Predictors of Disease Progression and Adverse Clinical Outcomes in Patients With Moderate Aortic Stenosis Using an Artificial Intelligence-Based Software Platform.

Patients with moderate aortic stenosis (AS) have a greater risk of adverse clinical outcomes than that of the general population. How this risk compares with those with severe AS, along with factors associated with outcomes and disease progression, is less clear. We analyzed serial echoes (from 2017 to 2019) from a single healthcare system using Tempus Next (Chicago, Illinois) software. AS severity was defined according to American Heart Association/American College of Cardiology guidelines. Outcomes of interest included death or heart failure hospitalization. We used Cox proportional hazards models and logistic regression to identify predictors of clinical outcome and disease progression, respectively. From 82,805 echoes for 61,546 patients, 1,770; 914; 565; and 1,463 patients had no, mild, moderate, or severe AS, respectively. Both patients with moderate and those with severe AS experienced a similar prevalence of adverse clinical outcomes (p = 0.45) that was significantly greater than that of patients without AS (p <0.01). In patients with moderate AS, atrial fibrillation (hazard ratio 3.29, 95% confidence interval 1.79 to 6.02, p <0.001) and end-stage renal disease (hazard ratio 3.34, 95% confidence interval 1.87 to 5.95, p <0.001) were associated with adverse clinical outcomes. One-third of patients with moderate AS with a subsequent echo (139/434) progressed to severe AS within 1 year. In conclusion, patients with moderate AS can progress rapidly to severe AS and experience a similar risk of adverse clinical outcomes; predictors include atrial fibrillation and low left ventricular ejection fraction. Machine learning algorithms may help identify these patients. Whether these patients may warrant earlier intervention merits further study.

Advanced penile lymphoma: Case report and review of the literature.

Primary penile lymphomas are extremely rare. They are aggressive neoplasms that can present as double-or triple-hit lymphomas, and because the associate with a high risk of central nervous system dissemination, treatment consists of high-dose chemotherapy regimens plus intrathecal prophylaxis. Pathology can be confused with squamous cell carcinoma of the penis, leading to inappropriate treatments and unnecessary amputations. We report the case of a patient diagnosed with clinical Stage IV penile non-Hodgkin lymphoma that was treated with a complete and durable response. In addition, we review the available literature on penile lymphoma.

Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck.

Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min-Max: 31-86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.

Durable complete remission with local therapies after neoadjuvant and adjuvant nivolumab in recurrent/metastatic head and neck cancer.

Up to 10-15% of patients with first-line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) present with platinum-refractory disease. The anti-PD1 nivolumab is the first therapeutic option in this setting achieving a 19.2% objective response rate and a 7.7-month median overall survival (OS). Given the poor prognosis of platinum-refractory patients, those showing slow progressive disease with no functional status deterioration should maintain nivolumab beyond progression in the absence of severe or unmanageable toxicities. Another strategy is to use local therapies such as radiotherapy and surgical tumor resection in cases of oligometastatic or oligoprogressive disease. Both strategies may significantly improve disease control and OS in these populations. We present the case of a patient with platinum-refractory disease treated with first-line nivolumab beyond progression who achieved a durable complete response after palliative radiation and surgical resection of five tumor lesions. To our knowledge, this is the first reported case of an R/M HNSCC treated with such a strategy outside a clinical trial and contributes to the evidence for combining anti-PD1 agents and local therapies in selected patients with R/M HNSCC.

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer.

