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restrictedNov 2022View details →

Dataset related to article "Artificial intelligence processing electronic health records to identify commonalities and comorbidities cluster at Immuno Center Humanitas"

This record contains raw data related to article “Artificial intelligence processing electronic health records to identify commonalities and comorbidities cluster at Immuno Center Humanitas”.   Background: Comorbidities are common in chronic inflammatory conditions, requiring multidisciplinary treatment approach. Understanding the link between a single disease and its comorbidities is important for appropriate treatment and management. We evaluate the ability of an NLP-based process for knowledge discovery to detect information about pathologies, patients' phenotype, doctors' prescriptions and commonalities in electronic medical records, by extracting information from free narrative text written by clinicians during medical visits, resulting in the extraction of valuable information and enriching real world evidence data from a multidisciplinary setting. Methods: We collected clinical notes from the Allergy Department of Humanitas Research Hospital written in the last 3 years and used it to look for diseases that cluster together as comorbidities associated to the main pathology of our patients, and for the extent of prescription of systemic corticosteroids, thus evaluating the ability of NLP-based tools for knowledge discovery to extract structured information from free text. Results: We found that the 3 most frequent comorbidities to appear in our clusters were asthma, rhinitis, and urticaria, and that 991 (of 2057) patients suffered from at least one of these comorbidities. The clusters which co-occur particularly often are oral allergy syndrome and urticaria (131 patients), angioedema and urticaria (105 patients), rhinitis and asthma (227 patients). With regards to systemic corticosteroid prescription volume by our clinicians, we found it was lower when compared to the therapy the patients followed before coming to our attention, with the exception of two diseases: Chronic obstructive pulmonary disease and Angioedema. Conclusions: This analysis seems to be valid and is confirmed by the data from the literature. This means that NLP tools could have significant role in many other research fields of medicine, as it may help identify other important, and possibly previously neglected clusters of patients with comorbidities and commonalities. Another potential benefit of this approach lies in its potential ability to foster a multidisciplinary approach, using the same drugs to treat pathologies normally treated by physicians in different branches of medicine, thus saving resources and improving the pharmacological management of patients.

Dataset related to the article "Cardiovascular magnetic resonance images with susceptibility artifacts: artificial intelligence with spatial-attention for ventricular volumes and mass assessment"

This record contains raw data related to the article "Cardiovascular magnetic resonance images with susceptibility artifacts: artificial intelligence with spatial-attention for ventricular volumes and mass assessment" Abstract Background Segmentation of cardiovascular magnetic resonance (CMR) images is an essential step for evaluating dimensional and functional ventricular parameters as ejection fraction (EF) but may be limited by artifacts, which represent the major challenge to automatically derive clinical information. The aim of this study is to investigate the accuracy of a deep learning (DL) approach for automatic segmentation of cardiac structures from CMR images characterized by magnetic susceptibility artifact in patient with cardiac implanted electronic devices (CIED). Methods In this retrospective study, 230 patients (100 with CIED) who underwent clinically indicated CMR were used to developed and test a DL model. A novel convolutional neural network was proposed to extract the left ventricle (LV) and right (RV) ventricle endocardium and LV epicardium. In order to perform a successful segmentation, it is important the network learns to identify salient image regions even during local magnetic field inhomogeneities. The proposed network takes advantage from a spatial attention module to selectively process the most relevant information and focus on the structures of interest. To improve segmentation, especially for images with artifacts, multiple loss functions were minimized in unison. Segmentation results were assessed against manual tracings and commercial CMR analysis software cvi42(Circle Cardiovascular Imaging, Calgary, Alberta, Canada). An external dataset of 56 patients with CIED was used to assess model generalizability. Results In the internal datasets, on image with artifacts, the median Dice coefficients for end-diastolic LV cavity, LV myocardium and RV cavity, were 0.93, 0.77 and 0.87 and 0.91, 0.82, and 0.83 in end-systole, respectively. The proposed method reached higher segmentation accuracy than commercial software, with performance comparable to expert inter-observer variability (bias ± 95%LoA): LVEF 1 ± 8% vs 3 ± 9%, RVEF − 2 ± 15% vs 3 ± 21%. In the external cohort, EF well correlated with manual tracing (intraclass correlation coefficient: LVEF 0.98, RVEF 0.93). The automatic approach was significant faster than manual segmentation in providing cardiac parameters (approximately 1.5 s vs 450 s). Conclusions Experimental results show that the proposed method reached promising performance in cardiac segmentation from CMR images with susceptibility artifacts and alleviates time consuming expert physician contour segmentation.

