Predicting individual outcomes after radical cystectomy in urothelial variants with Cancer of the Bladder Risk Assessment (COBRA) score.

OBJECTIVE: To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants. METHODS: Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes. RESULTS: A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66 years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77 months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8 months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14 months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93). CONCLUSIONS: In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy.

Adsorption of Carbon Dioxide and Nitrogen in Co3(ndc)3(dabco) Metal-Organic Framework.

Metal-organic frameworks (MOFs) are promising materials for processes such as carbon dioxide (CO2) capture or its storage. In this work, the adsorption of CO2 and nitrogen (N2) in Co3(ndc)3(dabco) MOF (ndc: 2,6-naphthalenedicarboxylate; dabco: 1,4-diazabicyclo[2.2.2]octane) is reported for the first time over the temperature range of 273-323 K and up to 35 bar. The adsorption isotherms are successfully described using the Langmuir isotherm model. The heats of adsorption for CO2 and N2, determined through the Clausius-Clapeyron equation, are 20-27 kJ/mol and 10-11 kJ/mol, respectively. The impact of using pressure and/or temperature swings on the CO2 working capacity is evaluated. If a flue gas with 15% CO2 is fed at 6 bar and 303 K and regenerated at 1 bar and 373 K, 1.58 moles of CO2 can be captured per kg of MOF. The analysis of the multicomponent adsorption of typical flue gas streams (15% CO2 balanced with N2), using the ideal adsorbed solution theory (IAST), shows that at 1 bar and 303 K, the CO2/N2 selectivity is 11.5. In summary, this work reports essential data for the design of adsorption-based processes for CO2 capture using a Co3(ndc)3(dabco) MOF, such as pressure swing adsorption (PSA).

Neurovascular and hemodynamic responses to mental stress and exercise in severe COVID-19 survivors.

Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.

Visual authoring of virtual reality conversational scenarios for e-learning.

The COVID-19 pandemic has led to face-to-face activities being developed in a virtual format that often offers a poor experience in areas such as education. Virtual Learning Environments have improved in recent years thanks to new technologies such as Virtual Reality or Chatbots. However, creating Virtual Learning Environments requires advanced programming knowledge, so this work is aimed to enable teachers to create these new environments easily. This work presents a set of extensions for App Inventor that facilitate the authoring of mobile learning apps that use Chatbots in a Virtual Reality environment, while simultaneously monitoring of student activity. This proposal is based on integrating block-based languages and Business Process Model and Notation diagrams. The developed extensions were successfully implemented in an educational app called Let's date!. A quantitative analysis of the use of these extensions in App Inventor was also carried out, resulting in a significant reduction in the number of blocks required. The proposed contribution has demonstrated its validity in creating virtual learning environments through visual programming and modelling, reducing development complexity.

Structure and thermodynamics of empty clathrate hydrates below the freezing point of water.

Recently prepared as a new H2O phase, ice XVI was obtained by degassing a Ne-sII clathrate hydrate under vacuum, however very little is known of that crystalline solid under temperatures (T ≤ 220 K) and pressures (p ≤ 5000 bar) relevant for the Earth's environment and geochemistry. In this work, atomically detailed calculations using long time-scale molecular simulations, seldom paralelled before, are employed to probe empty sII clathrate hydrates. It is found that the volumetric response to an applied pressure-temperature gradient is accurately described by the Parsafar and Mason equation of state with an accuracy of at least 99.7%. Structural deformation induced upon the crystals is interpreted by monitoring the unit cell length and isobaric thermal expansivity, whilst benchmarked against previous neutron diffraction measurements of ice XVI and hexagonal ice under room pressure conditions; a critical comparison is established with other sII guest occupied lattices (CH4, CO2 and CnH2n+2 with n = 2, 3, 4), often found in permafrost regions and in the margins of continental shelves. Such an analysis reveals that empty sII frameworks are slightly more stable to thermal deformation than their sI analogues and that hexagonal ice is the structurally most stable of the condensed H2O phases addressed here. Of paramount importance for the oil and natural gas industries, heat capacities obtained from enthalpy profiles are identical for the sI and sII empty clathrates up to 2000 bar and diverge by only ∼7.3% at 5000 bar. The canonical tetrahedral symmetry of water-bonded networks is analysed in terms of an angular and a distance order parameters, which are observed to decrease (increase) as pressure (temperature) increases (decreases). The results now being reported constitute a landmark for future studies dealing with high-pressure and very low-temperature conditions, characteristic of the Earth's permafrost environment and other planetary interiors, whilst contributing to expand our knowledge regarding the recently discovered ice XVI phase.

