Association of ABC and RENAL Scoring Systems With Morbidity in Partial Nephrectomy.

BACKGROUND/AIM: Different nephrometry scoring systems (NSSs) are used to evaluate the surgical complexity and outcomes of partial nephrectomy (PN) in patients with small renal tumors. This study aimed to assess the validity of nephrometry scoring systems towards aiding the preoperative planning of laparoscopic partial nephrectomy (PN). PATIENTS AND METHODS: Data of 77 patients who underwent partial nephrectomy at the Puerto Real University Hospital between January 2011 and December 2017 were retrospectively analyzed. Statistical analyses were carried out to determine whether there was an association between the complexity of the surgical procedure and the assigned nephrometry scores. RESULTS: Operative complications (bleeding volume, conversion to open surgery, perioperative bleeding, and postoperative fistula) were significantly associated with independent variables (age, sex, body mass index, radiological tumor size, and operative ischemia time) and with the classification of patients using arterial-based complexity (ABC) and radius endophytic/exophytic nearness anterior-posterior location (RENAL) scores. There was also a strong correlation between the RENAL and ABC scores [Cramer's V coefficient (0.682) and Fisher's test (p<0.0001)]. CONCLUSION: The RENAL and ABC scores are associated with the risk of the complexity of partial nephrectomy for T1 renal tumors, even for ≥T1b tumors and/or with complex anatomical features.

Snf1p/Hxk2p/Mig1p pathway regulates hexose transporters transcript levels, affecting the exponential growth and mitochondrial respiration of Saccharomyces cerevisiae.

The Crabtree effect molecular regulation comprehension could help to improve ethanol production with biotechnological purposes and a better understanding of cancer etiology due to its similarity with the Warburg effect. Snf1p/Hxk2p/Mig1p pathway has been linked with the transcriptional regulation of the hexose transporters and phenotypes associated with the Crabtree effect. Nevertheless, direct evidence linking the genetic control of the hexose transporters with modulation of the Crabtree effect phenotypes by the Snf1p/Hxk2p/Mig1p pathway is still lacking. In this sense, we provide evidence that SNF1 and HXK2 genes deletion affects exponential growth, mitochondrial respiration, and transcript levels of hexose transporters in a glucose-dependent manner. The Vmax of the hexose transporters with the high transcript levels was correlated positively with the exponential growth and negatively with the mitochondrial respiration. HXT2 gene transcript levels were the most affected by the deletion of the SNF1/HXK2/MIG1 pathway. Deleting the orthologous genes SNF1 and HXK2 in Kluyveromyces marxianus (Crabtree negative yeast) has an opposite effect compared to Saccharomyces cerevisiae in growth and mitochondrial respiration. Overall, these results indicate that the SNF1/HXK2/MIG1 pathway regulates transcript levels of the hexose transporters, which shows an association with the exponential growth and mitochondrial respiration in a glucose-dependent manner.

Treatment of Metastatic Castration-resistant Prostate Cancer Patients With Abiraterone Acetate and Prednisone and Corresponding Survival Prognostic Factors.

BACKGROUND/AIM: The aim of the study was to evaluate the combined treatment with abiraterone acetate and prednisone (AA+P) in patients with castration-resistant prostate cancer (mCPRC), and to identify the survival prognostic factors. PATIENTS AND METHODS: Patients diagnosed with mCPRC not previously treated with chemotherapy and administered with AA+P were classified into two groups: those with lower and higher survival rates (at 30 months vs. 60 months). RESULTS: A total of 53 patients were studied at the time of mCRPC diagnosis. Patients with the highest survival rate had suffered prostate cancer for >45 months. At the time of initial prostate cancer diagnosis, they belonged to the risk groups 1-4, had pain intensity measured according to the brief pain inventory (BPI) scale of 0-2, were treated with AA+P>16 months, and had the following tumour marker serum levels: LDH baseline ≤163 U/l, alkaline phosphatase at 6 months ≤56 U/l and PSA at 6 months ≤0.95 ng/ml. CONCLUSION: Good response to treatment with AA+P for patients with mCRPC was demonstrated. Factors that contributed to the higher prognostic accuracy were time suffering from prostate cancer, the intensity of the pain measured by the BPI scale, the duration of AA+P treatment, and tumour marker levels.

[Validity studies in laparoscopic simulation. Methodology and design considerations.] / Validación en simulación laparoscópica. Consideraciones metodológicas y de diseño.

