10 research outputs found
Predicting the Evolution of Lung Squamous Cell Carcinoma In Situ Using Computational Pathology
No full textLung squamous cell carcinoma in situ (SCIS) is the preinvasive precursor lesion of lung squamous cell carcinoma (SCC). Only around two-thirds of these lesions progress to invasive cancer, while one-third undergo spontaneous regression, which presents a significant clinical challenge due to the risk of overtreatment. The ability to predict the evolution of SCIS lesions can significantly impact patient management. Our study explores the use of computational pathology in predicting the evolution of SCIS. We used a dataset consisting of 112 H&E-stained whole slide images (WSIs) that were obtained from the Image Data Resource public repository. The dataset corresponded to tumors of patients who underwent biopsies of SCIS lesions and were subsequently followed up by bronchoscopy and CT scans to monitor for progression to SCC. We used this dataset to train two models: a pathomics-based ridge classifier trained on 80 principal components derived from almost 2000 extracted features and a deep convolutional neural network with a modified ResNet18 architecture. The performance of both approaches in predicting progression was assessed. The pathomics-based ridge classifier model obtained an F1-score of 0.77, precision of 0.80, and recall of 0.77. The deep learning model performance was similar, with a WSI-level F1-score of 0.80, precision of 0.71, and recall of 0.90. These findings highlight the potential of computational pathology approaches in providing insights into the evolution of SCIS. Larger datasets will be required in order to train highly accurate models. In the future, computational pathology could be used in predicting outcomes in other preinvasive lesions
Hemodynamic Effects of SGLT2 Inhibitors in Patients with and Without Diabetes Mellitus—A Narrative Review
No full textBackground: The current review aims to present the beneficial effects of SGLT2 inhibitors (dapagliflozin and empagliflozin) on several hemodynamic parameters such as blood pressure, filtration pressure at the level of the glomerular capillaries, and the improvement of the preload and afterload of heart muscle. In order to stop chronic kidney disease (CKD) from progressing, SGLT2 inhibitors have become an important disease-modifying treatment. Materials and methods: Recent clinical studies have shown the success of these drugs in treating heart failure, reducing the risk of cardiovascular events, hospitalization, and mortality. Results: The hemodynamic effects of SGLT2 inhibitors include a diuretic effect, due to reduced sodium reabsorption. Also, at this level, numerous studies have confirmed the beneficial effect of dapagliflozin in patients with chronic kidney disease, associated with a 44% reduced risk of progression in this pathology. SGLT2 inhibitors are associated with a reduction in blood pressure and weight loss, because of their diuretic effect, especially empagliflozin, which can explain the beneficial effects in patients with heart failure. In addition, mainly empagliflozin reduces stiffness and arterial resistance. Conclusions: Although the exact mechanism of action is unknown, SGLT2 inhibitors reduce the interstitial volume by blocking the tubular reabsorption of glucose. This leads to reduced blood pressure and enhanced endothelial function. Consequently, there have been improvements in hospitalization and fatality rates. Because of their beneficial effects, these medications have been guidelines for managing heart failure and chronic kidney disease
Clinicopathological correlations between colorectal cancer and genetic mutations
No full textObjective. Colorectal cancer is an oncological pathology that, unfortunately, has increased in terms of incidence in recent years. The presence of KRAS and BRAF mutations in colorectal cancer has significant clinical implications. As a result we want to conduct research that analyzes the impact of these mutations on patients diagnosed with colorectal cancer and also to observe the clinicopathological differences between mutant and wild-type tumors. Material and methods. We conducted a retrospective study in the period 2018-2022, including 118 patients diagnosed with colorectal cancer. The patients were subsequently divided into two groups equal in number of patients, depending on the presence or absence of mutations. Outcomes. After analyzing the data we were able to identify several differences between the two groups, regarding the histopathological type - mucinous correlated with the mutant tumors, the degree of infiltration of the locoregional lymph nodes (more N+ cases in the mutant group), the location of the primary tumor (right colon within the mutant tumors, the rectosigmoid region in the wild-type group), the location of secondary tumors (pulmonary ones with a triple incidence in the mutant group).