Novel chemo-immunotherapy (chemo-IO) combinations should be evaluated, which may be suitable for cisplatin-unfit or fluoropyrimide-ineligible patients with recurrent or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) to guarantee higher and deeper responses than IO alone. The aim of the present study was to review our experience using pembrolizumab-carboplatin-paclitaxel (pembro + CP) in patients with R/M SCCHN. This was a retrospective study of patients with R/M SCCHN who received pembro + CP in any-line via a compassionate-use program. The present study evaluated safety using Common Terminology Criteria for Adverse Events v4.0, compliance, overall response rate (ORR) and disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors 1.1, duration of treatment, progression-free survival (PFS) and overall survival (OS). Between March 2020 and August 2021, 10 patients were identified (median age, 64 years; female, 60%; Eastern Cooperative Oncology Group 2, 80%). A total of 8 patients received pembro + 3-weekly carboplatin-paclitaxel (3wkCP). A total of 2 patients received pembro + weekly carboplatin-paclitaxel (wkCP). Patients received a median of 3 lines (range, 0-6) of systemic therapy prior to pembro + CP and 80% received IO in previous lines. Grade 1-2 adverse events (AEs) occurred in 100% of patients. Grade 3-5 AEs occurred in 30% of patients [all grade 3 (anemia, neutropenia, thrombopenia, hypertension)]. The mean numbers of pembro + wkCP and pembro + 3wkCP cycles were 2.5 and 6. The ORR (n=7) was 14% (1/7) with one complete response. The DCR was 43% (3/7). The median PFS (n=7) and OS (n=10) times since pembro + CP were 5 months (95% CI, 1-9) and 6 months (95% CI, 0.5-14), respectively. In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high. Studies should be conducted to prospectively evaluate the safety and efficacy of this combination in patients with R/M SCCHN.

A Novel Reconstruction Method for Temperature Distribution Measurement Based on Ultrasonic Tomography.

The precise temperature distribution measurement is crucial in many industrial fields, where ultrasonic tomography (UT) has broad application prospects and significance. In order to improve the resolution of reconstructed temperature distribution images and maintain high accuracy, a novel two-step reconstruction method is proposed in this article. First, the problem of solving the temperature distribution is converted to an optimization problem and then solved by an improved version of the equilibrium optimizer (IEO), in which a new nonlinear time strategy and novel population update rules are deployed. Then, based on the low-resolution and high-precision images reconstructed by IEO, Gaussian process regression (GPR) is adopted to enhance image resolution and keep the reconstruction errors low. After that, the number of divided grids and the parameters of IEO are also further studied to improve the reconstruction quality. The results of numerical simulations and experiments indicate that high-resolution images with low reconstruction errors can be reconstructed effectively by the proposed IEO-GPR method, and it also shows excellent robust performance. For a complex three-peak temperature distribution, a competitive accuracy with 3.10% and 2.37% error at root-mean-square error and average relative error is achieved, respectively. In practical experiment, the root-mean-square error of IEO-GPR is 0.72%, which is at least 0.89% lower than that of conventional algorithms.

Clinical Predictors of Mortality in Patients with Moderate to Severe Mitral Regurgitation.

BACKGROUND: Mitral regurgitation is the most common form of valvular heart disease worldwide, however, there is an incomplete understanding of predictors of mortality in this population. This study sought to identify risk factors of mortality in a real-world population with mitral regurgitation. METHODS: All patients with moderate or severe mitral regurgitation were identified at a single center from January 1, 2016 to August 31, 2017. Multivariate regression was performed to evaluate variables independently associated with all-cause mortality. RESULTS: A total of 490 patients with moderate (76.3%) or severe (23.7%) mitral regurgitation due to primary (20.8%) or secondary (79.2%) etiology were identified. The mean age was 66.7 years; 50% were male. At a median follow-up of 3.1 years, the incidence of all-cause mortality was 30.1%, heart failure hospitalization 23.1%, and mitral valve intervention 11.6%. Of 117 variables, multivariate analysis demonstrated 5 that were independently predictive of mortality: baseline creatinine (hazard ratio [HR] 1.2; 95% CI, 1.0-1.3; P = .02), right atrial pressure by echocardiogram (HR 1.3; 95% CI, 1.07-1.55; P = .008), hemoglobin (HR 0.65; 95% CI, 0.52-0.83; P = .001), hospitalization for heart failure (HR 1.6; 95% CI, 1.1-2.4; P = .015), and mitral valve intervention (HR 0.40; 95% CI, 0.16-0.83; P = .049). CONCLUSION: In this retrospective, pragmatic analysis of patients with moderate or severe mitral regurgitation, admission for heart failure exacerbation, elevated right atrial pressure, renal dysfunction, anemia, and lack of mitral valve intervention were independently associated with increased risk of all-cause mortality. Whether these risk factors may better identify select patients who may benefit from more intensive monitoring or earlier intervention should be considered in future studies.

Enhanced Detection of Heart Valve Disease Using Integrated Artificial Intelligence at Scale.

