Prospective study of diagnostic accuracy in the detection of high-grade prostate cancer in biopsy-naïve patients with clinical suspicion of prostate cancer who underwent the Select MDx test.

OBJECTIVES: This study aimed to externally validate the diagnostic accuracy of the Select MDx test for Significant prostate cancer (Sig PCa) (ISUP > 1), in a contemporaneous, prospective, multicenter cohort with a prostate-specific antigen (PSA) between 3 and 10 ng/ml and a non-suspicious digital rectal examination. METHODS AND PARTICIPANTS: For all enrolled patients, the Select Mdx test, the risk calculator ERSPC3 + DRE, and a prostatic magnetic resonance imaging (MRI) were carried out. Subsequently, a systematic 12-core trans-rectal biopsy and a targeted biopsy, in the case of a prostate imaging-reporting and data system (PIRADS) > 2 lesion (max three lesions), were performed. To assess the accuracy of the Select MDx test in the detection of clinically Sig PCa, the test sensitivity was evaluated. Secondary objectives were specificity, negative predictive value (NPV), positive predictive value (PPV), and area under the curve (AUC). A direct comparison with the ERSPC + DRE risk calculator and MRI were also performed. We also studied the predictive ability to diagnose Sig PCa from the combination of the Select MDx test with MRI using clinical decision-curve analysis. RESULTS: There were 163 patients enrolled after meeting the inclusion criteria and study protocol. The Select MDx test showed a sensitivity of 76.9% (95% CI, 63.2-87.5), 49.6% specificity (95% CI, 39.9-59.2), 82.09% (95% CI, 70.8-90.4) NPV, and 41.67% (95% CI, 31.7-52.2) PPV for the diagnosis of Sig PCa. COR analysis was also performed, which showed an AUC of 0.63 (95% CI, 0.56-0.71). There were no differences in the accuracy of Select MDx, ERSPC + DRE, or MRI. The combination of Select MDX + MRI showed the highest impact in the decision-curve analysis, with an NPV of 93%. CONCLUSION: Our study showed a worse performance for the SelectMdx test than previously reported, within a cohort of patients with a PSA 3-10 ng/ml and a normal DRE, with results similar to those from ERSPC + DRE RC and MRI, but with an improvement in the usual PSA pathway. A combination of the Select Mdx test and MRI could improve accuracy, but studies specifically evaluating this scenario with a cost-effective analysis are needed.

Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study.

PURPOSE: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover. METHODS: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed. RESULTS: With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance (P < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports. CONCLUSION: The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.

[Prostate cancer and COVID-19 pandemia: Current recommendations.] / Cáncer de próstata y la pandemia Covid-19. Recomendaciones ante una nueva realidad.

OBJECTIVE: The objective of this publicationis to provide recommendations in the management of prostate cancer (PC) in a new reality framework based on the presence of COVID-19 disease. MATERIAL AND METHODS: The document is based on the scarce evidence on SARS/Cov-2 and the experience of the authors in handling COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Catalonia, Madrid and the Valencian Community. RESULTS: The authors defined different priorities for the different clinical situations in PC. Emergency/urgency (life-threatening or urgent even in normal situation), highpriority/elective urgency (potentially dangerous if postponed for more than 1 month), intermediate/electivepriority (it is recommended not to delay more than 6 months), low priority/delayed (can be postponed more than 6 months). According to this classification, the working panel agreed on the distribution of the different diagnostic, therapeutic and follow-up scenarios for PC. The risk of severe morbidity as a result of SARS-CoV-2 infection may out weigh the risk of PC morbidity/mortalityin many men; therefore, in the short term it is unlikely that delays in diagnosis or treatment can led to worse cancer outcomes. CONCLUSIONS: The COVID-19 pandemic has resulted in a challenge for our health system, which raises several considerations in the treatment of patients with PC. The redistribution of surgical procedures according to the degrees of priority is essential during the period of the pandemic and the transition to the new normality. The change of the out-clinics with the adequate security measures for healthcare practitioners and patients, andt he development of a telemedicine program is highly recommended.

