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.

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.

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.

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.

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.

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.

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.

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..

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.

Lung recruitment in neonatal high-frequency oscillatory ventilation with volume-guarantee.

BACKGROUND AND OBJECTIVES: The optimal lung volume strategy during high-frequency oscillatory ventilation (HFOV) is reached by performing recruitment maneuvers, usually guided by the response in oxygenation. In animal models, secondary spontaneous change in oscillation pressure amplitude (ΔPhf) associated with a progressive increase in mean airway pressure during HFOV combined with volume guarantee (HFOV-VG) identifies optimal lung recruitment. The aim of this study was to describe recruitment maneuvers in HFOV-VG and analyze whether changes in ΔPhf might be an early predictor for lung recruitment in newborn infants with severe respiratory failure. DESIGN AND METHODS: The prospective observational study was done in a tertiary-level neonatology department. Changes in ΔPhf were analyzed during standardized lung recruitment after initiating early rescue HFOV-VG in preterm infants with severe respiratory failure. RESULTS: Twenty-seven patients were included, with a median gestational age of 24 weeks (interquartile range [IQR]: 23-25). Recruitment maneuvers were performed, median baseline mean airway pressure (mPaw) was 11 cm H2 O (IQR: 10-13), median critical lung opening mPaw during recruitment was 14 cm H2 O (IRQ: 12-16), and median optimal mPaw was 12 cm H2 O (IQR: 10-14, p < 0.01). Recruitment maneuvers were associated with an improvement in oxygenation (FiO2 : 65.0 vs. 45.0, p < 0.01, SpO2/FiO2 ratio: 117 vs. 217, p < 0.01). ΔPhf decreased significantly after lung recruitment (mean amplitude: 23.0 vs. 16.0, p < 0.01). CONCLUSION: In preterm infants with severe respiratory failure, the lung recruitment process can be effectively guided by ΔPhf on HFOV-VG.

Influence of Loading Conditions on the Mechanical Performance of Multifilament Coreless UHMWPE Sutures Used in Orthopaedic Surgery.

This work studies the influence of loading velocity and previous cyclic loading history on the stiffness and strength of a multifilament coreless ultra-high-molecular-weight polyethylene (UHMWPE) surgical suture. Thread samples (n = 8) were subjected to a load-to-failure test at 0.1, 0.5, 1, 5, and 10 mm/s without previous loading history and after 10 cycles of loading at 1-10 N, 1-30 N, and 1-50 N. The experimental data were fitted to mathematical models to compute the stress-strain relation and the strength of the suture. The bilinear model involving two stress-strain ratios for low- and high-strain intervals was the best fit. The ratio in the low-strain range rose with loading speed, showing mean increases of 5.9%, 6.5%, 7.9%, and 7.3% between successive loading speeds. Without a previous loading history, this ratio was less than half than that at high strain. However, 10 cycles of 1-30 N or 1-50 N significantly increased the stress-strain ratio at a low strain level by 135% and 228%, respectively. The effect persisted after 2 min but vanished after 24 h. No influence was found on the suture strength. In conclusion, the stiffness of the studied suture was influenced by the strain level, loading velocity, and recent cyclic loading history. Conversely, the suture strength was not affected.

Biomechanical consequences of anterior root detachment of the lateral meniscus and its reinsertion.

Treatment of posterior meniscal roots tears evolved after biomechanical evidence of increased pressures on the tibiofemoral cartilage produced by this lesion and the subsequent accelerated development of arthritis or osteonecrosis observed clinically. However, little is known about the consequences of the detachment of the anterior roots. This in-vitro study analyzes the biomechanical changes in the tibiofemoral joint caused by avulsion of the anterior root of the lateral meniscus. The effectiveness of surgical root re-insertion to restore the pre-injured conditions is also evaluated. Using cadaveric knees at flexion angles from 0° to 90°, results show that the lesion significantly reduces the contact area and raises the pressure on the tibiofemoral cartilage of the injured compartment at all angles. Said modifications become larger at low flexion angles, which are the most frequent positions adopted by the knee in daily and sports activities, where they result similar to total meniscectomy. In-situ repair partially restores the contact biomechanics. Consequently, careful attention should be paid to proper diagnosis and treatment of detached anterior roots since the observed altered knee contact might induce similar degenerative problems in the cartilage as with completely detached posterior roots.

