Impact on cerebral hemodynamics of the use of volume guarantee combined with high frequency oscillatory ventilation in a neonatal animal respiratory distress model.

High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. However, the possible impact of this new ventilation technique on cerebral hemodynamics is unknown. To evaluate the cerebral hemodynamics effect of HFOV combined with VG in an experimental animal model of neonatal respiratory distress syndrome (RDS) due to surfactant deficiency compared with HFOV and CMV+VG (control group). Eighteen newborn piglets were randomized, before and after the induction of RDS by bronchoalveolar lavage, into 3 mechanical ventilation groups: CMV, HFOV and HFOV with VG. Changes in cerebral oxygen transport and consumption and cerebral blood flow were analyzed by non-invasive regional cerebral oxygen saturation (CrSO2), jugular venous saturation (SjO2), the calculated cerebral oxygen extraction fraction (COEF), the calculated cerebral fractional tissue oxygen extraction (cFTOE) and direct measurement of carotid artery flow. To analyze the temporal evolution of these variables, a mixed-effects linear regression model was constructed. After randomization, the following statistically significant results were found in every group: a drop in carotid artery flow: at a rate of -1.7 mL/kg/min (95% CI: -2.5 to -0.81; p < 0.001), CrSO2: at a rate of -6.2% (95% CI: -7.9 to -4.4; p < 0.001) and SjO2: at a rate of -20% (95% CI: -26 to -15; p < 0.001), accompanied by an increase in COEF: at a rate of 20% (95% CI: 15 to 26; p < 0.001) and cFTOE: at a rate of 0.07 (95% CI: 0.05 to 0.08; p < 0.001) in all groups. No statistically significant differences were found between the HFOV groups. CONCLUSION: No differences were observed at cerebral hemodynamic between respiratory assistance in HFOV with and without VG, being the latter ventilatory strategy equally safe. WHAT IS KNOWN: • Preterm have a situation of fragility of cerebral perfusion wich means that any mechanical ventilation strategy can have a significant influence. High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. Several studies have compared CMV and HFOV and their effects at hemodynamic level. It is known that the use of high mean airway pressure in HFOV can cause an increase in pulmonary vascular resistance with a decrease in thoracic venous return. WHAT IS NEW: • The possible impact of VAFO + VG on cerebral hemodynamics is unknown. Due the lack of studies and the existing controversy, we have carried out this research project in an experimental animal model with the aim of evaluating the cerebral hemodynamic repercussion of the use of VG in HFOV compared to the classic strategy without VG.

Impact of catheterized ductal closure on renal and cerebral oximetry in premature neonates.

Percutaneous catheter-based closure is increasingly utilized in premature newborns. While near-infrared spectroscopy (NIRS) has been examined for assessment of interventional closure in surgical ligation, its application in percutaneous transcatheter closure remains unexplored. This study aims to assess cerebral and renal hemodynamic changes using NIRS during percutaneous closure compared to surgical closure in preterm infants. A prospective observational study enrolled preterm infants born at 32 weeks of gestation or less and diagnosed with hsPDA between January 2020 and December 2022. These infants received either surgical or catheter-based closure of the PDA. Cerebral and renal oxygen saturation was monitored using the INVOS 5100 device from 12 h before the intervention until 24 h after. Linear mixed-effects models were used to analyze time-dependent variables. Twenty-two patients were enrolled, with catheter-based closure performed in 16 cases and conventional surgery in 6 cases. Following ductal closure, a significant increase in renal and cerebral oximetry was observed alongside a decrease in renal and cerebral tissue oxygen extraction. These changes were particularly pronounced in the renal territory. No differences were detected between catheterization and surgical closure.   Conclusion: An improvement in cerebral and renal oximetry following hsPDA closure was observed. However, we did not identify differences in this pattern based on the type of interventional procedure for PDA, whether surgery or catheterization. What is Known: • The presence of a significant ductus is common in premature patients. Studies have shown that it affects cerebral and renal hemodynamics negatively, leading to decreased oximetry values in these areas. It has been reported that closure of the ductus, either pharmacologically or surgically, results in improved oximetry values. What is New: • This study assess the impact of percutaneous closure of ductus, revealing increased oximetry values in cerebral and renal territories without significant differences compared to surgical ligation. Notably, renal oximetry values showed a greater increase, underscoring the importance of multi-location monitoring.

