Comparisons of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy, in third-line or later relapsed/refractory large B-cell lymphoma.

Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.

Development and benchmarking of a Deep Learning-based MRI-guided gross tumor segmentation algorithm for Radiomics analyses in extremity soft tissue sarcomas.

BACKGROUND: Volume of interest (VOI) segmentation is a crucial step for Radiomics analyses and radiotherapy (RT) treatment planning. Because it can be time-consuming and subject to inter-observer variability, we developed and tested a Deep Learning-based automatic segmentation (DLBAS) algorithm to reproducibly predict the primary gross tumor as VOI for Radiomics analyses in extremity soft tissue sarcomas (STS). METHODS: A DLBAS algorithm was trained on a cohort of 157 patients and externally tested on an independent cohort of 87 patients using contrast-enhanced MRI. Manual tumor delineations by a radiation oncologist served as ground truths (GTs). A benchmark study with 20 cases from the test cohort compared the DLBAS predictions against manual VOI segmentations of two residents (ERs) and clinical delineations of two radiation oncologists (ROs). The ROs rated DLBAS predictions regarding their direct applicability. RESULTS: The DLBAS achieved a median dice similarity coefficient (DSC) of 0.88 against the GTs in the entire test cohort (interquartile range (IQR): 0.11) and a median DSC of 0.89 (IQR 0.07) and 0.82 (IQR 0.10) in comparison to ERs and ROs, respectively. Radiomics feature stability was high with a median intraclass correlation coefficient of 0.97, 0.95 and 0.94 for GTs, ERs, and ROs, respectively. DLBAS predictions were deemed clinically suitable by the two ROs in 35% and 20% of cases, respectively. CONCLUSION: The results demonstrate that the DLBAS algorithm provides reproducible VOI predictions for radiomics feature extraction. Variability remains regarding direct clinical applicability of predictions for RT treatment planning.

Treatment Outcomes with Standard of Care in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Real-World Data Analysis.

INTRODUCTION: Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used. METHODS: This retrospective study utilized longitudinal data from 4226 real-world electronic health records to characterize outcomes in patients with R/R DLBCL. Eligible patients were diagnosed with DLBCL between January 2010 and March 2022 and had R/R disease treated with ≥ 1 prior systemic line of therapy (LOT), including ≥ 1 anti-CD20-containing regimen. RESULTS: A total of 573 patients treated with ≥ 1 prior LOT were included (31.2% and 13.4% with ≥ 2 and ≥ 3 prior LOTs, respectively). Median duration of follow-up was 7.7 months. Most patients (57.1%) were male; mean standard deviation (SD) age was 63 (14.7) years. Overall and complete response rates (95% confidence interval (CI) were 52% (48-56) and 23% (19-27). Median duration of response and duration of complete response were 3.5 and 18.4 months. Median progression-free and overall survival (95% CI) was 3.0 (2.8-3.3) and 12.9 (10.1-16.9) months, respectively. Patients with a higher number of prior LOTs, primary refractoriness, refractoriness to last LOT, refractoriness to last anti-CD20-containing regimen, and prior CAR T exposure had worse outcomes (i.e., challenging-to-treat R/R DLBCL) compared with those without these characteristics. CONCLUSIONS: Outcomes in patients with R/R DLBCL treated with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents remain poor, especially for those with challenging-to-treat R/R DLBCL. These findings underscore the unmet need for new, safe, and effective therapies, especially for challenging-to-treat R/R DLBCL populations.

Assessing the Quality of YouTube's Incontinence Information after Cancer Surgery: An Innovative Graphical Analysis.

