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BACKGROUND: It is controversial whether the use of a double-J stent (DJ) in patients with bladder cancer before radical cystectomy (RC) increases the risk of tumour seeding in the upper tract and thus the risk of metachronous upper tract urothelial carcinoma (UTUC). The aim of our study is to investigate the risk of upper tract recurrence after RC in patients previously managed with a DJ stent. METHODS: A total of 699 patients who had undergone RC between January 2003 and March 2022 with complete perioperative data and pathological outcome were included in our study. Patients treated preoperatively with a DJ stent were identified and compared for development of metachronous UTUC with those who did not receive prior internal stenting. Multivariable Cox regression analysis was used to determine predictors of UTUC occurrence among the possible pathological features; risk factors for mortality after RC were also examined. RESULTS: Of 699 patients, 117 (16.7%) were managed preoperatively with a DJ stent. The overall probability of metachronous UTUC was 1%, 4% and 6% at 1, 3 and 5 years, respectively. The groups with and without DJ stenting were comparable regarding their clinicopathologic features, except for the higher incidence of hydronephrosis in the DJ group. At similar follow-up periods (median follow-up 32 months), metachronous UTUC was detected in four (3.4%) patients in the DJ group and in 13 (2.2%) in the non-stented group (P=0.44). The median interval (IQR) from cystectomy to UTUC was 40.5 (20-49) months in the DJ group and 37 (24-82) in the non-stented group (P=0.7). In the multivariable analysis, only presence of CIS (HR 3.83, 95% CI 1.19-12.29, P=0.024) and positive ureteral margin (HR=5.2, 95% CI 1.38-19.57, P=0.015) were predictors of metachronous UTUC. The study is limited by the retrospective nature and relatively short follow-up. CONCLUSIONS: Ureteral stenting for management of hydronephrosis in patients with bladder cancer undergoing RC is a viable option, without higher risk for UTUC or mortality. Patients with positive ureteral margin and CIS are considered high-risk groups for upper tract recurrence and should receive long-term, rigorous follow-up.
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Carcinoma de Células de Transição , Cistectomia , Stents , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/efeitos adversos , Masculino , Feminino , Stents/efeitos adversos , Idoso , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Ureterais/cirurgia , Neoplasias Ureterais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Ureter/cirurgia , Ureter/patologia , Inoculação de Neoplasia , Fatores de RiscoRESUMO
Background: Pentafecta has recently been validated for reporting radical cystectomy (RC) outcomes in open, laparoscopic and robotic series. We aim in this review to explore the current role of pentafecta in the reporting of RC outcomes. Methods: A comprehensive literature search was performed in the PubMed database to identify relevant articles. The pentafecta achievement (PA) was defined originally as negative soft tissue surgical margin (NSTSM), lymph node (LN) dissection (LND) with removal of ≥16 LNs, absence of 90-days grade ≥3 Clavien-Dindo (CD) complications, a time interval of less than 3 months between the last transurethral resection of bladder tumor (TURBT) with evidence of muscle invasive bladder cancer (MIBC) and RC, and absence of local pelvic recurrence within 1 year. The definition was later modified and the last two criteria were replaced by absence of urinary diversion (UD) related complications and any clinical recurrence at one year. Results: Twelve studies with 4,946 patients were enrolled in the present review. All the studies were retrospective except one recently published randomized study comparing open and robotic-assisted RC. Pentafecta was totally achieved in 34% and main causes of missing pentafecta were the number of resected LNs and 90-days major complications. Type of UD, increasing age, advanced tumor stage, and decreasing surgical experience were the factors most commonly associated with a lower likelihood of PA. A positive correlation was seen between PA and long-term oncological outcome and quality of life. The main limitations in the present studies are their retrospective nature, relatively small sample size, and short median follow-up, most of which was less than 3 years. Conclusions: The new pentafecta definition provides a comprehensive tool for reporting RC outcomes by including measures of postoperative morbidity, functional outcomes and local cancer control. Pentafecta include standards that could be useful for improving surgical quality, surgical education and comparing different techniques. However, pentafecta is not yet suitable for perioperative risk stratification and patient counseling.
