Health Related Quality of Life and Cardiovascular Risk Factors.

Cardiovascular diseases (CVD) is associated with deteriorating of quality of life (QOL) and exercise capacity (EC) but less is known on how EC interplays with QOL. The present study explores the relationship between quality of life and cardiovascular risk factors in people who present in cardiology clinics. A total of 153 adult presentations completed the SF-36 Health Survey and provided data for hypertension, diabetes mellitus, smoking, obesity, hyperlipidemia and history of coronary heart disease. Physical capacity was assessed by treadmill test. were correlated with the scores of the psychometric questionnaires. Participants with longer duration on treadmill exercise score higher on the scale of physical functioning. The study found that treadmill exercise intensity and duration were associated with improved scores in dimensions of the physical component summary and the physical functioning of SF-36, respectively. The presence of cardiovascular risk factors is related to a decreased quality of life. Patients with cardiovascular diseases should undergo particularly detailed analysis of the quality of life along with specific mental factors such as depersonalization and posttraumatic stress disorder.

Left Axillary Access for Transcatheter Aortic Valve Implantation in a Patient With Two Dependent Internal Mammary Artery Grafts and a Permanent Left-Sided Implanted Pacemaker.

Transfemoral access has been established as the gold standard approach for the majority of patients undergoing transcatheter aortic valve implantation (TAVI). However, in cases with anatomical difficulties or severely diffused peripheral arterial disease, alternative vascular access may be considered such as the transaxillary approach. We present the case of a 92-year-old gentleman with exertional dyspnea due to severe symptomatic aortic stenosis and a history of peripheral femoro-femoral bypass surgery, coronary arterial bypass surgery and a permanent dual-chamber left-side implanted pacemaker. Due to the high surgical risk and the severe anatomical difficulties, the method of TAVI using the left axillary approach was opted. A 14-F vascular sheath was inserted with surgical cutdown and with fluoroscopic guidance while small injections of contrast confirmed the non-occlusive position and the patency of the left internal mammary artery (LIMA) graft. A stiff guidewire was used to cross the heavily calcified aortic valve and subsequently was placed into the left ventricle. Balloon aortic valvuloplasty was performed followed by a successful TAVI with no significant aortic regurgitation or paravalvular leak. The patient recuperated uneventfully and was discharged after 72 h. Axillary access for TAVI is a feasible option for high-risk patients with extended peripheral arteriopathy. To our knowledge this is the first case report describing the implantation of a newer type of intra-annular self-expanding valve platform in a nonagenarian patient with severe comorbidities and such a remarkable history of multiple previous interventions in the selected access site. Meticulous upfront strategy planning and efficient collaboration between specialties is of outmost importance in hybrid procedures for favorable clinical outcomes, especially in cases with challenging anatomies.

Understanding common key indicators of successful and unsuccessful cancer drug trials using a contrast mining framework on ClinicalTrials.gov.

Clinical trials are essential to the process of new drug development. As clinical trials involve significant investments of time and money, it is crucial for trial designers to carefully investigate trial settings prior to designing a trial. Utilizing trial documents from ClinicalTrials.gov, we aim to understand the common characteristics of successful and unsuccessful cancer drug trials to provide insights about what to learn and what to avoid. In this research, we first computationally classified cancer drug trials into successful and unsuccessful cases and then utilized natural language processing to extract eligibility criteria information from the trial documents. To provide explainable and potentially modifiable recommendations for new trial design, contrast mining was applied to discoverhighly contrasted patterns with a significant difference in prevalence between successful (completion with advancement to the next phase) and unsuccessful (suspended, withdrawn, or terminated) groups. Our method identified contrast patterns consisting of combinations of drug categories, eligibility criteria, study organization, and study design for nine major cancers. In addition to a literature review for the qualitative validation of mined contrast patterns, we found that contrast-pattern-based classifiers using the top 200 contrast patterns as feature representations can achieve approximately 80% F1 score for eight out of ten cancer types in our experiments. In summary, aligning with the modernization efforts of ClinicalTrials.gov, our study demonstrates that understanding the contrast characteristics of successful and unsuccessful cancer trials may provide insights into the decision-making process for trial investigators and therefore facilitate improved cancer drug trial design.

One-year duplex ultrasound-assessed closure outcomes of percutaneous endovenous microwave ablation for the treatment of varicose veins of the lower limbs.

