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BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).
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Morte Encefálica , Transplante de Coração , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Sobrevivência de Enxerto , Preservação de Órgãos , Doadores de Tecidos , Morte , Segurança do PacienteRESUMO
Bilastine, a new second generation antihistaminic drug, has been widely used for relieving symptoms of allergic rhinitis and urticaria without a sedative effect. A simple, cost-effective, and highly sensitive fluorimetric method was developed for the estimation of bilastine in human plasma, in addition to its pure state and tablets. The suggested method depended on binary complex formation of eosin with bilastine in a buffered medium at pH 4.2. The formed complex resulted in quantitative quenching of eosin emission at 538 nm after excitation at 335 nm. This method demonstrates a broad range of linearity, spanning from 200 to 1000 ng/mL, and exhibits exceptional sensitivity, with a limit of detection and quantitation of 30.85 and 93.48 ng/mL, respectively. In addition, this spectrofluorimetric method may be employed to determine the amount of bilastine in human plasma and tablets with satisfactory accuracy and excellent precision. Furthermore, the content uniformity of bilastine in commercially available tablets was successfully tested by this approach. Compared with the reference method, there were no significant variations in terms of precision or accuracy. In conclusion, the proposed protocol is highly recommended to quantitatively estimate bilastine in different quality control settings.
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Benzimidazóis , Piperidinas , Espectrometria de Fluorescência , Comprimidos , Humanos , Piperidinas/sangue , Piperidinas/química , Espectrometria de Fluorescência/métodos , Benzimidazóis/sangue , Benzimidazóis/química , Limite de Detecção , Azul de Eosina I/química , Concentração de Íons de HidrogênioRESUMO
Refractory hypoxemia during veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) may require an additional cannula (VV-V ECMO) to improve oxygenation. This intervention includes risk of recirculation and other various adverse events (AEs) such as injury to the lung, cannula malpositioning, bleeding, circuit or cannula thrombosis requiring intervention (i.e., clot), or cerebral injury. During the study period, 23 of 142 V-V ECMO patients were converted to VV-V utilizing two separate cannulas for bi-caval drainage with an additional upper extremity cannula placed for return. Of those, 21 had COVID-19. In the first 24 h after conversion, ECMO flow rates were higher (5.96 vs 5.24 L/min, p = .002) with no significant change in pump speed (3764 vs 3630 revolutions per minute [RPMs], p = .42). Arterial oxygenation (PaO2) increased (87 vs 64 mmHg, p < .0001) with comparable pre-oxygenator venous saturation (61 vs 53.3, p = .12). By day 5, flows were similar to pre-conversion values at lower pump speed but with improved PaO2. Unadjusted survival was similar in those converted to VV-V ECMO compared to V-V ECMO alone (70% [16/23] vs 66.4% [79/119], p = .77). In a mixed effect regression model, any incidence of AEs, demonstrated a negative impact on PaO2 in the first 48 h but not at day 5. VV-V ECMO improved oxygenation with increasing flows without a significant difference in AEs or pump speed. AEs transiently impacted oxygenation. VV-V ECMO is effective and feasible strategy for refractory hypoxemia on VV-ECMO allowing for higher flow rate and unchanged pump speed.
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AIMS: The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts. METHODS AND RESULTS: We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. CONCLUSION: We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.
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Ventrículos do Coração , Coração , Humanos , Arritmias Cardíacas , Fibrilação Ventricular/cirurgia , Potenciais de Ação/fisiologiaRESUMO
A fast, simple, accurate, precise, and cheap fluorimetric protocol has been proposed for analysis of a phosphodiesterase-IV inhibitor, namely drotaverine hydrochloride. Fluorimetric protocol is based on estimating the decrease in the eosin Y fluorescence intensity by quantitative addition of drotaverine at pH 3.1 (acetate buffer). An ion pair complex is formed, which leads to quenching in the fluorescence intensity of the dye without need of prior extraction at 534 nm (λex. 339 nm). Different reaction perimeters which influence the production of complex (ion pair between drotaverine and eosin) were deeply investigated and optimized. The developed fluorimetric protocol is capable for quantitative estimation of drotaverine in linear range of 0.4 to 2.5 µg mL-1. After method validation in respect to ICH guidelines, it was applied to determine drotaverine in its commercial preparation. By comparing with other reported method, the developed and validated fluorimetric protocol is capable for estimation of drotaverine in commercial preparation with good accuracy and excellent precision.