Dataset related to Article "A SINGLE-GROUP STUDY ON THE EFFECT OF ONABOTULINUMTOXINA IN PATIENTS WITH CHRONIC MIGRAINE ASSOCIATED TO MEDICATION OVERUSE HEADACHE: PAIN CATASTROPHIZING PLAYS A ROLE"_ submitted

THIS DATASET INCLUDES INFORMATION ON HEADACHE FREQUENCY, MEDICATION INTAKE, MIDAS SCORE, AVERAGE PAIN, HIT-6, ASC-12 AND PCS REFERRED TO PATIENTS RECEIVING ONABOTULINUMTOXINA AS PROPHYLAXIS FOR CM-MOH OVER 12 MONTHS.

restrictedMay 2022View details →

Dataset related to article: "Could We Safely Avoid a Second Resection in Selected Patients With T1 Non-Muscle-Invasive Bladder Cancer? Preliminary Results of Cost-Effectiveness Study From HUmanitas New Indications for ReTUR (HuNIRe) Multicenter Prospective Trial"

The paper reports the preliminary results of a study which aims to avoid re-turbt in patients who have pT1

Dataset related to the article: "N-acetylcysteine inhibits platelet function through the regeneration of the non-oxidative form of albumin"

This record contains raw data related to the article:  "N-acetylcysteine inhibits platelet function through the regeneration of the non-oxidative form of albumin" Abstract: N-acetylcysteine (NAC), is able to break down protein disulfides generating free thiols. This mechanism occurs on mixed disulfides of albumin (HSA) to form mercaptoalbumin (HMA), the main antioxidant species in the plasma. Circulating HSA exists in two main forms: the reduced form (HMA), and the oxidized forms, whose predominant modification is cystenylation (HSA-Cys). Increased levels of oxidized HSA were detected in several diseases associated with oxidative stress. This study showed that NAC inhibits platelet aggregation by restoring HMA. In addition, the regeneration of HMA by NAC inhibits platelet functions, such as intracellular calcium mobilization, reactive oxygen species generation, arachidonic acid metabolites synthesis, and adhesion to the collagen matrix. In our conditions, the exposure of platelet to NAC did not increased GSH levels. However, the inhibition of platelet aggregation was also detected following treatment of platelet-rich plasma with GSH, which, similarly to NAC, reduced HSA-Cys levels. Furthermore, this study shows that cysteine, another compound able to restore HMA by reducing the HSA-Cys content, inhibited platelet aggregation to a similar extent as NAC. The results obtained in this study suggest a new mechanism by which NAC can modulate platelet activation and suggest its possible use as an antiplatelet drug in conditions associated with oxidative stress.

Dataset related to article: "The impact of the isolation protocol on the release of extracellular vesicles by human platelets"

