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1.
Diabetes ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36342518

RESUMO

Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is caused by heterozygous inactivating mutations in glucokinase (GK, gene symbolGCK) and impaired glucose sensing. We investigated effects of dorzagliatin, a novel allosteric GK activator, on insulin secretion rates (ISR) and beta-cell glucose-sensitivity (ßCGS) in GCK-MODY and recent-onset type 2 diabetes. In a double-blind, randomized cross-over study, eight participants with GCK-MODY and 10 with type 2 diabetes underwent 2-hour 12-mmol/L hyperglycemic clamps following a single oral dose of dorzagliatin 75mg or matched placebo. Effects of dorzagliatin on wild-type and mutant GK enzyme activity were investigated using a nicotinamide adenine dinucleotide phosphate (NADP+) coupled assay with glucose-6-phosphate dehydrogenase (G6PD) in vitro. In GCK-MODY, dorzagliatin significantly increased absolute and incremental second-phase ISR versus placebo but not the acute insulin response. Dorzagliatin improved ßCGS in GCK-MODY with a upward and leftward shift in ISR-glucose response. Dorzagliatin increased basal ISR in type 2 diabetes with smaller changes in second-phase ISR compared with GCK-MODY. In vitro, dorzagliatin directly reduced the glucose half saturation concentration (S0.5) of wild-type GK and selected GK mutants to varying degrees. Dorzagliatin directly restored enzyme activity of select GK mutants and enhanced wild-type GK activity, thereby correcting the primary defect of glucose sensing in GCK-MODY.

2.
Int J Urol ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36349904

RESUMO

OBJECTIVES: Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated. METHODS: Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low-grade on URS biopsy) versus same grade (high-grade on URS biopsy) for high-grade UTUC tumors on radical nephroureterectomy (RNU) specimens. RESULTS: This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy-based low- and high-grade tumors, respectively. Median follow-up was 27.3 months. Patients with high-grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high-grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10-2.75; p = 0.018), cancer-specific (HR 1.94; 95% CI, 1.07-3.52; p = 0.03), and recurrence-free survival (HR 1.80; 95% CI, 1.13-2.87; p = 0.013). In subgroup analyses of patients with pT2-T4 and/or positive LN, its significant association retained. Furthermore, high-grade biopsy in clinically non-muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low-grade biopsy. CONCLUSIONS: High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low-grade UTUC that becomes upgraded to high-grade might carry a better prognosis than high-grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high-grade on RNU.

3.
Minerva Urol Nephrol ; 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36197700

RESUMO

BACKGROUND: Recently, the European Association of Urology Guidelines Panel updated the prognostic factor risk groups model for non-muscle-invasive bladder cancer (NMIBC) with the introduction of a new group of patients at Very high risk (VHR). Furthermore, three additional clinical risk factors (i.e., age > 70 years, multiple papillary tumors; tumor diameter > 3 cm) were proposed. However, the new scoring model was created by analyzing data from patients who did not receive BCG intravesical therapy. METHODS: This is a retrospective multicenter study analyzing data of 920 patients with HGT1 NMIBC that underwent ReTUR e following BCG intravesical therapy. Patients were stratified into risk groups according to the 2021 new EAU NMIBC prognostic factor risk groups model. This study aimed to identify variables related to disease progression in a large cohort of HGT1 NMIBC patients who underwent both Re-TURB and BCG intravesical immunotherapy. RESULTS: Median follow-up was 51 months (IQR 41-75), according to EAU NMIBC 2021 scoring model 179 (19.5%) patients were at VHR. Progression-free survival at 5 years was 68.2% and 59.9% for the whole sample and the VHR group, respectively. At multivariable regression model size >3 cm, multifocal tumor, concomitant CIS and LVI were identified as independently associated with disease progression. CONCLUSIONS: Although patients at VHR are more likely to experience disease progression during follow-up, the European Association of Urology (EAU) NMIBC 2021 scoring model appears to be suboptimal in patients who underwent ReTUR and intravesical BCG therapy.