PURPOSE: This study aims to investigate the safety and efficacy of a new device using microwave technology for the endovenous ablation of the great saphenous vein (GSV) causing symptomatic lower limb varicose veins (LLVV). MATERIALS AND METHODS: This prospective, single-arm, single-center, cohort study investigated the safety and effectiveness of endovenous microwave ablation for the treatment of symptomatic LLVV. Enrollment period was set between January and December 2020. Primary safety endpoint was the occurrence of procedure-related complications and primary efficacy endpoint was anatomical success defined as the duplex ultrasound (DUS)-proven GSV occlusion at 1 year follow-up. Secondary endpoints included 1-year clinical success (CEAP classification improvement), repeat procedures rate due to GSV recanalization, and pain assessment at 24 h post treatment. RESULTS: In total, 50 patients (42 female; mean age: 62 ± 12 years) with 64 limbs were treated. No procedure-related complications were noted. Technical success was 95.3% (61/64 GSVs), as three cases of GSV recanalization were detected. Clinical success was 100%, as in all cases symptoms improvement by at least one grade according to CEAP classification, was achieved. Mean CEAP grade significantly improved from 3.3 ± 0.72 (median: 3) at baseline to 1.8 ± 0.85 (median: 2) at 1-year (p < 0.0001). There were no repeat procedures due to GSC recanalization. The median 24-h VAS value was 2 (mean: 1.9 ± 1.4). CONCLUSIONS: Endovenous microwave ablation was safe and effective for the treatment of varicose veins, achieving high 1-year GSV occlusion rates.

Left Anterior Descending Artery Dissection in a Female Patient With History of Chest Radiation Treatment and Separate Ostia of the Left Coronary Arteries.

Obstructive and flow limiting coronary artery dissections can be a catastrophic clinical scenario, requiring urgent treatment and tailored approach for each case. A 55-year-old female patient, with a history of breast cancer, chest radiation treatments and hypertension presented with episodes of angina and significant area of reversible ischemia on single-photon emission computerized tomography (SPECT). Coronary angiogram revealed separate ostia of the left coronary arteries and three-vessel disease (SYNTAX (Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery) = 15); subsequent full revascularization was achieved successfully with two drug-eluting stents (DES) (mid left anterior descending artery (LAD), left circumflex coronary artery (LCx)) and one drug-coated balloon (posterior descending artery (PDA)). However, after a few hours the patient underwent an urgent second angiography due to ongoing chest pain and electrocardiogram (ECG) changes. Proximal complete occlusion of the anomalous LAD was displayed and a long dissection attributable to an intimal tear following first stent implantation was recorded (well expanded and apposed stent (proximal stent edges were implanted in an unhealthy vessel area infiltrated with fibrotic and calcified plaque) not detectable by conventional angiography). A second 3.5 × 38 mm DES was implanted optimally in the proximal LAD segment and overlapped with the first one, with immediate restoration of the flow and relief of the patient's symptoms. The patient was discharged symptom free and with recommendation for optimal medical treatment for secondary coronary artery disease (CAD) prevention. Conventional coronary angiography in patients with history of chest radiation treatment might not detect accurately the extent and characteristics of the underlying CAD. Appropriate use of intravascular imaging in these cases secures a safe approach for ambiguous lesions and facilitates treatment of iatrogenic coronary dissections following PCI.

Immune-Related Gene Signatures to Predict the Effectiveness of Chemoimmunotherapy in Triple-Negative Breast Cancer Using Exploratory Subgroup Discovery.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. Although immunotherapy has shown potential in TNBC patients, clinical studies have only demonstrated a modest response. Therefore, the exploration of immunotherapy in combination with chemotherapy is warranted. In this project we identified immune-related gene signatures for TNBC patients that may explain differences in patients' outcomes after anti-PD-L1+chemotherapy treatment. First, we ran the exploratory subgroup discovery algorithm on the TNBC dataset comprised of 422 patients across 24 studies. Secondly, we narrowed down the search to twelve homogenous subgroups based on tumor mutational burden (TMB, low or high), relapse status (disease-free or recurred), tumor cellularity (high, low and moderate), menopausal status (pre- or post) and tumor stage (I, II and III). For each subgroup we identified a union of the top 10% of genotypic patterns. Furthermore, we employed a multinomial regression model to predict significant genotypic patterns that would be linked to partial remission after anti-PD-L1+chemotherapy treatment. Finally, we uncovered distinct immune cell populations (T-cells, B-cells, Myeloid, NK-cells) for TNBC patients with various treatment outcomes. CD4-Tn-LEF1 and CD4-CXCL13 T-cells were linked to partial remission on anti-PD-L1+chemotherapy treatment. Our informatics pipeline may help to select better responders to chemoimmunotherapy, as well as pinpoint the underlying mechanisms of drug resistance in TNBC patients at single-cell resolution.