Conclusions. The study of genetic mutations and their role in colorectal cancer has provided valuable insights into the underlying mechanisms of this complex disease. It is an ever-evolving field that promises to have a profound impact on patient care, ultimately leading us toward more effective prevention, early
detection, and personalized therapies for colorectal cancer patients. By leveraging genetic information, clinicians can optimize treatment plans, minimize side effects, and increase the chances of successful outcomes for individual patients
Novel Immunohistochemical Profiling of Small-Cell Lung Cancer: Correlations Between Tumor Subtypes and Immune Microenvironment
No full textBackground/Objectives: Small-cell lung cancer (SCLC) is a highly aggressive malignancy with an emerging molecular classification based on the expression of the transcription factors ASCL1, NEUROD1, and POU2F3. This study aimed to explore the relationship between these novel subtypes and the tumor immune microenvironment (TIME), particularly CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). Methods: In 51 cases of patients with SCLC, immunohistochemical (IHC) stains for ASCL1, NEUROD1, POU2F3, CD56, Ki67, CD8, and CD4 were performed. H-scores for the novel transcription factors were calculated to determine tumor subtype. CD8+ and CD4+ TIL counts were averaged across 10 high-power fields. The Kruskal–Wallis test and subsequent post hoc Dunn tests were used to determine the differences in transcription factor expression and TILs across subtypes. Results: In our cohort, 68.62% of our cases were SCLC-A, 9.80% were SCLC-N, 7.84% were SCLC-P, and 13.72% were SCLC-I. Significant differences were observed in the expression of ASCL1, NEUROD1, and POU2F3 across subtypes. CD8+ TILs were more abundant in SCLC-P and SCLC-I. CD8+ TILs were negatively correlated with ASCL1 expression (p < 0.05) and positively correlated with POU2F3 expression (p < 0.005). Conclusions: This study highlights the need to integrate the novel SCLC classification with data regarding the TIME to better inform patient prognosis and treatment
Assessing the Role of Lipopolysaccharide (LPS) Receptor (CD14) in Septic Cardiomyopathy: The Value of Immunohistochemical Diagnostics
No full textSepsis-induced myocardial dysfunction (SIMD) is one of the major predictors of morbidity and mortality of sepsis. A high percentage of patients with SIMD develop a status similar to cardiogenic shock. A high level of bacterial lipopolysaccharide (LPS) associated with an overexpression of CD14 acts as the trigger for the release of a broad spectrum of cytokines. Our study aimed to understand the correlation between septic cardiomyopathy and CD14 immunohistochemical expression. The study included 29 patients who died of septic shock. Increased values of membranous CD14 and soluble CD14 in the heart tissue were correlated with adverse patient evolution. A high cellular expression of CD14 was noted in the study group vs. the control group (p = 0.0013). Therefore, a close positive association between the amount of LPS related to sCD14 and the cellular expression of mCD14 is probable. By extrapolation, we suggest that a large amount of sCD14 detected in the cardiac tissue will activate the mCD14–TRL4–LBP–LPS complex, which in turn will induce an inadequate immune response, resulting in heart damage proportional to the amount of LPS. CD14 could represent a valuable marker for septic cardiomyopathy; thus, apoptosis of cardiomyocytes could be foreseen by its high value
Magnetic resonance used as a differential diagnostic tool between inflammatory cancer of the sigmoid and acute sigmoid diverticulitis
No full textSigmoid diverticulitis is a common disease characterized by a well-standardized diagnostic approach and treatment. Colorectal cancer is the third most common malignancy worldwide, irrespective of gender. In 2020, CRC global-related mortality rate was estimated at 935 173 cases, with an incidence of 9.3% in men and 9.5% in women. The diagnosis of acute diverticulitis is always made by performing a contrast-enhanced-computed tomography (CT) of the abdomen. Current diagnosis guidelines do not recommend the use of a magnetic resonance imaging (MRI) for further and more precise assessment of a suspected sigmoid diverticulitis diagnosed by CT. Early lower-gastrointestinal (lower-GI) endoscopy is rarely conducted; thus, the diagnosis delay could have a negative impact over the oncological outcome of the disease. Few and scarce data can be found related to this issue, with only a recent Swedish study paying attention towards early identification of neoplastic disease residing on a background of sigmoid diverticulitis, facilitated by MRI. The purpose of this study is to evaluate the feasibility of systematically performing an abdominal MRI included in the primary assessment of acute diverticulitis already diagnosed by CT, in order to argument in favor of an early lower-GI endoscopy where a positive MRI for neoplasia is found