Parent Perception of Child Safety following Admission to a Neonatal Unit.

OBJECTIVE: Parent partnership is a key aspect of neonatal hospital care. However, there is a lack of information regarding parents' perception of neonatal safety. This study explores parents' opinions on safety during their child's hospitalization to identify points for improvement. STUDY DESIGN: We used a questionnaire, validated by the Spanish National Healthcare Authorities, on perception of safety with respect to hospital health care. RESULTS: Thirty-seven parents of 20 newborns treated in the neonatal intensive care unit (NICU) and 139 parents of newborns in intermediate care (IC) participated in this study. With regard to overall perception of safety, more than 96% of parents felt "very safe" or "fairly safe." In the NICU, an area for improvement detected was to ask parents more often their opinion about the care or treatment provided to their child. In IC, three points for improvement were identified from the group of parents whose child was admitted directly to IC: the consistency of the information received, the request for consent for procedures, and the request for an opinion on their child's care and treatment. Only four parents reported that their child suffered an incident. Regarding incident management, parents were not completely satisfied with the information they received. CONCLUSION: To the best of our knowledge, this is the first study of parent perception of patient safety in a neonatal unit using a validated questionnaire. Our findings suggest that parents can provide valuable information on neonatal safety, which can then be used to identify areas for improvement. KEY POINTS: · There is a lack of information regarding parents' perception of neonatal safety.. · This study explores parent's opinion about safety of their child during the hospitalization.. · Our findings suggest that parents can provide valuable information to identify improvement areas..

Improved tibiofemoral contact restoration after transtibial reinsertion of the anterior root of the lateral meniscus compared to in situ repair: a biomechanical study.

PURPOSE: To compare biomechanical behaviour of the anterior root of the lateral meniscus (ARLM) after a transtibial repair (TTR) and after an in situ repair (ISR), discussing the reasons for the efficacy of the more advantageous technique. METHODS: Eight cadaveric human knees were tested at flexion angles from 0° to 90° in four conditions of their ARLM: intact, detached, reinserted using TTR, and reinserted using ISR. Specimens were subjected to 1000 N of compression, and the contact area (CA), mean pressure (MP), and peak pressure (PP) on the tibial cartilage were computed. For the TTR, traction force on the sutures was registered. RESULTS: ARLM detachment significantly altered contact biomechanics, mainly at shallow flexion. After ISR, differences compared to the healthy group persisted (extension, CA 22% smaller (p = 0.012); at 30°, CA 30% smaller (p = 0.012), MP 21%, and PP 32% higher (both p = 0.017); at 60°, CA 28% smaller (p = 0.012), MP 32%, and PP 49% higher (both p = 0.025). With TTR, alterations significantly decreased compared to the injured group, with no statistical differences from the intact ones observed, except for CA at extension (15% decrease, p = 0.012) and at 30° (12% decrease, p = 0.017). The suture tension after TTR, given as mean(SD), was 36.46(11.75)N, 44.32(11.71)N, 40.38(14.93)N, and 43.18(14.89)N for the four tested flexion angles. CONCLUSIONS: Alterations caused by ARLM detachment were partially restored with both ISR and TTR, with TTR showing better results on recovering CA, MP, and PP in the immediate postoperative period. The tensile force was far below the value reported to cause meniscal cut-out in porcine models.

Effect of a new respiratory care bundle on bronchopulmonary dysplasia in preterm neonates.

The development of devices that can fix the tidal volume in high-frequency oscillatory ventilation (HFOV) has allowed for a significant improvement in the management of HFOV. At our institution, this had led to the earlier use of HFOV and promoted a change in the treatment strategy involving the use of higher frequencies (above 15 Hz) and lower high-frequency tidal volumes (VThf). The purpose of this observational study was to assess how survival without bronchopulmonary dysplasia grades 2 and 3 (SF-BPD) is influenced by these modifications in the respiratory strategy applied to preterm infants (gestational age < 32 weeks at birth) who required mechanical ventilation (MV) in the first 3 days of life. We compared a baseline period (2012-2013) against a period in which this strategy had been fully implemented (2016-2017). A total of 182 patients were exposed to MV in the first 3 days of life being a higher proportion on HFOV at day 3 in the second period 79.5% (n 35) in 2016-2017 vs 55.4% (n 31) in 2012-2013. After adjusting for perinatal risk factors, the second period is associated with an increased rate of SF-BPD (OR 2.28; CI 95% 1.072-4.878); this effect is more evident in neonates born at a gestational age of less than 29 weeks (OR 4.87; 95% CI 1.9-12.48).Conclusions : The early use of HFOV combined with the use of higher frequencies and very low VT was associated with an increase in the study population's SF-BPD. What is Known: • High-frequency ventilation with volume guarantee improve ventilation stability and has been shown to reduce lung damage in animal models. What is New: • The strategy of an earlier use of high-frequency oscillatory ventilation combined with the use of higher frequencies and lower tidal volume is associated to an increase in survival without bronchopulmonary dysplasia in our population of preterm infants.