Dataset related to article: "The impact of the isolation protocol on the release of extracellular vesicles by human platelets" Background: Platelet-derived extracellular vesicles (PEVs) are small vesicles released by activated platelets that are gaining growing interest in the field of vascular biology. The mode of platelet activation is a critical determinant of PEVs release, phenotype and function. However, only very limited information is available concerning the impact of the platelet purification procedure on PEVs release. Methods: Washed or isolated platelets were separated by differential centrifugations. For washed platelets, the platelet pellet was washed by resuspension in PIPES buffer and finally resuspended in HEPES buffer. Isolated platelets were obtained by directly resuspending the platelet pellet in HEPES, skipping the washing steps in PIPES buffer. PEVs release was induced in washed or isolated platelets by stimulation with different agonist and analysed by Nanoparticle Tracking Analysis. Results: Isolated platelets showed a higher release of PEVs upon adenosine diphosphate (ADP) stimulation compared to washed platelets, whereas PEVs released upon stimulation with strong agonists (thrombin, collagen, A23187, U46619) were similar in the two groups. This different responsiveness to ADP was also observed as a higher α-granules release and protein kinase C activation in isolated platelets compared to washed ones. Residual plasma contamination appeared to be essential for the ability of platelets to release PEVs in response to ADP. Conclusions: In conclusion, our study strongly suggests that procedure adopted for platelets preparation is a critical determinant of PEVs release upon ADP stimulation.

Dataset relate to the article "Oxidative Stress and Arginine/Nitric Oxide Pathway in Red Blood Cells Derived from Patients with Prediabetes"

This record contains row data relaed to the article "Oxidative Stress and Arginine/Nitric Oxide Pathway in Red Blood Cells Derived from Patients with Prediabetes" Abstract: The effects of the oral glucose tolerance test (OGTT) on red blood cells (RBCs) have not been thoroughly investigated, although it is known that the ingestion of 75-g glucose during OGTT results in a systemic state of inflammation and oxidative stress. Therefore, we evaluated the effect of OGTT on oxidative stress and L-Arginine/Nitric Oxide (L-Arg/NO) metabolic pathway in RBCs obtained from patients with prediabetes. Blood samples were collected from all participants before (T0) and at 10 (T1), 20 (T2), 30 (T3), 60 (T4), 90 (T5), 120 (T6), 150 (T7), and 180 (T8) minutes after glucose loading. Results showed a significant increase in oxidative stress status characterized by a rise in the GSSG/GSH ratio at T4 and T6 that went in parallel with a reduction of NO production in RBCs. In addition, in this time frame, increased exposure of phosphatidylserine on RBCs membrane was observed. These metabolic modifications were rescued at T8, together with an increase in activated RBC NO synthase expression. These findings provide a possible explanation of the phenomena occurring after glucose loading and suggest that, even in the early stages of diabetes, it may be important to avoid acute variations in glycemia in order to prevent diabetic complications.

Dtaset related to the article The double anaerobic threshold in heart failure: MECKI score database overview. ESC Heart Fail. 2022;9:2119-2124.

Aims: In heart failure (HF), anaerobic threshold (AT) may be indeterminable but its value held a relevant prognostic role. AT is evaluated joining three methods: V-slope, ventilatory equivalent, and end-tidal methods. The possible non-concordance between the V-slope (met AT) and the other two methods (vent AT) has been highlighted in healthy individuals and named double threshold (DT). Methods and results: We reanalysed 1075 cardiopulmonary exercise tests of HF patients recruited in the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score database. We identified DT in 43% of cases. Met AT precedes vent AT being met-ventΔVO2 221 (interquartile range: 129-319) mL/min. Peak VO2 , 1307 ± 485 vs. 1343 ± 446 mL/min (63 ± 17 vs. 63 ± 17 percentage of predicted), was similar between DT+ and DT- patients. Differently, DT+ showed a lower ventilatory vs. carbon dioxide production (VE/VCO2 ) slope (29.6 ± 6.1 vs. 31.0 ± 6.3), a lower peak exercise end-tidal oxygen tension (PetO2 ) 115.3 (111.5-118.9) vs. 116.4 (112.4-120.2) mmHg, and a higher carbon dioxide tension (PetCO2 ) 34.2 (30.9-37.1) vs. 32.4 (28.7-35.5) mmHg. Vent AT showed a significant higher VO2 , 957 ± 318 vs. 719 ± 252 mL/min, VCO2 , 939 ± 319 vs. 627 ± 226 mL/min, ventilation, 31.0 ± 8.3 vs. 22.5 ± 6.3 L/min, respiratory exchange ratio, 0.98 ± 0.08 vs. 0.87 ± 0.07, PetO2 , 108 (104-112) vs. 105 (101-109) mmHg, PetCO2 , 37 (34-40) vs. 36 (33-39) mmHg, and VE/VO2 ratio, 33.5 ± 6.7 vs. 32.6 ± 6.9, but lower VE/VCO2 ratio, 33 (30-37) vs. 36 (32-41), compared with met AT. At 2 year survival by Kaplan-Meier analysis, even adjusted for confounders, DT resulted not associated with survival. Conclusions: Double threshold is frequently observed in HF patients. DT+ is associated to a decreased ventilatory response during exercise.

