Invasive Therapeutic Strategies Research Articles

Sonodynamic therapy for adult-type diffuse gliomas: past, present, and future.

Intra-axial brain tumors persist as significant clinical challenges. Aggressive surgical resection carries risk of morbidity, and the blood-brain barrier (BBB) prevents optimal pharmacological interventions. There is a clear clinical demand for innovative and less invasive therapeutic strategies for patients, especially those that can augment established treatment protocols. Focused ultrasound (FUS) has emerged as a promising approach to manage brain tumors. Sonodynamic therapy (SDT), a subset of FUS, utilizes sonosensitizers activated by ultrasound waves to generate reactive oxygen species (ROS) and induce tumor cell death. This review explores the historical evolution and rationale behind SDT, focusing on its mechanisms of action and potential applications in brain tumor management. A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Preclinical studies have demonstrated the efficacy of various sonosensitizers, including 5-aminolevulinic acid (5-ALA), fluorescein, porphyrin derivatives, and nanoparticles, in conjunction with FUS for targeted tumor therapy and BBB disruption. Clinical trials have shown promising results in terms of safety and efficacy, although further research is needed to fully understand the potential adverse effects and optimize treatment protocols. Challenges such as skull thickness affecting FUS penetration, and the kinetics of BBB opening require careful consideration for the successful implementation of SDT in clinical practice. Future directions include comparative studies of different sonosensitizers, optimization of FUS parameters, and exploration of SDT's immunomodulatory effects. SDT represents a promising frontier in the treatment of aggressive brain tumors, offering hope for improved patient outcomes.

Exploration of a noninvasive radiomics classifier for breast cancer tumor microenvironment categorization and prognostic outcome prediction

Rationale and Objectives: Breast cancer progression and treatment response are significantly influenced by the tumor microenvironment (TME). Traditional methods for assessing TME are invasive, posing a challenge for patient care. This study introduces a non-invasive approach to TME classification by integrating radiomics and machine learning, aiming to predict the TME status using imaging data, thereby aiding in prognostic outcome prediction. Materials and MethodsUtilizing multi-omics data from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA), this study employed CIBERSORT and MCP-counter algorithms analyze immune infiltration in breast cancer. A radiomics classifier was developed using a random forest algorithm, leveraging quantitative features extracted from intratumoral and peritumoral regions of Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) scans. The classifer’s ability to predict diverse TME states were and their prognostic implications were evaluated using Kaplan-Meier survival curves. ResultsThree distinct TME states were identified using RNA-Seq data, each displaying unique prognostic and biological characteristics. Notably, patients with increased immune cell infiltration showed significantly improved prognoses (P < 0.05). The classifier, comprising 24 radiomic features, demonstrated high predictive accuracy (AUC of training set = 0.960, 95 % CI: 0.922, 0.997; AUC of testing set = 0.853, 95 % CI: 0.687, 1.000) in differentiating these TME states. Predictions from the classifier also correlated significantly with overall patient survival (P < 0.05). ConclusionThis study offers a detailed analysis of the complex TME states in breast cancer and presents a reliable, noninvasive radiomics classifier for TME assessment. The classifer’s accurate prediction of TME status and its correlation with prognosis highlight its potential as a tool in personalized breast cancer treatment, paving the way for more individualized and less invasive therapeutic strategies.

Optical Slot-Assisted Metasurface for IgG Protein Detection

The sensing of antigens plays a pivotal role in the early diagnosis of tumors by potentially revealing specific biomarkers associated with them. Early detection of tumors can facilitate targeted and less invasive therapeutic strategies. In the realm of Immunoglobulin G (IgG) protein detection, a high concentration may indicate tumor lesions or the presence of symptoms commonly detectable just through invasive diagnostic methods. IgG detection is feasible in blood samples or other biological fluids like saliva or urine. These non-invasive tests offer the advantage of being repeatable over time, reducing the need for invasive or painful procedures. In the pursuit of next-generation medical technologies aimed at flexible and compact sensing platforms, we proposed a refractometric system mainly based on a dielectric metasurface, operating at about 780 nm, featuring a 2D distribution of cells composed of dimers that support the optical slot effect. This effect allows for a large Q-factor, with a small footprint, and strong spatial confinement. Specifically, a Q-factor of 3.19 × 103 with a significant amplitude (> 0.7 a.u.) enables a sensitivity of 25 nm/RIU for IgG protein detection.