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BACKGROUND: Caregiver support is considered necessary after heart transplant (HT) and left ventricular assist device (LVAD) for patients with end-stage heart failure (HF). Few studies have demonstrated how caregivers differ by gender and race, and whether that impacts therapy eligibility. METHODS: We examined caregiver relationships among 674 patients (32% women, 55% Black) evaluated at Emory University from 2011 to 2017. Therapy readiness was assessed using the Stanford Integrated Assessment for Transplant (SIPAT). Evaluation outcome according to caregiver relationship was compared using χ2 analysis. Multivariable logistic regression determined the association between caregiver and eligibility according to gender and race. RESULTS: Women and Black patients were less likely to have spouses as their support person (P < .001). Women were less likely to be considered eligible for advanced therapies (adjusted odds ratio [aOR] .64, 95% confidence interval [CI] .46-.89; P = .008), with Black women having lower eligibility than White women (aOR .28, 95% CI .11-.72; P = .008). Social support and SIPAT scores did not significantly influence eligibility by gender or race. CONCLUSION: Lack of caregiver support is considered a relative contraindication to advanced therapies. Type of caregiver in our cohort varied according to race and gender but did not explain differences in eligibility for advanced therapies.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Cuidadores , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Estudos RetrospectivosRESUMO
Gram-negative bacteria cause infections such as skin infection, meningitis, and pneumonia in human being. Gram-negative bacteria are highly resistant to most availaible bactericidal drugs. One of the most commonly used Gram-negative bactericidal drug is Polymyxin B sulfate (PMS). In addition, it is used in cases of highly resistant Gram-negative bacterial infections. The widespread of PMS necessitate the development of an exceedingly sensitive and selective fluorimetric assay for its determination in pure form, different pharmaceutical dosage forms, and human plasma. The presented method is used to determine PMS in their dosage form (vials) and combined pharmaceutical formulations (skin and eye ointments) with a high degree of accuracy and selectivity. The described procedure relies on the structure of a derivative of a high degree of fluorescence called dihydropyridine, via the condensation of the amino moiety of PMS with two equivalents of acetylacetone in the presence of formaldehyde and Teorell buffer (pH = 3). The fluorescent product was measured at 471 nm (λex = 402 nm). The linearity ranged from 100-3000 ng mL-1 of PMS with an excellent r2 of 0.9998. LOD and LOQ were 27.16 ng mL-1 and 82.30 ng mL-1, respectively. Owing to the developed method's high selectivity, it was successfully utilized for assay of PMS, in the ointment, in the presence of oxytetracycline as an active ingredient. Furthermore, the procedure applied for the estimation of parenteral PMS in human plasma with very good mean recovery 97.42 ± 1.46.
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Antibacterianos/análise , Polimixina B/análise , Espectrometria de Fluorescência/métodos , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Soluções Tampão , Di-Hidropiridinas/química , Formas de Dosagem , Corantes Fluorescentes , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Polimixina B/administração & dosagem , Polimixina B/sangue , TemperaturaRESUMO
A great demand for discovering new therapeutic solutions has been considered all over the world for managing the rapidly progressing COVID-19 pandemic. Remdesivir (REM) and Favipiravir (FAV) are introduced as promising newly developed antiviral agents against the corona virus as evidenced by the clinical findings. Hence, the optimization of an analytical method for their simultaneous determination acquires potential importance in quality control labs and further confirmatory investigations. Herein, a green, sensitive, and selective densitometric method has been proposed and validated for determination of REM and FAV in pharmaceutical formulations and spiked human plasma on normal phase TLC plates. A solvent mixture of ethyl acetate-methanol-ammonia (8:2:0.2 by volume) has been chosen as developing mobile phase system. Well resolved spots have been detected at 235 nm with retardation factors (Rf) of 0.18 and 0.98 for REM and FAV, respectively. A validation study has been carried out in the light of ICH guidelines. Remdesivir and FAV have shown excellent sensitivities with quantitation limits down to 0.12 and 0.07 µg/band, respectively. The developed method has been successfully applied to tablet formulations and spiked plasma with excellent recoveries ranged from 97.21 to 101.31%. The greenness of the method has been evaluated using the standards of greenness profile and Eco-Scale. It has passed the four greenness profile quadrants and achieved 80 score in Eco-Scale.