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RATIONALE: Lung function in early adulthood is associated with subsequent adverse health outcomes. OBJECTIVES: To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function. METHODS: Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV1/FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in ~3200 participants at age 24 years in one of our cohorts. RESULTS: We identified four FEV1/FVC trajectories with strikingly similar latent profiles across cohorts (pooled N=6377): above average (49.5%); average (38.3%); below average (10.6%); and persistently low (1.7%). Male sex, wheeze, asthma diagnosis/medication and allergic sensitisation were associated with trajectories with diminished lung function in all cohorts. We found evidence of an increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC (with p values for the mean crude effects per-trajectory ranging from 0.10 to p<0.001). In this analysis, we considered trajectories as a pseudo-continuous variable; we confirmed the assumption of linearity in all the regression models. CONCLUSIONS: Childhood lung function trajectories may serve as predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood.
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Doenças Cardiovasculares , Humanos , Masculino , Feminino , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Criança , Adolescente , Capacidade Vital/fisiologia , Volume Expiratório Forçado/fisiologia , Adulto Jovem , Espirometria , Asma/fisiopatologia , Asma/epidemiologia , Ecocardiografia , Fatores de Risco de Doenças Cardíacas , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Adulto , Fatores de RiscoRESUMO
AIM OF THE STUDY: The aim of our study is to evaluate the difference in stricture rate between matched groups of Bricker and Wallace techniques for ureteroileal anastomosis. PATIENTS AND METHODS: A retrospective analysis of patients undergoing urinary diversion (UD) with Bricker and Wallace ureteroileal anastomosis at two university hospitals. Two groups of Bricker and Wallace patients were matched in a 1:1 ratio based on the age, sex, body mass index (BMI), Charlson comorbidity index (CCI), preoperative hydronephrosis, prior radiation therapy or abdominal surgery, pathologic T and N stages and 30-days-Clavien grade complications≥III. A multivariable Cox regression analysis was conducted to identify predictors of ureteroenteric stricture (UES) in all patients. RESULTS: Overall, 740 patients met the inclusion criteria and 209 patients in each group were propensity matched. At a similar median follow-up of 25 months, UES was detected in 25 (12%) and 30 (14.4%) patients in Bricker and Wallace groups, respectively (p = 0.56). However, only one patient in the Bricker group developed a bilateral stricture compared to 15 patients in the Wallace group, resulting in a significantly higher number of affected renal units in the Wallace group: 45 (10.7%) versus only 26 (6.2%) in the Bricker group (p = 0.00). On multivariable extended Cox analysis, prior radiotherapy, presence of T4 pelvic malignancy and nodal positive disease were independent predictor of UES formation. CONCLUSION: The technique of ureteroileal anastomosis itself does not increase the rate of stricture; however, conversion of two renal units into one is associated with a higher incidence of bilateral upper tract involvement.
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Anastomose Cirúrgica , Íleo , Pontuação de Propensão , Ureter , Derivação Urinária , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Anastomose Cirúrgica/efeitos adversos , Idoso , Derivação Urinária/efeitos adversos , Derivação Urinária/métodos , Ureter/cirurgia , Íleo/cirurgia , Constrição Patológica/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Obstrução Ureteral/cirurgia , Obstrução Ureteral/etiologia , Resultado do Tratamento , SeguimentosRESUMO
Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Renal biopsy is the gold standard for the diagnosis of LN. However, repeated biopsies are not always performed in clinical practice, and they carry some risk. Therefore, minimally invasive techniques, as urinary biomarkers, are promising tools for the diagnosis and monitoring of SLE. Previous studies evaluated urinary monocyte chemoattractant protein-1 (MCP-1) in patients with SLE, reported higher levels of urinary MCP-1 in patients with active LN than non-active LN. Other studies reported higher levels of urinary MCP-1 in LN patients with proliferative forms (III and IV). This study aimed to evaluate urinary MCP-1 as a noninvasive diagnostic biomarker tool for LN, and to determine its association with different LN histopathological stages and chronicity indices. The study included 40 SLE patients with biopsy-proven LN class II, III, IV or V, and 20 patients with inactive LN as a control group. In LN active patients, the mean creatinine was 1.71 ± 0.55 mg/dl, and 0.84 ± 0.10 mg/dl in the control group. The mean MCP-1 level was 618.4 ± 294.2 ng/l in active LN patients and 120.05 ± 87.53 ng/l in inactive LN patients. The receiver operating characteristic (ROC) curve analysis indicated a better diagnostic performance of MCP-1 than conventional biomarkers. At area under the curve of 0.990, the best cut-off level was >245 ng/L (sensitivity 97.5 %, Specificity 95 %). In conclusion, urinary MCP-1 distinguished active LN from inactive renal disease. It can be proposed as a good noninvasive diagnostic biomarker with a high sensitivity and specificity for detection of LN activity..