Dataset related to the article: Salvioni E, Mapelli M, Bonomi A, Magri D, Piepoli M, Frigerio M, et al. Pick Your Threshold: A Comparison Among Different Methods of Anaerobic Threshold Evaluation in Heart Failure Prognostic Assessment. Chest. 2022;162:1106-1115.

Background: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. Research question: What is the prognostic power of these different ways to report AT? Study design and methods: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. Interpretation: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

Dataset related to the article Mapelli M, Zagni P, Ferrara R, Calbi V, Mattavelli I, Muratori M, et al. Unexpected Huge Prevalence of Intracardiac Extension of Wilms Tumor-A Single Center Experience from a Ugandan Hospital. Children (Basel). 2022;9.

Wilms tumor (WT) is the most common primary renal malignancy in young children. WT vascular extension to the inferior vena cava (IVC) occurs in 4–10% of cases and can reach the right atrium (RA) in 1%. Data on WT clinical presentation and outcome in developing countries are limited. The aim of the present study is to describe the prevalence of intracardiac extension in a consecutive population of WT patients observed in a large non-profit Ugandan hospital. A total of 16 patients with a histological diagnosis of 29 WT were screened in a 6-month period. Patient n°2, a 3 y/o child, presented with a 3-week history of abdominal distension, difficulty in breathing, and swelling of the lower limbs. A cardiovascular system exam showed rhythmic heart sounds, a heart rate of 110 beats per minute, and a pansystolic murmur on the tricuspid area; the abdomen was grossly distended with a palpable mass in the right flank, hepatomegaly, and splenomegaly. An abdomen ultrasound showed an intra-abdominal tumor, involving the right kidney and the liver and extended to the IVC. An ultrasound guided biopsy showed a picture consistent with WT. Cardiac echo showed a huge, mobile, cardiac mass attached to the right side of the interatrial septum, involving the tricuspid valve annulus, causing a “functional” tricuspid stenosis. The patient died of cardiogenic shock 7 days after admission. Patient n°3, a 3 y/o child, presented with analogue symptoms and the same diagnosis. The cardiac echo showed a round mass in the RA. Thirteen more patients were screened with cardiac echo, showing a normal heart picture. In our limited series, we found WT cardiac extension in three patients over 16 (19%). Cardiac echo performed routinely can lead to a better staging, prognostic, and therapeutic assessment. In our setting, the intra-cardiac extension could be more frequent than previously reported and might have prognostic implications.

Dataset related to article "Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules"

This record contains raw data related to article “Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules" The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.

Dataset related to article "Frozen Section Analysis and Real-Time Magnetic Resonance Imaging of Surgical Specimen Oriented on 3D Printed Tongue Model to Assess Surgical Margins in Oral Tongue Carcinoma: Preliminary Results"