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A new, rapid, highly sensitive, and affordable spectrofluorimetric approach has been constructed and validated for the determination of octreotide in its authentic form and pharmaceutical dosage form. Octreotide is an important synthetic analog of the naturally occurring somatostatin hormone. The developed spectrofluorimetric approach is actually dependent on the measurement of octreotide native fluorescence at emission wavelength of 342 nm after excitation at 218 nm. At optimal reaction conditions, the calibration curve has been constructed over the concentration range 200-2000 ng ml-1 , with excellent linearity. The limits of detection and quantitation values were found to be 55 and 169 ng ml-1 , respectively. The developed approach has been effectively used to determine octreotide in its pharmaceutical ampoules, without interference from the excipients in the dosage form. The developed approach is simple, time-saving, and does not require multiple pretreatment steps for samples, costly apparatus, or dangerous materials. As a result, it can be used to detect and quantify octreotide acetate in quality control laboratories.
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Octreotida , Composição de Medicamentos , Espectrometria de Fluorescência , Calibragem , Preparações FarmacêuticasRESUMO
Following the sudden widespread of the novel coronavirus (COVID-19) which first appeared in Wuhan city. Remdesivir (REM) was the first medicine licensed by the US Food and Drug Administration (FDA) for COVID-19 infected hospitalized patients. Hence, there was an urgent demand for the optimization of efficient selective and sensitive methods to be developed for the determination of REM in pharmaceuticals as well as biological samples. A sensitive and simple green spectrofluorimetric method has been developed to determine REM in pharmaceutical formulation, in addition to, spiked human plasma. The technique involves measuring the native fluorescence of REM in distilled water at 410 nm followed by excitation at 241 nm, giving a linear relationship over the range 50.00-500.00 ng/mL, and then improving the sensitivity of REM through micellar formation using 2.00% w/v sodium dodecyl sulfate (SDS). A linear relationship has been obtained over the range 10.00-350.00 ng/mL having detection and quantitation limits of 2.34 and 7.10 ng/mL, respectively. Different analytical parameters have been carefully studied. A validation study has been conducted successfully in accordance with the FDA and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The developed methods' greenness was assessed utilizing a greenness profile and analytical eco-scale standards. Both methods were discovered to be environmentally friendly and could be successfully used for the determination of the studied drugs in pharmaceutical formulation and human plasma with good accuracy and high precision. As a result, the developed spectrofluorimetric methods could be ideally suited for determination of REM in quality control and medicinal laboratories.
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Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Humanos , Micelas , Espectrometria de Fluorescência/métodosRESUMO
Polymyxins (PMS), namely Colistin (CS) and polymyxin B (poly B), are antimicrobial drugs that have been recently used to treat multiresistant Gram-negative bacteria infections and their resurgence, owing to a lack of new antibiotics. A speedy, simple, and ultrasensitive spectrofluorimetric screening of PMS in pharmaceutical formulations and biological fluids was urgently required from this point forwards. A reaction between fluorescamine and the aliphatic amino moiety found in both drugs was performed in a slightly alkaline borate buffer (pH 8.5) resulted in highly fluorescent products measured at λem 460 (after λex 390.5 nm). Linear calibration curves were constructed over the concentration range 70-1800 ng ml-1 and 100 to 1400 ng ml-1 , with slope values of 0.273 and 0.286, correlation coefficients of 0.9998 and 0.9997, and determination coefficient of 0.9997 and 0.9994 for poly B and CS, respectively. The ultrasensitivity of the proposed method was demonstrated by the very low limit of quantification values of 67.56 ng ml-1 and 94.89 ng ml-1 for poly B and CS, respectively. The cited drugs were successfully determined in their intravenous market preparations by the prescribed method. Moreover, due to the high sensitivity, the suggested method was used to assay the investigated drugs in biological fluids.
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Antibacterianos , Polimixinas , Antibacterianos/farmacologia , Colistina/farmacologia , Fluorescamina , Bactérias Gram-Negativas , Humanos , Preparações Farmacêuticas , Espectrometria de Fluorescência/métodosRESUMO
A new sensitive and instantaneous spectrofluorimetric method for efficient determination of lomefloxacin (LMX) in its pure, dosage form and human plasma was designed. The developed method depends on formation of a metal-chelation compound of LMX as a ligand with zinc(II) in a buffer of acetate (pH 5.5). The following parameters; type of metal, concentration of metal, pH, type of buffer and diluting solvent were optimized. After carefully investigation; 0.2 mM zinc, 2.0 ml acetate buffer (pH 5.5) and water as diluting solvent were set as optimum reaction conditions. Under these conditions, a large increase in the intensity of the fluorescence of LMX was attained at 450 after excitation at 284 nm. The limits of detection and quantification were 5.8 and 1.9 ng ml-1 , respectively, with linearity range of 10.0 to 500.0 ng ml-1 . The binding mode of LMX and zinc(II) ion (Zn2+ ) was found to be 2:1, respectively, and confirmed by Job's plot method. Furthermore, it extended to the analysis of LMX in the spiked plasma of humans with percentage recovery (98.70 ± 0.97 to 100.30 ± 1.69%, n = 3).