BACKGROUND: Undertreatment of heart valve disease creates unnecessary patient risk. Poorly integrated healthcare data systems are unequipped to solve this problem. A software program using a rules-based algorithm to search the electronic health record for heart valve disease among patients treated by healthcare systems in the United States may provide a solution. METHODS: A software interface allowed concurrent access to picture archiving communication systems, the electronic health record, and other sources. The software platform was created to programmatically run a rules engine to search structured and unstructured data for identification of moderate or severe heart valve disease using guideline-reported values. Incidence and progression of disease as well as compliance with a care pathway were assessed. RESULTS: In 2 health institutions in the United States 60,145 patients had 77,215 echocardiograms. Moderate or severe aortic stenosis (AS) was identified at a rate of 9.1% of patients (5474 and 6910 echocardiograms) in this population. The precision and accuracy of the algorithm for the detection of moderate or severe AS was 92.9% and 98.6%, respectively. Thirty-five percent of patients (441/1265) with moderate stenosis and a subsequent echocardiogram progressed to severe stenosis (mean interval, 358 days). In 1 sample 70.3% of moderate AS patients lacked a 6-month echocardiogram or appointment. The platform enabled 100% accountability for all patients with severe AS. CONCLUSIONS: A rules-based software program enhances detection of heart valve disease and can be used to measures disease progression and care pathway compliance.

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study.

BACKGROUND: Axitinib monotherapy obtained approval in pre-treated mRCC patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified. PATIENTS AND METHODS: Retrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months vs. disease progression/refractory patients [RP]). A multivariate logistic-regression model was used to analyse clinical factors. Efficacy and safety were also analysed. RESULTS: In total, 157 patients who received axitinib in second or subsequent line were evaluated (91 LR and 66 RP). Older age at start of axitinib and haemoglobin levels > LLN were independent predictive factors for LR in multivariate analyses. In LR patients, median (m) PFS was 18.1 months, median overall survival was 36.0 months and objective response rate (ORR) was 45.5%. In 59 LR patients receiving axitinib in second-line, mPFS was 18.7 months, mOS was 44.8 months and ORR was 43.9%. mOS was significantly longer in second line compared to subsequent lines (44.8 vs. 26.5 months; P = .009). In LR vs. RP, mPFS with sunitinib in first-line was correlated with mPFS with axitinib in second-line (27.2 vs. 10.9 months P < .001). The safety profile was manageable and consistent with known data. CONCLUSIONS: This study confirms the long-term benefits of axitinib in a selected population, helping clinicians to select the best sequential approach and patients who could obtain a greater benefit from axitinib.

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer.

Patients with early-stage non-small-cell lung cancer (NSCLC) are candidates for curative surgery; however, despite multiple advances in lung cancer management, recurrence rates remain high. Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival (OS), but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients. The high efficacy of tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor-mutated (EGFR) in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease. Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment, in patients with resected EGFR-mutated NSCLC, and shown that they significantly prolong disease-free survival (DFS), but this benefit does not translate to OS. Recently, an interim analysis of the ADAURA trial demonstrated that, surprisingly, osimertinib improved DFS. This led to the study being stopped early, leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup. These targeted agents are also being evaluated in locally-advanced disease, with promising results, although prospective studies with larger sample sizes are needed to confirm these results. In this article, we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

Immunotherapy in microsatellite instability metastatic colorectal cancer: Current status and future perspectives.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent and deadly malignancies worldwide. This specific pathology is composed of various molecular entities, with distinct immunological phenotypes. In addition to KRAS, NRAS, and BRAF mutation status, other druggable alterations such as those in HER2, MET, NTRK, ALK, and ROS1 have been identified in recent years offering new therapeutic options for some patients with CRC. AIM: This review will focus on the molecular biology, immunological fingerprints, and current clinical evidence for the use of immunotherapy in patients with CRC. RELEVANCE FOR PATIENTS: High microsatellite instability (MSI-H) and mutations in mismatch repair genes constitute a new molecular entity within CRC, which is characterized by a high mutational and neoantigen burden, frequent immune cell infiltration, and where immune checkpoint inhibitors have shown high response and survival rates compared to microsatellite stable (MSS) tumors. Indeed, the approval of pembrolizumab in MSI-H tumors was the first agnostic FDA approval in solid tumors. While monotherapy with anti-programmed cell death protein-1 agents achieves objective response rates (ORR) of around 30% and 1-year overall survival (OS) rates of 76%, anti-PD1, and anti-CTLA4 combinations achieve a 55% ORR and a 1-year OS rate of 85%. Several ongoing trials are evaluating the use of different immunotherapy combinations, both in the advanced and early settings and in MSI-h and MSS CRCs.