T1 bladder carcinoma with variant histology: pathological features and clinical significance.

The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed. The endpoint of the study was disease-free survival and cancer-specific survival. Overall, variant histology was identified as a significant predictor of disease-free survival (P = 0.035). The presence of any specific variant histology (squamous, glandular, micropapillary, nested, microcystic, inverted growth, villous-like, basaloid, and lymphoepithelioma-like) was identified as a significant predictor of disease-free survival (P = 0.008) and cancer-specific survival (P = 0.0001) in HGT1 bladder cancer. Therefore, our results support including micropapillary HGT1 urothelial carcinoma within the aggressive high-risk category, as suggested by some recent clinical guidelines, but also favor nested, glandular, and basaloid to be placed in the high-risk category due to their potential of aggressive, life-threatening behavior and their limited response to bacillus Calmette-Guerin therapy. Conversely, the low-risk category would include urothelial carcinomas with squamous, inverted growth, or microcystic morphology, all with limited life-threatening potential and good response to current therapy. A very low-risk category would finally include patients whose tumors present villous-like or lymphoepithelioma-like morphology. In conclusion, our findings support the value of reporting the variant histology as a feature of variable aggressiveness in HGT1 urothelial carcinoma of the bladder.

Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis.

Molecular classification of bladder carcinoma is a relevant topic in modern bladder cancer oncology due to its potential to improve oncological outcomes. The available molecular classifications are generally based on transcriptomic profiles, generating highly diverse categories with limited correlation. Implementation of molecular classification in practice is typically limited due to the high complexity of the required technology, the elevated costs, and the limited availability of this technology worldwide. We have conducted a gene expression analysis using a four-gene panel related to luminal and basal subtypes in a series of 91 bladder cancer cases. NanoString-based gene expression analysis using typically luminal (GATA3+/KRT20+) and basal markers (KRT14+/KRT5+/GATA3low/-/KRT20low/-) classified urothelial bladder carcinoma samples as luminal, basal, and a third category (KRT14-/KRT5-/GATA3-/KRT20-), null/double negative (non-luminal/non-basal). These three categories were meaningful in terms of overall cancer-specific survival (p < 0.0001) or when classified as conventional urothelial carcinoma and variant histology urothelial carcinoma (p < 0.0001), NMIBC vs. MIBC (p < 0.001), or by AJCC stage category Ta (p = 0.0012) and T1 (p < 0.0001) but did not reach significance in T2-T4 (p = 0.563). PD-L1 expression (low vs. high) was also different according to molecular subtype, with high PD-L1 expression mostly seen in basal and null subtypes and carcinomas with variant histology (p = 0.002). Additionally, the luminal subtype was enriched in NMIBC with favorable cancer-specific survival (p < 0.0001). In contrast, basal and null subtypes resulted in aggressive MIBC tumors with shorter cancer-specific survival (p < 0.0001), some of which presented variant histology. In conclusion, a comprehensive evaluation of a gene classifier related to molecular taxonomy using NanoString technology is feasible. Therefore, it might represent an accessible and affordable tool in this rapidly expanding area of precision genomics.

Does Adding Standard Systematic Biopsy to Targeted Prostate Biopsy in PI-RADS 3 to 5 Lesions Enhance the Detection of Clinically Significant Prostate Cancer? Should All Patients with PI-RADS 3 Undergo Targeted Biopsy?

INTRODUCTION: Our aim was to assess the value of adding standard biopsy to targeted biopsy in cases of suspicious multiparametric magnetic resonance imaging (mp-MRI) and also to evaluate when a biopsy of a PI-RADS 3 lesion could be avoided. METHODS: A retrospective study of patients who underwent targeted biopsy plus standard systematic biopsy between 2016-2019 was performed. All the 1.5 T magnetic resonance images were evaluated according to PI-RADSv.2. An analysis focusing on the clinical scenario, lesion location, and PI-RADS score was performed. RESULTS: A total of 483 biopsies were evaluated. The mean age was 65 years, with a PSA density of 0.12 ng/mL/cc. One-hundred and two mp-MRIs were categorized as PI-RADS-3. Standard biopsy was most helpful in detecting clinically significant prostate cancer (csPCa) in patients in the active surveillance (AS) cohort (increasing the detection rate 12.2%), and in peripheral lesions (6.5%). Adding standard biopsy showed no increase in the detection rate for csPCa in patients with PI-RADS-5 lesions. Considering targeted biopsy in patients with PI-RADS 3 lesions, a higher detection rate was shown in biopsy-naïve patients versus AS and in patients with a previous negative biopsy (p = 0.002). Furthermore, in these patients, the highest rate of csPCa detection was in anterior lesions [42.9% (p = 0.067)]. CONCLUSIONS: Our results suggest that standard biopsy could be safely omitted in patients with anterior lesions and in those with PI-RADS-5 lesions. Targeted biopsy for PI-RADS-3 lesions would be less effective in peripheral lesions with a previous negative biopsy.