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/diagnóstico , Proteínas Quimioatraentes de Monócitos , Egito , Lúpus Eritematoso Sistêmico/diagnóstico , BiomarcadoresRESUMO
Introduction: Ureteroenteric stricture (UES) is the leading cause of renal function deterioration after radical cystectomy (RC) and urinary diversion (UD). The aim of the present review is to summarize studies that discussed the risk factors associated with UES development. Identifying the responsible factors is of importance to help surgeons to modify their treatment or follow-up strategies to reduce this serious complication. Materials and Methods: A comprehensive search of the literature using the PubMed database was conducted. The target of the search was only studies that primarily aimed to identify risk factors of UES after RC and UD. References of searched papers were also checked for potential inclusion. Results: The search originally yielded a total of 1357 articles, of which only 15 met our inclusion criteria, comprising 13, 481 patients. All the studies were observational, and retrospective published between 2013 and 2022. The natural history of UES and the reported risk factors varied widely across the studies. In 13 studies, a significant association between some risk factors and UES development was demonstrated. High body mass index (BMI) was the most frequently reported stricture risk factor, followed by perioperative urinary tract infection (UTI), robotic-assisted radical cystectomy (RARC), occurrence of post-operative Clavian grade ≥ 3 complications and urinary leakage. Otherwise, many other risk factors were reported only once. Conclusion: The literature is still lacking well-designed prospective studies investigating predisposing factors of UES. The available data suggest that the high BMI, RARC and complicated postoperative course are the main risk factors for stricture formation.
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Several precipitating factors of hepatic encephalopathy have been recognized and studied. Hepatic encephalopathy which is a frequent and grave complication of liver failure, is associated with multiple biochemical changes like high serum ammonia, mercaptan and phenol levels, low albumin levels and derangements in electrolytes. It is characterized by a range of neuronal and psychological aberrations mainly due to the inability of liver to metabolize different neurotoxic chemicals produced in the body. Hypokalemia is one of the most important findings in hepatic encephalopathy and postulated as a precipitating factor of the condition. The authors aimed to know the frequency of hypokalemia and its relation to the severity of hepatic encephalopathy. Methods: After taking approval from the hospital ethical review committee, a total of 5000 patients with hepatic encephalopathy were recruited by consecutive sampling. They were interviewed, examined and investigated for serum potassium levels and other precipitating factors of hepatic encephalopathy. Results: Total of 5000 patients including 3070 (61.4%) males and 1930 (38.6%) females, aging 13 years and above were studied. The frequency of hypokalemia was 78% (3900 patients). Relating the serum potassium level with the severity of hepatic encephalopathy, 1200 (60%) out of 2000 patients with serum potassium below 2.5 mEq/l were in grade 4 (40%) and 800 out of 2000 were in grade 3 encephalopathy. On the other hand, only 700 patients (6.4%) out 1100 with serum potassium above 3.4 mEq/l were in grade 4 encephalopathy. Conclusion: Hypokalemia is a frequent finding in patients with hepatic encephalopathy and found to be directly related to its severity.
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BACKGROUND: Antihypertensives bisoprolol fumarate (BIS) and perindopril arginine (PER) were simultaneously determined in their pure, bulk, and combined tablet dosage form. OBJECTIVE: This study develops a novel, reproducible, and accurate Reversed phase high-performance liquid chromatography (RP-HPLC) and Reversed phase ultra-performance liquid chromatography (RP-UPLC) with photodiode array detection techniques, which were then applied to in vitro dissolution studies. METHODS: The first RP-HPLC method relied on isocratic elution using a mobile phase of methanol-0.05 M phosphate buffer pH 2.6 (1 + 1, by volume), and separation was performed using a Thermo Hypersil C8 column (150 mm × 4.6 mm, 5 µm). Ion-pair UPLC was the second method. An acceptable resolution was achieved using an RP-C18 chromatographic column, Agilent Eclipse (100 × 2.1 mm, 1.7 µm), with a mobile phase containing 0.005 M sodium 1-heptane sulfonate-triethylamine (64 + 1 + 35, by volume), adjusted with phosphoric acid to a pH of 2.0. RP-HPLC used a 1.0 mL/min flow rate, while UPLC used 0.5 mL/min, and the two methods used detection at 210 nm. RESULTS: Calibration curves of BIS and PER were linear for RP-HPLC and RP-UPLC methods at 0.5-15 and 0.5-40 µg/mL, respectively. BIS and PER had RP-UPLC LODs of 0.22 and 0.10 µg/mL, respectively, and LOQs of 0.68 and 0.31 µg/mL, respectively. As a result, the approach has been effectively applied to in vitro dissolution testing for drugs in generic and reference products, showing that the two products are comparable. The Six Sigma approach was implemented to compare the recommended and United States Pharmacopeia (USP) procedures, which both exhibited process capability index (Cpk) >1.33. A content uniformity test demonstrated that the drugs in their dosage form met the acceptance limit (85-115%). The degradation products were reliably distinguished from pure drugs for a range of retention times. CONCLUSION: In their commercial drug product, the proposed method could be used in QC laboratories for concurrent testing, content uniformity, and in vitro dissolution investigations of BIS and PER. The methods were successfully validated per International Council for Harmonisation (ICH) guidelines. HIGHLIGHTS: This study is innovative since it is the first to establish and validate specific and reproducible UPLC and HPLC methods for the concurrent quantitation of the studied drugs in their binary mixture and application to lean Six Sigma, content uniformity, and comparative dissolution approaches.
