Expanding horizons: lung transplantation for non-IPF interstitial lung diseases.

OBJECTIVE: Interstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges. METHODS: Of all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups. RESULTS: Of the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years. CONCLUSIONS: This study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.

Single-Breath Simultaneous Measurement of DLNO and DLCO as Predictor of the Emphysema Component in COPD - A Retrospective Observational Study.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost. Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO). Methods: COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC). Results: Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema. Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.

Evaluation of micro-remnant niduses of arteriovenous malformations post-gamma knife radiosurgery by 3D-rotational angiography.

PURPOSE: Recent innovations in radiological imaging have enabled the detection of micro-remnant niduses of arteriovenous malformations (AVMs) after gamma knife radiosurgery (GKS), which have not been previously perceptible. Herein, we focus on the difficulty of evaluating micro-remnant AVMs after GKS that are hardly perceptible on conventional examinations and propose integrating follow-up three-dimensional rotational angiography (3D-RA) in the previous gamma plan as a solution. METHODS: We retrospectively searched NTT Medical Center Tokyo hospital database for patients with AVMs who underwent both two-dimensional digital subtraction angiography (2D-DSA) and 3D-RA as follow-up for GKS from February 2021 to January 2024. Patients with suspected nidus occlusion on the latest non-contrast-enhanced magnetic resonance angiography (NC-MRA) were included, and contrast-enhanced magnetic resonance angiography (CE-MRA), 2D-DSA, and 3D-RA were evaluated. RESULTS: Twelve patients with 13 AVM sites were defined as having complete nidus occlusion on upfront NC-MRA. On 2D-DSA, seven AVM sites showed the presence of slight remaining AVMs based on the detection of remnant drainage veins, however the nidus was not detected in three cases. Nevertheless, 3D-RA detected micro-remnant niduses in all seven AVM sites, and four patients underwent re-GKS. Nine patients with ten AVM sites also underwent CE-MRA, and six AVM sites were diagnosed with radiation-induced parenchymal injury. CONCLUSION: Importing the 3D-RA image into the treatment planning has the potential to be more helpful than NC-MRA or CE-MRA to detect micro-remnant AVMs and evaluate the true remnant volume, and may contribute to a more detailed treatment planning, thereby improving the results of GKS retreatment.

A 2-stage model of heterogenous treatment effects for brain atrophy in multiple sclerosis utilizing the MS PATHS research network.

BACKGROUND: Two-stage models of heterogenous treatment effects (HTE) may advance personalized medicine in multiple sclerosis (MS). Brain atrophy is a relatively objective outcome measure that has strong relationships to MS prognosis and treatment effects and is enabled by standardized MRI. OBJECTIVES: To predict brain atrophy outcomes for patients initiating disease-modifying therapies (DMT) with different efficacies, considering the patients' baseline brain atrophy risk measured via brain parenchymal fraction (BPF). METHODS: Analyses included patients enrolled in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network who started DMT and had complete baseline data and ≥ 6-month brain MRI follow-up. All brain MRIs were acquired using standardized acquisition sequences on Siemens 3T scanners. BPF change risk was derived by linear mixed effects models using baseline covariates. Model performance was assessed by predicted versus actual BPF change R2. Propensity score (PS) weighting was used to balance covariates between groups defined by DMT efficacy (high: natalizumab, alemtuzumab, ocrelizumab, and rituximab; moderate: dimethyl fumarate, fingolimod, and cladribine; low: teriflunomide, interferons, and glatiramer acetate). HTE models predicting 1 year change in BPF were built using a weighted linear mixed effects model with low-efficacy DMT as the reference. RESULTS: Analyses included 581 high-, 183 moderate-, and 106 low-efficacy DMT-treated patients. The mean and median number of brain MRI observations per treatment period were 2.9 and 3.0, respectively. Risk model performance R2=0.55. After PS weighting, covariate standardized mean differences were <10 %, indicating excellent balance across measured variables. Changes in BPF between baseline and follow-up were found to be statistically significant (p < 0.001), suggesting a pathological change. Patients with low brain atrophy risk had a similar outcome regardless of DMT selection. In patients with high brain atrophy risk, high- and moderate-efficacy DMTs performed similarly, while a 2-fold worse BPF change was predicted for patients selecting low-efficacy DMTs (p < 0.001). Similar results were observed in a sensitivity analysis adjusting for pseudoatrophy effects in a sub-population of patients treated with natalizumab. CONCLUSIONS: The relative benefit of selecting higher efficacy treatments may vary depending on patients' baseline brain atrophy risk. Poor outcomes are predicted in individuals with high baseline risk who are treated with low-efficacy DMTs.