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Fluoroquinolonas , Zinco , Humanos , Solventes , Espectrometria de FluorescênciaRESUMO
In this paper, two simple, rapid and highly sensitive spectrofluorimetric methods were developed and validated for nystatin determination in its pure form and pharmaceutical dosage form (oral suspension). The first method was based on measuring the nystatin native fluorescence after dilution with isopropyl alcohol at 407 nm (excitation 303 nm). The fluoresence intensity was linearly dependant on the nystatin concentration within the specified range 50-500 ng ml-1 . The second was based on micellar enhancement of nystatin fluorescence using sodium dodecyl sulphate (SDS). In the presence of 2% w/v SDS, an ~1.9-fold enhancement could be achieved in the relative fluorescence intensity of nystatin. The linear range for the second method was 20-100 ng ml-1 . The limits of quantification and detection were found to be 43.23 ng ml-1 and 14.27 ng ml-1 (Method I), 6.08 ng ml-1 and 2.0 ng ml-1 (Method II). According to percentage recoveries and relative standard deviations (RSDs) obtained, the proposed methods were precise (RSDs were less than 2%), reproducible, and accurate and could be successfully applied for quantitative estimation of nystatin in its dosage form. The statistical results of this method were compared with that of the reported method and showed excellent agreement with respect to accuracy and precision.
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Antifúngicos , Nistatina , Micelas , Dodecilsulfato de Sódio , Espectrometria de FluorescênciaRESUMO
A natural, accurate, extremely rapid, and precise spectrofluorometric method has been developed and validated for determination of salmeterol (SAL) xinafoate in its medicinal commercial form and spiked human plasma. The native SAL fluorescence has been measured at 415 nm (after 340 nm as excitation) in distilled water. Different factors affecting the native fluorescence consistency of SAL were surveyed and optimized. The suggested procedure was capable of SAL determination over concentrations ranging 200-2000 ng.mL-1 with excellent correlation coefficient of 0.9995. The limits of detection and quantification were estimated as 44.44 ng mL-1 and 134.66 ng mL-1 , respectively. The method has good accuracy and precision. The green spectrofluorometric method was used for determination of SAL in its commercial preparations and the results were in accordance with other reported methods regarding accuracy and precision. Moreover, the proposed procedure was enforced for stability indicating assay of SAL and for SAL determination in spiked human plasma. Nearly no cost, high sensitivity, and wide application make the proposed method ideally suited for analysis of SAL in quality control laboratories.
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Espectrometria de Fluorescência , Humanos , Xinafoato de SalmeterolRESUMO
A new, accurate, nonextractive, and sensitive fluorimetric approach was proposed and validated for the first time estimation of colistin sulfate and its inactive prodrug colistimethate sodium in its bulk form, pharmaceutical formulations, and human plasma. The approach relied on condensation between acetylacetone/formaldehyde and the primary amino moiety of nonfluorescent colistin in Teorell and Stenhagen buffer (pH 2.8) by the Hantzsch reaction to form a highly fluorescent dihydropyridine derivative. The fluorescent product was measured at 460 nm (λex = 402 nm). A plot of relative fluorescence intensity (RFI) versus concentration was rectilinear over the range 200-4000 ng ml-1 with excellent correlation (r) and determination (r2 ) coefficients of 0.9999 and 0.9998, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) were 40.91 and 123.99 ng ml-1 , respectively. The present procedure was useful for determination of colistin sulfate either in powder form for suspension or in its parenteral prodrug colistimethate sodium in vial formulation. The investigated approach was applied for in vitro quantification of this drug in spiked human plasma, with a per cent mean recovery of 98.24 ± 1.34. The proposed method is reliable, selective, and does not require tedious sample pretreatment steps, expensive instrumentation, or harmful reagents, all of which make it ideally suited for use in quality control laboratories.
