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.

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.

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.

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).

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.

Development and initial assessment of a training program for laparoscopic radical prostatectomy. First module: the urethrovesical anastomosis.

PURPOSE: We present our experience in the design and development of a training program in laparoscopic radical prostatectomy (LRP), and the validation of the first steps of the program by objective measurement of the attendants' skills improvement and subjective evaluation of its contents. MATERIALS AND METHODS: Our training model on LRP has a total duration of 42 hours, divided in two modules of 21 hours each, performed 1 month apart. Data included in the present study were obtained from the first module of our course. It begins with acquisition of basic knowledge in ergonomics and instrument concepts, after which the attendants develop essential laparoscopic dexterities through the performance of hands-on physical simulator tasks. During the second and third day, urologists performed urethrovesical anastomosis also in the physical simulator. Attendants' skills improvement was measured during the first module by registering surgical times and suturing quality of the anastomosis, the latter by means of a leak test. At the end of the training program, a subjective evaluation questionnaire on the different didactic and organizational aspects was handed out to the attendants. RESULTS: By comparing first and last anastomosis, we observed a significant decrease in surgical times (minutes) (T1 40.1±4.6 vs T6 24.01±3.34; P≤0.005) and an increase in intraluminal leak pressure (mm Hg) (T1 8.27±7.33 vs T6 21.09±6.72; P≤0.005). We obtained a highly positive score on all questions concerning the different topics and techniques included in the training program (≥9 points over 10). Regarding the attendants' self-assessment of acquired abilities, 78.3% considered themselves capacitated to perform the trained procedures on patients. CONCLUSIONS: Training obtained during the first module of our training model significantly decreased performance times for ex vivo urethrovesical anastomosis, simultaneously increasing its quality. In addition, validation of the training model was also demonstrated by the highly scored evaluation resulting from the attendants' assessment.

Ergonomic analysis of muscle activity in the forearm and back muscles during laparoscopic surgery: influence of previous experience and performed task.

PURPOSE: The first aim of this study is to analyze the muscle activity in back and forearm muscles in surgeons during laparoscopic dissection and suturing maneuvers. The second aim is to determine the influence of the surgeons' previous experience in laparoscopic surgery. METHODS: A total of 30 laparoscopic surgeons were divided in 3 groups: novice suturing, novice dissecting, and experts suturing. Electromyography data were collected from the trapezius, forearm flexors, and forearm extensors muscles, during the proposed tasks on physical simulator. RESULTS: Muscle activity was significantly lower in the expert group. Moreover, muscle activity in the trapezius was significantly higher during the completion of intracorporeal suturing when compared with that during dissection. CONCLUSIONS: Results obtained in this study show that the surgeons with a higher degree of laparoscopic experience exhibit a lower level of muscle activity when compared with the novice surgeons. Moreover, in accordance to our results, laparoscopic suturing involves a higher degree of muscle effort than during laparoscopic dissection.

[New technologies in partial nephrectomy]. / Nuevas tecnologías en la nefrectomía parcial.

OBJECTIVES: We aim to analyse the role of new technologies in management of small renal cancer. METHODS: We perform a non-systematic review of the literature in Medline, Cochrane Database of Systematic Reviews between period 2000-2012, using following mesh terms: partial nephrectomy, renal ablative technologies, and renal cancer. RESULTS: We don't review in this article ablative technologies such as cryotherapy, radiofrequency, as they are the subject of others manuscripts within this monographic issue. We focus on high intensity ultrasounds (HIFU) microwaves therapy, radiosurgery, laser and water jet dissection. CONCLUSIONS: New technologies in partial nephrectomy are under constant and vertiginous evolution. Although efficacy has been demonstrated in short term and isolated studies, more studies, better designed, with bigger sample size and longer follow up are needed.

Nuevas tecnologías en la nefrectomía parcial / New technologies in partial nephrectomy

OBJETIVO: Analizar el papel de las nuevas tecnologías en el manejo de los tumores renales. MÉTODOS: Se realizó una revisión no sistemática incluyendo las palabras clave nefrectomía parcial, técnicas ablativas renales, y cáncer renal en las bases de datos y fuentes de información tales como Medline, Cochrane Database of Systematic Reviews entre los periodos 2000 a 2012. RESULTADOS: No repasaremos en este artículo las técnicas ablativas para los tumores renales, tales como la crioablación, la ablación por radiofrecuencia (ARF), al ser objeto de otros artículos de este monográfico y nos centraremos en los ultrasonidos focalizados de alta intensidad (HIFU), la terapia con microondas (TM), la radiocirugía, las técnicas con láseres, y la hidrodisección. CONCLUSIONES: Las nuevas tecnologías en nefrectomía parcial tales como ultrasonidos focalizados de alta intensidad (HIFU), la terapia con microondas (TM), la radiocirugía, las técnicas con láseres, y la hidrodisección se encuentran actualmente en evolución constante y vertiginosa. Aunque han demostrado eficacia en estudios a corto plazo y aislados, se necesitan estudios mejor diseñados, con un tamaño muestral más elevado y un seguimiento más largo en el tiempo(AU)

