Aim
To compare safety and efficacy of insulin glargine and liraglutide in patients with type 2 diabetes (T2DM).
Methods
This randomized, multinational, open‐label trial included subjects treated for ...T2DM with metformin ± sulphonylurea, who had glycated haemoglobin (HbA1c) levels of 7.5–12%. Subjects were assigned to 24 weeks of insulin glargine, titrated to target fasting plasma glucose of 4.0–5.5 mmol/L or liraglutide, escalated to the highest approved clinical dose of 1.8 mg daily. The trial was powered to detect superiority of glargine over liraglutide in percentage of people reaching HbA1c <7%.
Results
The mean standard deviation (s.d.) age of the participants was 57 (9) years, the duration of diabetes was 9 (6) years, body mass index was 31.9 (4.2) kg/m2 and HbA1c level was 9.0 (1.1)%. Equal numbers (n = 489) were allocated to glargine and liraglutide. Similar numbers of subjects in both groups attained an HbA1c level of <7% (48.4 vs. 45.9%); therefore, superiority of glargine over liraglutide was not observed (p = 0.44). Subjects treated with glargine had greater reductions of HbA1c −1.94% (0.05) and −1.79% (0.05); p = 0.019 and fasting plasma glucose 6.2 (1.6) and 7.9 (2.2) mmol/L; p < 0.001 than those receiving liraglutide. The liraglutide group reported a greater number of gastrointestinal treatment‐emergent adverse events (p < 0.001). The mean (s.d.) weight change was +2.0 (4.0) kg for glargine and −3.0 (3.6) kg for liraglutide (p < 0.001). Symptomatic hypoglycaemia was more common with glargine (p < 0.001). A greater number of subjects in the liraglutide arm withdrew as a result of adverse events (p < 0.001).
Conclusion
Adding either insulin glargine or liraglutide to subjects with poorly controlled T2DM reduces HbA1c substantially, with nearly half of subjects reaching target levels of 7%.
Summary
The purpose of this study is to evaluate the effects of neonatal thymectomy in the functional capacity of the immune system. We selected a group of 23 subjects, who had undergone thymectomy ...in their first 30 days of life, during an intervention for congenital heart disease. Several parameters of the immune system were evaluated during their first 3 years of life. Lymphocyte populations and subpopulations (including naive, memory and effector subpopulations), T cell receptor (TCR) Vβ repertoire, response of T cells following in vitro stimulation by mitogen, quantification of immunoglobulins, TCR excision circles (TRECS) and interleukin (IL)‐7 were measured. We found that neonatal thymectomy produces long‐term diminution in total lymphocyte counts, especially in naive CD4+ and CD8+ T cells. Additionally, TRECS were decreased, and plasma IL‐7 levels increased. A statistically significant negative correlation was found between absolute CD4+ T cells and IL‐7 (r = −0·470, P = 0·02). The patients did not suffer more infectious events than healthy control children, but thymectomy in neonates resulted in a significant decrease in T lymphocyte levels and TRECS, consistent with cessation of thymopoiesis. This could produce a compromise in immune function later in life, especially if the patients suffer T cell depletion and need a reconstitution of immune function.
Metformin has antidiabetic, anticancer, and prolongevity effects, but seems to interfere with aerobic training mitochondrial adaptations. The primary mechanism of action has been suggested to be the ...inhibition of mitochondrial complex I. Recent papers (Wang et al. and Cameron et al.), however, provide evidence to deny the hypothesis of a direct action of metformin on complex I.
Summary
Aims To estimate the prevalence of diabetes mellitus, impaired fasting glucose and impaired glucose tolerance in a Canarian population according to the 1997 ADA and the 1985 WHO criteria; ...and to study the cardiovascular risk factors associated with these categories.
Methods A total of 691 subjects over 30 years old were chosen in a random sampling of the population (stratified by age and sex). An oral glucose tolerance test was performed (excluding known diabetic patients) and lipids were determined in the fasting state. Anthropometric and blood pressure measurements were performed, and history of smoking habits and medications was recorded.