4.
Minerva Urol Nephrol ; 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36197701

RESUMO

BACKGROUND: Incidentally diagnosed adrenal masses represent an entity that can result in either long term follow-up, surgical excision, or both. Understanding when and which adrenal masses are ultimately excised surgically is not well understood. We sought to understand the ultimate fate of these incidentalomas using a large population-based dataset. METHODS: The primary outcome of the study was determining the trend in adoption of surveillance vs. surgical excision according to socio-demographic, economic, and pathologic indices, and also provider specialty. Secondary outcomes were the assessment of perioperative complications, operative time, surgical approach, hospital stay, and provider specialty (general surgery vs. urology) among the cohort that underwent excision. RESULTS: Out of a total of n=91,560 adrenal masses, ultimately n=3,375 (3.83%) of these underwent surgical excision. In the surgical excision cohort, the incidence of aldosteronoma, functional adenoma/Cushing's disease, and adrenocortical carcinoma was higher than in the surveillance cohort. Those patients who were older, female, and with higher Charlson Comorbidity indexes (CCI) were less likely to undergo surgical resection. Factors that predicted for an increased probability of resection included obtaining more CT/MRI scans as well as general surgeons as primary physician providers. Over the study period, the vast majority of surgeries were performed by surgeons other than urologists (12.9%) and open and laparoscopic approaches dominated, with the robotic-assisted approach accounting for a minority of the surgical cases (23.9%). The minimally invasive surgery (MIS) approach independently predicted for both lower rates of complications and shorter hospital stay. CONCLUSIONS: In the US, adrenal incidentalomas are more likely to undergo surveillance rather than surgical resection. In our study, surgery is mainly offered for functional or malignant disease and the receipt of surgery can vary by physician specialty. A MIS approach independently predicted for both lower rates of complications and shorter hospital stay.

5.
Diabetologia ; 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36280617

RESUMO

AIMS/HYPOTHESIS: Endoplasmic reticulum (ER) stress and beta cell dedifferentiation both play leading roles in impaired insulin secretion in overt type 2 diabetes. Whether and how these factors are related in the natural history of the disease remains, however, unclear. METHODS: In this study, we analysed pancreas biopsies from a cohort of metabolically characterised living donors to identify defects in in situ insulin synthesis and intra-islet expression of ER stress and beta cell phenotype markers. RESULTS: We provide evidence that in situ altered insulin processing is closely connected to in vivo worsening of beta cell function. Further, activation of ER stress genes reflects the alteration of insulin processing in situ. Using a combination of 17 different markers, we characterised individual pancreatic islets from normal glucose tolerant, impaired glucose tolerant and type 2 diabetic participants and reconstructed disease progression. CONCLUSIONS/INTERPRETATION: Our study suggests that increased beta cell workload is accompanied by a progressive increase in ER stress with defects in insulin synthesis and loss of beta cell identity.

6.
BJU Int ; 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36251366

RESUMO

OBJECTIVES: To address the association of perioperative surgical checklist across variable surgical expertise with transurethral resection of bladder tumour (TURBT) accuracy and oncological outcomes in non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We relied on our prospective collaborative database of patients treated with TURBT between 2012 and 2017. Surgical experience was stratified into three groups: resident vs young vs expert consultants. The association of surgical experience with detrusor muscle (DM) presence and adherence to the standardised peri-procedural nine-items TURBT checklist was evaluated with logistic regression models. A Cox regression model was used to investigate the association of surgical experience with recurrence-free survival (RFS). RESULTS: A total of 503 patients were available for analysis. TURBT was performed by expert consultants in 265 (52.7%) patients, by young consultants in 149 (29.6%) and by residents in 89 (17.7%). Residents were more likely to have DM in the TURBT specimen than expert consultants (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.99, P = 0.04). Conversely, no differences in DM presence were seen between young vs expert consultants (OR 1.09, 95% CI 0.71-1.70, P = 0.69). The median checklist completion rate was higher for both residents and young consultants when compared to experts' counterparts (56% and 56% vs 44%, P = 0.009). When focusing on patients receiving a second-look TURBT, the persistent disease was associated with resident status (OR 4.24, 95% CI 1.14-17.70, P = 0.037) at initial TURBT. Surgical experience was not associated with 5-years RFS. CONCLUSION: Surgeon's experience in the case of adequate perioperative surgical checklist implementation was inversely associated with the presence of DM in the specimen but directly linked to higher probability of persistent disease at re-TURBT, although no 5-year RFS differences were noted.

