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1.
Urol Oncol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31956078

RESUMO

INTRODUCTION: Neoadjuvant chemotherapy (NAC) improves survival for patients undergoing radical cystectomy for muscle-invasive bladder cancer (MIBC). The overall survival (OS) advantage with NAC is primarily seen in patients who achieve pathological downstaging. However, a substantial number of patients achieve pathological downstaging following transurethral resection (TUR) without NAC. OBJECTIVES: To analyze the OS outcomes in patients who achieve pathological downstaging in the setting of NAC vs. TUR only. MATERIALS AND METHODS: We reviewed the National Cancer Database (NCDB) for patients diagnosed with MIBC who underwent radical cystectomy between 2004 and 2014. Patients who achieved complete downstaging (CD) (pT0N0) or noninvasive downstaging (NID) (pT0/Tis/TaN0) were further analyzed. OS was evaluated by comparing those who underwent NAC to those who underwent TUR only. RESULTS: A total of 24,763 patients with MIBC were identified. 1,781 (7.2%) patients had NID and 1,015 (4.1%) had CD. Of all patients, 3,838 (15.5%) underwent NAC. In patients with NID, 757 (42.5%) underwent NAC and 1024 (57.5%) had cystectomy after TUR only. In patients with CD, 465 (45.8%) had NAC, while 550 (54.2%) had TUR only. In both NID and CD, cT2 patients were more likely to have TUR only (P = 0.019, P < 0.001), cT3 patients were more likely to receive NAC (P = 0.008, P < 0.001). Compared to the TUR only group, NAC was associated with improved 5-year OS in those with NID, 77% compared to 68% (HR 0.68, 95% CI [0.52-0.90]), as well as those with CD, 80% vs. 70% (HR 0.59, 95% CI [0.39-0.89]). CONCLUSIONS: NAC was associated with significant overall survival benefit in the subset of patients who achieved CD and NID at radical cystectomy. Overall, NAC was underutilized in patients with MIBC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31791911

RESUMO

The presence of expired and unused Sulfacetamide (SA) drug in water led to a global need for the development of effective advanced method for the quantitative analysis and for minimizing its occurrence in the nature. To find new effective photochemical decomposition method close to that obtained by the well-known Fenton reaction, the photodegradation of SA was investigated in presence of dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and/or other common additives at two different wavelengths (365 and 256 nm). The role of DDQ in the degradation process of SA was evaluated in comparison to the other investigated π-acceptor systems (Chloranilic acid (CHL) and Picric acid (PA)). While the photodegradation process of SA was hardly to proceed in the absence of a catalyst and/or additive, addition of DDQ and NaNO2 to the solution of SA induced decomposition of about 94% of SA within 25 min upon the exposure to light source at 256 nm. On the other hand, SA was quantitatively analyzed by recording the absorbance of its charge transfer (CT) products with DDQ, CHL and PA at a certain wavelength. CHL is preferred with concentrated samples of SA, while PA is recommended for diluted samples of SA. SA â†’ DDQ has a widely range of stability over the pH range of 4.5-12.0. While SA â†’ CHL is stable only in the acidic medium (pH = 4.8-5.6), SA â†’ PA is steady in the basic medium (pH = 7.5-11.0). The nature of the DDQ CT complex was investigated in the solid state. The electronic structures of the complexes were studied by calculating the time dependent density functional theory (TDDFT) spectra.