Resilience Perception of a Mining Town in Eastern Amazonia: A Case Study of Canaã Dos Carajás, Brazil.

The ability of communities to react to risks and disturbances is for their balance, development, and sustainability. The concept of resilience provides a way to think about policies and actions for future changes in socioeconomic and ecological-environmental systems. This paper analyzes, in the context of mining, the perception of the resilience of Canaã dos Carajás population in Pará State, Brazilian Amazon. The methodology involved face-to-face interviews based on a structured questionnaire conducted on a sample of 140 residents stratified from 11 social actors in the Canaã community. This approach allowed the evaluation of resilience perception using 26 interview statements derived from six resilience theories. Our multivariate analysis found that the level of residents' perception of resilience was reasonable (with an average score of 3.04 ± 0.22 using a Likert scale, with a Cronbach's alpha of 0.788). The interviewees pointed out one positive and five negative factors that influenced the level of resilience in Canaã. According to residents' perceptions, the resilience of Canaã dos Carajás was moderate but could have been improved with more economic diversification, more infrastructure, and less inequality in access to services and participation in decision-making. The considered most relevant themes were problems caused by mining in the municipality, quality of life issues, difficulties dealing with change after the arrival of mining, and economic problems. This study contributes to the literature because it used theories as a conceptual orientation for the development of a resilience scale to measure resilience at the community level in the context of large-scale mining.

Block-Based Development of Mobile Learning Experiences for the Internet of Things.

The Internet of Things enables experts of given domains to create smart user experiences for interacting with the environment. However, development of such experiences requires strong programming skills, which are challenging to develop for non-technical users. This paper presents several extensions to the block-based programming language used in App Inventor to make the creation of mobile apps for smart learning experiences less challenging. Such apps are used to process and graphically represent data streams from sensors by applying map-reduce operations. A workshop with students without previous experience with Internet of Things (IoT) and mobile app programming was conducted to evaluate the propositions. As a result, students were able to create small IoT apps that ingest, process and visually represent data in a simpler form as using App Inventor's standard features. Besides, an experimental study was carried out in a mobile app development course with academics of diverse disciplines. Results showed it was faster and easier for novice programmers to develop the proposed app using new stream processing blocks.

Biomethane production through anaerobic co-digestion with Maize Cob Waste based on a biorefinery concept: A review.

Maize Cob Waste (MCW) is available worldwide in high amounts, as maize is the most produced cereal in the world. MCW is generally left in the crop fields, but due to its low biodegradability it has a negligible impact in soil fertility. Moreover, MCW can be used as substrate to balance the C/N ratio during the Anaerobic co-Digestion (AcoD) with other biodegradable substrates, and is an excellent precursor for the production of Activated Carbons (ACs). In this context, a biorefinery is theoretically discussed in the present review, based on the idea that MCW, after proper pre-treatment is valorised as precursor of ACs and as co-substrate in AcoD for biomethane generation. This paper provides an overview on different scientific and technological aspects that can be involved in the development of the proposed biorefinery; the major topics considered in this work are the following ones: (i) the most suitable pre-treatments of MCW prior to AcoD; (ii) AcoD process with regard to the critical parameters resulting from MCW pre-treatments; (iii) production of ACs using MCW as precursor, with the aim to use these ACs in biogas conditioning (H2S removal) and upgrading (biomethane production), and (iv) an overview on biogas upgrading technologies.

The Rising Incidence of Younger Patients With Colorectal Cancer: Questions About Screening, Biology, and Treatment.