TBX21 Methylation as a Potential Regulator of Immune Suppression in CMS1 Subtype Colorectal Cancer.

Cytotoxic T lymphocyte (CTL) infiltration is associated with survival, recurrence, and therapeutic response in colorectal cancer (CRC). Immune checkpoint inhibitor (ICI) therapy, which requires CTLs for response, does not work for most CRC patients. Therefore, it is critical to improve our understanding of immune resistance in this disease. We utilized 2391 CRC patients and 7 omics datasets, integrating clinical and genomic data to determine how DNA methylation may impact survival and CTL function in CRC. Using comprehensive molecular subtype (CMS) 1 patients as reference, we found TBX21 to be the only gene with altered expression and methylation that was associated with CTL infiltration. We found that CMS1 patients with high TBX21 expression and low methylation had a significant survival advantage. To confirm the role of Tbx21 in CTL function, we utilized scRNAseq data, demonstrating the association of TBX21 with markers of enhanced CTL function. Further analysis using pathway enrichment found that the genes TBX21, MX1, and SP140 had altered expression and methylation, suggesting that the TP53/P53 pathway may modify TBX21 methylation to upregulate TBX21 expression. Together, this suggests that targeting epigenetic modification more specifically for therapy and patient stratification may provide improved outcomes in CRC.

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer.

Breast cancer (BC) is the leading cause of death among female patients with cancer. Patients with triple-negative breast cancer (TNBC) have the lowest survival rate. TNBC has substantial heterogeneity within the BC population. This study utilized our novel patient stratification and drug repositioning method to find subgroups of BC patients that share common genetic profiles and that may respond similarly to the recommended drugs. After further examination of the discovered patient subgroups, we identified five homogeneous druggable TNBC subgroups. A drug repositioning algorithm was then applied to find the drugs with a high potential for each subgroup. Most of the top drugs for these subgroups were chemotherapy used for various types of cancer, including BC. After analyzing the biological mechanisms targeted by these drugs, ferroptosis was the common cell death mechanism induced by the top drugs in the subgroups with neoplasm subdivision and race as clinical variables. In contrast, the antioxidative effect on cancer cells was the common targeted mechanism in the subgroup of patients with an age less than 50. Literature reviews were used to validate our findings, which could provide invaluable insights to streamline the drug repositioning process and could be further studied in a wet lab setting and in clinical trials.

Cardiac amyloidosis presenting with coronary artery embolization.

Amyloid light-chain (AL) amyloidosis is a multisystemic disease. Among its clinical manifestations, vein and arterial thromboembolic events are included. We report the unusual case of a 57-year-old female patient with AL amyloidosis presenting with an ST segment elevation myocardial infarction due to coronary artery embolization (CE). The patient reported a history of exertional dyspnoea along with episodes of haemoptysis for the last few months. Her coronary angiography demonstrated embolization of the distal segment of the left anterior descending artery. The main findings of her cardiac ultrasound included concentric left ventricular hypertrophy, mildly impaired left ventricular systolic function, left atrium enlargement and a restrictive-like filling pattern, while her chest computed tomography (CT) demonstrated bilateral pleural effusions. Cardiac magnetic resonance imaging that was performed afterwards, indicated areas of microvascular infarction, a small apex infarct and findings compatible with possible amyloidosis, a diagnosis that was confirmed later by fat tissue biopsy. Patient was referred for an oncology consultation, started therapy with direct oral anticoagulants, angiotensin converting enzyme inhibitor, statins and anti-plasma cell therapy. She has been improving since then and has been free of cardiovascular events for a follow-up period of 12 months. Cardiologists ought to be aware of amyloidosis as a rare but possible cause of coronary embolization, while close collaboration with oncologists is required for the establishment of the correct diagnosis.

A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins.