OBJETIVO: El objetivo de esta publicaciónes proporcionar recomendaciones en el manejo del cáncer de próstata (CP) en el marco de la nueva realidad que supone la presencia de la COVID-19.MATERIALES Y MÉTODOS: El documento se basa en la escasa evidencia sobre SARS/CoV-2 y la experiencia de los autores en el manejo de la COVID-19 en sus instituciones incluyendo especialistas de Andalucía, Cantabria, Cataluña, Madrid y Comunidad Valenciana. RESULTADOS: Los autores definieron diferentes prioridades para los distintos supuestos clínicos en CP. Emergencia/urgencia (riesgo vital o urgencia aún en situación de normalidad), alta prioridad/urgencia electiva (potencialmente peligrosa si se pospone más de 1mes), prioridad intermedia/electiva (se recomienda no retrasar más de 6 meses), baja prioridad/demorable (se puede posponer más de 6 meses). Acorde a esta clasificación, el grupo de trabajo consensuó la distribución de los diferentes escenarios diagnósticos, terapéuticos y de seguimiento del CP. El riesgo de morbilidad grave como resultado de la infección por SARS-CoV-2puede superar el riesgo de morbi-mortalidad por CP en muchos hombres; por lo tanto, a corto plazo es pocoprobable que los retrasos en el diagnóstico o tratamiento conduzcan a peores resultados oncológicos. CONCLUSIONES: La pandemia COVID-19 ha resultado en un desafío para nuestro sistema de salud, lo que plantea varias consideraciones en el tratamiento de pacientes con CP. La planificación de los procedimientos quirúrgicos en función de los grados de prioridades imprescindible durante el periodo de pandemia y transición a la nueva normalidad. La reorganización de las consultas incluyendo la adaptación a las medidas de seguridad para profesionales y pacientes y el desarrollo de un programa de telemedicina es altamente recomendable.

Cáncer de próstata y la pandemia Covid-19. Recomendaciones ante una nueva realidad / Prostate cancer and COVID-19 pandemia: Current recommendations

OBJETIVO: El objetivo de esta publicaciónes proporcionar recomendaciones en el manejo del cáncer de próstata (CP) en el marco de la nueva realidad que supone la presencia de la COVID-19. MATERIALES Y MÉTODOS: El documento se basa en la escasa evidencia sobre SARS/CoV-2 y la experiencia de los autores en el manejo de la COVID-19 en sus instituciones incluyendo especialistas de Andalucía, Cantabria, Cataluña, Madrid y Comunidad Valenciana. RESULTADOS: Los autores definieron diferentes prioridades para los distintos supuestos clínicos en CP. Emergencia/urgencia (riesgo vital o urgencia aún en situación de normalidad), alta prioridad/urgencia electiva (potencialmente peligrosa si se pospone más de 1mes), prioridad intermedia/electiva (se recomienda no retrasar más de 6 meses), baja prioridad/demorable (se puede posponer más de 6 meses). Acorde a esta clasificación, el grupo de trabajo consensuó la distribución de los diferentes escenarios diagnósticos, terapéuticos y de seguimiento del CP. El riesgo de morbilidad grave como resultado de la infección por SARS-CoV-2puede superar el riesgo de morbi-mortalidad por CP en muchos hombres; por lo tanto, a corto plazo es pocoprobable que los retrasos en el diagnóstico o tratamiento conduzcan a peores resultados oncológicos. CONCLUSIONES: La pandemia COVID-19 ha resultado en un desafío para nuestro sistema de salud, lo que plantea varias consideraciones en el tratamiento de pacientes con CP. La planificación de los procedimientos quirúrgicos en función de los grados de prioridades imprescindible durante el periodo de pandemia y transición a la nueva normalidad. La reorganización de las consultas incluyendo la adaptación a las medidas de seguridad para profesionales y pacientes y el desarrollo de un programa de telemedicina es altamente recomendable

OBJECTIVE: The objective of this publication is to provide recommendations in the management of prostate cancer (PC) in a new reality framework based on the presence of COVID-19 disease. MATERIAL AND METHODS: The document is based on the scarce evidence on SARS/Cov-2 and the experience of the authors in handling COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Catalonia, Madrid and the Valencian Community. RESULTS: The authors defined different priorities for the different clinical situations in PC. Emergency/urgency (life-threatening or urgent even in normal situation), high priority/elective urgency (potentially dangerous if postponed for more than 1 month), intermediate/elective priority (it is recommended not to delay more than 6 months), low priority/delayed (can be postponed more than 6 months). According to this classification, the working panel agreed on the distribution of the different diagnostic, therapeutic and follow-up scenarios for PC. The risk of severe morbidity as a result of SARS-CoV-2 infection may outweigh the risk of PC morbidity/mortality in many men; therefore, in the short term it is unlikely that delays in diagnosis or treatment can led to worse cancer outcomes. CONCLUSIONS: The COVID-19 pandemic has resulted in a challenge for our health system, which raises several considerations in the treatment of patients with PC. The redistribution of surgical procedures according to the degrees of priority is essential during the period of the pandemic and the transition to the new normality. The change of the out-clinics with the adequate security measures for healthcare practitioners and patients, and the development of a telemedicine program is highly recommended

Mechanical Behavior of Masonry Mortars Made with Recycled Mortar Aggregate.