Epidermoid Cyst of the Uterine Cervix, an Unusual Location: Literature Review and Case Report
No full textEpidermoid cysts are most often benign cystic lesions, with uterine cervical localisation being very unusual. We present the case of a 52-year-old female patient diagnosed with an epidermoid cyst at the level of the uterine cervix. A bioptic and haemostatic uterine curettage was performed, followed by total hysterectomy with bilateral adnexectomy. The histopathologic analysis and immunohistochemical essay of the resection specimens confirmed the cervical epidermoid cyst. The presence of high-risk HPV (human papillomavirus) was only seen in the cervical mucosa. The exact etiopathogenesis is unknown, but postpartum cell implantation of reminiscent embryonic tissue can be involved in the development of these lesions
An Evidence-Based Update on the Potential Association between Rheumatoid Arthritis and Lymphangioleiomyomatosis
No full textLymphangioleiomyomatosis (LAM) represents an uncommon disorder characterized by cystic lung destruction and chronic respiratory failure. Lung damage caused by various mechanisms may represent a hypothesis for studying the association between LAM and rheumatoid arthritis (RA), which is the most prevalent autoinflammatory rheumatic disease and may affect the lungs as an extra-articular manifestation. Despite their distinct clinical presentations, the pathophysiology of both disorders includes dysregulated immunological function, abnormal cellular development, and inflammation. Current research suggests a potential relationship between RA and LAM, as some RA patients have been reported to develop LAM. However, the association of RA and LAM raises important therapeutic dilemmas. For this reason, the trajectory of a patient who was identified in our medical records as suffering from both LAM and RA, treated with many novel molecules and biological therapy, but with a negative outcome due to respiratory and multiorgan failure, has been exemplified. The delay in the diagnosis of LAM is due to a correlation between RA and LAM, worsening the vital prognosis and also hindering pulmonary transplantation. In addition, extensive research is essential for understanding the potential connection between these two disorders and discovering any similar mechanisms involved that may underlie their occurrence. This may contribute to the development of new therapeutic options that target shared pathways implicated in the pathogenesis of RA and LAM
Cohort profile: the ESC EURObservational Research Programme Non-ST-segment elevation myocardial infraction (NSTEMI) Registry
No full textAims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Non-ST-segment elevation myocardial infarction (NSTEMI) Registry aims to identify international patterns in NSTEMI management in clinical practice and outcomes against the 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without ST-segment-elevation. Methods and results Consecutively hospitalised adult NSTEMI patients (n = 3620) were enrolled between 11 March 2019 and 6 March 2021, and individual patient data prospectively collected at 287 centres in 59 participating countries during a two-week enrolment period per centre. The registry collected data relating to baseline characteristics, major outcomes (inhospital death, acute heart failure, cardiogenic shock, bleeding, stroke/transient ischaemic attack, and 30-day mortality) and guideline-recommended NSTEMI care interventions: electrocardiogram pre- or in-hospital, prehospitalization receipt of aspirin, echocardiography, coronary angiography, referral to cardiac rehabilitation, smoking cessation advice, dietary advice, and prescription on discharge of aspirin, P2Y12 inhibition, angiotensin converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB), beta-blocker, and statin. Conclusion The EORP NSTEMI Registry is an international, prospective registry of care and outcomes of patients treated for NSTEMI, which will provide unique insights into the contemporary management of hospitalised NSTEMI patients, compliance with ESC 2015 NSTEMI Guidelines, and identify potential barriers to optimal management of this common clinical presentation associated with significant morbidity and mortality