Dynamic spatiotemporal activation of a pervasive neurogenic competence in striatal astrocytes supports continuous neurogenesis following injury.

Adult neural stem cells (NSCs) are conventionally regarded as rare cells restricted to two niches: the subventricular zone (SVZ) and the subgranular zone. Parenchymal astrocytes (ASs) can also contribute to neurogenesis after injury; however, the prevalence, distribution, and behavior of these latent NSCs remained elusive. To tackle these issues, we reconstructed the spatiotemporal pattern of striatal (STR) AS neurogenic activation after excitotoxic lesion in mice. Our results indicate that neurogenic potential is widespread among STR ASs but is focally activated at the lesion border, where it associates with different reactive AS subtypes. In this region, similarly to canonical niches, steady-state neurogenesis is ensured by the continuous stochastic activation of local ASs. Activated ASs quickly return to quiescence, while their progeny transiently expand following a stochastic behavior that features an acceleration in differentiation propensity. Notably, STR AS activation rate matches that of SVZ ASs indicating a comparable prevalence of NSC potential.

Association of pancreatic atrophy patterns with intraductal extension of early pancreatic ductal adenocarcinoma: a multicenter retrospective study.

BACKGROUND: Focal pancreatic parenchymal atrophy (FPPA) and upstream pancreatic atrophy (UPA) may indicate the presence of early pancreatic cancer. In early pancreatic cancer, the tumor occasionally spreads laterally along the main pancreatic duct, presenting challenges in determining the extent of surgical resection. This study aimed to investigate the association of pancreatic atrophy pattern and intraductal cancer extension. METHODS: Thirty-two patients with early-stage pancreatic cancer who underwent surgery at five participating centers were enrolled. Pancreatic atrophy was defined as the narrowing of parenchyma compared to the surrounding parenchyma and was classified as either FPPA (partial atrophy surrounding the pancreatic duct stenosis) or UPA (global atrophy caudal to the site of duct stenosis). Intraductal cancer extension was defined as an extension exceeding 10 mm. RESULTS: Preoperative computed tomography revealed FPPA, UPA, and no parenchymal atrophy in 13, 13, and 6 patients. Cases with FPPA or UPA showed significantly longer cancer extensions than those without atrophy (P = 0.005 and P = 0.03, respectively). Intraductal cancer extension was present in all but one case of FPPA. 69% (9/13) of the cases with UPA showed intraductal cancer extension, whereas cases without atrophy showed no intraductal cancer extension. Importantly, two patients with FPPA or UPA showed positive resection margins during surgery and three patients with FPPA or UPA showed recurrence in the remnant pancreas. CONCLUSIONS: The presence of FPPA and UPA indicates lateral cancer extension in early-stage pancreatic cancer. Preoperative assessment of the pancreatic parenchyma may provide valuable insights for determining the extent of surgical resection.

New Onset of Acute and Chronic Hepatic Diseases Post-COVID-19 Infection: A Systematic Review.

The SARS-CoV-2 virus caused a pandemic in the 2020s, which affected almost every aspect of life. As the world is recovering from the effect of the coronavirus, the concept of post-COVID-19 syndrome has emerged. Multiple organ systems have been implicated, including the liver. We aim to identify and analyze the reported cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 22 studies met our inclusion criteria. Our results revealed that liver steatosis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis were the most reported liver associated complications post-COVID-19 infection. Moreover, complications like acute liver failure, hepatitis, and liver hemorrhage were also reported. The mechanism of liver injury post-COVID-19 infection is not fully understood. The leading proposed mechanisms include the involvement of the angiotensin-converting enzyme-2 (ACE-2) receptor expressed in the liver and the overall inflammatory state caused by COVID-19 infection. Future studies should incorporate longer follow-up periods, spanning several years, for better insight into the progression and management of such diseases.

Computed Tomography Findings of Patients Presenting With Headache: 4-Year Retrospective Two-Center Study in Central and Western Regions of Ghana.