3.
Adv Nutr ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31800007

RESUMO

Some evidence indicates that carotenoids may reduce the risk of bladder cancer (BC), but the association is unclear. We conducted a systematic review and meta-analysis of case-control and cohort studies investigating the relation between carotenoid intake or circulating carotenoid concentrations and BC risk in men and women. All relevant epidemiologic studies were identified by a search of PubMed and Scopus databases, and the Cochrane Library from inception to April 2019 with no restrictions. A random-effects model was used to calculate pooled RRs and their 95% CIs across studies for high compared with low categories of intake or circulating concentrations. We also performed a dose-response meta-analysis using the Greenland and Longnecker method and random-effects models. A total of 22 studies involving 516,740 adults were included in the meta-analysis. The pooled RRs of BC for the highest compared with the lowest category of carotenoid intake and circulating carotenoid concentrations were 0.88 (95% CI: 0.76, 1.03) and 0.36 (95% CI: 0.12, 1.07), respectively. The pooled RR of BC for the highest compared with lowest circulating lutein and zeaxanthin concentrations was 0.53 (95% CI: 0.33, 0.84). Dose-response analysis showed that BC risk decreased by 42% for every 1 mg increase in daily dietary ß-cryptoxanthin intake (RR: 0.58; 95% CI: 0.36, 0.94); by 76% for every 1 µmol/L increase in circulating concentration of α-carotene (RR: 0.24; 95% CI: 0.08, 0.67); by 27% for every 1 µmol/L increase in circulating concentration of ß-carotene (RR: 0.73; 95% CI: 0.57, 0.94); and by 56% for every 1 µmol/L increase in circulating concentrations of lutein and zeaxanthin (RR: 0.44; 95% CI: 0.28, 0.67). Dietary ß-cryptoxanthin intake and circulating concentrations of α-carotene, ß-carotene, and lutein and zeaxanthin were inversely associated with BC risk. The protocol was registered at PROSPERO as CRD42019133240.

4.
Urology ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31883879

RESUMO

OBJECTIVE: To determine if disparities in quality of surgical care exist between Hispanics and non-Hispanics undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: An observational cohort study was conducted retrospectively on patients who underwent radical cystectomy for urothelial carcinoma of the bladder at our institution between January 2005 and July 2018. Data was collected on demographic, clinical, and pathological characteristics of patients, including self-reported ethnicity. Univariable and multivariable logistic or linear regression analyses were used to evaluate the association of ethnicity with receipt of neoadjuvant chemotherapy, utilization of laparoscopic surgery, number of lymph nodes removed, and continent urinary diversion. RESULTS: We identified 507 patients in our database out of which, 136 (27%) were Hispanic and 371 (73%) were non-Hispanic. Compared to non-Hispanics, Hispanics had a higher body mass index (26.9 kg/m2 vs 28.2 kg/m2, P = .006) and lived further away from site of surgery (34 vs 96 miles, P = .02). No significant differences were observed in receipt of neoadjuvant chemotherapy, laparoscopic surgery, or number of lymph nodes removed during cystectomy between ethnicity groups. However, Hispanics were less likely than non-Hispanics to receive a continent urinary diversion on multivariable analysis (odds ratio 0.30, 95% confidence interval 0.10 - 0.92, P = .03). CONCLUSION: Disparity exists in the delivery of continent urinary diversions for Hispanic patients undergoing radical cystectomy for bladder cancer. Further investigation is needed to determine the potential causes for this disparity in care delivered.

5.
Life Sci ; 239: 117082, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31756345

RESUMO

AIM: Investigating the impact of 17ß-Estradiol/estrogen receptors in gentamicin-induced nephrotoxicity. MAIN METHODS: Three weeks post-ovariectomy or sham surgery for the Wistar albino female rats, thirty sham rats were randomly grouped (n = 6), received either vehicle or gentamicin; the estrogen receptors down regulator (fulvestrant); gentamicin plus fulvestrant; gentamicin plus the phytoestrogen (genistein). Forty-eight ovariectomized rats were randomly grouped (n = 6), treated with either vehicle or gentamicin; fulvestrant; gentamicin plus fulvestrant; genistein; gentamicin plus genistein; estradiol benzoate; gentamicin plus estradiol benzoate. Just post-treatment termination, the traditional kidney injury biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers (serum Kidney injury molecule -1, cystatin C, lactate dehydrogenase and, gamma-glutamyl transferase) were determined. Bovine serum albumin labeled with fluorescence isothiocyanate assessed megalin expression/endocytic functionality in the proximal tubules epithelial cells (PTECs). The immunohistochemical investigation for the same-sectioned slides of PTECs assessed the correlation between estrogen receptors α and megalin receptors expression. Histopathological examination of PTECs and subjective scoring system graded the damage markers. KEY FINDINGS: Estrogen receptor α expression was markedly dimensioned post-ovariectomy, co-localized and inversely correlated to megalin expression. Serum levels of the novel biomarkers were directly proportional to megalin expression in the PTECs and inversely correlated with estrogen receptor α expression. The injury was exaggerated in ovariectomized and intact rats received fulvestrant. Supplementation with estrogen or genistein ameliorated this injury. SIGNIFICANCE: Estrogen/estrogen receptors have a protective impact on gentamicin-induced acute kidney injury. Estrogen receptors antagonist exacerbate the injury, and oppositely, estrogens or phytoestrogens improve it.