BACKGROUND: Prostate and colorectum cancers rank among the most common cancers, and incontinence is a significant postsurgical issue affecting the physical and psychological well-being of cancer survivors. Social media, particularly YouTube, has emerged as a vital source of health information. While YouTube offers valuable content, users must exercise caution due to potential misinformation. OBJECTIVE: This study aims to assess the quality of publicly available YouTube videos related to incontinence after pelvic cancer surgery. METHODS: A search on YouTube related to "Incontinence after cancer surgery" was performed, and 108 videos were analyzed. Multiple quality assessment tools (DISCERN, GQS, JAMA, PEMAT, and MQ-VET) and statistical analyses (descriptive statistics and intercorrelation tests) were used to evaluate the characteristics and popularity, educational value, quality, and reliability of these videos, relying on novel graphical representation techniques such as Sankey and Chord diagrams. RESULTS: Strong positive correlations were found among quality rating scales, emphasizing agreement. The performed graphical analysis reinforced the reliability and validity of quality assessments. CONCLUSIONS: This study found strong correlations among five quality scales, suggesting their effectiveness in assessing health information quality. The evaluation of YouTube videos consistently revealed "high" quality content. Considering the source is mandatory when assessing quality, healthcare and academic institutions are reliable sources. Caution is advised with ad-containing videos. Future research should focus on policy improvements and tools to aid patients in finding high-quality health content.

Social inequalities in the use of physiotherapy in women diagnosed with breast cancer in Barcelona: DAMA cohort.

PURPOSE: This study aimed to analyze social inequalities in the use and access of physiotherapy service and its clinical and socio-economic determinants in women diagnosed with breast cancer in the hospital network of Barcelona. METHODS: Data from 2235 women belonging to the mixed (prospective and retrospective) DAMA Cohort were analyzed, including demographic, socio-economic, clinical, and breast cancer treatment outcomes. To determine the influence of such variables on access to physiotherapy, different Poisson regression models with robust variance (obtaining Prevalence Ratios and confidence intervals) were estimated. RESULTS: Although when experiencing different chronic and acute symptoms, only between 20 and 35% of women visited physiotherapist. Two out of 3 women reported to have received insufficient information about medical care and rehabilitation. Age of women, job occupation, education level, having a mutual or private insurance, as well as outcomes related to breast cancer, appear to be factors influencing the access to physiotherapy. CONCLUSIONS: Social and economic inequalities exist on the access to physiotherapy by women diagnosed with breast cancer, which is generally low, and may clearly impact on their functional recovery. Promoting strategies to reduce social bias, as well as improve communication and patient information regarding physiotherapy may be of interest for a better health care in breast cancer diagnosed women.

Risk Factors and Prevalence Associated With Conversion of Laparoscopic Cholecystectomy to Open Cholecystectomy: A Tertiary Care Hospital Experience in Western Mexico.

Introduction Laparoscopic cholecystectomy (LC) is a common procedure used for the treatment of different pathologies caused by gallstones in the gallbladder, and one of the most common indications is acute cholecystitis. The definitive treatment for acute cholecystitis is surgery, and LC is the gold standard. Nevertheless, transoperative complications (like intraoperative bleeding, anatomical abnormalities of the gallbladder, etc.) of LC and some other preoperative factors (like dilatation of bile duct, increased gallbladder wall thickness, etc.) can cause or be a risk factor for conversion to open cholecystectomy (OC). The objective of this study was to determine the risk factors and prevalence associated with the conversion from LC to OC in patients with gallbladder pathology and the indication for LC. Materials and methods This was a prospective cohort study. We included patients of both sexes over 18 years of age with gallbladder disease. To determine the risk factors associated with conversion, we performed a bivariate analysis and then a multivariate analysis. Results The rate of conversion to OC was 4.54%. The preoperative factors associated with conversion, in the bivariate analysis, were common bile duct dilatation (p=0.008), emergency surgery (p=0.014), and smoking (p=0.001); the associated intraoperative variables were: laparoscopic surgery duration (p <0.0001), Calot triangle edema (p=0.033), incapacity to hold the gallbladder with atraumatic laparoscopic tweezers (p=0.036), and choledocholithiasis (p=0.042). Laparoscopic Surgery duration was the only factor with a significant association in the multivariate analysis (p=0.0036); we performed a receiver operating characteristic (ROC) curve analysis and found a cut-off point of 120 minutes for the duration of laparoscopic surgery with a sensitivity and a specificity of 67 and 88%, respectively. Conclusion The prevalence of conversion from LC to OC is similar to that reported in the international literature. The risk factors associated with conversion to OC, in this study, should be confirmed in future clinical studies, in this same population, with a larger sample size.