OPINION STATEMENT: Colorectal cancer (CRC) is the third leading cancer diagnosed globally and an important cause of cancer-related mortality. Of interest, while we have witnessed a declining incidence trend over the past few decades in the older population, incidence rates for adolescents and young adults have been increasing steadily. Several factors may well explain this apparent epidemic in the young, namely a lack of routine screening and emerging lifestyle issues such as obesity, lack of exercise, and dietary factors. It is known that both environmental and genetic factors can increase the likelihood of developing CRC. Although inherited susceptibility is associated with the most striking increases in risk, and must always be considered in a young patient with CRC, the majority of CRCs are in fact sporadic rather than familial. Early-onset CRC is a truly heterogeneous disease, with mounting evidence to suggest that this patient population has a distinctive molecular profile, very different to late-onset CRC cases. Currently, both younger and older patients with CRC are treated in essentially the same manner, but with a better understanding of the molecular mechanisms underlying CRC in the young, we will have the opportunity to specifically tailor screening and clinical management strategies in this unique patient population in an effort to improve outcomes. The aim of this review is to outline our current knowledge of the distinguishing features of early-onset CRC, the ongoing research efforts, and the evolving evidence in this field.

Three decades of reference evapotranspiration estimates for a tropical watershed in the eastern Amazon.

This study estimated the reference evapotranspiration rate (ETo) for the Itacaiúnas River Watershed (IRW), Eastern Amazonia, and measured the accuracy of eight empirical equations: Penman-Monteith (PM), Priestley-Taylor (PT), Hargreaves and Samani (HS), Camargo (CAM), Thornthwaite (TH), Hamon (HM), Kharrufa (KF) and Turc (TC) using monthly data from 1980 to 2013. In addition, it verifies the regional applicability to the IRW using a for the Marabá-PA station. The methods TC and PM (FAO56) presented the best results, which demonstrate that radiation and higher temperatures are the dominant drivers in the Evapotranspiration process, while relative humidity and wind speed have a much smaller impact. The temporal and spatial variability of ETo for IRW show has strong seasonality, increasing during the dry season and decreasing during the rainy season. The statistical analyses at 1% level of significance, indicates that there is no correlation of the residuals between the dry and rainy seasons, and test of the physical parameters such as mean temperature, solar radiation and relative air humidity explains the variations of ETo.

Target Inhibition of IL-1 Receptor Prevents Ifosfamide Induced Hemorrhagic Cystitis in Mice.

PURPOSE: Hemorrhagic cystitis is an important dose limiting side effect of ifosfamide based cancer chemotherapy. Despite chemoprophylaxis inflammation can still be found in cystoscopy guided biopsies. Previous studies confirmed the role of TNF-α and IL-1ß. We evaluated the protective effect of the IL-1R antagonist anakinra and the anti-TNF-α antibody infliximab in experimental ifosfamide induced hemorrhagic cystitis. MATERIALS AND METHODS: Hemorrhagic cystitis was induced by an injection of ifosfamide (400 mg/kg intraperitoneally) in Swiss wild-type C57Bl/6, IL-1R-/-, TNFR1-/- or TNFR1/R2-/- mice. Mice were treated 30 minutes before ifosfamide with anakinra (100 mg/kg intraperitoneally), infliximab (5 mg/kg intraperitoneally) or vehicle. Visceral nociception was evaluated after hemorrhagic cystitis induction. At 12 hours the animals were sacrificed. Bladders were harvested to assess bladder wet weight, vascular permeability, macroscopic and microscopic findings, muscle contractility, and for cystometrography. Inflammatory cell infiltration was assessed by myeloperoxidase assay and flow cytometry. RESULTS: Anakinra attenuated hemorrhage, edema, neutrophil infiltration, visceral hyperalgesia and bladder dysfunction. IL-1R-/- mice also showed milder hemorrhagic cystitis. Infliximab inhibited bladder edema and visceral hyperalgesia without preventing hemorrhage, bladder dysfunction, neutrophils or accumulation. Additionally, the lack of TNFR1 decreased bladder edema but not cell infiltration whereas concomitant deficiency of TNFR1 and TNFR2 resulted in worse hemorrhagic cystitis. CONCLUSIONS: Anakinra is effective for preventing experimentally ifosfamide induced hemorrhagic cystitis. It seems that neutrophil and macrophage infiltration in this circumstance depends on IL-1 signaling through IL1R. Possibly TNFR2 has a protective role in hemorrhagic cystitis.

Improved virus purification processes for vaccines and gene therapy.