Recycling is an important habit to avoid waste. This paper evaluates the performance of masonry mortar, elaborated by replacing natural sand with recycled fine aggregate (RFA) obtained from mortar. Five families of mixtures were prepared with different replacement proportions: 20%, 40%, 60%, and 100%. A 1:4 volumetric cement-to-aggregate ratio was used for all mixtures by experimentally adjusting the amount of water to achieve the same consistency of 175 ± 5 mm. The effects of the following procedures were analyzed: (1) the use of a deconstruction technique to collect the RFA, (2) pre-wetting of the aggregates, and (3) the use of a commercial plasticizer. Experimental results show that it is possible to use this type of recycled fine aggregate as a substitute for natural sand by up to 60% in the manufacture of masonry mortar without significantly affecting its properties.

Correction: Effect of curcuminoids and curcumin derivate products on thioredoxin-glutathione reductase from Taenia crassiceps cysticerci. Evidence suggesting a curcumin oxidation product as a suitable inhibitor.

[This corrects the article DOI: 10.1371/journal.pone.0220098.].

Effect of curcuminoids and curcumin derivate products on thioredoxin-glutathione reductase from Taenia crassiceps cysticerci. Evidence suggesting a curcumin oxidation product as a suitable inhibitor.

Curcuma is a traditional ingredient of some Eastern cuisines, and the spice is heralded for its antitumoral and antiparasitic properties. In this report, we examine the effect of the curcuminoides which include curcumin, demethoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC), as well as curcumin degradation products on thioredoxin glutathione reductase from Taenia crassiceps cysticerci Results revealed that both DMC and BDMC were inhibitors of TGR activity in the micromolar concentration range. By contrast, the inhibitory ability of curcumin was a time-dependent process. Kinetic and spectroscopical evidence suggests that an intermediary compound of curcumin oxidation, probably spiroepoxide, is responsible. Preincubation of curcumin in the presence of NADPH, but not glutathione disulfide (GSSG), resulted in the loss of its inhibitory ability, suggesting a reductive stabilizing effect. Similarly, preincubation of curcumin with sulfhydryl compounds fully protected the enzyme from inhibition. Degradation products were tested for their inhibitory potential, and 4-vinylguaiacol was the best inhibitor (IC50 = 12.9 µM), followed by feruloylmethane (IC50 = 122 µM), vanillin (IC50 = 127 µM), and ferulic aldehyde (IC50 = 180 µM). The acid derivatives ferulic acid (IC50 = 465 µM) and vanillic acid (IC50 = 657 µM) were poor inhibitors. On the other hand, results from docking analysis revealed a common binding site on the enzyme for all the compounds, albeit interacting with different amino acid residues. Dissociation constants obtained from the docking were in accord with the inhibitory efficiency of the curcumin degradation products.

Differential expression of disulfide reductase enzymes in a free-living platyhelminth (Dugesia dorotocephala).

A search of the disulfide reductase activities expressed in the adult stage of the free-living platyhelminth Dugesia dorotocephala was carried out. Using GSSG or DTNB as substrates, it was possible to obtain a purified fraction containing both GSSG and DTNB reductase activities. Through the purification procedure, both disulfide reductase activities were obtained in the same chromatographic peak. By mass spectrometry analysis of peptide fragments obtained after tryptic digestion of the purified fraction, the presence of glutathione reductase (GR), thioredoxin-glutathione reductase (TGR), and a putative thioredoxin reductase (TrxR) was detected. Using the gold compound auranofin to selectively inhibit the GSSG reductase activity of TGR, it was found that barely 5% of the total GR activity in the D. dorotocephala extract can be assigned to GR. Such strategy did allow us to determine the kinetic parameters for both GR and TGR. Although It was not possible to discriminate DTNB reductase activity due to TrxR from that of TGR, a chromatofocusing experiment with a D. dorotocephala extract resulted in the obtention of a minor protein fraction enriched in TrxR, strongly suggesting its presence as a functional protein. Thus, unlike its parasitic counterparts, in the free-living platyhelminth lineage the three disulfide reductases are present as functional proteins, albeit TGR is still the major disulfide reductase involved in the reduction of both Trx and GSSG. This fact suggests the development of TGR in parasitic flatworms was not linked to a parasitic mode of life.

Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials.

Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the site of injury and adjacent segments. It is considered harmful because of its potential to aggravate secondary injury, and to interfere with axonal regeneration; it might also lead to an unfavorable environment for intralesional implants. Removal of hemorrhagic necrosis has been attempted before with variable results. The invasive nature of these procedures carries the risk of exacerbating damage to the injured cord. The overall objective for this study was to test several strategies for non-damaging removal of hemorrhagic necrosis and characterize the resulting cavity looking for a space for future intralesional therapeutic implants in rats with acute cord injury. Rats were subjected to graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three grades of myelotomy (extensive, medium sized, and small) were tested. Using the small surgical approach to debridement, early and late effects of the intervention were determined by histology and by analytical and behavioral analysis. Appearance and capacity of the resulting cavity were characterized. Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical approaches to debridement. However, bleeding in spared cord tissue was excessive after medium sized and extensive myelotomies but similar to control injured rats after small cord surgery. Small surgical approach to debridement produced no swelling nor acute inflammation changes, nor did it affect long-term spontaneous locomotor recovery, but resulted in modest improvement of myelination in rats subjected to both moderate and severe injuries. Cavity created after intervention was filled with 10 to 15 µL of hydrogel. In conclusion, by small surgical approach to debridement, removal of hemorrhagic necrosis was achieved after acute cord contusion thereby creating intramedullary spaces without further damaging the injured spinal cord. Resulting cavities appear suitable for future intralesional placement of pro-reparative cells or other regenerative biomaterials in a clinically relevant model of spinal cord injury.

Respuesta completa a los inhibidores de la tirosin kinasa en cáncer renal metastásico. Aportacion de 4 casos / Complete response to tyrosine kinase inhibitors in metastatic renal cancer. Report of four cases

OBJETIVOS: Describir la las respuestas completas obtenidas en nuestros pacientes con cáncer renal metastásico tratados con inhibidores de la tirosin kinasa. MÉTODOS: Entre junio de 2007 y diciembre del 2014 hemos tratado en nuestro servicio a 43 pacientes de cáncer renal metastásico con tratamiento antiangiogénicos. RESULTADOS: Un 9,3% (4/43) de los pacientes tratados con antiangiogénicos obtuvieron respuesta completa según criterios RECIST 1.1. En 3 de los 4 pacientes, la respuesta completa se obtuvo durante el tratamiento de primera línea con sunitinib a dosis de 50 mgrs/dia en esquema 4/2 y en el paciente restante la obtuvo con axitinib en segunda línea a dosis de 10 mgrs/dia. CONCLUSIONES: Los inhibidores de la tirosin kinasa pueden inducir respuestas completas en los pacientes con cáncer renal metastásico. La discontinuación del tratamiento con los inhibidores de la tirosin kinasa después de una respuesta completa puede ser una opción

OBJECTIVE: To describe the complete responses in our patients with metastatic renal cancer treated with tyrosine kinase inhibitors. MATERIAL AND METHODS: Between June 2007 and December 2014 we treated in our department 43 patients with metastatic renal cancer with antiangiogenic drugs. RESULTS: 9.3% (4/43) of the patients treated with antiangiogenic drugs obtained complete response according to RECIST 1.1 criteria. In 3 of the 4 patients, complete response was obtained during the first-line treatment with sunitinib at doses of 50 mgr/day in a 4/2 scheme and the remaining patient obtained it with second line axitinib at doses of 10 mgr/day. CONCLUSIONS: Tyrosine kinase inhibitors can induce complete responses in patients with metastatic renal cancer. Discontinuation of treatment with tyrosine kinase inhibitors after a complete response may be an option

Productividad en las nuevas técnicas endourológicas / No disponible

No disponible

Reproducibility of percutaneous nephrolithotomy in the Galdakao-modified supine Valdivia position.