The utility of intraoperative endoscopy in esophagogastric surgery.

Flexible endoscopy (FE) plays a major role in the diagnosis and treatment of gastrointestinal disease. Although its intraoperative use has spread over the years, its use by surgeons is still limited in our setting. FE training opportunities are different among many institutions, specialties, and countries. Intraoperative endoscopy (IOE) presents peculiarities that increase its complexity compared to standard FE. IOE has a positive impact on surgical results, due to increased safety and quality, as well as a reduction in the complications. Due to its innumerable advantages, its intraoperative use by surgeons is currently a current project in many countries and is part of the near future in others because of the creation of better structured training projects. This manuscript reviews and updates the indications and uses of intraoperative upper gastrointestinal endoscopy in esophagogastric surgery.

Plasma Biomarkers and Fractional Exhaled Nitric Oxide in the Diagnosis of Eosinophilic Esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic disease which requires endoscopy with biopsies for diagnosis and monitoring. We aimed to identify a panel of non-invasive markers that could help identify patients with active EoE. METHODS: In this prospective cohort study, we enrolled 128 children aged 5-18 years old, scheduled for endoscopy for suspected esophageal or peptic disease. On the day of the endoscopy, fractionated exhaled nitric oxide (FeNO) was measured; and blood was collected for peripheral absolute eosinophil count (AEC), plasma amino acids, and plasma polyamine analysis. Patients were grouped into controls (n = 91), EoE in remission (n = 16), or active EoE (n = 21), based on esophageal eosinophilia and history of EoE. RESULTS: AEC was not statistically significant different among the groups compared ( P = 0.056). Plasma amino acids: citrulline (CIT), ß-alanine (ß-ALA), and cysteine (CYS) were higher in active EoE compared to controls ( P < 0.05). The polyamine spermine was lower in active EoE versus controls ( P < 0.05). Receiver operator characteristic (ROC) curve to assess the predictive capability of a combined score made of FeNO, ß-ALA, CYS, and spermine had an area under curve (AUC) of 0.90 (95% CI: 0.80-0.96) in differentiating active EoE from controls and 0.87 (95% CI: 0.74-1.00) when differentiating active EoE from EoE in remission. CONCLUSION: A panel comprising FeNO, 2 plasma amino acids (ß-ALA, CYS) and the polyamine spermine can be used as a non-invasive tool to differentiate active EoE patients from controls.

The Liver Tumor Segmentation Benchmark (LiTS).

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094.

A Unified 3D Framework for Organs-at-Risk Localization and Segmentation for Radiation Therapy Planning.

Automatic localization and segmentation of organs-at-risk (OAR) in CT are essential pre-processing steps in medical image analysis tasks, such as radiation therapy planning. For instance, the segmentation of OAR surrounding tumors enables the maximization of radiation to the tumor area without compromising the healthy tissues. However, the current medical workflow requires manual delineation of OAR, which is prone to errors and is annotator-dependent. In this work, we aim to introduce a unified 3D pipeline for OAR localization-segmentation rather than novel localization or segmentation architectures. To the best of our knowledge, our proposed framework fully enables the exploitation of 3D context information inherent in medical imaging. In the first step, a 3D multi-variate regression network predicts organs' centroids and bounding boxes. Secondly, 3D organ-specific segmentation networks are leveraged to generate a multi-organ segmentation map. Our method achieved an overall Dice score of 0.9260 ± 0.18% on the VISCERAL dataset containing CT scans with varying fields of view and multiple organs.

Effectiveness of Pain Neuroscience Education in Patients with Fibromyalgia: A Systematic Review and Meta-Analysis.