This record contains raw data related to article “Frozen Section Analysis and Real-Time Magnetic Resonance Imaging of Surgical Specimen Oriented on 3D Printed Tongue Model to Assess Surgical Margins in Oral Tongue Carcinoma: Preliminary Results" Abstract Background: A surgical margin is the apparently healthy tissue around a tumor which has been removed. In oral cavity carcinoma, a negative margin is considered ≥ 5 mm, a close margin between 1 and 5 mm, and a positive margin ≤ 1 mm. Currently, the intraoperative surgical margin status is based on the visual inspection and tissue palpation by the surgeon and intraoperative histopathological assessment of the resection margins by frozen section analysis (FSA). FSA technique is limited and susceptible to sampling errors. Definitive information on the deep resection margins requires postoperative histopathological analysis. Methods: We described a novel approach for the assessment of intraoperative surgical margins by examining a surgical specimen oriented through a 3D-printed specific patient tongue with real-time Magnetic Resonance Imaging (MRI). We reported the preliminary results of a case series of 10 patients, prospectively enrolled, with oral tongue carcinoma who underwent surgery between February 2020 and April 2021. Two radiologists with 5 and 10 years of experience, respectively, in Head and Neck radiology in consensus evaluated specimen MRI and measured the distance between the tumor and the specimen surface. We performed intraoperative bedside FSA. To compare the performance of bedside FSA and MRI in predicting definitive margin status we computed the weighted sensitivity (SE), specificity (SP), accuracy (ACC), area under the ROC curve (AUC), F1-score, Positive Predictive Value (PPV), and Negative Predictive Value (NPV). To express the concordance between FSA and ex-vivo MRI we reported the jaccard index. Results: Intraoperative bedside FSA showed SE of 90%, SP of 100%, F1 of 95%, ACC of 0.9%, PPV of 100%, NPV (not a number), and jaccard of 90%, and ex-vivo MRI showed SE of 100%, SP of 100%, F1 of 100%, ACC of 100%, PPV of 100%, NPV of 100%, and jaccard of 100%. These results needed to be validated in a larger sample size of 21- 44 patients. Conclusion: The presented method allows a more accurate evaluation of surgical margin status, and the first clinical experiences underline the high potential of integrating FSA with ex-vivo MRI of the fresh surgical specimen.

Dataset related to article "Endoscopic ultrasound-guided fine-needle biopsy with or without macroscopic on-site evaluation: a randomized controlled noninferiority trial "

This record contains raw data related to article “Endoscopic ultrasound-guided fine-needle biopsy with or without macroscopic on-site evaluation: a randomized controlled noninferiority trial" Abstract BACKGROUND : The advantage of using the macroscopic on-site evaluation (MOSE) technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) performed with 22G Franseen needles has not been investigated. We aimed to compare EUS-FNB with MOSE vs. EUS-FNB performed with three needle passes. METHODS : This randomized trial involved 10 Italian referral centers. Consecutive patients referred for EUS-FNB of pancreatic or nonpancreatic solid lesions were included in the study and randomized to the two groups. MOSE was performed by gross visualization of the collected material by the endoscopists and considered adequate when a white/yellowish aggregate core longer than 10 mm was retrieved. The primary outcome was diagnostic accuracy. Secondary outcomes were specimen adequacy, number of needle passes, and safety. RESULTS : 370 patients with 234 pancreatic lesions (63.2 %) and 136 nonpancreatic lesions (36.8 %) were randomized (190 EUS-FNB with MOSE and 180 with standard EUS-FNB). No statistically significant differences were found between EUS-FNB with MOSE and conventional EUS-FNB in terms of diagnostic accuracy (90.0 % [95 %CI 84.8 %-93.9 %] vs. 87.8 % [95 %CI 82.1 %-92.2 %]; P = 0.49), sample adequacy (93.1 % [95 %CI 88.6 %-96.3 %] vs. 95.5 % [95 %CI 91.4 %-98 %]; P = 0.31), and rate of adverse events (2.6 % vs. 1.1 %; P = 0.28). The median number of passes was significantly lower in the EUS-FNB with MOSE group (1 vs. 3; P < 0.001). CONCLUSIONS : The accuracy of EUS-FNB with MOSE is noninferior to that of EUS-FNB with three needle passes. MOSE reliably assesses sample adequacy and reduces the number of needle passes required to obtain the diagnosis with a 22G Franseen needle.