OBJECTIVES: To describe a roadmap of the most representative milestones and considerations in the validation of surgical simulators, especially those of laparoscopic surgery. And additionally, help determine when in this process a simulator can be considered as validated. METHODS: A non-systematic review was carried out searching terms like simulation, validation, training, assessment, skills and learning curve, as well as providing the experience accumulated by our center. RESULTS: An ideal classical validation process should consist of the following steps: fidelity, verification/calibration/ reliability, subjective and objective strategies. Baseline tests of fidelity and verification/calibration/ technological reliability are not always detailed in the simulation literature. A simulator can be considered validated if, at least, satisfactorily completed any of the two main objective strategies, that is, constructive and/or criterion validity. CONCLUSIONS: The methodologies to validate simulators as useful and reliable for the improvement of psychomotor/ technical skills are widely analyzed, although there is a variety of approaches depending on the scientific reference consulted, not being implemented equally in all works. This apparent arbitrariness should be considered in advance because it can lead the researcher to misunderstandings, especially when the simulator will be regarded as valid.

OBJETIVOS: Describir una hoja de ruta de los hitos y consideraciones más representativos en la validación de simuladores quirúrgicos, especialmente los de cirugía laparoscópica. Y adicionalmente contribuir a determinar en qué momento de este proceso puede considerarse un simulador como validado.MÉTODOS: Se realizó una revisión no sistemática con los términos simulación, validación, formación, entrenamiento, evaluación, habilidades y curva de aprendizaje, además de aportar la experiencia acumulada por nuestro centro. RESULTADOS: Un proceso ideal clásico de validación debería constar de los siguientes pasos: Fidelidad, Verificación/ Calibración/Fiabilidad, estrategias subjetivas y objetivas. Las pruebas de inicio tanto de Fidelidad como de Verificación/Calibración/Fiabilidad tecnológica no siempre están descritas de manera explícita en los trabajos de validación de simuladores. Un simulador puede considerarse validado si al menos ha completado satisfactoriamente una validación de cualquiera de los dos grandes bloques de tipo objetivo, es decir, constructiva y/o de criterio. CONCLUSIONES: Los métodos que permiten validar simuladores como útiles y fiables para la mejora de habilidades de tipo psicomotor/técnico están ampliamente documentados aunque existe cierta variedad de enfoques en función de la referencia científica que se consulte, no aplicándose por igual en todos los trabajos. Esta aparente arbitrariedad debería ser conocida de antemano porque puede llevar al investigador a ciertos equívocos, especialmente a la hora de afirmar cuándo el simulador se considera plenamente validado.

[Evaluation of competencies in urology. Esscolap® basic, as aproximation to urologists skills improvement.] / Evaluación de competencias en Urología. Esscolap® basic, como aproximación a la mejora de las capacidades de los urólogos.

Urology needs models of competencies assessment, although there is a wide range of tools not yet integrated into the official training programs. CONTEXT: At present, there is no universal framework for measuring surgeons' level of competence. Urology training programs should provide and consider knowledge, pyschomotor/cognitive skills, and simulator, cadaver or animal models-based training. Validity is a complex concept that refers to the capacity of the evaluation tool, so it is necessary to demonstrate several types of validation to assure the capacity of a method, reinforced with different reliability tests and calculation of internal consistency between evaluators. OBJECTIVE: Based on a structured dossier of surgical skills, classified by groups, the ESSCOLAP® Basic system was proposed with 5 simulator tasks to evaluate basic laparoscopic skills. Once validated in the JUMISC (Spain), the tool was proposed to extend its scope and implementation in other locations. RESULTS: Our system has not yet demonstrated a full validity in the real clinical setting because a predictive validity needs to be demonstrated on the basis of clinical data. It also suffers from a certain range of subjectivity, thus implying clear and defined criteria for any situation. Factors like the number of evaluators and tasks to assess will influence the reliability tests that measure the degree of agreement between evaluators, so that a higher number of evaluated cases would imply a greater reliability of our system. Finally, we assume that the incorporation of this type of tools implies an added cost, charged to the public and private responsible institutions, which will only be considered cost-effective when it is demonstrated its real and positive traceability in health outcomes. CONCLUSIONS: ESSCOLAP® Basic, of quick and simple implementation capacity, has been validated and calibrated for the evaluation of basic technical skills in laparoscopy.

[Training in basic and advanced laparoscopy: Evaluation of a 30-year experience in a training program in Spain.] / Formación en cirugía laparoscópica urológica básica y avanzada: evaluación de 30 años de experiencia de un programa de formación en España.