Target volume-guarantee in high-frequency oscillatory ventilation for preterm respiratory distress syndrome: Low volumes and high frequencies lead to adequate ventilation.

BACKGROUND AND OBJECTIVES: Respiratory distress syndrome (RDS) and ventilation-induced lung injury lead to significant morbidity in preterm infants. High-frequency oscillatory ventilation with volume-guarantee (HFOV-VG) has been used as a rescue therapy and might lead to lower rates of death and bronchopulmonary dysplasia, especially when using low tidal volumes and high frequencies. The aim of the study was to define HFOV-VG parameters leading to adequate ventilation in the first 72 h of preterm RDS using a low volume and high-frequency strategy. DESIGN AND METHODS: Retrospective cohort study in a tertiary-level neonatology unit. Infants <32 weeks with severe respiratory insufficiency needing HFOV-VG were included. Patients were ventilated following a standard mechanical ventilation aiming for low tidal volumes and high frequencies. Clinical data, perinatal characteristics and high-frequency parameters corresponding with adequate ventilation were recorded. RESULTS: 116 patients were included. Median gestational age was 25 weeks (interquartile range [IQR] = 24-27), median birth weight 724 g (IQR = 600-900 g). HFOV-VG was started at 2 h, median high-frequency tidal volume was 1.63 ml/kg (IQR = 1.44-1.84) and median frequency was 16 Hz (IQR = 15-18). Weight-adjusted tidal volumes did not depend on gestational age, antenatal corticosteroids nor chorioamnionitis, and were inversely correlated with frequencies (R 2 = -0.10, p = .001). CONCLUSION: HFOV-VG can reach adequate ventilation at high frequencies when using adequate volumes, providing a feasible ventilation strategy that might be of help in preterm infants with RDS.

Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer.

A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.

New indicators for optimal lung recruitment during high frequency oscillator ventilation.

Previous research has demonstrated the potential benefit derived from the combination of high frequency oscillatory ventilation and volume guarantee mode (HFOV-VG), a procedure that allows us to explore and control very low tidal volumes. We hypothesized that secondary spontaneous change in oscillation pressure amplitude (∆Phf), while increasing the mean airway pressure (MAP) using HFOV-VG can target the lung recruitment. METHODS: A two-step animal distress model study was designed; in the first-step (ex vivo model), the animal's lungs were isolated to visually check lung recruitment and, in the second one (in vivo model), they were checked through arterial oxygen partial pressure improvement. Baseline measurements were performed, ventilation was set for 10 min and followed by bronchoalveolar lavage with isotonic saline to induce depletion of surfactant and thereby achieve a low compliance lung model. The high-frequency tidal volume and frequency remained constant and the MAP was increased by 2 cmH2 O (ex vivo) and 3 cmH2 O steps (in vivo) every 2 min. Changes in ΔPhf to achieve the fixed volume were recorded at the end of each interval to describe the maximum drop point as the recruitment point. RESULTS: Fourteen Wistar Han rats were included, seven on each sub-study described. After gradual MAP increments, a progressive decrease in ΔPhf related to recruited lung regions was visually demonstrated. In the in vivo model we detected a significant comparative decrease of ΔPhf, when measured against the previous value, after reaching a MAP of 11 cmH2 O up to 17 cmH2 O, correlating with a significant improvement in oxygenation. CONCLUSION: The changes in ∆Phf, linked to a progressive increase in MAP during HFOV-VG, might identify optimal lung recruitment and could potentially be used as an additional lung recruitment marker.

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.