Dataset related to article "Cold versus hot EMR for large duodenal adenomas "

This record contains raw data related to article “Cold versus hot EMR for large duodenal adenomas" Conventional endoscopic mucosal resection using electrocoagulation (hot EMR) for large (>20 mm), sporadic non-ampullary duodenal adenomas is associated with a high complication rate. Based on favourable colonic experience with cold EMR/without electrocautery, we performed a retrospective analysis comparing 33 patients treated this way to 101 patients who had hot EMR for their duodenal adenomas. Data were collected from four tertiary centres in two time periods. No serious adverse events (SAEs) occurred in the cold group, there were 17 intraprocedural SAEs (16.8%) and 26 postprocedural SAEs (25.7%) in the hot EMR group. Procedure time was significantly lower for cold EMR (49±25.1 min vs 96.9±56 min, p<0.01). Recurrence seen at first follow-up endoscopy was comparable in both groups (cold EMR: 4/33; 12.1% versus hot EMR: 21/101; 20.8%). This data suggests that cold EMR is a safe and feasible option for the removal of large non-ampullary duodenal adenomas

Dataset related to article "Effect of chemotherapy on tumour-vessel relationship in colorectal liver metastases"

This record contains raw data related to article “Effect of chemotherapy on tumour-vessel relationship in colorectal liver metastases" Abstract Chemotherapy is the fundamental companion of surgery for treatment of patients with colorectal liver metastases (CLMs)1 . When chemotherapy leads to tumour shrinkage, this is expected to have two major effects. It reduces tumour burden and, most relevant for surgeons, shrinkage may detach CLMs from vessels, enabling more conservative procedures and increasing resectabil- ity. Although the first effect is indisputable, the second one has not been confirmed completely by data. In two studies 6,7 with some limitations, including small sample size and low adoption of targeted therapies, tumour shrinkage led to regression of tumour–vessel contact in only one-fifth of patients. The authors’ group has pursued an aggressive ultrasound- guided parenchyma-sparing approach based on a vessel-sparing policy, scheduling tumour detachment from vessels or partial vein resection/reconstruction whenever possible since 2004. This has allowed accurate analysis of modification of the tumour–vessel relationship after chemotherapy. The aim of this study was to elucidate whether tumour shrinkage by chemother- apy corresponds to regression of CLM–vessel contact

Dataset related to article "Intrahepatic CD69 + Vδ1 T cells re-circulate in the blood of patients with metastatic colorectal cancer and limit tumor progression"

This record contains raw data related to article “Intrahepatic CD69 + Vδ1 T cells re-circulate in the blood of patients with metastatic colorectal cancer and limit tumor progression" Abstract Background: More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack of reliable prognostic markers. Vδ1 cells are a subset of tissue-resident gamma delta (γδ) T lymphocytes endowed with a broad array of antitumor functions and showing a natural high tropism for the liver. However, little is known about their impact in the clinical outcomes of CLM. Methods: We isolated human γδ T cells from peripheral blood (PB) and peritumoral (PT) tissue of 93 patients undergone surgical procedures to remove CLM. The phenotype of freshly purified γδ T cells was assessed by multiparametric flow cytometry, the transcriptional profiles by single cell RNA-sequencing, the functional annotations by Gene Ontology enrichment analyses and the clonotype by γδ T cell receptor (TCR)-sequencing. Results: The microenvironment of CLM is characterized by a heterogeneous immune infiltrate comprising different subsets of γδ tumor-infiltrating lymphocytes (TILs) able to egress the liver and re-circulate in PB. Vδ1 T cells represent the largest population of γδ TILs within the PT compartment of CLM that is greatly enriched in Vδ1 T effector (TEF) cells expressing constitutive high levels of CD69. These Vδ1 CD69+ TILs express a distinct phenotype and transcriptional signature, show high antitumor potential and correlate with better patient clinical outcomes in terms of lower numbers of liver metastatic lesions and longer overall survival (OS). Moreover, intrahepatic CD69+ Vδ1 TILs can egress CLM tissue to re-circulate in PB, where they retain a phenotype, transcriptional signature and TCR clonal repertoires resembling their liver origin. Importantly, even the increased frequencies of the CD69+ terminally differentiated (TEMRA) Vδ1 cells in PB of patients with CLM significantly correlate with longer OS. The positive prognostic score of high frequencies of CD69+ TEMRA Vδ1 cells in PB is independent from the neoadjuvant chemotherapy and immunotherapy regimens administered to patients with CLM prior surgery. Conclusions: The enrichment of tissue-resident CD69+ Vδ1 TEMRA cells re-circulating at high frequencies in PB of patients with CLM limits tumor progression and represents a new important clinical tool to either predict the natural history of CLM or develop alternative therapeutic protocols of cellular therapies.