The lack of globally established standards for learning urological laparoscopy has not prevented laparoscopic techniques from evolution and continuous development. Laparoscopy coexists with robotic surgery today, and in the last decade there have been many techniques that have undergone a boom with the use of a laparoscopic approach (total and partial nephrectomy, pyeloplasty, colposacropexy, etc.).We intend to evaluate the progressive incorporation of different surgical techniques in the laparoscopic learning program and, on the other hand, to analyze the evolution of training programs in urological laparoscopy to bring this type of techniques within the hospital surgical activity. We describe our 30-years experience in different training programs in urological laparoscopy that have been sponsored by the Spanish Association of Urology (AEU), and have undergone several validity studies to assess their capacity in order to evaluate effectively basic and advanced laparoscopic skills. We will also highlight the current and future trend towards training models based on surgical competences where individualized training, accreditation and specialization of tutors is crucial, and where the increase in the use of training and evaluation methods based on the simulation are increasingly common.

Discovery of VU0467485/AZ13713945: An M4 PAM Evaluated as a Preclinical Candidate for the Treatment of Schizophrenia.

Herein, we report the structure-activity relationships within a series of potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs). Compound 6c (VU0467485) possesses robust in vitro M4 PAM potency across species and in vivo efficacy in preclinical models of schizophrenia. Coupled with an attractive DMPK profile and suitable predicted human PK, 6c (VU0467485) was evaluated as a preclinical development candidate.

Outcomes of pediatric living donor kidney transplantation: A single-center experience.

Renal transplantation is the treatment of choice for children with ESRD offering advantages of improved survival, growth potential, cognitive development, and quality of life. The aim of our study was to compare the outcomes of LDKT vs DDKT performed in children at a single center. Retrospective chart review of pediatric patients who underwent kidney transplantation from 2005 to 2014 was performed. Ninety-one renal transplants were accomplished, and 31 cases (38.27%) were LDKT, and in 96.7% of the cases, the graft was obtained through laparoscopy. Thirty-four receptors weighted <25 kg. LDKT group had statistically significant lower cold ischemia times than DDKT one. Complication rate was 9.67% for LDKT and 18.33% for DDKT. eGFR was better in LDKT. Patient survival rate was 100% for LDKT and 98.3% for DDKT, and graft survival rate was 96.7% for LDKT and 88.33%-80% for DDKT at a year and 5 years. Our program of pediatric kidney transplantation has achieved optimal patient and graft survival rates with low rate of complications. Living donor pediatric kidney transplants have higher patient and better graft survival rates than deceased donor kidney transplants.

Laparoscopic Partial Nephrectomy With Potassium-titanyl-phosphate Laser Versus Conventional Laparoscopic Partial Nephrectomy: An Animal Randomized Controlled Trial.

OBJECTIVE: To explore the feasibility, safety, and short-term results of potassium-titanyl-phosphate (KTP) laser laparoscopic partial nephrectomy (KTP-LPN) vs conventional laparoscopic partial nephrectomy (C-LPN). MATERIALS AND METHODS: Thirty large white female pigs were randomized to KTP-LPN or C-LPN. Laparoscopic radical right nephrectomy was performed, and an artificial renal tumor was placed in the left kidney in 3 locations. A week later, 15 pigs underwent C-LPN and 15 underwent KTP-LPN. All C-LPNs were performed with renal ischemia. A 120-W setting was used, without arterial clamping in the KTP-LPN group. Follow-up was done at day 1, week 3, and week 6. Retrograde pyelography was performed at 6 weeks, followed by animal sacrifice and necropsy. RESULTS: All KTP-LPNs were performed without hilar clamping. C-LPNs were performed with hilar clamping, closing of the collecting system, and renorraphy. In the KTP laser group, 2 pigs died due to urinary fistula in the first week after surgery. In the C-LPN group, 1 pig died due to myocardial infarction and another due to malignant hyperthermia. Hemoglobin and hematocrit recovery were lower at 6 weeks in the KTP-LPN group. Renal function 24 hours after surgery was worse in the KTP-LPN group but recovered at 3 weeks and 6 weeks. No differences were observed in surgical margins. The necropsy showed no differences. Limitations of the study are the impossibility to analyze the collecting tissue sealing by the KTP, and the potential renal toxicity of the KTP laser. CONCLUSION: Although KTP-LPN is feasible and safe in the animal model, further studies are needed.

Synthesis and characterization of a series of chiral alkoxymethyl morpholine analogs as dopamine receptor 4 (D4R) antagonists.

Herein, we report the synthesis and structure-activity relationship of a series of chiral alkoxymethyl morpholine analogs. Our efforts have culminated in the identification of (S)-2-(((6-chloropyridin-2-yl)oxy)methyl)-4-((6-fluoro-1H-indol-3-yl)methyl)morpholine as a novel potent and selective dopamine D4 receptor antagonist with selectivity against the other dopamine receptors tested (<10% inhibition at 1µM against D1, D2L, D2S, D3, and D5).