Urban Intersection Classification: A Comparative Analysis.

Understanding the scene in front of a vehicle is crucial for self-driving vehicles and Advanced Driver Assistance Systems, and in urban scenarios, intersection areas are one of the most critical, concentrating between 20% to 25% of road fatalities. This research presents a thorough investigation on the detection and classification of urban intersections as seen from onboard front-facing cameras. Different methodologies aimed at classifying intersection geometries have been assessed to provide a comprehensive evaluation of state-of-the-art techniques based on Deep Neural Network (DNN) approaches, including single-frame approaches and temporal integration schemes. A detailed analysis of most popular datasets previously used for the application together with a comparison with ad hoc recorded sequences revealed that the performances strongly depend on the field of view of the camera rather than other characteristics or temporal-integrating techniques. Due to the scarcity of training data, a new dataset is created by performing data augmentation from real-world data through a Generative Adversarial Network (GAN) to increase generalizability as well as to test the influence of data quality. Despite being in the relatively early stages, mainly due to the lack of intersection datasets oriented to the problem, an extensive experimental activity has been performed to analyze the individual performance of each proposed systems.

CAPformer: Pedestrian Crossing Action Prediction Using Transformer.

Anticipating pedestrian crossing behavior in urban scenarios is a challenging task for autonomous vehicles. Early this year, a benchmark comprising JAAD and PIE datasets have been released. In the benchmark, several state-of-the-art methods have been ranked. However, most of the ranked temporal models rely on recurrent architectures. In our case, we propose, as far as we are concerned, the first self-attention alternative, based on transformer architecture, which has had enormous success in natural language processing (NLP) and recently in computer vision. Our architecture is composed of various branches which fuse video and kinematic data. The video branch is based on two possible architectures: RubiksNet and TimeSformer. The kinematic branch is based on different configurations of transformer encoder. Several experiments have been performed mainly focusing on pre-processing input data, highlighting problems with two kinematic data sources: pose keypoints and ego-vehicle speed. Our proposed model results are comparable to PCPA, the best performing model in the benchmark reaching an F1 Score of nearly 0.78 against 0.77. Furthermore, by using only bounding box coordinates and image data, our model surpasses PCPA by a larger margin (F1=0.75 vs. F1=0.72). Our model has proven to be a valid alternative to recurrent architectures, providing advantages such as parallelization and whole sequence processing, learning relationships between samples not possible with recurrent architectures.

Carcinoma bilateral de mama en crisis visceral / Bilateral breast carcinoma in visceral crisis

El carcinoma bilateral de mama es poco frecuente y raro, es bueno definir si ocurre de forma sincrónica o de forma metacrónica , definir si la lesión en la segunda mama es metástasis o un tumor primario usando criterios patológicos , el estadío y condición clínica . Ya que orienta en el pronóstico y tratamiento especializado a seguir. Presentamos el caso de una paciente con cáncer de mama ECIV por metástasis de mama contralateral en estado de crisis visceral al debut , con anatomía patológica de carcinoma ductal infiltrante de mama, grado 2, componente in situ ausente en ambas mama , RE(70%)RP(80%)Cerb2-,Ki67 30% en mama derecha y RE(100%)RP(80%)Cerb2-Ki67 20% en mama izquierda. Se realizó tomografía de tórax-abdomen-pelvis, evidenciándose derrame pleural bilateral y ascitis en gran volumen. Se decide iniciar tratamiento con quimioterapia sistémica alcanzándose respuesta completa radiológica y clínica. Tras conseguir buen control de la enfermedad se decidió iniciar primera línea hormonal.