Dataset related to article "The Histopathological Growth Pattern of Colorectal Liver Metastases Impacts Local Recurrence Risk and the Adequate Width of the Surgical Margin"

This record contains raw data related to article "The Histopathological Growth Pattern of Colorectal Liver Metastases Impacts Local Recurrence Risk and the Adequate Width of the Surgical Margin" Abstract Background: The histopathological growth pattern (HGP) of colorectal liver metastases (CLM) has been associated with prognosis. This study was designed to elucidate if the HGP is associated with local recurrence risk and impacts the adequate width of surgical margin. Methods: All consecutive patients resected for CLM in 2018-2019 were considered. HGP was prospectively classified as follows: desmoplastic, pushing, and replacement. Surgical margin was classified as follows: R0 (margin ≥ 1 mm), R1vasc (0-mm margin, tumor detachment from intrahepatic vessels), and R1par (tumor exposure along transection plane). R0 resections were further distinguished in R0min (1-mm margin) and R0wide (> 1-mm margin). Results: A total of 340 resection areas in 136 patients were analyzed (70 R0min, 143 R0wide, 31 R1vasc, 96 R1par). HGP was desmoplastic in 26 cases, pushing in 221, and replacement in 93. Thirty-six local recurrences occurred (11%, median follow-up 21 months): 1 after R0wide, 4 after R0min, 3 after R1vasc, and 28 after R1par resection. In R1par group, local recurrence rate was high independently of HGP (29%). In R1vasc and R0min groups, local recurrence risk was higher in the replacement group (R1vasc: 29% vs. 4% if pushing/desmoplastic; R0min: 11% vs. 4%). In R0wide group, local recurrence risk was low for all HGP ( < 1%). Independent predictors of local recurrence were replacement HGP (odds ratio = 1.654, P = 0.036), and R1par resection (odds ratio = 57.209, P < 0.001 vs. R0). Conclusions: Replacement HGP is associated with an increased risk of local recurrence. In these patients, a wide surgical margin should be pursued, because R1vasc and R0min resections could be insufficient. R1par resection is inadequate, independently of the HGP

Dataset related to the article "A token-mixer architecture for CAD-RADS classification of coronary stenosis on multiplanar reconstruction CT images"