6.
Urology ; 133: 172-173, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31706417
7.
Pharmaceuticals (Basel) ; 12(4)2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614832

RESUMO

The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring 2-(2'-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from Aß and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of aggregation were evaluated using thioflavin binding assays, whereas the interactions of the compounds with the peptides were studied by UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. The results indicate that the compounds modulate the aggregation of the investigated peptides using different mechanisms, suggesting that the reactivity of the metal center and the physicochemical properties of the metals (rather than those of the ligands and the geometry of the metal compounds) play a crucial role in determining the anti-aggregation properties.

8.
Dalton Trans ; 48(37): 14027-14035, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31490509

RESUMO

Au(iii) compounds bearing N,N-pyridylbenzimidazole derivatives with the ethyl (1) or propyl sulfonate (2) appendage react with the model protein hen egg white lysozyme (HEWL), forming adducts with different gold-containing fragments. The conformation of the enzyme, the exact gold binding sites and the oxidation state of Au in the adducts are unknown. Here we report a structural study on the reaction of 1 and 2 with HEWL in solution and solid state. In agreement with previously reported electrospray ionization mass spectra, the compounds degrade in their interaction with the protein. In the structure derived from HEWL crystals exposed to 1 for less than one day, three Au binding sites were identified: Au(i) ions are bound to the side chain of His15 and to the side chains of His15 and Asn93. The third gold centre is buried in the hydrophobic pocket of the protein via the binding to the side chain of Met105 and the trapping between the side chains of Trp28, Trp108 and Trp111. In a second crystal fished three hours later from the same drop, only one Au ion, probably in the +1 oxidation state, is observed; it binds the protein close to the side chains of Asn93 and His15. After three days of soaking, the colour of HEWL crystals obtained in the presence of 1 turned violet. In these crystals, anomalous signals attributable to Au are found on the protein surface; gold atoms are not directly coordinated to residue side chains. Longer exposure of HEWL crystals to 1 produces gold-free crystals. In the adduct of HEWL exposed to 2 for one day, three Au(i) ions are detected close to the side chains of both Asn93 and His15, the side chain of His15 and that of Met105. Longer exposure of HEWL crystals to 2 affords gold-free crystals. These structural data and those of the other protein/gold adducts available at the Protein Data Bank suggest that the reduction of Au(iii) into Au(i) is the basis of the mechanism of action of the biologically active gold(iii) compounds. Besides, Au(i) ions can undergo disproportionation into Au(iii) and Au(0) that can diffuse away from the protein crystals.