The downstream processing of virus particles for vaccination or gene therapy is becoming a critical bottleneck as upstream titers keep improving. Moreover, the growing pressure to develop cost-efficient processes has brought forward new downstream trains. This review aims at analyzing the state-of-the-art in viral downstream purification processes, encompassing the classical unit operations and their recent developments. Emphasis is given to novel strategies for process intensification, such as continuous or semi-continuous systems based on multicolumn technology, opening up process efficiency. Process understanding in the light of the pharmaceutical quality by design (QbD) initiative is also discussed. Finally, an outlook of the upcoming breakthrough technologies is presented.

Endohedral confinement of a DNA dodecamer onto pristine carbon nanotubes and the stability of the canonical B form.

Although carbon nanotubes are potential candidates for DNA encapsulation and subsequent delivery of biological payloads to living cells, the thermodynamical spontaneity of DNA encapsulation under physiological conditions is still a matter of debate. Using enhanced sampling techniques, we show for the first time that, given a sufficiently large carbon nanotube, the confinement of a double-stranded DNA segment, 5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3', is thermodynamically favourable under physiological environments (134 mM, 310 K, 1 bar), leading to DNA-nanotube hybrids with lower free energy than the unconfined biomolecule. A diameter threshold of 3 nm is established below which encapsulation is inhibited. The confined DNA segment maintains its translational mobility and exhibits the main geometrical features of the canonical B form. To accommodate itself within the nanopore, the DNA's end-to-end length increases from 3.85 nm up to approximately 4.1 nm, due to a ~0.3 nm elastic expansion of the strand termini. The canonical Watson-Crick H-bond network is essentially conserved throughout encapsulation, showing that the contact between the DNA segment and the hydrophobic carbon walls results in minor rearrangements of the nucleotides H-bonding. The results obtained here are paramount to the usage of carbon nanotubes as encapsulation media for next generation drug delivery technologies.

Honing the Hunt: A Comprehensive Review of Cell-free Tumor DNA to Predict Neoadjuvant Therapy Efficacy in Bladder Cancer.

OBJECTIVE: To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer. METHODS: A systematic review was conducted from September 2023 to October 2023. Selected studies from the MEDLINE and clinical trial databases were critically analyzed regarding the clinical efficacy of cell-free DNA as a predictive instrument after neoadjuvant therapy in bladder cancer. The methodological quality assessment was based on the QUADAS-2 tool. RESULTS: In this systematic review, we analyzed 5 studies encompassing a cumulative patient cohort of 780 individuals diagnosed with muscle-invasive bladder cancer, with a median follow-up ranging from 6 to 23 months. Among these studies, 4 primarily focused on detecting and analyzing circulating tumor DNA in plasma, while 1 study uniquely utilized cell-free tumor DNA in urine samples. The diagnostic accuracy of cell-free DNA in plasma ranges from 79% to 100%, indicating a variable yet significant predictive capability. In contrast, the study utilizing urinary cell-free DNA demonstrated an accuracy of 81% in predicting treatment response post-neoadjuvant chemotherapy. CONCLUSION: Cell-free DNA is emerging as a valuable biomarker for predicting response to neoadjuvant chemotherapy in patients with muscle-invasive bladder tumors.

Robotic-assisted approaches to urachal carcinoma: A comprehensive systematic review of the safety and efficacy outcomes.

Introduction: Surgical intervention is the treatment of choice in patients with urachal carcinoma. Due to complications and to reduce hospital stay from open surgery, minimally invasive approaches are desirable. Nowadays, robotic-assisted surgery has become increasingly popular, and robot-assisted cystectomy can be performed in patients with urachal carcinoma with low complication rates. Methods: We performed a systematic review to search for studies that evaluated patients who underwent robotic-assisted surgery for urachal carcinoma. The outcomes of interest were the type of cystectomy performed, whether there was umbilicus resection, total operative time, console time, intraoperative complications, estimated blood loss, postoperative complications, time of hospitalisation, positive surgical margins and the presence of documented tumour recurrence. Results: In this study, we evaluated three cohorts comprising a total of 21 patients. The median follow-up period ranged from 8 to 40 months. Medium age was between 51 and 54 years, with a majority (63.1%) being male. One patient (5.2%) underwent a radical cystectomy, and 19 patients (94.7%) underwent to partial cystectomy. Umbilical resections were performed in all cases, and pelvic lymphadenectomy in 14 cases (73.6%). Recurrence occurred in three patients at a median of 17 months postoperation, two cases in the trocar insertion site. Additionally, there was one death, which was attributed to postoperative cardiovascular complications. Conclusion: Robotic-assisted partial cystectomy has a low incidence of adverse outcomes in patients with urachal carcinoma. Controlled studies, ideally randomised, are warranted to establish the comparative efficacy and safety of the robotic-assisted cystectomy approach relative to open surgery.