Objectives: The radiographic assessment of the head is a crucial part of headache care. A computed tomography (CT) scan enables a more detailed analysis of the condition and more focused care. This study examined head CT scans to determine what kinds of anomalies were present in patients with headaches as their primary complaint. Methods: We evaluated 4 years' worth of CT scan data from head exams conducted at two diagnostic facilities in Ghana's western and central regions. We examined data on 477 patients with a headache as their primary complaint between January 2017 and December 2020. We employed chi-square and Fisher's exact tests (where applicable) to compare head CT diagnoses between age groups, gender, headache subtypes, and brain lesion subgroups. Results: There were 53.5% (n = 255) females and 46.5% (n = 222) males in the study. The average age of patients was 38.67 ± 17.23 years, with an annual rate of abnormal CT diagnoses ranging from 35.9% in 2017 to 45.4% in 2022. Abnormal head CT diagnoses are strongly correlated with age groups and patient gender (p = 0.011 and p = 0.009, respectively). Of the 202 patients, 15.3% and 24.3% were classified as intracranial lesions and extracranial lesions, respectively. Maxillary sinusitis affected nearly 60% of the patients, while tumors and hemorrhages affected 25.2% and 11.9%, respectively. Conclusions: A CT scan of the head is essential to detect abnormalities in nearly 50% of patients suffering from various degrees of headache. Sinusitis, brain tumors, and hemorrhage were common lesions detected. It is crucial to create local standard operating procedures to promote better utilization of this type of imaging service, particularly among patients who have been diagnosed with headaches.

Purinergic Signaling in Non-Parenchymal Liver Cells.

Purinergic signaling has emerged as an important paracrine-autocrine intercellular system that regulates physiological and pathological processes in practically all organs of the body. Although this system has been thoroughly defined since the nineties, recent research has made substantial advances regarding its role in aspects of liver physiology. However, most studies have mainly targeted the entire organ, 70% of which is made up of parenchymal cells or hepatocytes. Because of its physiological role, the liver is exposed to toxic metabolites, such as xenobiotics, drugs, and fatty acids, as well as to pathogens such as viruses and bacteria. Under injury conditions, all cell types within the liver undergo adaptive changes. In this context, the concentration of extracellular ATP has the potential to increase dramatically. Indeed, this purinergic response has not been studied in sufficient detail in non-parenchymal liver cells. In the present review, we systematize the physiopathological adaptations related to the purinergic system in chronic liver diseases of non-parenchymal liver cells, such as hepatic stellate cells, Kupffer cells, sinusoidal endothelial cells, and cholangiocytes. The role played by non-parenchymal liver cells in these circumstances will undoubtedly be strategic in understanding the regenerative activities that support the viability of this organ under stressful conditions.

MRI Evaluation of Mass-Like and None-Mass-Like-Proven Breast Cancer from Moderate-to-High Background Enhancement.

Background: Breast cancer is considered one of the most prevalent cancers among females worldwide. The aim of this study was to assess the magnetic resonance imaging (MRI) patterns of female breast cancer, and also the prevalence of mass-like and nonmass-like lesions among these patients. Materials and Methods: 32 patients with proven breast cancer (based on their pathologic findings and background parenchymal enhancement [BPE] of their magnetic resonance [MR] images) were included in this cross-sectional study which was performed from 2017 to 2019 in Isfahan, Iran, using a1.5 Tesla (Achieva Philips, Netherland) MRI scanner system. The MR sequences (noncontrast image and at least two contrast-enhanced images) were done in the prone position for studied patients. Results: It was found that 68.8% (n = 44) and 31.2% (n = 20) of breast cancers were suffered from moderate and severe BPE, respectively. Furthermore, the prevalence of mass-like nonmass-like and both tumors were 43.8%, 43.8%, and 12.4%, respectively. Pathological studies indicated that 50%, 37.5%, and 12.5% of cancers were ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and DCIS, respectively. In addition, a significant relationship between MRI characteristics and pathologic findings was found for IDC and DCIS (P = 0.03). Conclusion: Based on the results of this study, the relationship between BPE level and MRI finding including mass-like or nonmass-like lesions in biopsy-proven breast cancers was not significant.

Concomitant Parenchymal, Subarachnoid, and Ventricular Neurocysticercosis in Rome, Italy: A Case Report with a 4-Year Follow-Up.

Neurocysticercosis (NCC) is caused by the larval stage of Taenia solium. This parasitic disease is endemic in many areas of the world and is emerging in Europe. NCC can affect different brain regions, but simultaneous involvement of the parenchymal, subarachnoid, and ventricular regions is rare. We report the case of a 39-year-old woman from Honduras, resident in Rome for 10 years, who presented to the Emergency Department complaining of headaches, transient hemianopsia, and bilateral papilledema. MRI showed a concomitant parenchymal, subarachnoid, and ventricular involvement in the brain. T. solium IgG antibodies were detected in the blood. The etiological diagnosis of NCC was obtained by identifying T. solium in cerebrospinal fluid using Next Generation Sequencing. Endoscopic neurosurgery with the placement of a ventricular shunt and medical long-term anti-parasitic treatment with a cumulative number of 463 days of albendazole and 80 days of praziquantel were performed. A successful 4-year follow-up is reported. NCC is one of the most common parasitic infections of the human CNS, but it is still a neglected tropical disease and is considered to be an emerging disease in Europe. Its diagnosis and clinical management remain a challenge, especially for European clinicians.