9.
Urology ; 133: 164-174, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401220

RESUMO

OBJECTIVE: To address the overarching question whether chemoradiation therapy (CMT) offers overall survival (OS) similar to that of radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC), we performed analyses using the National Cancer Database. MATERIALS AND METHODS: Patients diagnosed with MIBC in 2004-2014 who underwent RC or received primary CMT were identified in the National Cancer Database. Survival was estimated using the weighted Kaplan-Meier method, and propensity score-weighted Cox proportional hazards model were used to evaluate association of clinicopathologic features with outcome. RESULTS: Of 484,367 patients with a diagnosis of bladder cancer, 35,856 underwent RC and 4050 received CMT. After applying the exclusion/inclusion criteria, data for 15,854 patients who underwent RC and 2083 who received CMT were available for analysis. Five-year OS was 40.4% in the RC group and 29.4% in the CMT group (P <.001). OS was significantly shorter in the CMT group than in the RC group in both multivariate analysis (hazards ratio [HR] 1.15, 95% CI 1.08-1.22; P <.001) and propensity score-weighted analysis (HR 1.18, 95% CI 1.07-1.30; P <.001). Interaction terms indicated better survival after RC in patients younger than 70 years (HR 1.61, 95% CI 1.34-1.93; P <.001); subgroup analyses identified a survival benefit in patients with N0/N1 disease who underwent RC (HR 1.21, 95% CI 1.09-1.33; P <.001). CONCLUSION AND RELEVANCE: OS after 1 year of treatment was increased in RC group compared to CMT group in patient with MIBC. Further studies are required to identify optimal treatment for specific patients.

10.
Adv Urol ; 2019: 3590623, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31164907

RESUMO

Objective: To develop software to assess the potential aggressiveness of an incidentally detected renal mass using images. Methods: Thirty randomly selected patients who underwent nephrectomy for renal cell carcinoma (RCC) had their images independently reviewed by engineers. Tumor "Roughness" was based on image algorithm of tumor topographic features visualized on computed tomography (CT) scans. Univariant and multivariant statistical analyses are utilized for analysis. Results: We investigated 30 subjects that underwent partial or radical nephrectomy. After excluding poor image-rendered images, 27 patients remained (benign cyst = 1, oncocytoma = 2, clear cell RCC = 15, papillary RCC = 7, and chromophobe RCC = 2). The mean roughness score for each mass is 1.18, 1.16, 1.27, 1.52, and 1.56 units, respectively (p < 0.004). Renal masses were correlated with tumor roughness (Pearson's, p=0.02). However, tumor size itself was larger in benign tumors (p=0.1). Linear regression analysis noted that the roughness score is the most influential on the model with all other demographics being equal including tumor size (p=0.003). Conclusion: Using basic CT imaging software, tumor topography ("roughness") can be quantified and correlated with histologies such as RCC subtype and could lead to determining aggressiveness of small renal masses.

11.
J Minim Invasive Gynecol ; 26(5): 877-882, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30193971

RESUMO

STUDY OBJECTIVE: Because laparoscopic ovarian cystectomy of endometriomas is known to adversely impact patient ovarian reserve, the search for other techniques of surgical management is ongoing. The present study was undertaken to evaluate laparoscopic cyst deroofing as a feasible alternative. STUDY DESIGN: Prospective, randomized clinical trial (Canadian Task Force classification I). SETTING: University maternity hospital. PATIENTS: Women diagnosed with unilateral or bilateral ovarian endometriomas. INTERVENTIONS: Patients were managed with either laparoscopic ovarian cystectomy or cyst deroofing. MEASUREMENTS AND MAIN RESULTS: A total of 122 women with endometriomas were randomized to either laparoscopic cystectomy (group 1) or laparoscopic cyst deroofing (group 2). The primary endpoint was the effect on ovarian reserve based on changes in anti-Müllerian hormone (AMH) values. At 1 month postsurgery, anti-Müllerian hormone values were significantly decreased (p < .001) from preoperative values, from 4.25 ± 0.87 ng/mL to 1.66 ± 1.02 ng/mL in group 1 and from 4.2 ± 1.69 ng/mL to 2.15 ± 1.48 ng/mL in group 2. In addition, antral follicle count and ovarian volume decreased significantly (p < .001) in both groups by 1 month postsurgery. The decreases in these 3 parameters were more significant (p < .001) in group 1 than in group 2. CONCLUSION: Laparoscopic cyst deroofing of endometriomas appears to be a promising alternative to laparoscopic cystectomy, with less postoperative decrease in ovarian reserve; however, the higher rate of endometrioma recurrence warrants future clinical research to determine the optimal surgical management of endometriomas.