Stem Cell-Based Therapy and Cell-Free Therapy as an Alternative Approach for Cardiac Regeneration.

The World Health Organization reports that cardiovascular diseases (CVDs) represent 32% of all global deaths. The ineffectiveness of conventional therapies in CVDs encourages the development of novel, minimally invasive therapeutic strategies for the healing and regeneration of damaged tissue. The self-renewal capacity, multilineage differentiation, lack of immunogenicity, and immunosuppressive properties of mesenchymal stem cells (MSCs) make them a promising option for CVDs. However, growing evidence suggests that myocardial regeneration occurs through paracrine factors and extracellular vesicle (EV) secretion, rather than through differentiation into cardiomyocytes. Research shows that stem cells secrete or surface-shed into their culture media various cytokines, chemokines, growth factors, anti-inflammatory factors, and EVs, which constitute an MSC-conditioned medium (MSC-CM) or the secretome. The use of MSC-CM enhances cardiac repair through resident heart cell differentiation, proliferation, scar mass reduction, a decrease in infarct wall thickness, and cardiac function improvement comparable to MSCs without their side effects. This review highlights the limitations and benefits of therapies based on stem cells and their secretome as an innovative treatment of CVDs.

Novel patch biomaterial treatment for colon diverticulosis in swine model.

Current leading managements for diverticular disease cannot prevent the recurrence of diverticulitis, bleeding and/or other complications. There is an immediate need for developing new minimal invasive therapeutic strategies to prevent and treat this disease. Through a biomechanical analysis of porcine colon with diverticular lesions, we proposed a novel adhesive patch concept aiming at mechanical reconstruction of the diseased colon wall. This study aims to evaluate the surgical feasibility (safety and efficacy) of pulmonary visceral pleura (PVP) patch therapy using a pig model of diverticulosis. Six female Yucatan miniature pigs underwent collagenase injection (CI) for the development of diverticular lesions. The lesions in each animal either received patch implantation (treated group, n = 40 for 6 pigs) or left intact (untreated group, n = 44 for 6 pigs). The normal colonic wall in each animal received patch implantation at two spots to serve as control (n = 12 for 6 pigs). After 3months of observation, the performance and safety of the patch treatment were evaluated through macroscopic and histological examination. We found that 95% of pouch-like herniation of the mucosa was prevented from the colon wall with the treatment. The pouch diameter was significantly reduced in the treated group as compared to the untreated group (p < 0.001). The patch application caused a significant increase in the levels of collagen of the colon tissue as compared to the untreated and control groups (p < 0.001). No difference was found in the lymphocyte and macrophage inflammatory infiltrate between the groups. Our results suggest that patch treatment efficiently inhibits the diverticular pouch deformation and promotes the healing of the colon wall with a normal inflammatory response, which may minimize the risk of diverticulosis reoccurrence and complications over time.

The impact of COVID-19 on clinical outcomes among acute myocardial infarction patients undergoing early invasive treatment strategy.

BackgroundThe implications of coronavirus disease 2019 (COVID‐19) infection on outcomes after invasive therapeutic strategies among patients presenting with acute myocardial infarction (AMI) are not well studied.HypothesisTo assess the outcomes of COVID‐19 patients presenting with AMI undergoing an early invasive treatment strategy.MethodsThis study was a cross‐sectional, retrospective analysis of the National COVID Cohort Collaborative database including all patients presenting with a recorded diagnosis of AMI (ST‐elevation myocardial infarction (MI) and non‐ST elevation MI). COVID‐19 positive patients with AMI were stratified into one of four groups: (1a) patients who had a coronary angiogram with percutaneous coronary intervention (PCI) within 3 days of their AMI; (1b) PCI within 3 days of AMI with coronary artery bypass graft (CABG) within 30 days; (2a) coronary angiogram without PCI and without CABG within 30 days; and (2b) coronary angiogram with CABG within 30 days. The main outcomes were respiratory failure, cardiogenic shock, prolonged length of stay, rehospitalization, and death.ResultsThere were 10 506 COVID‐19 positive patients with a diagnosis of AMI. COVID‐19 positive patients with PCI had 8.2 times higher odds of respiratory failure than COVID‐19 negative patients (p = .001). The odds of prolonged length of stay were 1.7 times higher in COVID‐19 patients who underwent PCI (p = .024) and 1.9 times higher in patients who underwent coronary angiogram followed by CABG (p = .001).ConclusionThese data demonstrate that COVID‐19 positive patients with AMI undergoing early invasive coronary angiography had worse outcomes than COVID‐19 negative patients.