Electrical velocimetry for non-invasive monitoring of the closure of the ductus arteriosus in preterm infants.

Closure of a patent ductus arteriosus (PDA) in preterm infants modifies cardiac output and induces adaptive changes in the hemodynamic situation. The present study aims to analyze those changes, through a non-invasive cardiac output monitor based on blood electrical velocimetry, in preterm babies. A prospective observational study of preterm infants with a gestational age of less than 28 weeks, and a hemodynamic significant PDA, requires intravenous ibuprofen or surgical closure. All patients were monitored with electrical velocimetry before treatment and through the following 72 h. Two groups were defined, ibuprofen and surgical closure. Variations of cardiac output were analyzed from the basal situation and at 1, 8, 24, 48, and 72 h on each group. During a 12-month period, 18 patients were studied. The median gestational age in the ibuprofen group (12/18) was 26+5 weeks (25+5-27+3) with a median birth weight of 875 (670-1010) g. The cardiac output index (CI) value was 0.29 l/kg/min (0.24-0.34). Among the patients with confirmed ductus closure (50%), a significant CI decrease was shown (0.24 vs 0.29 l/kg/min; P 0.03) after 72 h (three ibuprofen doses). A statistically significant decrease in systolic volume (SVI) was found: 1.62 vs 1.88 ml/kg, P 0.03 with a decrease in contractility (ICON), 85 vs 140, P 0.02. The gestational age in the surgical group (6/18) was 25+2 weeks (24-26+3) with a median weight of 745 (660-820) g. All patients in this group showed a decrease in the immediate postoperative CI (1 h after surgery) 0.24 vs 0.30 l/kg/min, P 0.05, and a significant decrease in contractility (ICON 77 vs 147, P 0.03). In addition, a no statistically significant decrease in SVI (1.54 vs 1.83 ml/kg, P 0.06), as well as an increase in systemic vascular resistance (10,615 vs 8797 dyn/cm2, P 0.08), were detected. This deterioration was transient without significant differences in the remaining periods of time evaluated. CONCLUSION: The surgical closure of the PDA in preterm infants causes a transient deterioration of cardiac function linked to a documented decrease in the left ventricular output. The hemodynamic changes detected after pharmacological PDA closure are similar but those patients present a better clinical tolerance to changes in the cardiac output. What is Known: • Surgical ductus closure generates acute hemodynamic changes in cardiac output and left ventricular function. What is New: • The hemodynamic changes detected after pharmacological ductus closure are similar to those found in the surgical closure. Electrical velocimetry can detect those changes.

The role of suture cutout in the failure of meniscal root repair during the early post-operative period: a biomechanical study.

PURPOSE: To assess the role of suture cutout in the mechanics of failure of the repaired posterior meniscal root during the early post-operative period when using sutures of different shape. METHODS: Twenty medial porcine menisci were randomized in two groups depending on the suture shape used to repair the posterior root: thread or tape. The sutured menisci were subjected to cyclic loading (1000 cycles, (10, 30) N) followed by load-to-failure testing. Residual displacements, stiffness, and ultimate failure load were determined. During tests, the tissue-suture interface was recorded using a high-resolution camera. RESULTS: In cyclic tests, cutout progression at the suture insertion points was not observed for any specimen of either group and no differences in residual displacements were found between use of thread or tape. In load-to-failure tests, suture cutout started in all menisci at a load close to the ultimate failure and all specimens failed by suture pullout. Suture tape had a greater ultimate load with no other differences. CONCLUSIONS: In a porcine model of a repaired posterior meniscal root subjected to cyclic loads representative of current rehabilitation protocols in the early post-operative period under restricted loading conditions, suture cutout was not found as a main source of permanent root displacement when using suture thread or tape. Suture cutout progression started at high loading levels close to the ultimate load of the construct. Tape, with a meniscus-suture contact area larger than thread, produced higher ultimate load.