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Bisoprolol , Perindopril , Arginina , Bisoprolol/análise , Perindopril/análise , Solubilidade , Gestão da Qualidade TotalRESUMO
Cardiac tumors are uncommon and can be classified as either primary benign, primary malignant, or metastatic. Cardiac tumors have a wide range of presentations, which can lead to delays in diagnosis and treatment. Primary cardiac tumors can also affect nearby structures, and there have been a few reported cases of coronary artery involvement with various underlying causes. In this case report, we describe a patient with a primary cardiac sarcoma (angiosarcoma) that had spread to other parts of the body and caused occlusion of the right coronary artery.
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Robotic-assisted laparoscopic partial nephrectomy (RALPN) is becoming a standard treatment for localized renal tumors worldwide. Data on the learning curve (LC) of RALPN are still insufficient. In the present study, we have attempted to gain further insight in this area by evaluating the LC using cumulative summation analysis (CUSUM). A series of 127 robotic partial nephrectomies were performed by two surgeons at our center between January 2018 and December 2020. CUSUM analysis was used to evaluate LC for operative time (OT). The different phases of surgical experience were compared in terms of perioperative parameters and pathologic outcomes. In addition, multivariate linear regression analysis was used to confirm the results of the CUSUM analysis by adjusting the phases of surgical experience for the other confounding factors that may affect OT. The median age of patients was 62 years, mean BMI was 28, and mean tumor size was 32 mm. Tumor complexity was classified as low, intermediate, and high risk according to the PADUA score in 44%, 38%, and 18%, respectively. The mean OT was 205 min, and trifecta was achieved in 72.4%. According to the CUSUM diagram, the LC of OT was divided into three phases: initial learning phase (18 cases), plateau phase (20 cases), and mastery phase (subsequent cases). The mean OT was 242, 208, and 190 min in the first, second, and third phases, respectively (P < 0.001). Surgeon experience phases were significantly associated with OT in multivariate analysis considering other preoperative and operative parameters. Surgical outcome was comparable between the three phases in terms of complications and achievement of trifecta; hospital stay was shorter in the mastery phase than in the first 2 phases (4 days vs 5 days, P = 0.02). The LC for RALPN is divided into 3 performance phases with CUSUM. Mastery of surgical technique was achieved after performing 38 cases. The initial learning phase of RALPN has no negative impact on surgical and oncologic outcomes .
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Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Curva de Aprendizado , Laparoscopia/métodos , Nefrectomia/métodos , Neoplasias Renais/cirurgia , Estudos RetrospectivosRESUMO
Erythropoietin (EPO) resistance is frequently reported in hemodialysis (HD) patients. Metabolic syndrome (MetS) is a common biochemical condition that comprises central obesity, dyslipidemia, hypertension, and hyperglycemia. The present study aimed to assess the relation between MetS and EPO resistance in HD patients. The present multicentric study included 150 patients with EPO resistance and 150 patients without EPO resistance. Short-acting EPO resistance was diagnosed if the erythropoietin resistance index is ≥1.0 IU/kg/gHb. Comparison between patients with EPO resistance and patients without resistance revealed that the former group had significantly higher body mass index, lower hemoglobin levels, lower albumin levels, higher ferritin levels, and higher high-sensitivity C-reactive protein (hsCRP) levels. In addition, patients in the EPO resistance group had significantly higher frequency of MetS (75.3% vs 38.0%, p < 0.001) and higher number of MetS components (2.7 ± 1.3 vs 1.8 ± 1.6, p < 0.001). Multivariate logistic regression analysis identified lower albumin levels (OR (95% CI): 0.072 (0.016-0.313), p < 0.001), higher ferritin levels (OR (95% CI): 1.05 (1.033-1.066), p< 0.001), higher hsCRP levels (OR (95% CI): 1.041 (1.007-1.077), p = 0.018), and MetS (OR (95% CI): 36.68 (2.893-465.05), p = 0.005) as predictors of EPO resistance in the studied patients. The present study identified MetS as a predictor of EPO resistance in HD patients. Other predictors include serum ferritin, hsCRP, and albumin levels.
