogeniônico até 24 horas. A concentração das soluções de cloridrato de vancomicina e heparina sódica apresentaram variação com redução a 22°C acompanhada de aumento de potencial hidrogeniônico. Observou-se formação de precipitado por inspeção visual da associação cloridrato de vancomicina e heparina sódica (T3). Conclusão: evidenciou-se estabilidade farmacológica do cloridrato de vancomicina (5 mg/mL) e incompatibilidade física com heparina sódica (100 UI/mL) após três horas de associação nas soluções de selo antimicrobiano estudadas.

Abstract Objective: to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and association time. Method: an experimental study designed for the analysis of hydrogenionic potential and concentration by means of high-efficiency liquid chromatography of vancomycin hydrochloride (n=06) and vancomycin hydrochloride and heparin sodium (n=06). The solutions studied were submitted to absence of light, as well as to 22°C and 37°C. Analyses in triplicate (n=192) were performed at the initial moment (T0) and three (T3), eight (T8) and 24 hours (T24) after preparation. The data were submitted to analysis of variance (p≤0.05). Results: concentration of the antimicrobial at 22°C presented a reduction (T0-T8) and a subsequent increase (T24); hydrogenionic potential decreased significantly over time. At 37°C, the concentration increased up to T3 and decreased at T24, with a reduction of hydrogenionic potential up to 24 hours. Concentration of the vancomycin hydrochloride and heparin sodium solutions varied with a reduction at 22°C, accompanied by increased hydrogenionic potential. Precipitate formation was observed by visual inspection of the vancomycin hydrochloride-heparin sodium association (T3). Conclusion: pharmacological stability of vancomycin hydrochloride (5 mg/mL) and physical incompatibility with heparin sodium (100 IU/mL) were evidenced after three hours of association in the antimicrobial seal solutions studied.

Resumen Objetivo: verificar la estabilidad del clorhidrato de vancomicina en soluciones de sellado antimicrobiano solo y combinado con heparina sódica según la temperatura y el tiempo de combinación. Método: estudio experimental diseñado para analizar el potencial de hidrógeno y la concentración por cromatografía líquida de alta resolución de soluciones de clorhidrato de vancomicina (n=06) y de clorhidrato de vancomicina y heparina sódica (n=06). Las soluciones estudiadas fueron sometidas a ausencia de luz, 22°C y 37°C. Se realizaron análisis por triplicado (n=192) en el momento inicial (T0), a las tres (T3), ocho (T8) y 24 horas (T24) después de la preparación. Los datos fueron sometidos a análisis de varianza (p≤0,05). Resultados: la concentración de antimicrobiano a 22°C mostró una reducción (T0-T8) y un posterior aumento (T24); el potencial de hidrógeno disminuyó significativamente con el tiempo. A 37°C, la concentración aumentó hasta T3 y disminuyó en T24, el potencial de hidrógeno disminuyó hasta las 24 horas. La concentración de las soluciones de clorhidrato de vancomicina y heparina sódica mostró variación con la reducción a 22°C acompañada de un aumento del potencial de hidrógeno. Mediante inspección visual se observó la formación de un precipitado al combinar clorhidrato de vancomicina y heparina sódica (T3). Conclusión: el clorhidrato de vancomicina (5 mg/ml) presentó evidencia de estabilidad farmacológica e incompatibilidad física con la heparina sódica (100 UI/ml) después de las tres horas de haberse realizado la combinación en las soluciones de sellado antimicrobiano estudiadas.