Results The prevalence of diabetes was 15.9% (1997 ADA) and 18.7% (1985 WHO); the prevalence of impaired fasting glucose and impaired glucose tolerance was 8.8 and 17.1%, respectively. The age‐adjusted prevalence of diabetes (Segi's standard world population) for the population aged 30–64 years was 12.4% (1985 WHO). The risk factors significantly associated with diabetes (1997 ADA and 1985 WHO) were age, body mass index; waist‐to‐hip ratio, systolic and mean blood pressure, triglycerides, total cholesterol and low HDL‐cholesterol. Age, body mass index and systolic blood pressure were associated with impaired fasting glucose and impaired glucose tolerance; triglycerides were also associated with impaired fasting glucose.
Conclusions The prevalence of diabetes mellitus and glucose intolerance in Guía is one of the highest among studied Caucasian populations. The new 1997 ADA criteria estimate a lower prevalence of diabetes. Impaired fasting glucose also had a lower prevalence than impaired glucose intolerance and the overlap of these categories was modest.
Numerous population studies confirm the high prevalence of hypertension in type II diabetic (DM2) subjects and that intensive antihypertensive treatment is more beneficial to diabetic than to ...nondiabetic hypertensive subjects, yet not many of these are specific to Spain. To assess the degree of blood pressure (BP) control and the effects of antihypertensive drugs in the medical management of hypertension in diabetic patients in specialist care centres throughout Spain, we studied the socio-demographic, clinical and relevant laboratory parameters of 796 hypertensive patients with DM2 (mean age 66.09 (95% confidence interval (CI): 64.08-68.10). The percentage of diabetic patients responding positively to BP control measures was lower when compared to the nondiabetic population in both Spain and Europe. The degree of control was poorer for systolic than for diastolic BP, yet 40.6% of the patients were only on monotherapy. The fact that antihypertensive treatment was modified in only 40% of the poorly controlled patients was also highly significant and could be attributed to a nonstringent use of clinical guidelines. Among the other differences between well-controlled and poorly controlled patients, we found that well-controlled patients presented with lower levels of cholesterol and triglycerides, a lower prevalence of excess weight/obesity, and a greater prevalence of cardiovascular and/or cerebrovascular disease despite having a greater percentage of patients on antiplatelet therapy. Better application of therapeutic guidelines and the prevention and treatment of compounding factors could improve the response rate to BP control measures in poorly controlled patients.
Abstract Aim To explore the frequency of hypoglycaemic episodes, their risk factors, and associations with patient-reported outcomes in patients with type 2 diabetes enrolled in the PANORAMA ...cross-sectional study. Methods Five thousand seven hundred and eighty-three patients aged ≥ 40 years with type 2 diabetes duration ≥ 1 year were recruited in nine European countries. Patients reported severe and non-severe hypoglycaemic episodes during the past year at a single study visit. Patient-reported outcomes were measured by the Audit of Diabetes-Dependent Quality of Life, Diabetes Treatment Satisfaction Questionnaires, Hypoglycaemia Fear Survey-II, and EQ-5D Visual Analog Scale. Results During the previous year, 4.4% of the patients experienced ≥1 severe hypoglycaemic episode; among those without severe hypoglycaemia, 15.7% experienced ≥1 non-severe episode. Patients experiencing any hypoglycaemic episode reported a greater negative impact of diabetes on quality of life, greater fear of hypoglycaemia, less treatment satisfaction and worse health status than those with no episodes. In multivariate analyses hypoglycaemia was significantly associated with longer diabetes duration; presence of microvascular and, to a lesser extent, macrovascular complications; treatment with insulin, glinides or sulfonylureas; and use of self-monitoring blood glucose. Conclusion In patients with type 2 diabetes, severe hypoglycaemic episodes were not uncommon and one in five experienced some form of hypoglycaemia during the previous year. Hypoglycaemia was associated with more negative patient-reported outcomes. The risk of hypoglycaemia increased with diabetes duration, presence of diabetes-related complications, use of self-monitoring blood glucose, insulin secretagogues, and insulin treatment.
To report our initial experience with robotic radical prostatectomy as an outpatient procedure.
Retrospective analysis of patients who underwent RRP as MAS (Major Ambulatory Surgery) at our center ...between March 2021 and May 2022. We collected baseline patient characteristics, intraoperative outcomes and postoperative data (need for unplanned medical care and complications at one month after surgery). Oncologic characteristics at disease diagnosis (PSA, staging, ISUP, MRI) and postoperative pathologic outcomes were collected.