Scoring system for prediction of overall survival in patients with renal cell carcinoma T3aN0M0.

Objective: We aim to create a new score to predict postoperative overall survival in patients with nonmetastatic T3aN0 renal cell carcinoma. Methods: We reviewed the clinical data of adult patients who underwent radical nephrectomy for renal cell carcinoma between December 2007 and January 2022 in a single tertiary oncological institution. Clinical characteristics, clinical-pathological staging and histopathological characteristics were analysed. Survival analyses were determined using the Kaplan-Meier curve. A nomogram was established using Cox proportional hazard regression to identify the prognostic factors affecting the overall survival. The area under the curve, calibration curves and decision curve analysis were used to evaluate prognostic efficacy. Results: We analyzed 362 patients classified as pT3aN0M0 stage with a median follow-up of 40 months. According to Cox univariate and multivariate analyses, weight loss greater than 5% in 6 months before surgery, stage V chronic kidney disease after radical nephrectomy, sarcomatoid pattern, and coagulative tumor necrosis were identified as predictors of overall survival. We developed a score and performed internal and external validation. The time-dependent receiver operating characteristic curve, area under the curve value and calibration curve analysis showed good prediction ability of the score. The nomogram can effectively predict and stratify overall survival after radical nephrectomy in patients with pT3aN0M0 renal cell carcinoma. Conclusion: Patients with pT3aN0MO renal cell carcinoma exhibited different characteristics, and those with unfavourable characteristics deserve greater attention during follow-up. This nomogram provides an accurate prediction of overall survival after radical nephrectomy.

High Dose Chemotherapy With Autologous Stem Cell Transplant for Patients With Advanced Germ Cell Tumors: Real-World Evidence From a Tertiary Cancer Center in Brazil.

BACKGROUND: High-dose chemotherapy followed by stem cell transplant (HDCT) is potentially curative for patients with refractory germ cell tumors (rGCT). There is scarce real-world data supporting its implementation in low- and middle-income countries. We described the experience of our tertiary cancer center in Sao Paulo, Brazil. METHODS: We identified male patients ≥18 years-old with rGCT referred to HDCT after board discussion. Clinical data, including delays in HDCT protocol, were extracted from medical records, and survival outcomes were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazard were used to determine effects on overall survival (OS). RESULTS: From January 2013 to January 2023, 34 patients were referred and considered eligible to receive 2 cycles of HDCT. Most patients had primary testicular tumors (82%), nonseminomatous histology (88%), and poor International Germ Cell Collaborative Group (IGCCCG) (79%). Twenty-three patients received HDCT (1 cycle, n = 8; 2 cycles, n = 15). Main reasons for not receiving any HDCT were death due to progressive disease (n = 1), performance deterioration (n = 7), and failure of stem cell mobilization (n = 3). OS at 2 years was 36.7% for the eligible population, 56.1% for patients who underwent at least 1 HDCT, and 77.1% for those who had ≥2 cycles. The 2-year OS rate for patients not given HDCT was 0%. All patients had delays in protocol, and poor-risk patients had longer intervals from referral to protocol initiation (0.7 vs. 1.8 month, P < .01). CONCLUSION: Outcomes of patients who received ≥1 HDCT were encouraging; however, only 15 from 34 eligible patients were able to receive the planned 2 cycles of HDCT. Further strategies to minimize treatment delays in low- and middle-income countries are needed.

Artificial intelligence for predicting response to neoadjuvant chemotherapy for bladder cancer A comprehensive systematic review and meta-analysis.