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The preparation of adsorbents plays a vital role in the adsorption method. In particular, many adsorbents with high specific surface areas and unique shapes are essential for the adsorption strategy. A Zn-Mg-Al/layer double hydroxide (LDH) was designed in this study using a simple co-precipitation process. Adsorbent based on Zn-Mg-Al/LDH was used to remove crystal violet (CV) from the wastewater. The impacts of the initial dye concentration, pH, and temperature on CV adsorption performance were systematically examined. The adsorbents were analyzed both before and after adsorption using FTIR, XRD, and SEM. The roughness parameters and surface morphologies of the produced LDH were estimated using 3D SEM images. Under the best conditions (dose of adsorbent = 0.07 g and pH = 9), the maximum adsorption capacity has been achieved. Adsorption kinetics studies revealed that the reaction that led to the adsorption of CV dye onto Zn-Mg-Al/LDH was a pseudo-second-order model. Additionally, intraparticle diffusion suggests that Zn-Mg-Al/LDH has a fast diffusion constant for CV molecules (0.251 mg/(g min1/2)). Furthermore, as predicted by the Langmuir model, the maximal Zn-Mg-Al/LDH adsorption capacity of CV was 64.80 mg/g. The CV dimensionless separation factor (RL) onto Zn-Mg-Al/LDH was 0.769, indicating that adsorption was favorable. The effect of temperature was performed at 25, 35, and 45 °C in order to establish the thermodynamic parameters ∆Ho, ∆So, and ∆Go. The computed values indicated exothermic and spontaneous adsorption processes. The study presented here might be used to develop new adsorbents with enhanced adsorption capabilities for the purpose of protecting the water environment.
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RATIONALE: Early-life exposures may influence lung function at different stages of the life course. However, the relative importance of characteristics at different stages of infancy and childhood are unclear. OBJECTIVES: To examine the associations and relative importance of early-life events on lung function at age 24â years. METHODS: We followed 7545 children from the Avon Longitudinal Study of Parents and Children from birth to 24â years. Using previous knowledge, we classified an extensive list of putative risk factors for low lung function, covering sociodemographic, environmental, lifestyle and physiological characteristics, according to timing of exposure: 1) demographic, maternal and child; 2) perinatal; 3) postnatal; 4) early childhood; and 5) adolescence characteristics. Lung function measurements (forced vital capacity (FVC), forced expiratory volume in 1â s (FEV1), FEV1/FVC and forced expiratory flow at 25-75% of FVC) were standardised for sex, age and height. The proportion of the remaining variance explained by each characteristic was calculated. The association and relative importance (RI) of each characteristic for each lung function measure was estimated using linear regression, adjusted for other characteristics in the same and previous categories. RESULTS: Lower maternal perinatal body mass index (BMI), lower birthweight, lower lean mass and higher fat mass in childhood had the largest RI (0.5-7.7%) for decreased FVC. Having no siblings, lower birthweight, lower lean mass and higher fat mass were associated with decreased FEV1 (RI 0.5-4.6%). Higher lean mass and childhood asthma were associated with decreased FEV1/FVC (RI 0.6-0.8%). CONCLUSIONS: Maternal perinatal BMI, birthweight, childhood lean and fat mass and early-onset asthma are the factors in infancy and childhood that have the greatest influence on early-adult lung function.