Analysis of the therapeutic evolution in the management of airway infantile hemangioma.

AIM: To analyze the evolution in the management of airway infantile hemangioma (AIH) and to report the results from 3 pediatric tertiary care institutions. METHODS: A retrospective study of patients with diagnosis of AIH and treated in 3 pediatric tertiary care institutions from 1996 to 2014 was performed. RESULTS: Twenty-three patients with diagnosis of AIH were identified. Mean age at diagnosis was 6 mo (range, 1-27). Single therapy was indicated in 16 patients and 7 patients received combined therapy. Two therapeutic groups were identified: Group A included 14 patients who were treated with steroids, interferon, laser therapy and/or surgery; group B included 9 patients treated with oral propranolol. In group A, oral corticosteroids were used in 9 patients with a good response in 3 cases (no requiring other therapeutic option), the other patients required additional treatment options. Cushing syndrome was observed in 3 patients. One patient died of a fulminant sepsis. Open surgical excision and endoscopic therapy were performed in 11 patients (in 5 of them as a single treatment) with a response rate of 54.5%. Stridor persisted in 2 cases, and one patient died during the clinical course of bronchial aspiration. In group B, oral propranolol was used in 9 patients (in 8 of them as a single treatment) with a response rate of 100%, with an mean treatment duration of 7 mo (range, 5-10); complications were not observed. CONCLUSION: Our experience and the medical literature support the use of propranolol as a first line of treatment in AIH.

Discovery, characterization and biological evaluation of a novel (R)-4,4-difluoropiperidine scaffold as dopamine receptor 4 (D4R) antagonists.

Herein, we report the synthesis and structure-activity relationship of a novel series of (R)-4,4-difluoropiperidine core scaffold as dopamine receptor 4 (D4) antagonists. A series of compounds from this scaffold are highly potent against the D4 receptor and selective against the other dopamine receptors. In addition, we were able to confirm the active isomer as the (R)-enantiomer via an X-ray crystal structure.

Porcine Model In The Laparoscopic Liver Surgery Training.

The aim of the study was to evaluate the possibility to use live anesthetized pigs as a model for laparoscopic liver resection. During two days laparoscopy course two trainees were operating on two live animals performing exposure of the liver, Pringle manoeuver, division of liver ligaments, dissecting of the structures inside the hepatoduodenal ligament, dissection of the hepatic veins and left lateral liver sectionectomy. Exposure of the liver and Pringle manoeuver were performed correctly within 50 and 35 minutes. Left lateral sectionectomy has been performed correctly within 2 hours. The full dissection of the hepatoduodenal ligament and exposure of the hepatic veins were judged as insufficient by experienced laparoscopic tutors. There was one injury to the suprahepatic vena cava that was managed laparoscopically. The porcine model can be used as an advanced training for laparoscopic liver surgery.

Low temperature conditioning of garlic (Allium sativum L.) "seed" cloves induces alterations in sprouts proteome.

Low-temperature conditioning of garlic "seed" cloves substitutes the initial climatic requirements of the crop and accelerates the cycle. We have reported that "seed" bulbs from "Coreano" variety conditioned at 5°C for 5 weeks reduces growth and plant weight as well as the crop yields and increases the synthesis of phenolic compounds and anthocyanins. Therefore, this treatment suggests a cold stress. Plant acclimation to stress is associated with deep changes in proteome composition. Since proteins are directly involved in plant stress response, proteomics studies can significantly contribute to unravel the possible relationships between protein abundance and plant stress acclimation. The aim of this work was to study the changes in the protein profiles of garlic "seed" cloves subjected to conditioning at low-temperature using proteomics approach. Two sets of garlic bulbs were used, one set was stored at room temperature (23°C), and the other was conditioned at low temperature (5°C) for 5 weeks. Total soluble proteins were extracted from sprouts of cloves and separated by two-dimensional gel electrophoresis. Protein spots showing statistically significant changes in abundance were analyzed by LC-ESI-MS/MS and identified by database search analysis using the Mascot search engine. The results revealed that low-temperature conditioning of garlic "seed" cloves causes alterations in the accumulation of proteins involved in different physiological processes such as cellular growth, antioxidative/oxidative state, macromolecules transport, protein folding and transcription regulation process. The metabolic pathways affected include protein biosynthesis and quality control system, photosynthesis, photorespiration, energy production, and carbohydrate and nucleotide metabolism. These processes can work cooperatively to establish a new cellular homeostasis that might be related with the physiological and biochemical changes observed in previous studies.