12.
BMC Urol ; 18(1): 100, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413194

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression is believed to be associated with bladder cancer (BC) progression and poor clinical outcomes. In vivo studies have linked EGFR subcellular trafficking and chemo-resistance to cisplatin-based chemotherapies. This has not been studied in the clinical adjuvant setting. We aimed to investigate the prognostic significance of EGFR expression in patients receiving cisplatin-based adjuvant chemotherapy following radical cystectomy for advanced BC. METHODS: The database from the Urology and Nephrology Center at Mansoura University was reviewed. BC patients who were treated with radical cystectomy and adjuvant chemotherapy for adverse pathological features or node positive disease were identified. Patients who underwent palliative cystectomy, had histological diagnoses other than pure urothelial carcinoma, or received adjuvant radiotherapy were excluded from the study. Immunohistochemical staining for EGFR expression was performed on archived bladder specimens. The following in vitro functional analyses were performed to study the relationship of EGFR expression and chemoresponse. RESULTS: The study included 58 patients, among which the mean age was 57 years old. Majority of patients had node positive disease (n = 53, 91%). Mean follow up was 26.61 months. EGFR was overexpressed in 25 cystectomy specimens (43%). Kaplan-Meier analysis revealed that EGFR over-expression significantly correlated with disease recurrence (p = 0.021). Cox proportional hazard modeling identified EGFR overexpression as an independent predictor for disease recurrence (p = 0.04). Furthermore, in vitro experiments demonstrated that inhibition of EGFR may sensitize cellular responses to cisplatin. CONCLUSIONS: Our findings suggest that EGFR overexpression is associated with disease recurrence following adjuvant chemotherapy for advanced BC. This may aid in patient prognostication and selection prior to chemotherapeutic treatment for BC.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fator de Crescimento Epidérmico/biossíntese , Regulação Neoplásica da Expressão Gênica , Neoplasias Musculares/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/fisiologia , Fator de Crescimento Epidérmico/genética , Receptores ErbB/biossíntese , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/tratamento farmacológico , Invasividade Neoplásica/patologia , Valor Preditivo dos Testes , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
13.
Arch Gynecol Obstet ; 298(6): 1115-1122, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30291483

RESUMO

PURPOSE: The commonest surgical procedure for women is cesarean delivery. Postpartum hemorrhage and intra-operative blood during cesarean delivery is a major concern to all obstetricians. This study was conducted to assess the efficacy of the adjuvant use of misoprostol and oxytocin in decreasing intra-operative blood loss in cesarean delivery. METHODS: This was a double-blinded randomized clinical trial including 636 term pregnant woman scheduled for cesarean section at Ain Shams University Maternity Hospital, Cairo, Egypt, between February 2013 and February 2014. Participants received either 400-µg misoprostol rectally or sublingually or placebo before cesarean section together with 5-IU oxytocin IV. The main outcome measure was intra-operative blood loss. Difference between the three groups was analyzed using one-way ANOVA test (for numeric variables) and Chi-square test (for categorical variables). P < 0.05 was considered statistically significant. RESULTS: Intra-operative blood loss was higher in patients who did not receive misoprostol (Placebo Group) (295-1075 ml, 641.7 ± 135.7) than those who received it, regardless the route of administration, rectal (135-830 ml, 457.5 ± 140.7; P < 0.001), and sublingual (135-680 ml, 357.8 ± 129.7; P < 0.001). In addition, sublingual route was associated with significantly lower estimated intra-operative blood loss compared to rectal administration (P < 0.001). CONCLUSIONS: Misoprostol with oxytocin is an effective drug-combination for decreasing intra-operative blood loss during cesarian section with clinical superiority to sublingual over rectal route.