We identified a total of 35 patients with an average age of 60,8 ± 6,88 years and a BMI of 27 ± 2,9 Kg/m2. All patients had a low anesthetic risk and 25.71% had undergone previous abdominal surgery. The surgical time was 151,66 ± 42,15 min and the average blood loss was 301,2 ± 184,38 mL. Two patients (5.7%) were admitted for one night and 7 patients (20%) consulted the emergency department in the following month, of which 3 (8.57%) were readmitted. We recorded one intraoperative complication, seven mild postoperative complications (Clavien I-II) and one severe complication (Clavien IIIb). The severe complication occurred on the eighth postoperative day and was not related to the procedure being ambulatory.
The absence of serious complications in the immediate postoperative period supports RRP in MAS as a safe technique for selected patients.
Reportar nuestra experiencia inicial de prostatectomía radical robótica en régimen ambulatorio.
Análisis retrospectivo de los pacientes intervenidos de PRR en CMA en nuestro centro entre marzo de 2021 y mayo de 2022. Recopilamos las características basales de los pacientes, resultados intraoperatorios y datos del postoperatorio (necesidad de asistencia médica no planificada y complicaciones al mes de la cirugía). Se recogieron las características oncológicas al diagnóstico de la enfermedad (PSA, estadificación, ISUP, RMN) y el resultado anatomopatológico tras la intervención.
Identificamos un total de 35 pacientes con una edad promedio de 60,8 ± 6,88 años y un IMC de 27 ± 2,9 Kg/m2. Todos presentaban un riesgo anestésico bajo y un 25,71% tenía alguna cirugía abdominal previa. El tiempo quirúrgico fue de 151,66 ± 42,15 minutos y el sangrado promedio fue de 301,2 ± 184,38 mililitros. Dos pacientes (5,7%) ingresaron la primera noche de la cirugía y 7 pacientes (20%) consultaron en urgencias en el mes siguiente, de los cuales 3 (8,57%), reingresaron. Registramos una complicación intraoperatoria, siete complicaciones postoperatorias leves (Clavien I-II) y una complicación grave (Clavien IIIb). La complicación grave transcurrió al octavo día postoperatorio y no tuvo relación con la ambulatorización del procedimiento.
La ausencia de complicaciones graves en el postoperatorio inmediato avala la PRR en régimen de CMA como una técnica segura dirigida a pacientes seleccionados.
The EAU proposed a progression and death risk classification in patients with biochemical recurrence after radical prostatectomy (PR).
To validate the EAU BCR-risk classification in our setting and ...to find factors related to progression and death.
Multicenter, retrospective, observational study including 2140 patients underwent RP between 2011 and 2015. Patients with BCR were identified and stratified in low risk (PSA-DT >1yr and pGS <8) or high-risk (PSA-DT ≤1yr or pGS ≥8) grouping. PSA and metastatic free survival (PSA-PFS, MFS), cancer specific survival (CSS) and overall survival (OS) were calculated (Kaplan Meier curves and log-rank test). Independent risk factors were identified (Cox regression).
427 patients experienced BCR (32.3% low-risk and 67.7% high-risk). Median PSA-PFS was 135,0 mo (95% CI 129,63-140,94) and 115,0 mo (95% CI 104,02-125,98) (p<0,001), for low and high-risk groups, respectively. There were also significant differences in MFS and OS. The EAU BCR risk grouping was independent factor for PSA-progression (HR 2.55, p 0.009). Time from PR to BCR, was an independent factor for metastasis onset (HR 0.43, 95% CI 0.18−0.99; p 0.044) and death (HR 0.17, 95% CI 0.26.0.96; 23 p 0.048). Differences in MFS (p 0.001) and CSS (p 0.004) were found for <12, ≥12–<36 and ≥36 months from PR to BCR. Others independent factors were early salvage radiotherapy and PSA at BCR.
High-risk group is a prognostic factor for biochemical progression, but it has a limited accuracy on MP and death in our setting. The inclusion of other factors could increase its predictive power.
La EAU propuso una clasificación del riesgo de progresión y muerte en pacientes con recidiva bioquímica tras prostatectomía radical (PR).
Validar la clasificación de riesgo de RB de la EAU en nuestro contexto e identificar los factores asociados con la progresión y la muerte.