Use of denosumab in a dialysis patient with bone metastases from breast cancer and hepatorenal polycystic disease: a case report.

Cancer patients with severe renal dysfunction represent a challenge for the physician. This is the first case report on the use of denosumab in a dialysis patient with bone metastases. We present the clinical case of a 45-year-old woman who had hepatorenal polycystic disease, diagnosed during childhood, and stage IV chronic kidney failure at the time of breast cancer diagnosis. Three years after surgery plus adjuvant hormonal therapy she suffered a further worsening of renal function, requiring dialysis, and very advanced bone metastasis in the hip with severe pain. As pamidronate was the only bone agent available in the center, she received it for 4 months (before a dialysis session), during which time the bone metastases stabilized. In March 2014, the patient switched to denosumab (which had become available in the center), and continued with hormone therapy. Seven months after denosumab initiation, the patient had almost complete pain relief, and the bone metastases exhibited radiological improvement. The tolerability was excellent, without any related adverse event. There were no changes in albumin-adjusted serum calcium, serum phosphorus, and intact parathyroid hormone, except for a transient and mild hypocalcemia at 3 months and an increase in intact parathyroid hormone levels, which required adjustment of vitamin D analog dose. Denosumab can be administered to prevent skeletal-related events in patients with bone metastasis from solid tumors and severely impaired renal function, even in those requiring dialysis. In this particular patient, the safety was good.

Comparative Biomechanical Study on Contact Alterations After Lateral Meniscus Posterior Root Avulsion, Transosseous Reinsertion, and Total Meniscectomy.

PURPOSE: To compare the effects of lateral meniscus posterior root avulsion left in situ, its repair, and meniscectomy on contact pressure distribution in both tibiofemoral compartments at different flexion angles. METHODS: Eight cadaveric knees were tested under compressive 1000 N load for 4 lateral meniscus conditions (intact, posterior root avulsion, transosseous root repair, and total meniscectomy) at flexion angles 0°, 30°, 60°, and 90°. Contact area and pressure distribution were registered using K-scan pressure sensors inserted between menisci and tibial plateau. RESULTS: In the lateral compartment, root detachment decreased contact area (P = .017, 0° and 30°; P = .012, 60° and 90°) and increased mean (P = .012, all angles) and maximum (P = .025, 0° and 30°; P = .017, 60°; P = .012, 90°) pressures relative to intact condition. Repair restored all measured parameters close to intact at 0°, but effectiveness decreased with flexion angle, yielding no significant effect at 90°. Meniscectomy produced higher decreases than root avulsion in contact area (P = .012, 0° and 90°; P = .05, 30° and 60°) and increases in mean (P = .017, 0° and 30°; P = .018, 90°) and maximum pressure (P = .012, 0°; P = .036, 30°). In the medial compartment, lesion changed the contact area at high flexion angles only, while meniscectomy induced greater changes at all angles. CONCLUSIONS: Lateral meniscus posterior root avulsion generates significant alterations in contact area and pressures at lateral knee compartment for flexion angles between full extension and 90°. Meniscectomy causes greater disorders than the avulsion left in situ. Transosseous repair with a single suture restores these alterations to conditions close to intact at 0° and 30° but not at 60° and 90°. CLINICAL RELEVANCE: Altered contact mechanics after lateral meniscus posterior root avulsion might have degenerative consequences. Transosseous repair with one suture should be revised to effectively restore contact mechanics at high flexion angles.

Prognostic relevance of early AKI according to pRIFLE criteria in children undergoing cardiac surgery.