Assuntos
Cesárea/métodos , Misoprostol/uso terapêutico , Ocitócicos/uso terapêutico , Administração Retal , Administração Sublingual , Adulto , Método Duplo-Cego , Feminino , Humanos , Misoprostol/administração & dosagem , Misoprostol/farmacologia , Ocitócicos/administração & dosagem , Ocitócicos/farmacologia , Gravidez , Estudos Prospectivos , Adulto Jovem
14.
Dalton Trans ; 47(30): 10130-10138, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30004541

RESUMO

Pd(ii) and Pt(ii) compounds bearing N,N-pyridylbenzimidazole derivatives with an alkylated sulfonate or phosphonium side chain are able to bind the model protein lysozyme both covalently and non-covalently as an entire compound or as a product of a hydrolysis reaction. The interactions with the protein and the origin of the different behaviors of these complexes were unknown hitherto. Here, we present four crystal structures of their adducts with lysozyme. Pt- and Pd-containing fragments bind the protein with different stoichiometries close to the side chains of His15, Asp87, Asp101 and Asn77. The compounds bearing a phosphonium side chain degrade during the reaction with lysozyme. Data show the origin of the non-covalent mode of binding of Pd and Pt compounds bearing a sulfonate side chain, which drives the recognition process by forming a series of H-bonds and coulombic interactions with positively charged residue side chains. In a separate experiment, the structure of the adduct that is formed when the Pd(ii) compound containing an alkylated sulfonate group reacts with ribonuclease A was also determined. In this structure, the sulfonate-Pd(ii) complex binds the side chain of His105 on the surface of the protein and the side chain of the catalytically important His119 residue. Altogether, our data provide a structural basis for understanding the behavior of the analyzed Pd(ii)- and Pt(ii)-based cisplatin analogues in their reactions with proteins and show the first structural characterization of an adduct comprising a cisplatin analogue that is non-covalently bound to a protein. The results suggest that functionalization of a ligand system with a sulfonate group can significantly alter the protein-binding activity and thus the overall pharmacological profile of Pd(ii)- and Pt(ii)-based drugs.

15.
Dalton Trans ; 47(10): 3459-3468, 2018 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-29431787

RESUMO

New cisplatin analogue Pd(ii) and Pt(ii) complexes bearing charged pyridylbenzimidazole derivatives furnished with either an alkylated sulfonate or a phosphonium side chain were synthesized, fully characterized and tested for their antimicrobial and cytotoxic activities against noncancerous human embryonic kidney cells (HEK293). The interactions with CT-DNA were investigated using UV/vis spectroscopy. Assignment of the electronic transitions was performed with the aid of TDDFT. The complexes showed interesting antifungal activity against Candida albicans and Cryptococcus neoformans. The Pd(ii) complex conjugated with alkylated triphenylphosphonium exhibited higher cytotoxicity (CC50 = 8.932 µg mL-1, equivalent to 12 nM) than the others. The reactivity towards hen egg white lysozyme (HEWL) was investigated by electrospray ionization mass spectrometry. The formation of DNA- and HEWL-adducts was achieved via the noncovalent and covalent interactions.