Estudio multicéntrico, retrospectivo y observacional que incluyó a 2140 pacientes sometidos a PR entre 2011 y 2015. Los pacientes con RB fueron identificados y estratificados en grupos de riesgo bajo (TD-PSA >1 año y pGS <8) o alto (TD-PSA <=1 año o pGS=>8). Se calcularon el PSA y la supervivencia libre de metástasis (SLP-PSA, SLM), la supervivencia cáncer específica (SCE) y la supervivencia global (SG) (curvas de Kaplan Meier y log-rank test). Se identificaron factores de riesgo independientes (regresión de Cox).
Un total de 427 pacientes experimentaron RB (32,3% de bajo riesgo y 67,7% de alto riesgo). La mediana de SLP-PSA fue de 135,0 m (IC 95% 129,63-140,94) y 115,0 m (IC 95% 104,02-125,98) (p<0,001) para los grupos de bajo y alto riesgo, respectivamente. Hubo diferencias significativas en la SLM y la SG. El grupo de riesgo de RB de la EAU fue un factor independiente de progresión del PSA (HR 2,55; p 0,009). El tiempo transcurrido entre la PR y la RB fue un factor independiente de aparición de metástasis (HR 0,43; IC 95%: 0,18-0,99; p 0,044) y muerte (HR 0,17; IC 95%: 0,26-0,96; 23 p 0,048). Se hallaron diferencias en la SLM (p 0,001) y la SCE (p 0,004) para <12, ≥ 12-<36 y ≥36 meses transcurridos entre la PR y la RB. Otros factores independientes fueron la radioterapia de rescate precoz y el PSA en el momento de aparición de la RB.
El grupo de riesgo alto es un factor pronóstico de progresión bioquímica, pero tiene una precisión limitada sobre la PM y la muerte en nuestro entorno. La inclusión de otros factores podría aumentar su poder predictivo.
Metachronous oligorecurrence in prostate cancer (PCa) occurs in patients with localized disease who, after failed radical treatment, develop oligometastases. Metastasis-directed stereotactic ...radiotherapy (SBRT) aims to delay androgen deprivation therapy. In this study, we report our experience to elucidate the role of SBRT in a selected population of patients with metachronous oligorecurrence.
Retrospective analysis of patients treated with SBRT for oligorecurrent PCa between November 2015 and December 2020. We detailed clinicopathological characteristics at disease onset (age, PSA, stage, primary treatment), clinical scenario at diagnosis of oligorecurrence (PSA, PSA velocity, metastases characteristics), progression-free survival, castration resistance-free survival, dose, and toxicity of SBRT.
Thirty-eight SBRT treatments were applied to 13 lymph node and 25 bone metastases in a total of 28 patients. After a follow-up of 34.57 months (21.17–57.59), 17 patients had radiological progression of the disease and 11 presented castration resistant PCa. PFS and CRFS were 21.93 and 44.13 months, respectively. Only 2 patients presented grade 1 toxicity.
In patients with metachronous oligorecurrent PCa, SBRT constitutes a safe and effective treatment that allows delaying the onset of androgen deprivation therapy and the time to castration resistance, assuming low levels of toxicity.
La oligorrecurrencia metacrónica en el cáncer de próstata (CaP) la constituyen los pacientes que empezaron con enfermedad localizada y que, tras un tratamiento radical fallido, desarrollan oligometástasis. La radioterapia estereotáctica (SBRT) dirigida a las metástasis busca retrasar el inicio de la privación androgénica. En este estudio, mostramos nuestra experiencia para elucidar el papel de la SBRT en una población seleccionada de pacientes con oligorrecurrencia metacrónica.
Análisis retrospectivo de pacientes tratados con SBRT por CaP oligorrecurrente entre noviembre de 2015 y diciembre de 2020. Detallamos las características clinicopatológicas al inicio de la enfermedad (edad, PSA, estadificación, tratamiento primario), escenario clínico al diagnóstico de la oligorrecurrencia (PSA, velocidad del PSA, características de las metástasis), supervivencia libre de progresión, supervivencia hasta la resistencia a la castración, dosis y toxicidad de la SBRT. Solo 2 pacientes presentaron toxicidad de grado 1.
La SBRT en pacientes con CaP en situación de oligorrecurrencia metacrónica constituye un tratamiento seguro y efectivo que permite retrasar el inicio de la terapia de radiación androgénica y el tiempo hasta la resistencia a la castración, con niveles bajos de toxicidad.
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