To demonstrate that percutaneous nephrolithotomy (PCNL) in the Galdakao-modified supine Valdivia position can be safely and effectively reproduced by different surgeons. A multicentre retrospective cross-sectional case study on 317 patients was conducted. The centres enrolled were four hospitals from the Spanish National Health System and provided data for consecutive PCNL from January 2008 to December 2010. The patients were divided into two groups: the Galdakao group (134; operated on by the master PCNL surgeon) and the other surgeons group (183; operated on by the other surgeons). The results of the technique were analysed relative to success and complications. Finally, a multivariate analysis introducing the covariates age, gender, BMI, ASA and type of stone was performed (backward stepwise logistic regression). The univariate analysis did not reveal differences in age, gender and ASA scores (p > 0.05) between the Galdakao group and the other surgeons group. The success rate was 80.6 % in the Galdakao group and 72.7 % in the other surgeons group (p = 0.01), and the complication rate was 16.4 and 26.2 %, respectively (p = 0.03). Complications were categorised based on the Clavien classification, and no differences were discovered between the groups (p = 0.19). The logistic regression confirmed only the surgeon and the stone type as independent predictive variables. PCNL in the Galdakao-modified supine Valdivia position is feasible for the use by different urologic surgeons. The results depend on the surgeon's experience, but with specific training and, maybe, selecting the simplest cases at the beginning, it is possible to achieve competitive results.

Transvaginal NOTES-assisted laparoscopic nephrectomy: a survival study in a sheep model.

BACKGROUND: This study aims to evaluate the feasibility and usefulness of an ovine model in order to perform natural orifice translumenal endoscopic surgery (NOTES) approach and laparoscopic nephrectomy for research and training purposes. METHODS: Ten healthy female sheep were used to perform transvaginal NOTES-assisted right laparoscopic nephrectomy using a flexible 12-mm gastroscope through a vaginal access and two additional 5- and 10-mm trocars placed in the abdomen. The renal artery, the renal vein, and the ureter were dissected, and ligation was accomplished by using laparoscopic clips. The right kidney was retrieved transvaginally after enlarging the vaginal trocar incision. All data related with the surgical procedure, perioperative, and postoperative outcomes were recorded. The animals were monitored after surgery for a 30-day period with daily clinical follow-up. RESULTS: We established a useful animal model of transvaginal NOTES-assisted laparoscopic nephrectomy, performing the transvaginal approach and the abdomen exploration with no complications in any animals. The renal artery, the renal vein, and the ureter were identified, clipped, and transected combining the 5-mm laparoscopic access and the endoscopic vision in the whole group. Mean operative time was 86 ± 14.49 min, estimated blood loss was less than 20 ml in all cases, and there was no bleeding or laceration of adjacent organs. The animals recovered successfully in all cases postoperatively. After 1 month, exploratory laparotomy did not show alterations in abdominal cavity, and the vaginotomy incision healed completely in every animal. CONCLUSIONS: This experiment shows that transvaginal NOTES-assisted laparoscopic nephrectomy in ovine model is feasible and reproducible while offering an innovative possibility to help surgeons with this recent technology in the treatment of renal cancer. Well-managed experimental studies need to be carried out to determine the safety and efficacy of NOTES in the treatment of renal cancer.

Neoplasia gástrica epitelial polipóide maligna / Malignant gastric elevated epithelial neoplasia

Foi realizada uma análise retrospectiva no Instituto Nacional de Câncer (INCa), no período de 1986 a 1990, dos portadores de lesäo gástrica epitelial polipóide maligna, diagnosticados por endoscopia. Essas lesöes foram classificadas ou como câncer precoce tipo I, ou como câncer avançado Bormann I. Foram selecionadas cinco casos dessas lesöes, de um total de 173 casos de câncer gástrico registrados no grupo de Estômago, e que foram tratados cirurgicamente. A intençäo da cirurgia foi radical, as margens cirúrgicas estavam livres de neoplasia, näo foi encontrada metástase à distância e näo houve morte pós-operatória. O adenocarcinoma foi o tipo histológico mais encontrado e o terço inferior do estômago a localizaçäo predominante. Nesses tumores observou-se maior sobrevida no de menor diâmetro e de melhor prognóstico quanto à classificaçäo morfopatológica, grau de diferenciaçäo histológica e estadiamento. Os resultados desse trabalho foram comparáveis foram comparáveis aos da literatura, sendo eficientes tanto a abordagem diagnóstica quanto o tratamento realizado no INCa