BACKGROUND: Acute renal injury increases risk of death after cardiac surgery. The objective of the study was to evaluate the ability of the pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) criteria to characterize the development of postoperative renal damage in children after cardiopulmonary bypass (CPB) and to evaluate the relationship between the severity of kidney injury and mortality, pediatric intensive care unit (PICU) length of stay, and the duration of mechanical ventilation (MV). METHODS: In this retrospective study including children undergoing CPB surgery during a 3-year period in the PICU of a tertiary hospital, demographic, clinical, surgery-related, and postoperative clinical data were collected. Kidney damage was assessed with pRIFLE criteria. RESULTS: Four hundred and nine patients were included. Early acute kidney injury (AKI) was found in 82 patients (achieving categories Risk 44; Injury 16; Failure 22). Early AKI was associated with younger age (P = 0.010), longer CPB, deep hypothermic circulatory arrest (DHCA) use, ICU stay >12 days, MV >4 days, and death (P < 0.001). Controlling the effect of age, CPB, DHCA use, previous cardiac surgeries, and Risk Adjustment in Congenital Heart Surgery Surgical Severity Score (RACHS-1), early AKI development proved to predict ICU stay >12 days [odds ratio (OR) 3.5; 95% confidence interval (CI) 1.9-6.5, P < 0.001)] and need of MV >4 days (OR 5.1; 95% CI 2.6-10.2, P < 0.001). CONCLUSIONS: Early AKI when evaluated with the pRIFLE criteria can predict prolonged ICU stay, need of prolonged MV, and mortality.

Giant cell carcinoma of the urinary bladder : Clinicopathologic analysis and oncological outcomes.

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60-90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50-90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

Predictive and prognostic biomarkers in urological tumours.

Advancements in cutting-edge molecular profiling techniques, such as next-generation sequencing and bioinformatic analytic tools, have allowed researchers to examine tumour biology in detail and stratify patients based on factors linked with clinical outcome and response to therapy. This manuscript highlights the most relevant prognostic and predictive biomarkers in kidney, bladder, prostate and testicular cancers with recognised impact in clinical practice. In bladder and prostate cancer, new genetic acquisitions concerning the biology of tumours have modified the therapeutic scenario and led to the approval of target directed therapies, increasing the quality of patient care. Thus, it has become of paramount importance to choose adequate molecular tests, i.e., FGFR screening for urothelial cancer and BRCA1-2 alterations for prostate cancer, to guide the treatment plan for patients. While no tissue or blood-based biomarkers are currently used in routine clinical practice for renal cell carcinoma and testicular cancers, the field is quickly expanding. In kidney tumours, gene expression signatures might be the key to identify patients who will respond better to immunotherapy or anti-angiogenic drugs. In testicular germ cell tumours, the use of microRNA has outperformed conventional serum biomarkers in the diagnosis of primary tumours, prediction of chemoresistance, follow-up monitoring, and relapse prediction.

Prediction of Clinically Significant Prostate Cancer by a Specific Collagen-related Transcriptome, Proteome, and Urinome Signature.

BACKGROUND AND OBJECTIVE: While collagen density has been associated with poor outcomes in various cancers, its role in prostate cancer (PCa) remains elusive. Our aim was to analyze collagen-related transcriptomic, proteomic, and urinome alterations in the context of detection of clinically significant PCa (csPCa, International Society of Urological Pathology [ISUP] grade group ≥2). METHODS: Comprehensive analyses for PCa transcriptome (n = 1393), proteome (n = 104), and urinome (n = 923) data sets focused on 55 collagen-related genes. Investigation of the cellular source of collagen-related transcripts via single-cell RNA sequencing was conducted. Statistical evaluations, clustering, and machine learning models were used for data analysis to identify csPCa signatures. KEY FINDINGS AND LIMITATIONS: Differential expression of 30 of 55 collagen-related genes and 34 proteins was confirmed in csPCa in comparison to benign prostate tissue or ISUP 1 cancer. A collagen-high cancer cluster exhibited distinct cellular and molecular characteristics, including fibroblast and endothelial cell infiltration, intense extracellular matrix turnover, and enhanced growth factor and inflammatory signaling. Robust collagen-based machine learning models were established to identify csPCa. The models outcompeted prostate-specific antigen (PSA) and age, showing comparable performance to multiparametric magnetic resonance imaging (mpMRI) in predicting csPCa. Of note, the urinome-based collagen model identified four of five csPCa cases among patients with Prostate Imaging-Reporting and Data System (PI-IRADS) 3 lesions, for which the presence of csPCa is considered equivocal. The retrospective character of the study is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Collagen-related transcriptome, proteome, and urinome signatures exhibited superior accuracy in detecting csPCa in comparison to PSA and age. The collagen signatures, especially in cases of ambiguous lesions on mpMRI, successfully identified csPCa and could potentially reduce unnecessary biopsies. The urinome-based collagen signature represents a promising liquid biopsy tool that requires prospective evaluation to improve the potential of this collagen-based approach to enhance diagnostic precision in PCa for risk stratification and guiding personalized interventions. PATIENT SUMMARY: In our study, collagen-related alterations in tissue, and urine were able to predict the presence of clinically significant prostate cancer at primary diagnosis.

