Urine metabolomic analysis in clear cell and papillary renal cell carcinoma: A pilot study.

Renal cell carcinoma (RCC) is one of the most lethal type of tumors and is twice more frequent in men than in women. Initial symptoms are unspecific and belated thus increasing mortality. Moreover, current diagnostic and monitoring tools are harmful for the patient and unspecific in low-grade tumors. Therefore, novel minimally-invasive markers are needed to diagnose and monitor RCC patients. Urine represents the ideal sample source of non-invasive biomarkers for RCC. In our study we aimed to identify a urine metabolomic profile characteristic of RCC patients with diagnostic purposes and also to identify a profile with prognostic value. By an UPLC-Q-ToF MS untargeted metabolomic analysis, we compared the metabolomic profile of 23 RCC patients (14 clear cell RCC and 9 papillary RCC) before surgery and that of 23 healthy controls. Additionally, for the first time, we compared the metabolomic profile of these RCC patients pre-nephrectomy and 3 months and one year post-nephrectomy. We identified the dysregulated metabolomic variables by querying their exact mass against those presented in the Metlin and Human Metabolome Database. Next, we experimentally confirmed their identity. Both RCC subtypes showed similar metabolomic patterns at all stages. 51 metabolomic variables were significantly increased in RCC compared to controls and, among them, 4 were selected as potential discriminant metabolites between groups. We could experimentally confirm the identity of p-cresol glucuronide thus describing for the first time an increase in this metabolite in urine of RCC patients (fold change = 2.922, P = .012). Additionally, we confirmed that no metabolomic differences occur 3 months post-nephrectomy in RRC, while 188 variables were significantly increased one year post-nephrectomy. Of the 15 most discriminant metabolomic variables, we could experimentally confirm the identity of isobutyryl-l-carnitine (fold change = 2.098, P = .004) and l-proline betaine (fold change = 3.328, P = .004), for the first time. In summary, we have identified urine p-cresol glucuronide as potential diagnostic marker for RCC and isobutyryl-l-carnitine and l-proline betaine as potential prognostic markers. When confirmed in an independent cohort of RCC patients, these markers may improve the diagnosis and monitoring of RCC patients thus reducing current harmful diagnostic procedures. SIGNIFICANCE: The high-radiation dose of current imaging techniques available to diagnose and monitor renal cell carcinoma (RCC) are harmful for the patient and unspecific in low-grade tumors. Our untargeted metabolomic analysis carried out in urine samples from RCC patients and healthy individual reveals p-cresol glucuronide as potential diagnostic marker for RCC. Additionally, the analysis of RCC urine samples one year post-nephrectomy reveals isobutyryl-l-carnitine and l-proline betaine as potential prognostic markers. These novel non-invasive urine biomarkers may improve RCC management thus reducing the use of current harmful diagnostic techniques.

Fine-Tuning ER Stress Signal Transducers to Treat Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motoneurons and paralysis. The mechanisms underlying neuronal degeneration in ALS are starting to be elucidated, highlighting disturbances in motoneuron proteostasis. Endoplasmic reticulum (ER) stress has emerged as an early pathogenic event underlying motoneuron vulnerability and denervation in ALS. Maintenance of ER proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) is an ER-located kinase and endoribonuclease that operates as a major ER stress transducer, mediating the establishment of adaptive and pro-apoptotic programs. Here we discuss current evidence supporting the role of ER stress in motoneuron demise in ALS and build the rational to target IRE1 to ameliorate neurodegeneration.

Evaluation of Adult Acute Scrotum in the Emergency Room: Clinical Characteristics, Diagnosis, Management, and Costs.

OBJECTIVE: To evaluate the clinic characteristics, diagnosis, management, and costs of the adult acute scrotum in the emergency room (ER). Acute scrotum is a syndrome characterized by intense, acute scrotal pain that may be accompanied by other symptoms. It is usual in children and commonly found as well in adults, with different causal pathologies between these groups. METHODS: Between November 2013 and September 2014, 669 cases of adult acute scrotum who presented to our ER were prospectively analyzed. Patients under 15 years of age were excluded. Patient age, reason for consultation, investigations performed, final diagnosis, management, and costs were evaluated. For the statistical analysis, the Mann-Whitney, Kruskal-Wallis U, and chi-square tests were used. RESULTS: A total of 669 cases of acute scrotum were analyzed. The mean age at presentation was 40.2 ± 17.3 years. The most presented diagnoses were orchiepididymitis (28.7%), epididymitis (28.4%), symptoms of uncertain etiology (25.1%), and orchitis (10.3%). Diagnostic tests were carried out in 57.8% of cases. Most cases were treated as outpatients (94.2%), with 5.83% admitted and 1% undergoing surgical treatment. Overall, 13.3% of patients represented to the ER. Abnormal results in blood and urine tests were more common among older patients and infectious pathologies. The average cost generated by an acute scrotum ER consult was 195.03€. CONCLUSION: Infectious pathologies are the most common causes of acute scrotum at ER. Abnormal blood and urine tests are unusual and are more common in older patients and infectious pathologies.

Continuation rate of combined hormonal contraception: a prospective multicenter study.

BACKGROUND: Data from clinical trials regarding continuation of use and contraceptive efficacy do not always apply to the general public. Therefore, a study among typical users was conducted to assess the continuation rate at the end of 12 cycles of combined hormonal contraceptive methods, reasons for discontinuation, and the Pearl index. METHODS: Prospective, observational, and multicenter study of 3443 women aged 18 to 49 years starting one of the three combined hormonal contraception methods available in Spain (the vaginal ring, the contraceptive pill, and the transdermal skin patch). RESULTS: The study population (intention-to-treat analysis) included 3443 women, of whom 45.4% were included in the vaginal ring group, 42.6% the pill group, and 12.1% the skin patch group. The continuation rate at 12 cycles was 45.9% for the pill, 42.3% for the vaginal ring, and 26.0% for the skin patch. The Pearl index was 0.61 (95% confidence interval [CI] 0-1.2) for the pill, 0.61 (95% CI 0-1.1) for the vaginal ring, and 2.34 (95% CI 0.3-9) for the skin patch (p<0.001). CONCLUSION: At 12 cycles, the vaginal ring and the pill showed similar continuation rates and effectiveness, which were significantly higher than the skin patch.

Fracción de eyección ventricular en pacientes con enfermedad pulmonar obstructiva crónica irreversible a la altura de Bogotá

Se presenta un estudio utilizando el método de angiocardiografía radionuclear de equilibrio (MUGA), para la valoración de la fracción de eyeccion ventricular derecha (FEVD) en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Aunque no se encontró una correlación estadísticamente significativa entre la FEVD y el grado de severidad de la función ventilatoria establecido por prubas de función pulmonar y gasimetría arterial, se observó que ésta tendía a disminuir a medida que la función respiratoria se deterioraba progresivamente en el grupo de pacientes estudiados. En especial en el grupo con volumen espiratorio forzado en el primer segundo menor de 1 lt/sg y con una presión arterial de CO2 mayor de 36 mm Hg a nivel de Bogotá, se encontraron altos índices de correlación entre la FEVD y los parámetros de funcion pulmonar y gasimetría arterial. Igualmente se encontró que el valor de la FEVD era menor en pacientes con cuadro clínico de cor pulmonar que en el grupo restante. En general no se encontró un compromiso de la fracción de eyección del ventrículo izquierdo (FEVI) en ninguno de los grupos estudiados, aun aquellos con un mayor compromiso de la función cardiopulmonar. Se plantea la utilidad de la FEVD como índice independiente en la valoración de la gravedad clínica del paciente con EPOC