PURPOSE: To assess the effects of pain neuroscience education (PNE) on patients with fibromyalgia in terms of pain intensity, fibromyalgia impact, anxiety, and pain catastrophizing. METHODS: A systematic review with meta-analysis of randomized controlled trials was conducted. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated with RStudio software (RStudio, Boston, MA) for relevant outcomes and were pooled in a meta-analysis with the random effects model. RESULTS: A total of eight studies were included. The meta-analysis showed statistically significant differences in pain intensity with a moderate clinical effect in seven studies at the post-intervention assessment (SMD: -0.76; 95% CI: -1.33 to -0.19; P < 0.05) with evidence of significant heterogeneity (P < 0.05, I2 = 92%), but it did not show statistically significant differences in fibromyalgia impact, anxiety, and pain catastrophizing (P > 0.05). With regard to the follow-up assessment, only the fibromyalgia impact showed significant improvements, with a very small clinical effect in nine studies (SMD: -0.44; 95% CI: -0.73 to -0.14; P < 0.05) and evidence of significant heterogeneity (P < 0.05, I2 = 80%). After the application of a sensitivity analysis with the PNE face-to-face interventions, the meta-analysis showed a significant decrease in pain intensity, with a moderate clinical effect at the post-intervention and follow-up assessments without evidence of significant heterogeneity (P < 0.05, I2 = 10%). CONCLUSIONS: There is low-quality evidence that in patients with fibromyalgia, PNE can decrease the pain intensity in the post-intervention period and the fibromyalgia impact in the follow-up period. However, it appears that PNE showed no effect on anxiety and pain catastrophizing.

High dietary ω-6:ω-3 PUFA ratio and simple carbohydrates as a potential risk factors for gallstone disease: A cross-sectional study.

BACKGROUND & AIMS: Gallstone disease (GD) is a major cause for consultation at general surgery services worldwide. In fact, GD has a strong relationship with environmental factors. However, specific characteristics in the Mexican population have not been established. The aim of this study was to compare the dietary components, physical activity, body composition and serum lipids in women with and without GD. METHODS: 54 women with GD and 75 without GD from West Mexico were enrolled in a cross-sectional study. Dietary intake was obtained through a habitual day food record and analyzed using the Nutritionist Pro™ software. Physical activity was evaluated in accordance with WHO recommendations. Body fat percentage (BF%) was estimated by bioimpedance (InBody 370) and serum lipids were measured using dry chemistry (Vitros-250 Analyzer). Student's t-test and binary logistic regression model were used. RESULTS: Women with GD presented a higher BF% (40 ± 8.7 vs 35.21 ± 9.8%, p = 0.004), an elevated dietary ω-6:ω-3 polyunsaturated fatty acids (PUFA) ratio (18.0 ± 11.4 vs 10.9 ± 4.7, p<0.001) and a higher simple carbohydrates (sCH) intake (28.3 ± 17.8 vs 13.23 ± 8.2%, p<0.001) as well as lower HDL-cholesterol levels (37.43 ± 8.5 vs 46.6 ± 12.02 mg/dL, p<0.001) compared with women without GD. Furthermore, it was foun d a higher ω-6:ω-3 PUFA ratio (OR: 3.9, 95% CI 1.52-10.38, p = 0.005) and excessive sCH consumption (OR: 7.4, 95% CI 1.92-28.65, p = 0.004). CONCLUSION: We suggest that a high dietary ω-6:ω-3 PUFA ratio and an excessive sCH intake are associated with an increased risk of GD in women.

Geometry-Aware Neural Solver for Fast Bayesian Calibration of Brain Tumor Models.

Modeling of brain tumor dynamics has the potential to advance therapeutic planning. Current modeling approaches resort to numerical solvers that simulate the tumor progression according to a given differential equation. Using highly-efficient numerical solvers, a single forward simulation takes up to a few minutes of compute. At the same time, clinical applications of tumor modeling often imply solving an inverse problem, requiring up to tens of thousands of forward model evaluations when used for a Bayesian model personalization via sampling. This results in a total inference time prohibitively expensive for clinical translation. While recent data-driven approaches become capable of emulating physics simulation, they tend to fail in generalizing over the variability of the boundary conditions imposed by the patient-specific anatomy. In this paper, we propose a learnable surrogate for simulating tumor growth which maps the biophysical model parameters directly to simulation outputs, i.e. the local tumor cell densities, whilst respecting patient geometry. We test the neural solver in a Bayesian model personalization task for a cohort of glioma patients. Bayesian inference using the proposed surrogate yields estimates analogous to those obtained by solving the forward model with a regular numerical solver. The near real-time computation cost renders the proposed method suitable for clinical settings. The code is available at https://github.com/IvanEz/tumor-surrogate.