Close-looped graft suturing improves mechanical properties of interference screw fixation in ACL reconstruction.

PURPOSE: In anterior cruciate ligament reconstruction with looped soft-tissue grafts, an interference screw is frequently used for tibial fixation. This study compared three alternatives thought to improve the initial mechanical properties of direct bioabsorbable interference screw fixation: suturing the graft to close the loop, adding a supplementary staple, or increasing the oversize of the screw diameter relative to the bone tunnel from 1 to 2 mm. METHODS: Twenty-eight porcine tibiae and porcine flexor digitorum profundus tendons were randomized into four testing groups: a base fixation using 10-mm-diameter screw with open-looped graft, base fixation supplemented by an extracortical staple, base fixation but closing the looped graft by suturing its ends, and base fixation but using an 11-mm screw. Graft and bone tunnel diameters were 9 mm in all specimens. Constructs were subjected to cyclic tensile load and finally pulled to failure to determine their structural properties. RESULTS: The main mode of failure in all groups was pull-out of tendon strands after slippage past the screw. The sutured graft group displayed significantly lower residual displacement (mean value reduction: 47-67 %) and higher yield load (mean value increase: 38-54 %) than any alternative tested. No other statistical differences were found. CONCLUSIONS: Suturing a soft-tissue graft to form a closed loop enhanced the initial mechanical properties of tibial fixation with a bioabsorbable interference screw in anterior cruciate ligament reconstructions using a porcine model, and thus, this may be an efficient means to help in reducing post-operative laxity and early clinical failure. No mechanical improvement was observed for an open-looped tendon graft by adding an extracortical staple to supplement the screw fixation or by increasing the oversize of the screw to tunnel diameter from 1 to 2 mm.

[Biobanking: the basis for molecular research in uro-oncology]. / Banco de tumores: la base para la investigación molecular en uro-oncología.

OBJECTIVES: The advances in cancer translational research, as well as the study of its changes and interactions, depend basically on the procurement of case series (individuals affected and non affected controls) which supply high quality samples and other associated data. Biobanks have shown they are indispensable tools for the advance of uro-oncological research. METHODS: Bibliographic review based on biobanks with focus on Urology. RESULTS AND CONCLUSIONS: Well-organized, large biobanks are a key element in research in Uro-oncology. The integration of theses resources with molecular sciences and various "omics", together with powerful available bioinformatic tools enable the advance in the knowledge of development of uro-oncological diseases, with strong implications at the time of very advanced therapeutic strategies. However,in Spain, these valuable collections of tissue material and biological fluids are usually not much in use, mainly due to fragmentation, low accessibility, lack of proper management strategies (such as lack of consensus about standard operative procedures), limited specific policies of use and distribution, as well as lack of a comprehensive base in which the research needs are reflected under interdisciplinar and multi-institutional focus. We must add the frequent ignorance of the high scientific potential of these institutions in the urological world. The development of the Spanish National Plan of Biobanks brings light for the better use of these materials by the uro-oncological community. We present a general view on the biobank topic, which may serve as a model for future debates about their use in uro-oncology. This approach is based in data from the literature and results of discussions in various international forums.

Pleomorphic giant cell carcinoma of the prostate: clinicopathologic analysis and oncological outcomes.