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Colistina , Pró-Fármacos , Colistina/análogos & derivados , Formaldeído , Humanos , Espectrometria de FluorescênciaRESUMO
OBJECTIVES: We investigated sex-based differences in eligibility for and outcomes after receipt of advanced heart failure (HF) therapies. BACKGROUND: Although women are more likely to die from HF than men, registry data suggest that women are less likely to receive heart transplant (HT) or left ventricular assist device (LVAD) for largely unknown reasons. METHODS: We performed a single-center retrospective cohort study of patients evaluated for advanced HF therapies from 2012 to 2016. Logistic regression was used to determine the association of sex with eligibility for HT/LVAD. Competing risks and Kaplan-Meier analysis were used to examine survival. RESULTS: Of 569 patients (31% women) evaluated, 223 (39.2%) were listed for HT and 81 (14.2%) received destination (DT) LVAD. Women were less likely to be listed for HT (adjusted odds ratio [OR] 0.36, 95% confidence interval [CI] 0.21-0.61; P < .0001), based on allosensitization (P < .0001) and obesity (P = .02). Women were more likely to receive DT LVAD (adjusted OR 2.29, 95% CI 1.23-4.29; P = .01). Survival was similar between men and women regardless of whether they received HT and DT LVAD or were ineligible for therapy. CONCLUSION: Women are less likely to be HT candidates, but more likely to receive DT LVAD.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Idoso , Feminino , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Medicare , Estudos Retrospectivos , Caracteres Sexuais , Resultado do Tratamento , Estados UnidosRESUMO
The 2018 Revised United Network for Organ Sharing Heart Allocation System (HAS) was proposed to reclassify status 1A candidates into groups of decreasing acuity; however, it does not take into account factors such as body mass index (BMI) and blood group which influence waitlist (WL) outcomes. We sought to validate patient prioritization in the new HAS at our center. We retrospectively evaluated patients listed for heart transplantation (n = 214) at Emory University Hospital from 2011 to 2017. Patients were reclassified into the 6-tier HAS. Multistate modeling and competing risk analysis were used to compare outcomes of transplantation and WL death/deterioration between new tiers. Additionally, a stratified sensitivity analysis by BMI and blood group was performed. Compared with tier 4 patients, there was progressively increasing hazard of WL death/deterioration in tier 3 (HR: 2.52, 95% CI: 1.37-4.63, P = .003) and tier 2 (HR: 5.03, 95% CI: 1.99-12.70, P < .001), without a difference in transplantation outcome. When stratified by BMI and blood group, this hierarchical association was not valid in patients with BMI ≥30 kg/m2 and non-O blood groups in our cohort. Therefore, the 2018 HAS accurately prioritizes the sickest patients in our cohort. Factors such as BMI and blood group influence this relationship and iterate that the system can be further refined.
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Transplante de Coração , Obtenção de Tecidos e Órgãos , Índice de Massa Corporal , Humanos , Estudos Retrospectivos , Medição de Risco , Estados Unidos , Listas de EsperaRESUMO
PURPOSE: Despite paucity of data, there exists growing popularity of catheter-based extraction methods for intravascular thrombi and vegetations. We describe a large single center experience with vacuum-assisted extraction techniques (VAET) for right-sided intravascular and cardiac masses. METHODS: We retrospectively reviewed the perioperative course of patients undergoing VAET between 2014 and 2019. Primary outcomes were survival and freedom from recurrent bacteremia. Procedural success was a composite definition of survival, majority of mass extraction, absence of recurrent bacteremia, and valve function not requiring further intervention during index hospitalization. RESULTS: Of the entire cohort (n = 58), 48% and 52% underwent VAET for vegetations and sterile thrombi, respectively. Of those with positive cultures, the most common organism isolated was Staphylococcus aureus (48%). Preoperative active bacteremia was present in 36% (21/58) and of these patients, 76% (16/21) had neither recurrent nor persistent bacteremia post-op. The majority of masses (67%, 38/58) were debulked with an average reduction in size of 42%. Conversion to open surgery occurred in 3.5% (2/58). Intraoperative and 30-day survival were 98% (57/58) and 90% (28/31), respectively. Overall success was 86% (50/58). The prevalence of moderate/severe tricuspid regurgitation was 37% pre-op and 61% post-op. Average length of intensive care unit and overall hospital stay was 5.6 and 16 days, respectively. CONCLUSIONS: In this single center experience, VAET was conducted safely with a high degree of success and freedom from short-term recurrent bacteremia. This minimally invasive procedure is an attractive alternative to traditional open techniques for removal of right-sided intravascular and cardiac masses.