Successful conservative management of pathological mandibular fracture resulting from chronic osteomyelitis in a 90‐year‐old woman

AbstractBackgroundWe report the successful conservative management of a pathological mandibular fracture resulting from chronic osteomyelitis in a super‐elderly patient.Case PresentationA 90‐year‐old woman was admitted because of an external dental fistula with purulent drainage. Radiographs showed extensive bone destruction in the mandible. Long‐term antibiotic therapy and chin cap immobilization resulted in satisfactory bone healing 1 year after treatment initiation, which suggests that a conservative approach is alternative or complementary to surgical resection for a mandibular fracture, especially in older patients at high risk of severe postoperative complications.ConclusionAs the population ages, the number of such cases will rise; therefore, minimally invasive therapeutic strategies must be developed.

A practical guide on the use of imiquimod cream to treat lentigo maligna.

Lentigo maligna (LM) is a common insitu melanoma subtype arising on chronically sun-damaged skin and mostly affects the head and neck region. Localisation in cosmetically sensitive areas, difficulty to obtain wide resection margins and advanced patient age/comorbidities have encouraged investigation of less invasive therapeutic strategies than surgery in managing complex cases of LM. Radiotherapy and imiquimod have emerged as alternative treatment options in this context. The treatment of LM with imiquimod cream can be challenging due to the nature of the disease including its often large size, variegated appearance, involvement of adnexal structures, poorly defined peripheral edge and frequent localisation close to sensitive structures such as the eyes and lips, and elderly patients with multiple comorbidities. Prolonged and unpredictable inflammatory reaction and side effects and compliance with a patient-delivered therapy can also be challenging. In the literature to date, studies evaluating the use of imiquimod to treat LM have utilised varying methodologies and provided short follow-up and these limitations have impaired the development of clear guidelines for dosage and management of side effects. Based on our multidisciplinary experience and review of the literature, we propose practical clinical strategies for the use of imiquimod for treating LM, detailing optimal administration procedures in various clinical scenarios and long-term management, with the aim of facilitating optimal patient outcomes.

Current Minimally Invasive Surgical Concepts for Sacral Insufficiency Fractures.

An increasing incidence of sacral insufficiency fractures in geriatric patients has been documented, representing a major challenge to our healthcare system. Determining the accurate diagnosis requires the use of sectional imaging, including computed tomography and magnetic resonance imaging. Initially, non-surgical treatment is indicated for the majority of patients. If non-surgical treatment fails, several minimally invasive therapeutic strategies can be used, which have shown promising results in small case series. These approaches are sacroplasty, percutaneous iliosacral screw fixation (S1 with or without S2), trans-sacral screw fixation or implantation of a trans-sacral bar, transiliac internal fixator stabilisation, and spinopelvic stabilisation. These surgical strategies and their indications are reported in detail. Generally, treatment-related decision making depends on the clinical presentation, fracture morphology, and attending surgeon's experience.

Evaluation of treatment options for postoperative and spontaneous chylothorax in adults.

Both postoperative and spontaneous chylothorax remain therapeutic challenges without recommendations for a standardized treatment approach. Regardless of its aetiology, patients with chylothorax experience prolonged hospitalization and suffer from the associated complications or the invasive therapy administered. We conducted a retrospective, observational review of adult patients with chylothorax treated between January 2010 and September 2019. The primary end point was successful management with sustained cessation and/or controlled chylous output. Therapy duration, inpatient stay and the incidence of complications were evaluated as secondary end points. Of the 36 patients included (22 men; median age 63 years), 24 patients (67%) suffered from a postoperative accumulation of chylous fluid in the pleural space; in the remaining 12 (33%) patients, chylothoraces occurred spontaneously. Initial conservative treatment was successful in 42% (n = 15); in the other 20 cases (56%) additional invasive therapeutic strategies were followed. A complicated course requiring more than 1 treatment was seen in 54% (n = 13) of the postoperative and in 58% (n = 7) of the spontaneous cases. The median length of hospitalization was significantly longer in the postoperative group (37.5 vs 15.5 days; P = 0.016). Serious complications were observed only in the postoperative group (P = 0.28). There were no in-hospital deaths. Basic treatment of both postoperative and spontaneous chylothorax should include dietary measures in all patients. Additional sclerosing radiotherapy and interventional or surgical therapy are often necessary. The choice of therapeutic approach should be indicated, depending on the aetiology and development of the chylothorax. Early, multimodal treatment is recommended.