BACKGROUND: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. METHODS: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed; total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. RESULTS: mRNA of TLRs 2, 3, 4 and 8; interleukin-6; TNF-a; metalloproteinase-2; tissue inhibitor of metalloproteinase-1; tumor protein 53; cysteinyl aspartate specific proteinase-3; and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. CONCLUSIONS: HCD increases the levels of TLRs; inflammatory, fibrotic and apoptotic factors; and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins.

Cardiovascular toxicity of breast cancer treatment: an update.

Novel chemotherapeutic agents have marked a new era in oncology during the past decade, prolonging significantly the overall survival of breast cancer patients. Nevertheless, contemporary antineoplastic treatments can frequently cause adverse cardiovascular side effects. Common manifestations of chemotherapy-induced cardiotoxicity include cardiomyopathy, ischemia, conduction disturbances, hypertension and thromboembolic events, while the type of the treatment regimen administered crucially determines clinical outcome. The aim of this literature review is to analyze the incidence and the underlying mechanisms of cardiovascular toxicity caused by agents approved for breast cancer, as well as to describe ways of monitoring and treating the cardiotoxic effects in breast cancer patients. Moreover, our work intends to provide an easy-to-grasp synopsis of recent and clinically meaningful advances in the field.

Explainable artificial intelligence in high-throughput drug repositioning for subgroup stratifications with interventionable potential.

Enabling precision medicine requires developing robust patient stratification methods as well as drugs tailored to homogeneous subgroups of patients from a heterogeneous population. Developing de novo drugs is expensive and time consuming with an ultimately low FDA approval rate. These limitations make developing new drugs for a small portion of a disease population unfeasible. Therefore, drug repositioning is an essential alternative for developing new drugs for a disease subpopulation. This shows the importance of developing data-driven approaches that find druggable homogeneous subgroups within the disease population and reposition the drugs for these subgroups. In this study, we developed an explainable AI approach for patient stratification and drug repositioning. Contrast pattern mining and network analysis were used to discover homogeneous subgroups within a disease population. For each subgroup, a biomedical network analysis was done to find the drugs that are most relevant to a given subgroup of patients. The set of candidate drugs for each subgroup was ranked using an aggregated drug score assigned to each drug. The proposed method represents a human-in-the-loop framework, where medical experts use the data-driven results to generate hypotheses and obtain insights into potential therapeutic candidates for patients who belong to a subgroup. Colorectal cancer (CRC) was used as a case study. Patients' phenotypic and genotypic data was utilized with a heterogeneous knowledge base because it gives a multi-view perspective for finding new indications for drugs outside of their original use. Our analysis of the top candidate drugs for the subgroups identified by medical experts showed that most of these drugs are cancer-related, and most of them have the potential to be a CRC regimen based on studies in the literature.

Vascular Inflammation and Cardiovascular Burden in Metastatic Breast Cancer Female Patients Receiving Hormonal Treatment and CDK 4/6 Inhibitors or Everolimus.

Background: Chemotherapy regimens for breast cancer treatment can promote vascular dysfunction and lead to high cardiovascular risk. Purpose: To investigate the cardiovascular burden and vascular inflammation in metastatic breast cancer patients receiving CDK 4/6 inhibitors or everolimus in addition to standard hormonal treatment. Methods: 22 consecutive female patients with metastatic breast cancer were enrolled. Relative wall thickness (RWT) and left ventricle mass (LVM) measurements by transthoracic echocardiography were obtained followed by 24-h ambulatory blood pressure monitoring, and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Uptake of the radiotracer in the aortic wall was estimated as tissue-to-background ratio (TBR). Each patient was assessed for the aforementioned parameters before the initiation and after 6 months of treatment. Results: At follow up, patients assigned to CDK 4/6 treatment demonstrated increased 24-h systolic blood pressure (SBP) (p = 0.004), daytime SBP (p = 0.004) and night time SBP (p = 0.012) (Group effect). The 24-h mean arterial pressure measurements were also higher in CDK 4/6 population, in comparison to everolimus that displayed firm values (Group effect- p = 0.035, Interaction effect-p = 0.023). Additionally, 24 h diastolic blood pressure recordings in CDK 4/6 therapy were higher opposed to everolimus that remained consistent (Interaction effect- p = 0.010). In CDK 4/6 group, TBR aorta also increased significantly, whereas TBR values in everolimus remained stable (Interaction effect-p = 0.049). Both therapeutic regimens displayed statistically significant damaging effect to RWT and LVM. Conclusion: CDK 4/6 inhibitors and hormonal treatment can lead to increased vascular inflammation, and higher blood pressure compared to the combination of everolimus and hormonal treatment. Moreover, both treatment strategies promoted left ventricle remodeling.