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Asma , Pulmão , Criança , Feminino , Adulto , Gravidez , Adolescente , Humanos , Pré-Escolar , Adulto Jovem , Estudos Longitudinais , Peso ao Nascer , Capacidade Vital/fisiologia , Volume Expiratório Forçado , Comportamentos Relacionados com a SaúdeRESUMO
Importance: Accelerated diagnostic protocols (ADPs) for chest pain using high-sensitivity troponin (hsTn) levels have excellent sensitivity and negative predictive value for rapid risk stratification of patients with chest pain. However, little is known about the outcomes of patients who are discharged despite abnormal ADP results, ie, after "ruling-in" with a modest elevation of hsTn. Objective: To determine outcomes of patients discharged following ADP, including those who were ruled in with modestly elevated levels of hsTnT but discharged nonetheless. Design, Setting, and Participants: This retrospective cohort study included patients with chest pain who presented to the emergency departments (EDs) of a large multisite health system ED between January 2017 to September 2019. Patients were assessed using an ADP, had a peak hsTnT level measured between the limit of quantitation and 52 ng/L, were discharged, and had follow-up in the electronic medical record. Data analysis was conducted from January 2017 to September 2019. Exposures: Application of an hsTnT ADP. Main Outcomes and Measures: Thirty-day major adverse cardiac events (MACE), including myocardial infarction, urgent coronary revascularization, and all-cause death, comparing patients who were discharged following ADP-concordant vs ADP-discordant results. Results: Of 10â¯342 patients with chest pain (mean [SD] age 51 [17] years; 5902 [57%] women) discharged following ADP, 29 (0.28%) had MACE. Patients with MACE were older (median [IQR] age, 66 [53-75] years vs 50 [38-62] years; P < .001) and more likely to have prior CAD (12 [41.4%] vs 1805 [17.5%]; P = .002) and hyperlipidemia (13 [44.8%] vs 2248 [21.8%]; P = .006). Additionally, patients with MACE were 5-fold more likely to have been discharged despite ADP discordance (16 [55.2%] vs 1145 [11.1%]; P < .001). A multivariable logistic regression analysis revealed only ADP discordance was independently associated with MACE (odds ratio, 6.42 [95% CI, 2.94-14.0]; P < .001). When stratified by peak hsTnT level, there were no differences in MACE between ADP-concordant and -discordant discharges provided the peak hsTnT measured was less than 12 ng/L. In contrast, patients with peak hsTnT level between 12 and 51 ng/L were significantly more likely to have MACE if they were discharged after ADP-discordant vs -concordant hsTnT series (14 of 609 [2.30%] vs 5 of 1047 [0.48%]; P < .002). Notably, a HEART (history, electrocardiogram, age, risk factors, troponin) score of 4 or greater retrospectively identified the most ADP-discordant discharges (13 of 16 [81.3%]) who had MACE. Conclusions and Relevance: In this cohort study, an hsTnT ADP identified patients who could be discharged from the ED with low 30-day risk of MACE, provided the discharge was based on ADP-concordant "rule-out." Conversely, the rate of MACE was significantly higher among patients discharged despite ADP discordance. Most patients with ADP-discordant discharges who experienced MACE had a HEART score of 4 or greater, suggesting that application of this score may augment discharge decisions of patients despite ADP-discordant troponin series.
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Síndrome Coronariana Aguda , Dor no Peito , Alta do Paciente , Troponina , Síndrome Coronariana Aguda/diagnóstico , Difosfato de Adenosina , Adulto , Idoso , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Genome-wide association studies have provided many genetic markers that can be used as instrumental variables to adjust for confounding in epidemiological studies. Recently, the principle has been applied to other forms of bias in observational studies, especially collider bias that arises when conditioning or stratifying on a variable that is associated with the outcome of interest. An important case is in studies of disease progression and survival. Here, we clarify the links between the genetic instrumental variable methods proposed for this problem and the established methods of Mendelian randomisation developed to account for confounding. We highlight the critical importance of weak instrument bias in this context and describe a corrected weighted least-squares procedure as a simple approach to reduce this bias. We illustrate the range of available methods on two data examples. The first, waist-hip ratio adjusted for body-mass index, entails statistical adjustment for a quantitative trait. The second, smoking cessation, is a stratified analysis conditional on having initiated smoking. In both cases, we find little effect of collider bias on the primary association results, but this may propagate into more substantial effects on further analyses such as polygenic risk scoring and Mendelian randomisation.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Viés , Estudo de Associação Genômica Ampla/métodos , Humanos , Análise dos Mínimos Quadrados , Análise da Randomização Mendeliana/métodos , Relação Cintura-QuadrilRESUMO
Estimated genetic associations with prognosis, or conditional on a phenotype (e.g. disease incidence), may be affected by collider bias, whereby conditioning on the phenotype induces associations between causes of the phenotype and prognosis. We propose a method, 'Slope-Hunter', that uses model-based clustering to identify and utilise the class of variants only affecting the phenotype to estimate the adjustment factor, assuming this class explains more variation in the phenotype than any other variant classes. Simulation studies show that our approach eliminates the bias and outperforms alternatives even in the presence of genetic correlation. In a study of fasting blood insulin levels (FI) conditional on body mass index, we eliminate paradoxical associations of the underweight loci: COBLLI; PPARG with increased FI, and reveal an association for the locus rs1421085 (FTO). In an analysis of a case-only study for breast cancer mortality, a single region remains associated with more pronounced results.