Bilateral breast carcinoma is rare and infrequent , it is good to define if it occurs synchronously or metachronously, to define if the lesion in the second breast is metastasis or a primary tumor using pathological criteria, the state and clinical condition . For the prognosis and specialized treatment to follow. We present the case of a patient with ECIV breast cancer due to contralateral breast metastasis in a state of visceral crisis at debut, with pathological anatomy of grade 2 infiltrating ductal carcinoma of the breast, absent in situ component in both breast , RE (70%) , RP (80%), Cerb2 negative, Ki67 30% in the right breast and RE (100%) RP (80%) Cerb2-Ki67 20% left breast. A chest-abdomen-pelvis tomography was performed, showing pleural effusion. bilateral and large volume ascites. It was decided to start treatment with systemic chemotherapy, reaching a complete radiological and clinical response. After achieving good control of the disease, the first hormonal line will be sought.

Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity.

Background: Botulinum NeuroToxin-A (BoNT-A) relieves muscle spasticity and increases range of motion necessary for stroke rehabilitation. Determining the effects of BoNT-A therapy on brain neuroplasticity could help physicians customize its use and predict its outcome. Objective: The purpose of this study was to investigate the effects of Botulinum Toxin-A therapy for treatment of focal spasticity on brain activation and functional connectivity. Design: We used functional Magnetic Resonance Imaging (fMRI) to track changes in blood oxygen-level dependent (BOLD) activation and functional connectivity associated with BoNT-A therapy in nine chronic stroke participants, and eight age-matched controls. Scans were acquired before BoNT-A injections (W0) and 6 weeks after the injections (W6). The task fMRI scan consisted of a block design of alternating mass finger flexion and extension. The voxel-level changes in BOLD activation, and pairwise changes in functional connectivity were analyzed for BoNT-A treatment (stroke W0 vs. W6). Results: BoNT-A injection therapy resulted in significant increases in brain activation in the contralesional premotor cortex, cingulate gyrus, thalamus, superior cerebellum, and in the ipsilesional sensory integration area. Lastly, cerebellar connectivity correlated with the Fugl-Meyer assessment of motor impairment before injection, while premotor connectivity correlated with the Fugl-Meyer score after injection. Conclusion: BoNT-A therapy for treatment of focal spasticity resulted in increased brain activation in areas associated with motor control, and cerebellar connectivity correlated with motor impairment before injection. These results suggest that neuroplastic effects might take place in response to improvements in focal spasticity.

Personalizing first-line treatment in advanced colorectal cancer: Present status and future perspectives.

BACKGROUND: Colorectal cancer is one of the most frequent neoplasms worldwide, and the majority of patients are diagnosed in advanced stages. Metastatic colorectal cancer (mCRC) harbors several mutations with different prognostic and predictive values; KRAS, NRAS, and BRAF mutations are the best known. Indeed, RAS and BRAF molecular status are associated with a different response to monoclonal antibodies (Anti-epidermal growth factor receptor and anti-vascular endothelial growth factor receptor agents), which are usually added to chemotherapy in first-line, and thus allow to select the optimal therapy for patients with mCRC. Furthermore, sidedness is an important predictive and prognostic factor in mCRC, which is explained by the different molecular profile of left and right-sided tumors. Recently, microsatellite instability-high has emerged as a predictive factor of response and survival from immune checkpoint inhibitors in mCRC. Finally, several other alterations have been described in lower frequencies, such as human epidermal growth factor receptor-2 overexpression/amplification, PIK3CA pathway alterations, phosphatase and tension homolog loss, and hepatocyte growth factor/mesenchymal-epithelial transition factor pathway dysregulation, with several targeted therapies already demonstrating activity or being tested in currently ongoing clinical trials. AIM: To review the importance of studying the predictive and prognostic roles of the molecular profile of mCRC, the changes occurred in recent years and how they would potentially change in the near future, to guide physicians in treatment decisions. RELEVANCE FOR PATIENTS: Today, several different therapeutic options can be offered to patients in the first-line setting of mCRC. Therapies at present approved or under investigation in clinical trials will be thoroughly reviewed, with special emphasis on the molecular rationale behind them. Understanding the molecular status, resistance mechanisms and potential new druggable targets may allow physicians to choose the best therapeutic option in the first-line mCRC.