7.
World J Urol ; 40(11): 2771-2779, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36203101

RESUMO

PURPOSE: To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR - baseline eGFR; Δ2 = 6 months eGFR - POD-1 eGFR; Δ3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. RESULTS: A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up. CONCLUSION: Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.


Assuntos
Injúria Renal Aguda , Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Sistema Urinário , Neoplasias Urológicas , Humanos , Masculino , Lactente , Nefroureterectomia , Carcinoma de Células de Transição/cirurgia , Nefrectomia , Taxa de Filtração Glomerular , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Neoplasias Urológicas/cirurgia , Rim/cirurgia , Rim/fisiologia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Neoplasias Ureterais/cirurgia
8.
Endocrinol Diabetes Metab ; 5(6): e371, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36239048

RESUMO

INTRODUCTION: The aim of the present study was to evaluate the effect of 18-week monotherapy with imeglimin on glucose tolerance and on insulin secretion/sensitivity in type 2 diabetic (T2D) patients. METHODS: The study was an 18-week, double-blind clinical trial in T2D subjects previously treated with stable metformin therapy and washed out for 4 weeks. Subjects were randomized 1:1 to receive a 1500 mg bid of imeglimin or placebo. The primary endpoint was the effect of imeglimin vs placebo on changes from baseline to week 18 in glucose tolerance (glucose area under the curve [AUC]) during a 3 h-glucose tolerance test [OGTT]). Secondary endpoints included glycaemic control and calculated indices of insulin secretion and sensitivity. RESULTS: A total of 59 subjects were randomized, 30 receiving imeglimin and 29 receiving placebo. The study met its primary endpoint. Least squares (LS) mean difference between treatment groups (imeglimin - placebo) for AUC glucose from baseline to week 18 was -429.6 mmol/L·min (p = .001). Two-hour post-dose fasting plasma glucose was significantly decreased with LS mean differences of -1.22 mmol/L (p = .022) and HbA1c was improved with LS mean differences of -0.62% (p = .013). The AUC0-180min ratio C-peptide/glucose [LS mean differences of 0.041 nmol/mmol (p < .001)] and insulinogenic index were significantly increased by imeglimin treatment. The increase in insulin secretion was associated with an increase in beta-cell glucose sensitivity. Additionally, the insulin sensitivity indices derived from the OGTT Stumvoll (p = .001) and Matsuda (not significant) were improved in the imeglimin group vs placebo. Imeglimin was well tolerated with 26.7% of subjects presenting at least one treatment-emergent adverse event versus 58.6% of subjects in the placebo group. CONCLUSIONS: Results are consistent with a mode of action involving insulin secretion as well as improved insulin sensitivity and further support the potential for imeglimin to improve healthcare in T2D patients.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Secreção de Insulina , Hipoglicemiantes/efeitos adversos , Glicemia , Método Duplo-Cego
10.
Cancers (Basel) ; 14(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36139591