OBJECTIVES: We aim to analyse the role of new technologies in management of small renal cancer. METHODS: We perform a non-systematic review of the literature in Medline, Cochrane Database of Systematic Reviews between period 2000-2012, using following mesh terms: partial nephrectomy, renal ablative technologies, and renal cancer. RESULTS: We don’t review in this article ablative technologies such as cryotherapy, radiofrequency, as they are the subject of others manuscripts within this monographic issue. We focus on high intensity ultrasounds (HIFU) microwaves therapy, radiosurgery, laser and water jet dissection. CONCLUSIONS: New technologies in partial nephrectomy are under constant and vertiginous evolution. Although efficacy has been demonstrated in short term and isolated studies, more studies, better designed, with bigger sample size and longer follow up are needed(AU)

Seasonal variations of biochemical, pigment, fatty acid, and sterol compositions in female Crassostrea corteziensis oysters in relation to the reproductive cycle.

Wild female Crassostrea corteziensis oyster (n=245) were analyzed over one year to understand the main ecophysiological events associated to gonad development. Different indicators (mainly biochemical) were analyzed to infer: i) utilization and accumulation of energy reserves (e.g. neutral lipids, carbohydrates, proteins; vitellogenin), ii) membrane components provided by the diet as essential nutrients and indicative of cell proliferation (e.g. highly unsaturated fatty acids linked to phospholipids, sterols), iii) indicators of food availability (chlorophyll a in water, pigments in tissues, specific fatty acids and sterols), iv) gonad development (e.g. gonad coverage area, vitellin). A PCA analysis was applied to 269 measured variables. The first PC (PC1) was composed of total carbohydrate and lipid concentration, percentage of esterified sterols, fatty acids specific of diatoms; 16:1n-7/16:0, 20:5n-3 in neutral lipids with positive loadings and non methylene-interrupted fatty acids (NMI) in neutral lipids with negative loadings. The second PC (PC2) was composed of 18:4n-3 in lipid reserves and the concentration of zeaxanthin, a pigment typical of cyanobacteria with positive loadings and the proportion of 20:4n-6 in polar lipids with negative loading. The third PC (PC3) was composed of gonad coverage area (GCA) and the concentration of vitellin. Variation in GCA confirms that gonad development began in April with an extended period of spawning and rematuration from April to November. The PCA further shows that a second period of minimal maturation from November to March corresponds to the accumulation of reserves (PC1) together with an initial high availability of food (PC2) at the beginning of this period. These two periods are in accordance with the classical periods of allocation of energy to reserves followed by gonad development reported for several mollusks.

Overcoming the recalcitrance for the conversion of kenaf pulp to glucose via microwave-assisted pre-treatment processes.

This study evaluates the pre-treatment of cellulose from kenaf plant to yield sugar precursors for the production of ethanol or butanol for use as biofuel additives. In order to convert the crystalline cellulosic form to the amorphous form that can undergo enzymatic hydrolysis of the glycosidic bond to yield sugars, kenaf pulp samples were subjected to two different pre-treatment processes. In the acid pre-treatment, the pulp samples were treated with 37.5% hydrochloric acid in the presence of FeCl(3) at 50 °C or 90 °C whereas in the alkaline method, the pulp samples were treated with 25% sodium hydroxide at room temperature and with 2% or 5% sodium hydroxide at 50 °C. Microwave-assisted NaOH-treatment of the cellulose was also investigated and demonstrated to be capable of producing high glucose yield without adverse environmental impact by circumventing the use of large amounts of concentrated acids i.e., 83-85% phosphoric acid employed in most digestion processes. The treated samples were digested with the cellulase enzyme from Trichoderma reesei. The amount of glucose produced was quantified using the Quantichrom(™) glucose bioassay for assessing the efficiency of glucose production for each of the treatment processes. The microwave-assisted alkaline pre-treatment processes conducted at 50 °C were found to be the most effective in the conversion of the crystalline cellulose to the amorphous form based on the significantly higher yields of sugar produced by enzymatic hydrolysis compared to the untreated sample.