This record contains raw data related to the article "A token-mixer architecture for CAD-RADS classification of coronary stenosis on multiplanar reconstruction CT images" A B S T R A C T Background and objective: In patients with suspected Coronary Artery Disease (CAD), the severity of stenosis needs to be assessed for precise clinical management. An automatic deep learning-based algorithm to classify coronary stenosis lesions according to the Coronary Artery Disease Reporting and Data System (CAD-RADS) in multiplanar reconstruction images acquired with Coronary Computed Tomography Angiography (CCTA) is proposed. Methods: In this retrospective study, 288 patients with suspected CAD who underwent CCTA scans were included. To model long-range semantic information, which is needed to identify and classify stenosis with challenging appearance, we adopted a token-mixer architecture (ConvMixer), which can learn structural relationship over the whole coronary artery. ConvMixer consists of a patch embedding layer followed by repeated convolutional blocks to enable the algorithm to learn long-range dependences between pixels. To visually assess ConvMixer performance, Gradient-Weighted Class Activation Mapping (Grad-CAM) analysis was used. Results: Experimental results using 5-fold cross-validation showed that our ConvMixer can classify significant coronary artery stenosis (i.e., stenosis with luminal narrowing ≥50%) with accuracy and sensitivity of 87% and 90%, respectively. For CAD-RADS 0 vs. 1–2 vs. 3–4 vs. 5 classification, ConvMixer achieved accuracy and sensitivity of 72% and 75%, respectively. Additional experiments showed that ConvMixer achieved a better trade-off between performance and complexity compared to pyramid-shaped convolutional neural networks. Conclusions: Our algorithm might provide clinicians

Dataset related to the article "Cardiac magneticresonanceforprophylactic implantable-cardioverter defibrillator therapy international study:prognosticvalueofcardiac magnetic resonance-derivedrightventricular parameters substudy"

This record contains partial raw data related to the article “Cardiac magneticresonanceforprophylactic implantable-cardioverter defibrillator therapy international study:prognosticvalueofcardiac magnetic resonance-derivedrightventricular parameters substudy" Aims: Right ventricular (RV) systolic dysfunction (RVSD) has been recognized as an important determinant of outcomes in heart failure (HF) patients. However, assessment of RV volumes is challenging as the geometric complexity of the RV prohibits quantitative assessment by traditional 2D-echocardiography. Cardiac magnetic resonance (CMR) is the gold standard for RV chamber quantification with its high spatial resolution, precise definition of anatomy, and excellent reproducibility. In this study, we sought to investigate the incremental prognostic value of CMR-derived RV volumetric parameters in a large cohort of HF patients with reduced ejection fraction (HFrEF). Methods and Results: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n=2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan–Meier curves and cox regression were used to  investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8±14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0±10.8. Median follow-up was 959 days (interquartile range: 560–1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio=1.44; 95%CI[1.09–1.91]; P=0.01). On subgroup analyses,the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHAIII/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function. Conclusions: RV dysfunction is an independent predictor of all-cause mortality in a large cohort of patients with HFrEF, with the prognostic value of RV dysfunction being more pronounced in select subgroups; likely reflecting the importance of RV function in the early stages of HF progression.

Dataset related to the article "Prediction of myocardial blood flow under stress conditions by means of a computational model"

This record contains raw data related to the article “Prediction of myocardial blood flow under stress conditions by means of a computational model” Purpose. Quantification of myocardial blood flow (MBF) and functional assessment of coronary artery disease (CAD) can be achieved through stress myocardial computed tomography perfusion (stress-CTP). This requires an additional scan after the resting coronary computed tomography angiography (cCTA) and administration of an intravenous stressor. This complex protocol has limited reproducibility and non-negligible side effects for the patient. We aim to mitigate these drawbacks by proposing a computational model able to reproduce MBF maps. Methods. A computational perfusion model was used to reproduce MBF maps. The model parameters were estimated by using information from cCTA and MBF measured from stress-CTP (MBFCTP) maps. The relative error between the computational MBF under stress conditions (MBFCOMP) and MBFCTP was evaluated to assess the accuracy of the proposed computational model. Results. Applying our method to 9 patients (4 control subjects without ischemica vs 5 patients with myocardial ischemia), we found an excellent agreement between the values of MBFCOMP and MBFCTP. In all patients, the relative error was below 8% over all the myocardium, with an average-in-space value below 4%. Conclusion. The results of this pilot work demonstrate the accuracy and reliability of the proposed computational model in reproducing MBF under stress conditions. This consistency test is a preliminary step in the framework of a more ambitious project which is currently under investigation, i.e. the construction of a computational tool able to predict MBF avoiding the stress protocol and potential side effects while reducing radiation exposure.