RESUMO

We compared perioperative outcomes after on-clamp versus off-clamp robot-assisted partial nephrectomy (RAPN) for >7 cm renal masses. A multicenter dataset was queried for patients who had undergone RAPN for a cT2cN0cM0 kidney tumor from July 2007 to February 2022. The Trifecta achievement (negative surgical margins, no severe complications, and ≤ 30% postoperative estimated glomerular filtration rate (eGFR) reduction) was considered a surrogate of surgical quality. Overall, 316 cases were included in the analysis, and 58% achieved the Trifecta. A propensity-score-matched analysis generated two cohorts of 89 patients homogeneous for age, ASA score, preoperative eGFR, and RENAL score (all p > 0.21). Compared to the on-clamp approach, OT was significantly shorter in the off-clamp group (80 vs. 190 min; p < 0.001), the incidence of sRFD was lower (22% vs. 40%; p = 0.01), and the Trifecta rate higher (66% vs. 46%; p = 0.01). In a crude analysis, >20 min of hilar clamping was associated with a significantly higher risk of sRFD (OR: 2.30; 95%CI: 1.13-4.64; p = 0.02) and with reduced probabilities of achieving the Trifecta (OR: 0.46; 95%CI: 0.27-0.79; p = 0.004). Purely off-clamp RAPN seems to be a safe and viable option to treat cT2 renal masses and may outperform the on-clamp approach regarding perioperative surgical outcomes.

11.
Eur Urol Open Sci ; 44: 33-36, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36046617

RESUMO

Partial nephrectomy (PN) may be recommended for selected patients with advanced-stage (>cT2) renal cell carcinoma (RCC) with the aim of avoiding dialysis and chronic kidney disease-related comorbidities. The spread of robotic surgery has led to expansion of PN indications to more challenging scenarios and even frontier surgeries, including advanced-stage RCC. Here we describe the management of a patient with a solitary kidney diagnosed with multiple cT3a (renal vein thrombus) RCC who was treated using a conservative robotic approach. The most crucial surgical considerations for this procedure were: (1) tailored planning of the surgical approach using three-dimensional reconstruction software; (2) accurate boundary delineation for the tumors and thrombus; (3) avoiding unnecessary warm ischemia time; (4) performing an anatomical excision to follow eventual tumor bulging; and (5) en bloc removal of the main lesion and its thrombus. No perioperative complications were recorded. Histopathology revealed clear cell RCC for all four lesions with nucleolar grade 3 and negative surgical margins. At 12-mo follow-up the patient was disease-free. When performed by an experienced surgeon, PN plus venous thrombus excision for imperative cases with cT3 RCC may represent a valid treatment option with valuable oncological and functional outcomes. Patient summary: We describe the case of patient who had a single kidney with multiple kidney tumors and tumor extension into a blood vessel. The patient was treated with robot-assisted removal of the tumors, sparing as much kidney tissue as possible. This technique was found to be safe and effective, with no complications and good intermediate-term results.

14.
Int Urol Nephrol ; 54(12): 3171-3177, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35962907

RESUMO

PURPOSE: To report our experience with the non-transecting dorsal mucosal anastomosis plus ventral oral graft urethroplasty (NTAVOG) for the repair of tight bulbar urethral strictures. METHODS: Data of 68 men with tight bulbar strictures underwent NTAVOG urethroplasty between 2012 and 2019 were retrospectively revised. The urethra was opened ventrally; the dorsal scarred mucosa was excised preserving the spongiosum; the mobilized mucosal edges were anastomosed to recreate the dorsal urethral plate; the repaired urethral plate was augmented by the ventral oral graft and the spongiosum was closed over it. Successful urethral reconstruction was defined as normal voiding without the need for any postoperative procedure. Sexual function was investigated using a validated questionnaire. RESULTS: Median follow-up was 58 months (IQR 38-63) and mean stricture length was 1 cm (IQR 1-1.5). Of 68 cases, 56 (82.4%) were successful and 12 (17.6%) were failures requiring re-treatment. At multivariable analysis, no preoperative factor was significantly associated with recurrence. None of the preoperatively sexually active 53 patients reported postoperative erectile impairment and all were satisfied with their sexual life. The main limitation is the retrospective design. CONCLUSIONS: In cases of tight bulbar stricture, the NTAVOG urethroplasty provides adequate urethral augmentation by preserving the spongiosum and avoiding postoperative sexual complications. We presented a series of patients undergone non-transecting dorsal anastomosis plus ventral oral graft urethroplasty for tight bulbar stricture. This treatment seems to be safe and with limited postoperative complications thanks to the preservation of the corpus spongiosum.