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Estudo de Associação Genômica Ampla , Algoritmos , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Viés , Índice de Massa Corporal , Neoplasias da Mama/mortalidade , Biologia Computacional , Jejum , Predisposição Genética para Doença , Humanos , Aprendizado de Máquina , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
INTRODUCTION: In this study we aim to compare clinicopathological characteristics and cancer specific survival between patients treated with radical cystectomy for pure squamous cell carcinoma (SCC) and urothelial carcinoma with squamous differentiation (SqD). PATIENTS AND METHODS: We reviewed data of 1737 consecutive patients treated with radical cystectomy and urinary diversion between January 2004 and February 2014. Only patients with pure SCC or SqD were included in the analysis. Squamous differentiation was defined as intercellular bridges or keratinization in the tumor. Clinicopathological data and recurrence free survival (RFS) were compared between patients diagnosed with SCC and SqD. RESULTS: SCC and SqD were found in 318 and 223 patients, respectively. Mean age was 57 ± 8.3 years in SCC and 58.8 ± 7.8 in SqD (P = .008). A higher proportion of female patients was observed in SCC group compared to SqD (31.8% vs. 22% P < .0001). Patients with SqD were more likely to have extravesical (58.3% vs. 46.2%: P = .006) and nodal positive disease (34.5% vs. 14.5%: P < .0001) than pure SCC patients. Bilharzial eggs were found in 61% of SCC vs. 46% of SqD (P = .001).; The median (IQR) follow up period for SCC and SqD was 63 (12-112) months and 23 months (9-74.7), respectively. The 5-year RFS for SCC and SqD were 77% and 59.8 %, respectively (P < .0001).; Multivariate cox regression analysis identified advanced pT stage (OR: 1.9, 95% CI: 1.3-2.86, P = .0001), nodal positive disease (OR: 1.6, 95% CI: 1.1-2.48, P = .01) and SqD histology (OR: 1.6, 95% CI: 1.14-2.31, P = .007 as independent predictors of 5-year RFS. CONCLUSION: Patient with SCC had significantly higher 5-year RFS in comparison to SqD. The higher rate of extravesical disease and lymph node metastasis in SqD patients is indicative of aggressive behavior of this histologic type.
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Carcinoma de Células Escamosas , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/patologia , Cistectomia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
AIMS: To measure how cigarette packaging (standardised packaging and branded packaging) and health warning size affect visual attention and pack preferences among Colombian smokers and non-smokers. DESIGN: To explore visual attention, we used an eye-tracking experiment where non-smokers, weekly smokers and daily smokers were shown cigarette packs varying in warning size (30%-pictorial on top of the text, 30%-pictorial and text side-by-side, 50%, 70%) and packaging (standardised packaging, branded packaging). We used a discrete choice experiment (DCE) to examine the impact of warning size, packaging and brand name on preferences to try, taste perceptions and perceptions of harm. SETTING: Eye-tracking laboratory, Universidad Nacional de Colombia, Bogotá, Colombia. PARTICIPANTS: Participants (n = 175) were 18 to 40 years old. MEASUREMENTS: For the eye-tracking experiment, our primary outcome measure was the number of fixations toward the health warning compared with the branding. For the DCE, outcome measures were preferences to try, taste perceptions and harm perceptions. FINDINGS: We observed greater visual attention to warning labels on standardised versus branded packages (F[3,167] = 22.87, P < 0.001) and when warnings were larger (F[9,161] = 147.17, P < 0.001); as warning size increased, the difference in visual attention to warnings between standardised and branded packaging decreased (F[9,161] = 4.44, P < 0.001). Non-smokers visually attended toward the warnings more than smokers, but as warning size increased these differences decreased (F[6,334] = 2.92, P = 0.009). For the DCE, conditional trials showed that increasing the warning size from 30% to 70% reduced preferences to try (odds ratio [OR] = 0.48, 95% CI = [0.42,0.54], P < 0.001), taste perceptions (OR = 0.61, 95% CI = [0.54,0.68], P < 0.001); and increased harm perceptions (OR = 0.78, 95% CI = [0.76,0.80], P < 0.001). Compared with branded packaging, standardised packaging reduced our DCE outcome measures with ORs ranging from OR = 0.25 (95% CI = [0.17,0.38], P < 0.001) to OR = 0.79 (95% CI = [0.67,0.93], P < 0.001) across two brands. These effects were more pronounced among non-smokers, males and younger participants. Unconditional trials showed similar results. CONCLUSIONS: Standardised cigarette packaging and larger health warnings appear to decrease positive pack perceptions and have the potential to reduce the demand for cigarette products in Colombia.