INTRODUCTION: Neoadjuvant cisplatin-based combination chemotherapy (NAC) followed by radical cystectomy is the standard of care for cisplatin-fit patients harboring muscle-invasive bladder cancer (MIBC). Prediction of response to NAC is essential for clinical decision-making regarding alternatives in case of non-response, and bladder-sparing in case of complete response. This research aimed to assess the performance of machine learning in predicting therapeutic response following NAC treatment in patients with MIBC. METHODS: A systematic review adhering to the PRISMA guidelines was conducted until July 2023. The study integrated articles relating to artificial intelligence and NAC response in MIBC from various databases. The quality of articles was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 (QUADAS-2). A meta-analysis was subsequently performed on selected studies to determine the sensitivity and specificity of machine learning algorithms in predicting NAC response. RESULTS: Of 655 articles identified, 12 studies comprising 1523 patients were included, and four studies were eligible for meta-analysis. The sensitivity and specificity of the studies were 0.62 (95% confidence interval [CI] 0.50-0.72) and 0.82 (95% CI 0.72-0.89), respectively, with a heterogeneity score (I2) of 38.5%. The machine learning algorithms used computed tomography, genetic, and anatomopathologic data as input and exhibited promising potential for predicting NAC response. CONCLUSIONS: Machine-learning algorithms, especially those using computed tomography, genetic, and pathologic data, demonstrate significant potential for predicting NAC response in MIBC. Standardization of methodologic data analysis and response criteria are needed as validation studies.

Surviving the Storm: Challenges of Bladder Cancer Care During the COVID-19 Pandemic.

PURPOSE: To evaluate the impact of the COVID-19 pandemic on the care of patients with bladder cancer in a tertiary oncology center. MATERIALS AND METHOD: We performed a retrospective analysis of patients admitted to a tertiary cancer center for the treatment of bladder cancer between 2019 and 2022. Surgical volumes, patient demographics, clinical characteristics, and postoperative outcomes were compared across these years. RESULTS: A total of 463 patients with bladder cancer were admitted in the period, and 78 patients underwent radical cystectomy . The distribution of TMN stages between admitted patients remained consistent across the years, with no statistically significant differences. Patients who underwent RC in 2020 presented more advanced disease at surgery (pT3/pT4 stage) (P = .045; 95% CI, 0.18-0.55) and had a longer hospital stay compared to other years (P = .024; 95% CI, 10.26-41.27). CONCLUSIONS: The COVID-19 pandemic posed significant challenges for the treatment of patients with bladder cancer. These results highlight the need to adapt health systems to unforeseen challenges, emphasizing the clinical impact on patients with advanced stages of the disease and the repercussions on their overall survival.

Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4.

BACKGROUND: 5-Fluorouracil (5-FU) induces intestinal mucositis, which is characterized by epithelial ulcerations in the mucosa and clinical manifestations, such as pain and dyspeptic symptoms. Cytokines participate in the inflammatory and functional events of intestinal mucositis. IL-4 is an important mediator of intestinal inflammation, with either anti-inflammatory or pro-inflammatory functions, depending on the model of intestinal inflammation. This study aimed to evaluate the role of IL-4 in 5-FU-induced intestinal mucositis. METHODS: IL-4+/+ or IL-4-/- mice (25-30 g) were intraperitoneally injected with 5-FU (450 mg/Kg) or saline (C). After 3 days, the mice were sacrificed and the duodenum was evaluated for epithelial damage, MPO activity and cytokine concentration. RESULTS: 5-FU induced significant damage in the intestinal epithelium of IL-4+/+ mice (reduction in the villus/crypt ratio: control=3.31±0.21 µm, 5-FU=0.99±0.10 µm). However, the same treatment did not induce significant damage in IL-4-/- mice (5-FU=2.87±0.19 µm) compared to wild-type mice. 5-FU-induced epithelial damage increased the MPO activity (neutrophil number) and the level of pro-inflammatory cytokines (IL-4, TNF-α, IL-1ß and CXCL-8) in the duodenum. These results were not observed in IL-4-/- mice treated with 5-FU. CONCLUSION: Our data suggest that IL-4 participates as a pro-inflammatory cytokine in a 5-FU-induced intestinal damage model and suggests that IL-4 antagonists may be novel therapeutics for this condition.