16.
J Thorac Cardiovasc Surg ; 155(5): 1938-1950, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29395211

RESUMO

BACKGROUND: In international guidelines, risk estimation for thoracic ascending aortic aneurysm (TAAA) is based on aortic diameter. We previously introduced the aortic size index (ASI), defined as aortic size/body surface area (BSA), as a predictor of aortic dissection, rupture, and death. However, weight might not contribute substantially to aortic size and growth. We seek to evaluate the height-based aortic height index (AHI) versus ASI for risk estimation and revisit our natural history calculations. METHODS: Aortic diameters and long-term complications of 780 patients with TAAA were analyzed. Growth rate estimates, yearly complication rates, and survival were assessed. Risk stratification was performed using regression models. The predictive value of AHI and ASI was compared. RESULTS: Patients were stratified into 4 categories of yearly risk of complications based on their ASI and AHI. ASIs (cm/m2) of ≤2.05, 2.08 to 2.95, 3.00 to 3.95 and ≥4, and AHIs (cm/m) of ≤2.43, 2.44 to 3.17, 3.21 to 4.06, and ≥4.1 were associated with a 4%, 7%, 12%, and 18% average yearly risk of complications, respectively. Five-year complication-free survival was progressively worse with increasing ASI and AHI. Both ASI and AHI were shown to be significant predictors of complications (P < .05). AHI categories 3.05 to 3.69, 3.70 to 4.34, and ≥4.35 cm/m were associated with a significantly increased risk of complications (P < .05). The overall fit of the model using AHI was modestly superior according to the concordance statistic. CONCLUSIONS: Compared with indices including weight, the simpler height-based ratio (excluding weight and BSA calculations) yields satisfactory results for evaluating the risk of natural complications in patients with TAAA.


Assuntos
Aneurisma da Aorta Torácica/etiologia , Estatura , Superfície Corporal , Técnicas de Apoio para a Decisão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/fisiopatologia , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
17.
Urol Oncol ; 36(3): 103-108, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29429897

RESUMO

Intravesical instillation of live attenuated bacillus Calmette-Guérin (BCG) is the gold standard for patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). BCG-failures include a heterogenous population of patients who share a designation of disease recurrence or progression following BCG and include patients with complete unresponsiveness to BCG, patients who respond initially but develop relapse and, in some cases, patients who are intolerant to BCG due to side effects. Given the efficacy and relatively rapid approval of several monoclonal antibodies against PD-L1 or PD-1 for advanced and metastatic bladder cancer, the role of these checkpoint inhibitors in BCG-relapsing disease at various disease stages is under consideration. Data supporting a role for immune checkpoint inhibitors is largely theoretical with limited supportive data from animal models and from clinical evidence of increased PD-L1 expression in BCG-unresponsive tumors. Current trials in BCG-unresponsive disease are underway and expected to provide insight regarding these concepts.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Recidiva Local de Neoplasia/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Falha de Tratamento , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
18.
Cardiology ; 139(3): 139-146, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29346780

RESUMO

BACKGROUND: Multiple studies have quantified the relationship between aortic size and risk of dissection. However, these studies estimated the risk of dissection without accounting for any increase in aortic size from the dissection process itself. OBJECTIVES: This study aims to compare aortic size before and after dissection and to evaluate the change in size consequent to the dissection itself. METHODS: Fifty-five consecutive patients (29 type A; 26 type B) with aortic dissection and incidental imaging studies prior to dissection were identified and compared to a control group of aneurysm patients (n = 205). The average time between measurement at and prior to dissection was 1.7 ± 1.9 years (1.9 ± 2.0 years mean inter-image time in the control group). A multivariate regression model controlling for growth rate, age, and gender was created to estimate the effect of dissection itself on aortic size. RESULTS: The mean aortic sizes at and prior to dissection were 54.2 ± 7.0 and 45.1 ± 5.7 mm for the ascending aorta, and 47.1 ± 13.8 and 39.5 ± 13.1 mm for the descending aorta, respectively. The multivariable analysis revealed a significant impact of the dissection itself (p < 0.001) and estimated an increase in size of 7.65 mm (ascending aorta) and 6.38 mm (descending aorta). Thus, a proportional estimate of 82.8% (ascending aorta) and 80.8% (descending aorta) of dissections are made at a size lower than the guideline-recommended threshold (55 mm). CONCLUSIONS: The aortic diameter increases substantially due to aortic dissection itself and, thus, aortas are being dissected at clinically meaningfully smaller sizes than natural history analyses have previously suggested. These findings have important implications regarding the size at which the risk of dissection is increased.