Tumor Sink Effect in 68Ga-PSMA-11 PET: Myth or Reality?

We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, ≤25 cm3), low (quintile 2, 25-189 cm3), moderate (quintile 3, 189-532 cm3), high (quintile 4, 532-1,355 cm3), or very high (quintile 5, ≥1,355 cm3) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range [IQR], 47-1,076 cm3). The median SUVmean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7-11.8), 26.0 (IQR, 20.0-33.4), 3.7 (IQR, 3.0-4.7), and 5.3 (IQR, 4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUVmean of the salivary glands (r = -0.44, P < 0.001), kidneys (r = -0.34, P < 0.001), and liver (r = -0.30, P < 0.001) and a weak negative correlation with the spleen SUVmean (r = -0.16, P = 0.002). Patients with a very high PSMA-VOL (quintile 5, ≥1,355 cm3) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of -38.1%, -40.0%, -43.2%, and -34.9%, respectively (P < 0.001). Conclusion: Tumor sequestration affects 68Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of 68Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.

Risk factors for the development of postoperative complications in patients with metastatic kidney cancer treated with cytoreductive nephrectomy.

BACKGROUND: The role of cytoreductive nephrectomy on the treatment of metastatic renal cell carcinoma (mRCC) is controversial due to its high complexity. OBJECTIVE: To identify risk factors associated to postoperative complications in patients with mRCC after cytoreductive nephrectomy. METHOD: We conducted a retrospective, observational study in 67 patients who underwent cytoreductive nephrectomy for the management of mRCC. Demographic, perioperative and clinicopathologic -characteristics were registered. Surgical complications were classified using the Clavien-Dindo system; major complications were those of grade 3 or higher. We performed a binary logistic regression analysis to identify risk factors associated with surgical complications. RESULTS: Mean age was 56 years (37-83). Symptoms were present in 58 patients (89.7%). Weight loss was the predominant symptom (50.8%). Mean tumor diameter was 10.8 cm (4.6-22.5 cm). The rate of postoperative complications was 65%; 21 patients (31.4%) had major complications. Risk factors were estimated blood loss > 500 ml (OR 44.5, CI 95% 2.51-789, p = 0.01) and tumor diameter > 10 cm (OR 17.9, CI 95% 1.2-273, p = 0.04). CONCLUSIONS: Cytoreductive nephrectomy is a good option in highly selected patients with mRCC. Our major complication rate was 31.4%. Risk factors associated were blood loss and tumor diameter.

ANTECEDENTES: El papel de la nefrectomía citorreductora como tratamiento del carcinoma de células renales metastásico (CCRm) es controversial debido a su alta complejidad. OBJETIVO: Identificar factores de riesgo para complicaciones posquirúrgicas en pacientes con CCRm tratados con nefrectomía citorreductora. MÉTODO: Estudio retrospectivo, observacional, de 67 pacientes tratados con nefrectomía citorreductora por CCRm. Se registraron las características demográficas, perioperatorias y clinicopatológicas. Las complicaciones posquirúrgicas fueron clasificadas con el sistema Clavien-Dindo (mayores aquellas de grado 3 o superior). Se realizó un análisis de regresión logística binaria para identificar factores de riesgo para complicaciones. RESULTADOS: La edad media fue de 56 años (rango: 37-83), y 58 pacientes (89.7%) presentaron síntomas, predominando la pérdida de peso (50.8%). El diámetro tumoral medio fue de 10.8 cm (rango: 4.6-22.5). Un 65% tuvo complicaciones posquirúrgicas; en el 31.4% fueron mayores. Los factores de riesgo asociados fueron el sangrado transoperatorio ≥ 500 ml (odds ratio [OR]: 44; intervalo de confianza del 95% [IC 95%]: 2.51-789; p = 0.01) y el diámetro tumoral > 10 cm (OR: 17.9; IC 95%: 1.2-273; p = 0.04). CONCLUSIONES: La nefrectomía citorreductora es una opción de tratamiento para pacientes estrictamente seleccionados. Nuestra tasa de complicaciones mayores fue del 31.4%. Los factores de riesgo asociados fueron el sangrado transoperatorio y el diámetro tumoral.