Assuntos
Cirurgiões , Estreitamento Uretral , Masculino , Humanos , Estreitamento Uretral/cirurgia , Estreitamento Uretral/etiologia , Estudos Retrospectivos , Constrição Patológica/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Mucosa Bucal/transplante , Resultado do Tratamento , Uretra/cirurgia , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/cirurgia
15.
Eur J Surg Oncol ; 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35970622

RESUMO

BACKGROUND: Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is surging worldwide. Aim of the study was to perform a multicentric cost-analysis of RARC by comparing the gross cost of the intervention across hospitals in four different European countries. METHODS: Patients who underwent RARC + ICUD were recruited from eleven European centers in four European countries (Belgium, France, Netherlands, and UK) between 2015 and 2020. Costs were divided into six parts: cost for hospital stay, cost for ICU stay, cost for surgical theater occupation, cost for transfusion, cost for robotic instruments, and cost for stapling instruments. These costs were individually assessed for each patient. RESULTS: A total of 490 patients were included. Median operative time was 300(270-360) minutes and median hospital length-of-stay was 11(8-15) days. The average total cost of RARC was 14.794€ (95%CI 14.300-15.200€). A significant difference was found for the total cost, as well as the various subcosts abovementioned, between the four included countries. Different sets and types of robotic instruments were used by each center, leading to a difference in cost of robotic instrumentation. Nearly 84% of costs of RARC were due to hospital stay (42%), ICU stay (3%) and operative time (39%), while 16% of costs were due to robotic (8%) and stapling (8%) instruments. CONCLUSION: Costs and subcosts of RARC + ICUD vary significantly across European countries and are mainly dependent of hospital length-of-stay and operative time rather than robotic instrumentation. Decreasing length-of-stay and reducing operative time could help to decrease the cost of RARC and make it more widely accessible.

17.
J Minim Invasive Gynecol ; 29(10): 1178-1183, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35817366

RESUMO

STUDY OBJECTIVE: To investigate the clinical and surgical predictors of urinary tract endometriosis (UTE) relapse. DESIGN: Retrospective single institutional study. SETTING: Italian multidisciplinary referral center for endometriosis. PATIENTS: Consecutive patients affected by UTE and surgically treated between January 2016 and March 2020. INTERVENTION: Surgical excision for UTE. Uni- and multivariate logistic regression analyses were fitted to evaluate clinical and surgical predictors of recurrence. MEASUREMENTS AND MAIN RESULTS: A total of 105 female age-reproductive patients were enrolled. Median age was 32 years (interquartile range, 24-37). Ureteral involvement was recorded in 53 patients (50.5%), being unilateral and bilateral in 46 patients (43.8%) and 7 patients (6.7%), respectively. Bladder involvement occurred in 52 patients (49.5%). Open surgical approach was performed in 24 cases (22.9%), whereas 30 patients (28.5%) and 51 patients (48.6%) were treated with laparoscopic and robot-assisted approach, respectively. Overall, 53 patients (50.5%) received adjuvant hormonal therapy. At a median follow-up of 39 months (interquartile range, 22-51), 30 patients (28.6%) experienced disease relapse, with 14 recurrences (13.3%) recorded at the level of the urinary tract. At multivariable analysis, age at first surgery <25 years (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.10-1.84; p = .02) and the presence of a concomitant autoimmune disease (OR, 1.45; 95% CI, 1.24-2.17; p = .02) were found as predictors of deep infiltrating endometriosis recurrence, whereas adjuvant postsurgical therapy showed a protective role (OR, 0.83; 95% CI, 0.53-0.98; p = .01). CONCLUSIONS: Young age (<25 years) and the presence of autoimmune diseases were significant predictors for the development of disease recurrence, whereas adjuvant hormonal therapy showed a protective role.