Assuntos
Aneurisma Dissecante/patologia , Aneurisma Dissecante/prevenção & controle , Aorta/patologia , Aneurisma Aórtico/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Dissecante/diagnóstico por imagem , Aorta/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Aortografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto Jovem
19.
Eur J Med Chem ; 144: 330-348, 2018 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-29275232

RESUMO

Being responsible for the development of many cancer types, EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal growth factor Receptor 2) were the focus of this study where a series of novel 4-anilino-furo[2,3-d]pyrimidine derivatives was designed, synthesized and biologically evaluated. Modification of the solvent accessible 5-position side chain greatly affected the in-vitro EGFR/HER2 inhibitory activity. Three derivatives bearing 5-carboxylic acid side chain, namely the 3-chloroanilino derivative (8c), the 3-bromoaniline (8d) and the lapatinib analogue (10) demonstrated the most significant submicromolar EGFR inhibition. Surprisingly, the in-vitro assay of the ester 7h and its acid analogue 10 showed a significant variation of results between the antiproliferative activity against A549 cell line (IC50 0.5 and 21.4 µM) respectively and EGFR inhibitory activity (18% and 100%) respectively, suggesting that 7h might be a prodrug for 10. This assumption was also affirmed by the in-vivo results, where the in-vivo antitumor assessment against EAC (Ehrlich Ascites Carcinoma) solid tumor model revealed that 7h and 8d (10 mg/kg dose) exhibited antitumor activity comparable to that of gefitinib at the same dose, exhibiting TGI% of 67%, 71% and 70%, respectively. This effect could be explained, at least partly, via activation of apoptosis, where 7h and 8d caused more than 2-fold increase of caspase 3 and cytochrome c expression than the control group which is comparable to that of gefitinib-treated group. Finally, 7h was the most effective apoptotic inducer, resulting in a significant elevation in annexin V-FITC-positive apoptotic cells (both early and late apoptosis) by 25 and 79-folds, respectively, compared to control, which is higher than that of gefitinib (22 and 61-folds, respectively).


Assuntos
Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Descoberta de Drogas , Receptores ErbB/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/metabolismo , Feminino , Humanos , Camundongos , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
20.
Urology ; 110: 98-103, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28893633

RESUMO

OBJECTIVE: To compare recovery outcomes between laparoscopic donor nephrectomy (LDN) and open donor nephrectomy within a specified enhanced recovery program (ERP) for left kidney donations. PATIENTS AND METHODS: A phase III randomized trial was conducted between January 2013 and June 2015; eligible left-side donors were randomized to laparoscopic or open donor nephrectomy in a 1:1 ratio with recovery optimized within a standardized ERP. The primary outcome was patient-reported measure of physical fatigue, as measured by the physical fatigue domain of the translated Multidimensional Fatigue Inventory 20. Secondary outcomes included other donor recovery outcomes, postoperative pain scores, hospital stay, perioperative complications, and graft outcomes. RESULTS: A total of 224 donors (laparoscopy, n = 113; open surgery, n = 111) were randomly allocated. Six weeks postoperatively, physical fatigue domain scores in Multidimensional Fatigue Inventory 20 were significantly lower in the LDN group (mean: laparoscopy, 8.2 ± 3.2 vs open surgery, 13.05 ± 2.9) (P = .007). Median total hospital stay was also significantly shorter in the LDN group (median: laparoscopy, 2; interquartile range, 1-5 vs open surgery, 4; interquartile range, 2-9 days) (P = .002). LDN was associated with less pain scores and less non-opioid analgesic requirements. Warm ischemia times were not significantly different in both groups (mean: laparoscopy, 2.5 ± 0.8 vs open surgery, 2.2 ± 0.6) (P = .431). CONCLUSION: Even when optimized within an ERP, LDN was associated with less general and physical fatigue and better physical function at 6 weeks postoperatively when compared with open surgery for left kidney donations.


Assuntos
Transplante de Rim , Laparoscopia , Nefrectomia , Coleta de Tecidos e Órgãos/métodos , Humanos , Complicações Pós-Operatórias/epidemiologia , Recuperação de Função Fisiológica
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