We report on the clinicopathologic features of 27 pleomorphic giant cell carcinoma (PGCC) cases of the prostate identified in 20 patients with an age range of 51 to 84 years (68 ± 9; median 71 years). Charlson comorbidity index ranged from 3 to 12. Serum PSA ranged from 4.30 to 662 ng/mL (median 13 ng/mL). On histologic examination, bizarre giant cells with pleomorphic nuclei characterized pleomorphic giant cell carcinoma of the prostate. PGCC component was present in 5% to 100%, with half of the patients presenting with ≥ 20%. Half of the patients initially presented with T4 and 26% with T3 disease. All patients were considered Gleason scores of 9 to 10 (ISUP grade 5). A combination of hormone therapy with chemotherapy with or without radiation therapy was applied in 68% of patients. On follow-up, 14 patients (52%) were alive with disease (1-69 months) or dead of disease (1-38 months). Patients diagnosed earlier with lower TNM stage had longer survival than those diagnosed at a later T-stage or with metastatic disease (p = 0.02). The percentage of PGCC was not related to survival in the current study. Molecular alterations in 3 samples showed a microsatellite-stable disease with low tumor mutation burden and variable PTEN, PTCH1, KDM6A, ARv7, and PIK3CA loss/alteration, TP53 mutation, TMPRSS2-ERG fusion, and MYC, PIK3CB, RICTOR, or IRS2 amplification. Our findings suggest that PGCC is a rare and aggressive subtype of prostate carcinoma whose recognition may steer clinicians to adopt more aggressive treatments and investigate new therapeutic strategies.

Clinical utility of checkpoint inhibitors against metastatic bladder cancer: overcoming challenges to find a way forward.

INTRODUCTION: Cisplatin-based chemotherapy is currently considered the gold-standard treatment for metastatic urothelial carcinoma (mUC). Nevertheless, most mUC patients develop resistance to chemotherapy. Immune checkpoint inhibitors (ICI) have emerged as a therapeutic option for mUC. ICI are used as both first- and second-line therapy for patients with mUC but also for maintenance following chemotherapy and durable responses may be expected in these settings. AREAS COVERED: Patients with mUC who experience progression after platinum-based chemotherapy regimens, those who are cisplatin-ineligible and have positive PD-L1 expression, and those who are platinum-ineligible, regardless of PD-L1 status, are the target population. The role of ICI monotherapy or drug combinations and newer proposals for mUC therapy are reviewed. The current status of biomarkers to guide ICI treatments in mUC is also provided, focusing on PD-L1, tumor mutational load, and liquid biopsies using ctDNA. EXPERT OPINION: Current challenges to improve the role of ICI in mUC could be summarized as i) development of better drugs; ii) advances in drug-combinations schemes; iii) development of novel biomarkers and techniques to better select patients for this treatment; iv) providing the drugs in the optimal clinical setting; v) promoting trials covering more demographic and clinical heterogeneity (i.e. wider age range, gender, and diverse clinical representation).

Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype.

This study evaluated a panel including the molecular taxonomy subtype and the expression of 27 genes as a diagnostic tool to stratify bladder cancer patients at risk of aggressive behavior, using a well-characterized series of non-muscle invasive bladder cancer (NMIBC) as well as muscle-invasive bladder cancer (MIBC). The study was conducted using the novel NanoString nCounter gene expression analysis. This technology allowed us to identify the molecular subtype and to analyze the gene expression of 27 bladder-cancer-related genes selected through a recent literature search. The differential gene expression was correlated with clinicopathological variables, such as the molecular subtypes (luminal, basal, null/double negative), histological subtype (conventional urothelial carcinoma, or carcinoma with variant histology), clinical subtype (NMIBC and MIBC), tumor stage category (Ta, T1, and T2-4), tumor grade, PD-L1 expression (high vs. low expression), and clinical risk categories (low, intermediate, high and very high). The multivariate analysis of the 19 genes significant for cancer-specific survival in our cohort study series identified TP53 (p = 0.0001), CCND1 (p = 0.0001), MKI67 (p < 0.0001), and molecular subtype (p = 0.005) as independent predictors. A scoring system based on the molecular subtype and the gene expression signature of TP53, CCND1, or MKI67 was used for risk assessment. A score ranging from 0 (best prognosis) to 7 (worst prognosis) was obtained and used to stratify our patients into two (low [score 0-2] vs. high [score 3-7], model A) or three (low [score 0-2] vs. intermediate [score 3-4] vs. high [score 5-7], model B) risk categories with different survival characteristics. Mean cancer-specific survival was longer (122 + 2.7 months) in low-risk than intermediate-risk (79.4 + 9.4 months) or high-risk (6.2 + 0.9 months) categories (p < 0.0001; model A); and was longer (122 + 2.7 months) in low-risk than high-risk (58 + 8.3 months) (p < 0.0001; model B). In conclusion, the molecular risk assessment model, as reported here, might be used better to select the appropriate management for patients with bladder cancer.