Assuntos
Endometriose , Laparoscopia , Doenças Ureterais , Sistema Urinário , Adulto , Endometriose/complicações , Endometriose/cirurgia , Feminino , Humanos , Laparoscopia/efeitos adversos , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Doenças Ureterais/prevenção & controle , Doenças Ureterais/cirurgia
18.
Eur J Cancer Care (Engl) ; 31(6): e13666, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35869594

RESUMO

OBJECTIVE: To assess whether socio-economic disparities exist on access to care, treatment options and outcomes among patients with renal mass amenable of surgical treatment within the universal healthcare system. METHODS: Data of consecutive patients submitted to partial nephrectomy (PN) or radical nephrectomy (RN) at our Institution between 2017 and 2020 were retrospectively evaluated. Patients were grouped according to their income level (low, intermediate, and high) based on the Indicator of Equivalent Economic Situation national criterion. Survival analysis was performed. Cox regression models were employed to analyse the impact of socio-economic variables on survival outcomes. RESULTS: One thousand forty-two patients were included (841 PN and 201 RN). Patients at the lowest income level were found more likely symptomatic and with a higher pathological tumour stage in the RN cohort (p > 0.05). The guidelines adherence on surgical indication rate as well as the access to minimally invasive surgery did not differ according to patient's income level in both cohorts (p > 0.05). Survival curves were comparable among the groups. Cox regression analysis showed that none of the included socio-economic variables was associated with survival outcomes in our series. CONCLUSIONS: Universal healthcare system may increase the possibility to ensure egalitarian treatment modalities for patients with renal cancer.

19.
Eur Urol Open Sci ; 41: 74-80, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35813257

RESUMO

Background: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non-muscle-invasive disease. Objective: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2-4N0M0 MIBC. Design setting and participants: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19-0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84-3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66-3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p < 0.001). Conclusions: Patients with primary MIBC have better pathologic response rates to NAC in comparison to patients with secondary MIBC. Chemoresistance might be related to the different genomic profile of primary versus secondary MIBC. Patient summary: We investigated the treatment response to neoadjuvant chemotherapy (NAC; chemotherapy received before the primary course of treatment) and survival for patients with a primary diagnosis of muscle-invasive bladder cancer (MIBC) in comparison to patients with a history of non-muscle-invasive bladder cancer that progressed to MIBC. Patients with primary MIBC had a better response to NAC but this did not translate to better survival after accounting for other tumor characteristics.

20.
Physiol Rep ; 10(13): e15354, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35785485

RESUMO

Type 2 diabetes (T2D) risk is lower in females than males. It has been reported that females have greater pancreatic 𝛽-cell function than males, which may at least in part contribute to the T2D risk in females. 𝛽-cell function is influenced by exercise training; however, previous trials comparing 𝛽-cell function between the sexes have not included participants matched for training status. Furthermore, the acute effects of different modes of exercise on 𝛽-cell function, and whether sex inherently influences these effects, are largely unexamined. Males and females (12/sex) completed a 120-min oral glucose tolerance test (OGTT) at rest (CON) and following acute bouts of high-intensity interval exercise (HIIE), moderate intensity continuous (MIC) exercise, and low-load high-repetition (LLHR) resistance exercise to assess whether sex inherently influences baseline and/or post-exercise pancreatic function in the absence of pathology. We found no sex differences in basal pancreatic 𝛽-cell function. Females had greater basal insulin clearance following MIC exercise compared to males (p = 0.01) and males tended to have a higher potentiation ratio following HIIE (p = 0.07). Females also had lower glucose sensitivity following MIC exercise compared to HIIE (p = 0.007) and LLHR (p = 0.003). Insulin clearance during the OGTT was greater following HIIE as compared with CON and MIC exercise (p = 0.02). 2-H oral glucose insulin sensitivity was greater following LLHR compared to CON (p = 0.01). Acute bouts of different modes of exercise do not differentially influence 𝛽-cell function but do influence insulin clearance and insulin sensitivity. Therefore, sex and exercise mode interact to differentially influence insulin clearance and glucose sensitivity.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Glicemia , Exercício Físico/fisiologia , Feminino , Glucose , Humanos , Insulina , Resistência à Insulina/fisiologia , Masculino
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