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Embolectomia/métodos , Vácuo , Trombose Venosa/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Humanos , Estudos Retrospectivos , Fatores de TempoRESUMO
Helicobacter pylori (H. pylori) infection is common and can result in gastric and duodenal ulcers, and in some cases, gastric lymphoma and cancer. Omeprazole (OMP)-in combination with clarithromycin (CLR), amoxicillin (AMX), tinidazole (TND), or metronidazole (MET)-is used in double or triple combination therapy for eradication of H. pylori. However, the roles of the drugs other than OMP are not clearly understood. Therefore, in the present study, we aimed to investigate any effects of these drugs on OMP metabolism by wild-type CYP2C19 using spectroscopy and enzyme kinetics. The dissociation constants (Kd) for CYP2C19 with OMP, CLR, AMX, TND, and MET were 8.6, 126, 156, 174, and 249 µM, respectively. The intrinsic clearance of OMP was determined to be 355 mL/min/µmol of CYP2C19. Metabolism of OMP was significantly inhibited by 69, 66, 28, and 40% in the presence of CLR, TND, AMX, and MET, respectively. Moreover, the combination of CLR and TND resulted in 76% inhibition of OMP metabolism, while the combination of AMX and MET resulted in 48% inhibition of OMP metabolism. Both combinations of drugs not only have antibacterial effects, but also enhance the effect of OMP by inhibiting its metabolism by CYP2C19. These results indicate that drug-drug interactions of co-administered drugs can cause complex effects, providing a basis for OMP dose adjustment when used in combination therapy for H. pylori eradication.
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Antibacterianos/farmacologia , Citocromo P-450 CYP2C19/metabolismo , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Omeprazol/farmacologia , Amoxicilina/química , Amoxicilina/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Cromatografia Líquida de Alta Pressão , Claritromicina/química , Claritromicina/farmacologia , Citocromo P-450 CYP2C19/química , Combinação de Medicamentos , Humanos , Metronidazol/química , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Omeprazol/antagonistas & inibidores , Omeprazol/metabolismo , Tinidazol/química , Tinidazol/farmacologiaRESUMO
OBJECTIVE: To compare the effect of Paracetamol/Prednisolone versus Paracetamol/Ibuprofen on post-operative recovery after adult tonsillectomy. BACKGROUND: Various analgesic protocols have been proposed for the control of post-tonsillectomy morbidity with need for better control in adult population for having higher severity of post-operative pain and risk of secondary post-tonsillectomy bleeding. METHODS: This is a prospective cohort study conducted on 248 patients with age of 12â¯years or older distributed as two equal groups; the first one receiving Paracetamol/Prednisolone and the second one receiving Paracetamol/Ibuprofen. Both groups were compared at 7â¯days post-operative regarding pain at rest, tiredness of speech, dietary intake, and decrease in sleep duration. Both groups were compared regarding incidence of nausea and vomiting at 2â¯days post-operative. The incidence and severity of secondary post-tonsillectomy hemorrhage was compared between the two groups. RESULTS: Pain at rest (no swallowing - no talking) was less in group I but not reaching statistical significance (pâ¯=â¯0.36). In addition, dietary intake was better in group I but not reaching statistical significance (Pâ¯=â¯0.17). However, talking ability was better with statistically significant difference (Pâ¯=â¯0.03) in group I. Impairment of sleep was less with group II but not reaching statistical significance (pâ¯=â¯0.31). The incidence of vomiting at second post-operative day was less in group I with statistical significance (pâ¯=â¯0.049). The incidence of secondary post-tonsillectomy bleeding was significantly higher in group II with statistical significance (pâ¯=â¯0.046). The severity of bleeding episodes was also significantly higher in group II (pâ¯=â¯0.045). CONCLUSION: Both ibuprofen and prednisolone were effective as a part of post-operative medication regimen after adult tonsillectomy. However, prednisolone was superior to ibuprofen regarding improvement of pain at rest, dietary intake, tiredness of speech and post-operative nausea and vomiting. However, ibuprofen had a better impact on sleep. The incidence and severity of secondary post-tonsillectomy hemorrhage were significantly higher with ibuprofen favoring the selection of prednisolone to be combined with paracetamol in the post-operative medication protocol following tonsillectomy.