Age influence on resistance and deformation of the human sutured meniscal horn in the immediate postoperative period.

Introduction: To preserve knee function, surgical repair is indicated when a meniscal root disinsertion occurs. However, this surgery has not yet achieved complete recovery of the joint´s natural biomechanics, with the meniscus-suture interface identified as a potentially determining factor. Knowing the deformation and resistance behavior of the sutured meniscal horn and whether these properties are preserved as the patient ages could greatly contribute to improving repair outcomes. Methods: A cadaveric experimental study was conducted on human sutured menisci classified into three n = 22 age groups (young ≤55; 55 < middle-aged ≤75; 75 < old) were subjected to load-to-failure test by suture pulling. Meniscal thickness at the suture hole was measured and the applied traction force and tissue deformation in the suture area in the direction of traction were recorded during the test. The traction load that initiated the meniscal cut-out, Fc, maximum load borne by the meniscus, Fu, tissue stress at the cut-out initiation, Sc, and equivalent stiffness modulus at the suture area, ms, were calculated. Results: At the tissue level, the resistance in terms of Sc decrease with age (young: 47.2 MPa; middle-aged: 44.7 MPa; old: 33.8 MPa) being significantly different between the young and the old group (p = 0.015). Mean meniscal thickness increased with age (young: 2.50 mm; middle-aged: 2.92 mm; old: 3.38 mm; p = 0.001). Probably due to thickening, no differences in resistance were found at the specimen level, i.e., in Fc (overall mean 58.2 N) and Fu (overall mean 73.6 N). As for elasticity, ms was lower in the old group than in the young group (57.5 MPa vs. 113.6 MPa, p = 0.02) and the middle-aged one (57.5 MPa vs. 108.0 MPa, p = 0.04). Conclusion: Regarding the influence of age on the sutured meniscal horn tissue, in vitro experimentation revealed that meniscal horn specimens older than 75 years old had a more elastic tissue which was less resistant to cut-out than younger menisci at the suture hole area. However, a thickening of the meniscal horns with age, which was also found, leveled out the difference in the force that initiated the tear, as well as in the maximum force borne by the meniscus in the load-to-failure test.

The Proportion of Meniscus Tears Considered Repairable, and Thus Repaired, Increased During a Single Surgeon's Practice of 20 Years.

Purpose: The purpose of this study was to evaluate practice patterns of a single surgeon with respect to meniscectomy and meniscal repair over a 20-year period at a single institution. Methods: A cross-sectional descriptive study was carried out by reviewing the surgical data from the past 20 years (2002-2021) of patients who underwent arthroscopic primary meniscal surgery. Age, sex, knee and meniscus affected, morphology of the meniscal tear, meniscal radial location, location on the axial plane, tissue quality, and associated injuries were recorded. An analysis of the evolution of the characteristics of the meniscal lesions was performed according to the presence of degenerative tissue, the repairability of the lesion, and the treatment performed. Categorical data were represented in contingency tables and compared using the χ2 test for significance of differences, which was set at P < .05. Results: In total, 1,892 cases were included. A decrease in degenerative meniscal tears was found, from 63.2 in 2002 to 2006 to 9.7% in 2017 to 2021 (P < .001), while repairable tears increased from 1.6% to 82.3% P < .001); in the same periods, arthroscopic partial meniscectomy procedures declined from 75.7% to 17.7% (P < .001) while meniscal repair increased from 0.4% to 81.3% (P < .001). All types of tears increased significantly their repairability, although longitudinal tears, root tears, and ramp lesions showed the highest possibilities for repair. Conclusions: In the present study, a drastic change in the attitude toward meniscal preservation in the past 20 years was observed, with a large increase in the proportion of tears considered repairable found in primary arthroscopic surgery (to 80% of cases) and a decrease in degenerative meniscus tears (to less than 10%). Clinical Relevance: In the past 2 decades, arthroscopic knee surgery has evolved such that more meniscus tears are deemed repairable, and fewer tears considered degenerative are indicated for arthroscopy.