ADAR-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair.

The maintenance of genomic stability requires the coordination of multiple cellular tasks upon the appearance of DNA lesions. RNA editing, the post-transcriptional sequence alteration of RNA, has a profound effect on cell homeostasis, but its implication in the response to DNA damage was not previously explored. Here we show that, in response to DNA breaks, an overall change of the Adenosine-to-Inosine RNA editing is observed, a phenomenon we call the RNA Editing DAmage Response (REDAR). REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP. Moreover, depletion of the RNA editing enzyme ADAR2 renders cells hypersensitive to genotoxic agents, increases genomic instability and hampers homologous recombination by impairing DNA resection. Such a role of ADAR2 in DNA repair goes beyond the recoding of specific transcripts, but depends on ADAR2 editing DNA:RNA hybrids to ease their dissolution.

Short- and mid- term impact of tobacco smoking on donor renal function following living kidney donation at a tertiary referral hospital

Background: The negative impact of tobacco smoking on renal function has been widely studied. However, there is limited knowledge about the effect of smoking on pre-operative and post-operative renal function in living kidney donors. Objective: The objective of the study was to evaluate the short- and mid-term impact of smoking on donor renal function. Methods: This is a retrospective study of 308 patients who underwent living donor nephrectomy (LDN) at a tertiary referral hospital. We compared baseline characteristics as well as functional outcomes following LDN according to history of tobacco smoking. Estimated glomerular filtration rate (eGFR) was calculated with the modification of diet in renal disease equation in 6 time periods: pre-operative, 1 week, 1 month, 6 months, 12 months, and 24 months after surgery. We performed a Kaplan-Meier analysis for chronic kidney disease (CKD) outcome and binary logistic regression analysis to identify risk factors associated with CKD at 24 months of follow-up. Results: Among donors, 106 (34.4%) reported a smoking history before nephrectomy. Smoking donors had worse pre-operative eGFR than non-smokers (90 ± 26.3 mL/min/1.73m2 vs. 96 ± 27 mL/min/1.73 m2, respectively; p = 0.02) and lower eGFR at 1 week (p = 0.01), 1 month (p ≤ 0.01), 6 months (p = 0.01), and 12 months (p = 0.01) after LDN. Tobacco smoking (OR 3.35, p ≤ 0.01) and age ≥ 40 years at donation (OR 6.59, p ≤ 0.01) were associated with post-operative development of CKD at 24 months after LDN. Conclusions: Living kidney donors with a tobacco smoking history had an increased risk of developing chronic kidney disease following nephrectomy. Smoking-cessation strategies should be implemented.

Development and External Validation of Deep-Learning-Based Tumor Grading Models in Soft-Tissue Sarcoma Patients Using MR Imaging.

BACKGROUND: In patients with soft-tissue sarcomas, tumor grading constitutes a decisive factor to determine the best treatment decision. Tumor grading is obtained by pathological work-up after focal biopsies. Deep learning (DL)-based imaging analysis may pose an alternative way to characterize STS tissue. In this work, we sought to non-invasively differentiate tumor grading into low-grade (G1) and high-grade (G2/G3) STS using DL techniques based on MR-imaging. METHODS: Contrast-enhanced T1-weighted fat-saturated (T1FSGd) MRI sequences and fat-saturated T2-weighted (T2FS) sequences were collected from two independent retrospective cohorts (training: 148 patients, testing: 158 patients). Tumor grading was determined following the French Federation of Cancer Centers Sarcoma Group in pre-therapeutic biopsies. DL models were developed using transfer learning based on the DenseNet 161 architecture. RESULTS: The T1FSGd and T2FS-based DL models achieved area under the receiver operator characteristic curve (AUC) values of 0.75 and 0.76 on the test cohort, respectively. T1FSGd achieved the best F1-score of all models (0.90). The T2FS-based DL model was able to significantly risk-stratify for overall survival. Attention maps revealed relevant features within the tumor volume and in border regions. CONCLUSIONS: MRI-based DL models are capable of predicting tumor grading with good reproducibility in external validation.