Platypnea-orthodeoxia syndrome developed with the progression of pulmonary parenchymal involvement: A case report.

Platypnea-orthodeoxia syndrome (POS) attributed to patent foramen ovale (PFO) can be caused by a variety of clinical conditions. A 70-year-old woman was admitted to our hospital for further evaluation of POS. Her symptoms developed along with the spread of infiltrative shadows in both lower lung fields during the preceding 2 years. Contrast transthoracic echocardiography with agitated saline revealed grade III intracardiac right-to-left shunting, presumably across a PFO. Transesophageal echocardiography demonstrated severe tricuspid regurgitation (TR) caused by the prolapse of the anterior leaflet. Bidirectional shunt flow, mainly from right-to-left across a PFO, that increased in the sitting position was also observed. She was diagnosed as having PFO associated with severe primary TR. Therefore, tricuspid valve repair and direct PFO closure were performed. Her symptoms resolved completely soon after the operation and her oxygen saturation was maintained. This patient's disease seemed to have worsened with the spread of pulmonary parenchymal involvement, which caused ventilation-perfusion mismatch and elevation of alveolar pressures. Echocardiography is an essential imaging modality in addition to other diagnostic examinations and imaging studies when assessing the pathogenesis in patients with POS. Learning objective: Platypnea-orthodeoxia syndrome (POS) associated with patent foramen ovale may be caused by a variety of clinical conditions, and POS in our patient may be caused by the worsening of pulmonary parenchymal involvement. Examinations to evaluate all causes of POS are essential for making the diagnosis. Contrast transthoracic echocardiography was useful in assessing the cause of POS.

Dosimetric implications of kidney anatomical volume changes in 177Lu-DOTATATE therapy.

INTRODUCTION: This study aims to evaluate the use of CT-based whole kidney parenchyma (WKP) segmentation in 177Lu-DOTATATE dosimetry. Specifically, it investigates whether WKP volumes change during treatment and evaluates the accuracy of applying a single delineated WKP volume for dosimetry. Furthermore, it aims to determine the cause of WKP volume changes-whether caused by radiation or amino acid infusion-by comparing them with spleen volume changes as a marker for radiation-induced alterations. METHODS: SPECT/CT images of 18 patients were acquired over the abdomen approximately 4 h (h) (D0), 24 h (D1), 48 h (D2) and 168 h (D7) post-administration of 177Lu-DOTATATE. CT guided WKP volumes were measured before (baseline) and during treatment. Kidney activity concentrations at each time point were derived from CT-segmented WKP overlaid on SPECT scans. The accuracy of using WKP segmentation from a single CT for all time points was assessed against the gold standard of segmenting each WKP individually. Time-integrated activity calculations were based on a tri-exponential curve fit of the kidney activity concentration over time. Kidney absorbed doses were estimated under the assumption of local energy deposition. Additionally, the impact of various partial volume correction methods on dosimetry was evaluated. RESULTS: Whole-kidney parenchyma (WKP) volumes, ranging from 31 to 243 mL, showed a gradual increase from baseline (mean ± SD = 130.6 ± 46.1 mL) at the initial time points D0 (138.5 ± 44.7 mL) and D1 (139.4 ± 41.6 mL), followed by a slight decrease at D2 (132.8 ± 44.5 mL) and a further decrease at D7 (129.2 ± 42.7 mL). The volume increase at D0 and D1 was statistically significant. Spleen volume did not change during treatment, suggesting that amino acid infusion rather than irradiation effects caused WKP volume changes. Bland-Altman analysis revealed WKP volume biases of 8.77% (D0 vs. BL), 10.77% (D1 vs. BL), 1.10% (D2 vs. BL), and 1.10% (D7 vs. BL), with corresponding uncertainties of 24.4%, 23.6%, 25.4%, and 25.4%, respectively. When WKP segmentation from a single CT is applied across all SPECTs, these WKP volume changes could overestimate the activity concentration and mean absorbed doses up to 4.3% and 2.5%, respectively. The absorbed dose uncertainties using a recovery coefficient (RC) of 0.85 for single-time-point WKP delineation increase the absorbed dose uncertainty by 4% compared to the use of patient-specific RCs and time specific segmentation of WKP volumes. CONCLUSIONS: Kidney volume exhibited significant variation form D0 to D7, affecting the precision of dosimetry calculation, primarily due to errors in whole-kidney parenchyma (WKP) delineation. Notably, using WKP segmentation from a single CT scan applied to sequential SPECT images introduce further uncertainty and may lead to an overestimation of the absorbed dose. The fluctuations in kidney volume are most likely attributable to amino acid infusion.