Clinical presentation, management and in-hospital outcomes of Acute coronary syndrome patients in real world scenario in developing countries

Background: With the introduction of a huge armamentarium of invasive and noninvasive therapeutic strategies, the mortality related to acute coronary syndrome (ACS) has decreased across the world over the past 20 years, but the mortality remains high among Indian patients due to limited resource settings. Even in India, there is significant difference in health infrastructure in different part of country. This study was performed to evaluate the presentation, management and outcomes of ACS patients admitted in a high volume tertiary center of north India. Enrolment of the study done prior to covid pandemic. Materials and Methods: 3511 ACS patients &gt;18 year of age were included for this prospective observational study. All patients were evaluated with detailed clinical history and examination, ECG, Troponin, and detailed echocardiography. Patients were treated as per current guideline recommendation which included primary percutaneous coronary intervention (PCI), pharmacoinvasive therapy, thrombolysis or medical management only. Data was analysed for age, sex, risk factors, type of ACS, treatment given and complications if any. Those patients who underwent invasive approach also evaluated for coronary anatomy pattern and variables. Results: Study population had younger mean age of 57.2 years, male preponderance (67%) and very high tobacco intake (46%). Out of all ACS patients 39% were STEMI (55% anterior wall myocardial infarction, 43% inferior wall myocardial infarction) and 61% were NSTEMI/USA. In STEMI subgroup, only 18% had primary PCI, while 42% received thrombolytic therapy as primary management. Nearly half of the patients who received thrombolytic therapy underwent pharmacoinvasive treatment (47.5%). A large number of late presenters (32% of all STEMI) did not receive any reperfusion therapy in index admission while few of them (6%) underwent invasive revascularization. Coronary anatomy evaluation showed multivessel disease in 53.1%. Left anterior descending artery was most common vessel involved (69.3%) among all ACS patients underwent coronary angiography. Most of the STEMI patients who underwent invasive route received PCI while very low rate for referral for CABG (2.1%). Major complications noted in study included left ventricular failure/cardiogenic shock (11.7%), advance AV blocks (8.2%), VT/VF (2.8%), Ventricular septal rupture (0.7%) and stent thrombosis (0.5%). In hospital mortality remained high (11.5%) mainly due to late presenters. Conclusion: ACS management specially STEMI care is still needs a boost in north India. With primary PCI rate of only 18% and more than one third being late presenters not receiving any reperfusion therapy, there is urgent need of robust primary and referral health care system. As compared to other part of India, tobacco intake is alarmingly high (46%) and needs widespread health awareness in community of tobacco ill effects.

Evaluation of cartilage biomechanics and knee joint microenvironment after different cell-based treatments in a sheep model of early osteoarthritis.

Aiming to prevent cartilage damage during early osteoarthritis (OA), the therapeutic challenge is to restore and maintain the physiological and functional properties of such a tissue with minimally invasive therapeutic strategies. Accordingly, an in vivo model of early OA in sheep was here treated through three different cell therapies (culture expanded ADSCs, SVF, and culture expanded AECs) thus to preserve the joint surface from the progression of the pathology. Three months after the treatment injections, their performance was assessed through mechanical automated mapping (Young's modulus and cartilage thickness), gross evaluation of articular surfaces, and biochemical analysis of the synovial fluid. No severe degeneration was observed after threemonths from OA induction. Cartilage mechanical properties were crucial to identify early degeneration. All the treatments improved the macroscopic cartilage surface aspect and reduced pro-inflammatory cytokines in the synovial fluid. Among the three treatments, SVF highlighted the best performance while ADSCs the worst. Despite that the evaluated experimental time is an early follow-up and, thus, longer trial is mandatory to properly assess treatments effectiveness, the proposed multidisciplinary approach allowed to obtain preliminary, but also crucial, results concerning the reduction in OA signs on cartilage properties, in osteophyte development and in all the inflammatory markers.