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Fumantes , Produtos do Tabaco , Adolescente , Adulto , Colômbia , Humanos , Masculino , não Fumantes , Rotulagem de Produtos/métodos , Embalagem de Produtos , Fumar , Adulto JovemRESUMO
BACKGROUND: Substitution urethroplasty using buccal mucosal grafts can be performed by several approaches including ventral onlay graft, dorsal onlay graft, or ventral urethrotomy with dorsal inlay graft. Our study aims to evaluate the surgical outcome of dorsolateral buccal mucosal graft for long segment anterior urethral stricture >6 cm in patients with Lichen sclerosus (LS). METHODS: A retrospective study included patients who underwent repair for long segment anterior urethral stricture >6 cm due to LS between January 2013 and April 2019. All patients were followed-up at 3, 6, 9, and 12 months postoperatively and then yearly by clinical symptoms, uroflowmetry, and calculation of post-void residual urine volume. Retrograde urethrogram was requested for patients with voiding symptoms or decreased maximum flow rate. Stricture recurrence that required subsequent urethrotomy or urethroplasty was considered failure. The success rate and surgical complications were collected and analyzed. RESULTS: Thirty patients were identified. The median age (range) was 39 (25-61) years and a median (range) stricture length was 8 (6-14) cm. Most of postoperative complications were of minor degree. The success rate at median follow-up of 15 (12-24) months was 86.5%. The median maximum flow rate increased significantly from 6 (2-11) ml/s preoperatively to 18 (range: 6-23) ml/s at the 6th month (p value < 0.001). CONCLUSION: Dorsolateral buccal mucosal grafts urethroplasty for long anterior urethral stricture caused by LS has a high success rate and low risk of complications including stricture recurrence.
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Líquen Escleroso e Atrófico , Estreitamento Uretral , Adulto , Humanos , Líquen Escleroso e Atrófico/complicações , Líquen Escleroso e Atrófico/cirurgia , Masculino , Mucosa Bucal , Estudos Retrospectivos , Resultado do Tratamento , Uretra/cirurgia , Estreitamento Uretral/etiologia , Estreitamento Uretral/cirurgia , Procedimentos Cirúrgicos Urológicos MasculinosRESUMO
Objective: To evaluate the outcome of microscopic subinguinal varicocelectomy on sperm DNA fragmentation (SDF) and pregnancy rate in men with normal semen parameters. Patients and methods: A pilot study that included male patients with a minimum of a 1-year history of male subfertility, normal semen parameters, a high percentage of SDF, and clinically palpable varicoceles. Microscopic subinguinal varicocelectomy was carried out for 45 patients (study group), while 40 patients had no intervention (control group). Semen analysis and SDF were measured before and at 6 months after the varicocelectomy. The pregnancy rate was assessed at the 6- and 12-month follow-ups. Results: Between July 2014 and January 2019, 85 subfertile men were included in the study and completed 12 months of follow-up. The two groups were comparable in terms of their age, body mass index, infertility duration, infertility type, varicoceles laterality, and varicoceles grade (P values = 0.84, 0.34. 0.35, 1, 0.39, and 0.46, respectively). At 6 months after varicocelectomy, the mean SDF was reduced in both groups, and this reduction was statistically higher in the varicocelectomy group (P < 0.001). After 1-year, spontaneous pregnancy was achieved in 62% of the patients in the varicocelectomy group compared to 30% in the control group (P = 0.009). Conclusion: Varicocelectomy has a positive impact on SDF and spontaneous pregnancy in infertile men with clinically palpable varicoceles and normal semen parameters. Abbreviations: BMI: body mass index; DFI: DNA fragmentation Index; SDF: sperm DNA fragmentation.