Lower respiratory tract microbiome and lung cancer risk prediction in patients with diffuse lung parenchymal lesions.

Objective: In clinical practice, imaging manifestations of diffuse lung parenchymal lesions are common and indicative of various diseases, making differential diagnosis difficult. Some of these lesions are eventually diagnosed as lung cancer. Methods: Because respiratory microorganisms play an important role in lung cancer development, we searched for microbial markers that could predict the risk of lung cancer by retrospectively analyzing the lower respiratory tract (LRT) microbiome of 158 patients who were hospitalized in the First Affiliated Hospital of Guangzhou Medical University (March 2021-March 2023) with diffuse lung parenchymal lesions. The final diagnosis was lung cancer in 21 cases, lung infection in 93 cases, and other conditions (other than malignancy and infections) in 44 cases. The patient's clinical characteristics and the results of metagenomic next-generation sequencing of bronchoalveolar lavage fluid (BALF) were analyzed. Results: Body mass index (BMI) and LRT microbial diversity (Shannon, Simpson, species richness, and Choa1 index) were significantly lower (P< 0.001, respectively) and Lactobacillus acidophilus relative abundance in the LRT was significantly higher (P< 0.001) in patients with lung cancer. The relative abundance of L. acidophilus in BALF combined with BMI was a good predictor of lung cancer risk (area under the curve = 0.985, accuracy = 98.46%, sensitivity = 95.24%, and specificity = 100.00%; P< 0.001). Conclusion: Our study showed that an imbalance in the component ratio of the microbial community, diminished microbial diversity, and the presence of specific microbial markers in the LRT predicted lung cancer risk in patients with imaging manifestations of diffuse lung parenchymal lesions.

The added value of superb microvascular imaging for renal cortical thickness measurement in chronic kidney disease.

PURPOSE: The aim of this study was to evaluate renal parenchymal thickness and renal cortical thickness measurements on brightness mode ultrasound (B-mode US) and B-mode US + Superb Microvascular Imaging (SMI) technique, comparing with computed tomography (CT) or magnetic resonance imaging (MRI) serving as a reference standard. METHODS: Renal parenchymal thickness and renal cortical thickness measurements were obtained from B-mode US, B-mode US + SMI, and CT/MRI in a group of healthy subjects and a group of patients with chronic kidney disease (CKD). The mean differences and correlations of renal parenchymal thickness and renal cortical thickness were analyzed using dependent pair t-test and Pearson's correlation, respectively. RESULTS: The mean difference in renal cortical thickness measurements between B-mode US + SMI and CT/MRI was lower than the mean difference between B-mode US alone and CT/MRI. Additionally, renal cortical thickness measured using B-mode US + SMI showed a stronger correlation with values obtained from CT/MRI than values measured using standard B-mode US alone. CONCLUSION: The measurement of renal cortical thickness by B-mode US + SMI is more accurate than that by B-mode US alone.

Prognostic Impact and Genomic Backgrounds of Renal Parenchymal Infiltration or Micronodular Spread in Nonmetastatic Clear Cell Renal Cell Carcinoma.