Preclinical Imaging for the Study of Mouse Models of Thyroid Cancer

Thyroid cancer, which represents the most common tumors among endocrine malignancies, comprises a wide range of neoplasms with different clinical aggressiveness. One of the most important challenges in research is to identify mouse models that most closely resemble human pathology; other goals include finding a way to detect markers of disease that common to humans and mice and to identify the most appropriate and least invasive therapeutic strategies for specific tumor types. Preclinical thyroid imaging includes a wide range of techniques that allow for morphological and functional characterization of thyroid disease as well as targeting and in most cases, this imaging allows quantitative analysis of the molecular pattern of the thyroid cancer. The aim of this review paper is to provide an overview of all of the imaging techniques used to date both for diagnosis and theranostic purposes in mouse models of thyroid cancer.

Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease.

Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas. Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Several studies showed that leiomyomas have a monoclonal origin. Accumulating evidence converges on the risk factors and mechanisms of tumorigenesis: the translocation t (12;14) and deletion of 7q were found in the highest percentages of recurrence; dysregulation of the HMGA2 gene has been mapped within the critical 12q14-q15 locus. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has been poorly explored. The growth factors with mitogenic activity, such as transforming growth factor-β3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion. The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future.

A multiparameter model predicting in-hospital mortality in malignant cerebral infarction

The early identification of patients with large hemisphere infarctions (LHIs) at risk of fatal brain edema may result in better outcomes. A quantitative model using parameters obtained at admission may be a predictor of in-hospital mortality from LHI.This prospective study enrolled all patients with LHI involving >50% of the middle cerebral artery (MCA) admitted to our neurological intensive care unit within 48 hours of symptom onset. Early clinical and radiographic parameters and the baseline CHADS2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke [double weight]) were analyzed regarding their ability to predict patient outcomes.Seventy-seven patients with LHIs were identified, 33 (42.9%) with complete MCA infarction (CMCA), and 44 (57.1%) with incomplete MCA infarction (IMCA). The predictors of CMCA score included: >1/3 early hypodensity in computed tomography findings, hyperdense MCA sign, brain edema, initial National Institutes of Health Stroke Scale (NIHSS) score ≥17, and stroke in progression during the 1st 5 days of admission. The cutoff CMCA score was 2, with a sensitivity of 81.8% and specificity of 70.5%. Mortality score 1, used for predicting in-hospital mortality from LHI, included CMCA and CHADS2 scores ≥4 (sensitivity 100.0%, specificity 57.4%), and mortality score 2 included CMCA and CHADS2 scores ≥4, and NIHSS score ≥26, during the 1st 5 days (sensitivity 100.0%, specificity 91.7%).Patients qualifying for a mortality score of 2 were at high-risk of in-hospital mortality from LHI. These findings may aid in identifying patients who may benefit from invasive therapeutic strategies, and in better describing the characteristics of those at risk of mortality.

Magnetic resonance imaging features of uterine sarcoma and mimickers

Uterine myometrial tumors are predominantly benign conditions that affect one-third of women and represent the main indication for hysterectomy. Preoperative imaging is of utmost importance for characterization and for precise mapping of myometrial tumors to best guide therapeutic strategy. New minimally invasive therapeutic strategies including morcellation, myolysis, uterine artery embolization and image-guided radiofrequency or focused ultrasound ablation have been developed for the treatment of uterine leiomyoma. However, preoperative differentiation between atypical leiomyomas and leiomyosarcomas is critical on imaging as uterine sarcoma requires a specific surgical technique to prevent dissemination. A single, rapidly growing uterine tumor, associated with endometrial thickening and ascites, in post-menopausal women is suspicious of uterine endometrial stromal sarcoma and carcinosarcoma. Suggestive magnetic resonance imaging features have been described, but overlap in imaging appearance between uterine leiomyosarcomas and cellular leiomyomas makes it challenging to ascertain the diagnosis. This review aims to illustrate the imaging features of uterine sarcomas and potential mimickers to make the reader more familiar with this serious condition which needs special consideration.

Valvular endothelial cells: Guardians or destroyers of aortic valve integrity?