Application of failure mode and effect analysis in laparoscopic colon surgery training.

AIM: To evaluate if application of failure mode and effect analysis (FMEA) to laparoscopy training can help surgeons acquire laparoscopy skills. METHODS: After preparing a FMEA matrix of laparoscopic sigmoidectomy, we have introduced it during three laparoscopy courses. Forty-eight surgeons, divided into 24 teams of two surgeons, have participated in three courses. During each course, every team has performed three laparoscopic sigmoidectomies in three experimental animals (1 OR session every day). Risk priority number (RPN) has been calculated for every surgery, and the results have been discussed at the end of each training day with all participants. RESULTS: We have observed a decline in the median RPN from 1339 during the first OR session through 62 during second OR session to reach 0 in the third OR session. Only two teams out of 24 were not able to reach a RPN of less than 300 during third OR session. When the type of failures were analysed, we have observed a shift from procedure-type failures to technical failures that depended on each participant technical abilities. CONCLUSION: Application of FMEA principles to laparoscopy training can help acquire non-technical skills necessary for safe laparoscopic surgery.

Identification of positive allosteric modulators VU0155094 (ML397) and VU0422288 (ML396) reveals new insights into the biology of metabotropic glutamate receptor 7.

Metabotropic glutamate receptor 7 (mGlu7) is a member of the group III mGlu receptors (mGlus), encompassed by mGlu4, mGlu6, mGlu7, and mGlu8. mGlu7 is highly expressed in the presynaptic active zones of both excitatory and inhibitory synapses, and activation of the receptor regulates the release of both glutamate and GABA. mGlu7 is thought to be a relevant therapeutic target for a number of neurological and psychiatric disorders, and polymorphisms in the GRM7 gene have been linked to autism, depression, ADHD, and schizophrenia. Here we report two new pan-group III mGlu positive allosteric modulators, VU0155094 and VU0422288, which show differential activity at the various group III mGlus. Additionally, both compounds show probe dependence when assessed in the presence of distinct orthosteric agonists. By pairing studies of these nonselective compounds with a synapse in the hippocampus that expresses only mGlu7, we have validated activity of these compounds in a native tissue setting. These studies provide proof-of-concept evidence that mGlu7 activity can be modulated by positive allosteric modulation, paving the way for future therapeutics development.

Comparison of single access devices during cut and suturing tasks on simulator.

BACKGROUND: Published comparisons of the different available laparoendoscopic single-site surgery (LESS) devices focused on its economic cost and technical aspects. With this study, we aimed to objectively compare the use of three different LESS access devices in controlled experimental tasks. MATERIALS AND METHODS: Twenty subjects participated in simulator trials. A cut and an intracorporeal suturing task were carried out. Three single access devices (SILS: SILS(TM) Port, GPN. GelPOINT Advanced Access Platform, and XCN: XCONE) were used according to a randomized nine-session schedule. Completion time was registered and performance objectively assessed with task-specific rating scales. Two blinded expert raters worked over video recordings of the hands-on sessions. RESULTS: Participants showed improvement with all devices on total cut completion times and significantly for SILS (P = 0.017). The GPN decreased its adapted Global Rating Scale score (P = 0.002) from the first (W1) to the last week (W9). On the suture task, XCN constituted the device with longer completion times compared with SILS (P < 0.001) and to GPN (P < 0.001). There was significant improvement in times from W1 to W9 with XCN (P < 0.001), SILS (P = 0.003), and GPN (P < 0.001). On average summative score, we observed significant improvement in performance with all devices from W1 to W9 (SILS: P = 0.003; GPN: P = 0.001; and XCN: P < 0.001). CONCLUSIONS: Although we advise surgeons to focus on the specific procedures and patient characteristics to select the most adequate access device to maintain procedural safety standards, single-use devices appear to confer an easier adaptation to LESS surgery.

Early postoperative complications of transvaginal access in minimally invasive sigmoid colon procedures.

OBJECTIVES: The aim of the study was to evaluate early (the first 30 days) postoperative complications after transvaginal resection of the sigmoid colon. MATERIAL AND METHODS: A total of 23 laparoscopy-assisted transvaginal resections of the sigmoid colon and 1 NOTES transvaginal sigmoid resection were performed in the course of 3 years. Postoperative complications were recorded in a prospective manner. RESULTS: In the group of 24 patients operated on using the transvaginal approach, 6 (25%) complications were recorded, including 3 urinary tract infections, 2 vaginal bleedings, and 1 abdominal trocar site hernia. CONCLUSION: Early postoperative complication rate after transvaginal resection of the sigmoid colon is relatively low and the clinical complications are not severe.