A subset of clear cell renal cell carcinomas (ccRCCs) exhibits various growth patterns that infiltrate the normal renal parenchyma; however, our understanding of its association with cancer aggressiveness is incomplete. Here, we show that the morphology of the tumor interface with normal renal parenchyma is robustly associated with cancer recurrence after surgery, even when compared with the TNM staging system or the World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade in nonmetastatic ccRCC. Hematoxylin and eosin-stained slides of whole tissue sections from surgical specimens were analyzed using a cohort of 331 patients with nonmetastatic ccRCC treated with radical nephrectomy. The patients were classified into 10 subgroups based on our classification algorithms for assessing the tumor interface with normal renal parenchyma. Among the 10 subgroups, 4 subgroups consisting of 40 patients (12%) were identified to have aggressive forms of nonmetastatic ccRCC associated with poor prognosis and unified as renal parenchymal infiltration or micronodular spread (RPI/MNS) phenotypes. Multivariable analyses showed that RPI/MNS phenotypes were robustly associated with shorter disease-free survival, independently of existing pathological factors including the TNM staging system and WHO/ISUP nuclear grade. The hazard ratio was highest for RPI/MNS (4.62), followed by WHO/ISUP grades 3 to 4 (2.11) and ≥pT3a stage (2.05). In addition, we conducted genomic analyses using next-generation sequencing of infiltrative lesions in 18 patients with RPI/MNS and tumor lesions in 33 patients without RPI/MNS. Results showed that alterations in SETD2 and TSC1 might be associated with RPI/MNS phenotypes, whereas alterations in PBRM1 might be associated with non-RPI/MNS phenotypes. These data suggest that RPI/MNS may be associated with aggressive genomic backgrounds of ccRCC, although more comprehensive analyses with a larger sample size are required. Future studies may further elucidate the clinical implications of RPI/MNS, particularly for deciding the indication of adjuvant treatment after nephrectomy.

Clinical Significance of Combined Density and Deep-Learning-Based Texture Analysis for Stratifying the Risk of Short-Term and Long-Term Breast Cancer in Screening.

Assessing a woman's risk of breast cancer is important for personalized screening. Mammographic density is a strong risk factor for breast cancer, but parenchymal texture patterns offer additional information which cannot be captured by density. We aimed to combine BI-RADS density score 4th Edition and a deep-learning-based texture score to stratify women in screening and compare rates among the combinations. This retrospective study cohort study included 216,564 women from a Danish populations-based screening program. Baseline mammograms were evaluated using BI-RADS density scores (1-4) and a deep-learning texture risk model, with scores categorized into four quartiles (1-4). The incidence rate ratio (IRR) for screen-detected, interval, and long-term cancer were adjusted for age, year of screening and screening clinic. Compared with subgroup B1-T1, the highest IRR for screen-detected cancer were within the T4 category (3.44 (95% CI: 2.43-4.82)-4.57 (95% CI: 3.66-5.76)). IRR for interval cancer was highest in the BI-RADS 4 category (95% CI: 5.36 (1.77-13.45)-16.94 (95% CI: 9.93-30.15)). IRR for long-term cancer increased both with increasing BI-RADS and increasing texture reaching 5.15 (4.31-6.16) for the combination of B4-T4 compared with B1-T1. Deep-learning-based texture analysis combined with BI-RADS density categories can reveal subgroups with increased rates beyond what density alone can ascertain, suggesting the potential of combining texture and density to improve risk stratification in breast cancer screening.

Robotic liver parenchymal transection using the SynchroSeal.

BACKGROUND: There is much heterogeneity in the instrumentation used for parenchymal transection in minimally invasive liver surgery. Instruments specifically designed for robotic parenchymal transection of the liver are lacking. We aim to gain insight into the safety and effectiveness of the SynchroSeal (Intuitive Surgical, Inc., Sunnyvale, CA), a novel bipolar electrosurgical device, in the context of liver surgery. METHODS: The present study is a post-hoc analysis of prospectively collected data from patients undergoing robotic liver resection (RLR) using the SynchroSeal in two high-volume centres. The results of the SynchroSeal were compared with that of the previous generation bipolar-sealer; Vessel Sealer Extend (Intuitive Surgical, Inc., Sunnyvale, CA) using propensity score matching, after excluding the first 25 Vessel Sealer procedures per center. RESULTS: During the study period (February 2020-March 2023), 155 RLRs meeting the eligibility criteria were performed with the SynchroSeal (after implementation in June 2021) and 145 RLRs with the Vessel Sealer. Excellent outcomes were achieved when performing parenchymal transection with the SynchroSeal; low conversion rate (n = 1, 0.6%), small amounts of intraoperative blood loss (median 40 mL [IQR 10-100]), short hospital stays (median 3 days [IQR 2-4]), and adequate overall morbidity (19.4%) as well as severe morbidity (11.0%). In a matched comparison (n = 94 vs n = 94), the SynchroSeal was associated with less intraoperative blood loss (48 mL [IQR 10-143] vs 95 mL [IQR 30-200], p = 0.032) compared to the Vessel Sealer. Other perioperative outcomes were similar between the devices. CONCLUSION: The SynchroSeal is a safe and effective device for robotic liver parenchymal transection.