Atherosclerosis and calcific aortic valve disease (CAVD) are two distinct, morbid processes that share similar pathophysiological events. Both diseases are characterized by recruitment of immune cells, activation of inflammatory pathways, proliferation/differentiation of resident elements, remodeling of extracellular matrix and calcium deposition [ 1 Bentzon J.F. Otsuka F. Virmani R. Falk E. Mechanisms of plaque formation and rupture. Circ. Res. 2014; 114: 1852-1866 Crossref PubMed Scopus (1057) Google Scholar , 2 Yutzey K.E. et al. Calcific aortic valve disease: a consensus summary from the alliance of investigators on calcific aortic valve disease. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 2387-2393 Crossref PubMed Scopus (180) Google Scholar ]. However, while the actual impact of intimal calcification on plaque stability is still controversial [ [3] Otsuka F. Sakakura K. Yahagi K. Joner M. Virmani R. Has our understanding of calcification in human coronary atherosclerosis progressed?. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 724-736 Crossref PubMed Scopus (281) Google Scholar ], no uncertainty exists about the clinical harmful consequences of calcium deposition within the aortic valve. As a matter of fact, progressive stiffness of calcified leaflets leads to reduction of aortic valve area, which results in chronic left ventricular pressure overload. Clinical manifestations of the advanced disease are syncope, angina and inevitable progression towards end-stage heart failure. Aging is the major risk factor for CAVD and this explains way the disease prevalence is growing in the countries with the highest life expectancy (about 3% of Americans aged 75 and over are affected) [ [4] Mozaffarian D. et al. Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation. 2015; 131: e29-322 Crossref PubMed Scopus (5504) Google Scholar ]. Nevertheless, several basic and clinical science studies performed in the last two decades clearly demonstrated that arterial and valve calcification should be considered as an active, finely regulated biological process, which is mainly characterized by the activation of osteogenic programs and/or the lost of anti-calcific defense mechanisms within the vascular/valve tissue [ 2 Yutzey K.E. et al. Calcific aortic valve disease: a consensus summary from the alliance of investigators on calcific aortic valve disease. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 2387-2393 Crossref PubMed Scopus (180) Google Scholar , 5 Demer L.L. Tintut Y. Inflammatory, metabolic, and genetic mechanisms of vascular calcification. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 715-723 Crossref PubMed Scopus (240) Google Scholar ]. These new data are of great relevance since nowadays the only treatments available to cure CAVD consist of invasive therapeutic strategies (namely surgical or transcatheter aortic valve replacement) and there is a substantial need of new pharmacological targets. Valvular interstitial cells suppress calcification of valvular endothelial cellsAtherosclerosisVol. 242Issue 1PreviewCalcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes to valvular calcification is unknown. We hypothesized that aortic VECs undergo osteogenic differentiation via an EndMT process that can be inhibited by valvular interstitial cells (VICs). Full-Text PDF Open Access

Multimarker proteomic profiling for the prediction of cardiovascular mortality in patients with chronic heart failure.

Risk stratification of patients with systolic chronic heart failure (HF) is critical to better identify those who may benefit from invasive therapeutic strategies such as cardiac transplantation. Proteomics has been used to provide prognostic information in various diseases. Our aim was to investigate the potential value of plasma proteomic profiling for risk stratification in HF. A proteomic profiling using surface enhanced laser desorption ionization - time of flight - mass spectrometry was performed in a case/control discovery population of 198 patients with systolic HF (left ventricular ejection fraction <45%): 99 patients who died from cardiovascular cause within 3 years and 99 patients alive at 3 years. Proteomic scores predicting cardiovascular death were developed using 3 regression methods: support vector machine, sparse partial least square discriminant analysis, and lasso logistic regression. Forty two ion m/z peaks were differentially intense between cases and controls in the discovery population and were used to develop proteomic scores. In the validation population, score levels were higher in patients who subsequently died within 3 years. Similar areas under the curves (0.66 – 0.68) were observed for the 3 methods. After adjustment on confounders, proteomic scores remained significantly associated with cardiovascular mortality. Use of the proteomic scores allowed a significant improvement in discrimination of HF patients as determined by integrated discrimination improvement and net reclassification improvement indexes. In conclusion, proteomic analysis of plasma proteins may help to improve risk prediction in HF patients.

Admission insulin resistance index in non diabetic patients with acute coronary syndrome; clinical and angiographic features

The clinical implication of insulin resistance has extended beyond diabetes mellitus to include ischemic heart disease, dyslipidemia, hypertension and features of metabolic syndrome. Non diabetic patients with acute coronary syndrome and elevated admission insulin resistance index (AIRI) may have certain clinical angiographic and therapeutic strategies. It was aimed to illustrate the value of AIRI in non diabetic patients with acute coronary syndrome (ACS) and identify the angiographic CAD severity in relation to AIRI. Cross sectional study. Includes 120 non diabetic patients presenting with acute chest pain who were admitted to the Coronary Care Unit. Admission glucose and insulin concentration were measured and the AIRI were calculated. ECG was carried out and the cases were grouped as; unstable angina (UA) (40 cases) and acute myocardial infarction (AMI) (40 cases). They were compared to 40 cases of the stable angina (SA) group and the control group (40 cases). The studied cases were examined clinically stressing on the other criteria of insulin resistance syndrome. The following laboratory tests were undertaken including random plasma glucose, HBA1-c, lipid profile, cardiac enzymes (CK-MB, LDH, troponin T). The angiographic study was carried out for patients of each diseased group and 20 cases of the stable angina group. AIRI was significantly elevated in AMI (3.9 ± 0.1) and UA (3.01 ± 0.2) when compared to the group of SA and the control group. AIRI was significantly higher in AMI when compared to the UA group. Coronary angiography revealed one coronary vessel involvement in 10%, 20%, and 10% of SA, UA and AMI, respectively. While, two vessel involvement was detected in 0%, 30%, and 60% of SA, UA and AMI, respectively. Three coronary vessel disease was not detected in SA but was evident in 5% of UA and 30% of AMI. The relation of AIRI of the studied groups by the calculated Chi-square revealed a significant elevation of AIRI in AMI and UA. Cases with three vessel affection demonstrated higher AIRI. Elevated AIRI can predict coronary artery events in non diabetic patients with acute chest pain. Multiple coronary vessel involvement is common in such cases and suitable planned invasive therapeutic strategies have to be considered.

Admission insulin resistance index in nondiabetic patients with acute coronary syndrome: clinical and angiographic features

Abstract Background The clinical implication of insulin resistance has extended beyond diabetes mellitus to include ischemic heart disease, dyslipidemia, hypertension, and features of metabolic syndrome. Nondiabetic patients with acute coronary syndrome and elevated admission insulin resistance index (AIRI) may have certain clinical angiographic and therapeutic strategies. Objectives The study aimed to illustrate the value of AIRI in nondiabetic patients with acute coronary syndrome and identify the angiographic coronary artery disease severity in relation to AIRI. Study design This study was cross-sectional in design. Patients and methods This study included 120 nondiabetic patients presenting with acute chest pain who were admitted to the coronary care unit. Admission glucose and insulin concentrations were measured and the AIRI was calculated. ECG was carried out and the patients were grouped as follows: those with unstable angina (UA) (40 cases) and those with acute myocardial infarction (AMI) (40 cases). They were compared with 40 patients with stable angina (SA) and a group of controls (40 individuals). The studied participants were examined clinically stressing on the other criteria for insulin resistance syndrome. The following laboratory tests were undertaken, including random plasma glucose, HBA1-c, lipid profile, cardiac enzymes (CK-MB, LDH), and troponin T. An angiographic study was carried out for patients from each diseased group and for 20 patients who had suffered a first attack in the SA group. Results AIRI was significantly elevated in the AMI (3.9 ± 0.1) and UA (3.01 ± 0.2) groups when compared with the SA and control groups. AIRI was significantly higher in the AMI group when compared with the UA group. Coronary angiography revealed one coronary vessel involvement in 10, 20, and 10% of patients in the SA, UA, and AMI groups, respectively, whereas two-vessel involvement was detected in 0, 30, and 60% of patients in the SA, UA, and AMI groups, respectively. Three-coronary-vessel disease was not detected in the SA group but was evident in 5% of UA and 30% of AMI patients. The relation of AIRI in the studied groups on the basis of the χ2-test revealed significant elevation of AIRI in the AMI and UA groups. Cases with three-vessel affection demonstrated higher AIRI. Conclusion Elevated AIRI can predict coronary artery events in nondiabetic patients with acute chest pain. Multiple coronary vessel involvement is common in such cases and suitable planned invasive therapeutic strategies have to be considered.