Copper metabolism as a unique vulnerability in cancer.

The last 25 years have witnessed tremendous progress in identifying and characterizing proteins that regulate the uptake, intracellular trafficking and export of copper. Although dietary copper is required in trace amounts, sufficient quantities of this metal are needed to sustain growth and development in humans and other mammals. However, copper is also a rate-limiting nutrient for the growth and proliferation of cancer cells. Oral copper chelators taken with food have been shown to confer anti-neoplastic and anti-metastatic benefits in animals and humans. Recent studies have begun to identify specific roles for copper in pathways of oncogenic signaling and resistance to anti-neoplastic drugs. Here, we review the general mechanisms of cellular copper homeostasis and discuss roles of copper in cancer progression, highlighting metabolic vulnerabilities that may be targetable in the development of anticancer therapies.

Bone marrow involvement in sarcoidosis: an elusive extrapulmonary manifestation.

Sarcoidosis is a granulomatous disease with various extrapulmonary manifestations. We describe a 51-year-old African American woman with a history of cutaneous sarcoidosis admitted with bicytopenia. Suspicion for systemic sarcoidosis was established after contrast-enhanced computerized tomography of the chest, abdomen and pelvis showed a pulmonary nodule, diffuse lymphadenopathy and hepatosplenomegaly. Cytopenias in sarcoidosis, when present, may reflect bone marrow infiltration. Hence, biopsy was obtained and bone marrow sarcoidosis was diagnosed. This manifestation, in spite of ethnic and gender predilection, is rarely seen. As with other forms of sarcoidosis, treatment comprises of corticosteroids. Abbreviations: ANCA: Antineutrophil cytoplasmic antibody; BM: Bone marrow; BMS: Bone marrow sarcoidosis; CT: Computerized tomography; HIV: Human immunodeficiency virus; HLA: Human leukocyte antigen; MRI: Magnetic resonance imaging.

Idiopathic hip chondrolysis: a case report of a Caucasian HLA-B27 positive adolescent with a history of long walking.

Idiopathic hip chondrolysis is a rare disorder, the pathophysiology of which has not been fully elucidated. Several theories have been proposed regarding the cause of the disease with some of them involving autoimmune-mediated cartilage destruction. There are several similar features between idiopathic hip chondrolysis and rheumatologic diseases such as juvenile idiopathic arthritis, so whether these two disorders are different or not is still debatable. This case report aims to help comprehending this complex disorder by presenting a case of idiopathic hip chondrolysis with apparent risk factors, such as repetitive microtrauma and presence of HLA-B27 antigens. A 15-year-old HLA-B27 positive male presented with idiopathic hip chondrolysis after excessive walking. Initial treatment consisted of medications including corticosteroids, protected weight bearing and surgical soft tissue release. After failure of all these modalities in restoring the decreased range of motion of the hip, a course of a TNF-inhibitor, etanercept was tried. Alleviation of pain achieved early in the treatment period, but range of motion remained mainly unchanged. Although there was a brief improvement of stiffness for a short period after surgery which lasted for about 3 months, stiffness came back afterwards. Administration of a TNF inhibitor in the following period significantly improved his range of motion. The presence of laboratory findings indicating an autoimmune tendency in this patient supports the hypothesis of susceptibility of these patients to autoimmune reactions, while excessive walking was an apparent trigger factor. In future, traditional treatments may be abandoned in favor of novel medications targeting immunologic pathways.

From anemia to polycythemia in 4 weeks.

Primary polycythemia (PCV) may coexist in otherwise asymptomatic patients particularly in the presence of unsuspecting conditions such as Thrombotic thrombocytopenic purpura (TTP). In presumed "idiopathic TTP," autoimmune conditions such as rheumatoid arthritis (RA) should be investigated as a possible etiology for TTP. Standardization of targeted therapy with immunomodulatory agents may be recommended for this subset of patients.

The potential role of HER2 upregulation in metastatic breast cancer to the uterus: a case report.

Abnormal uterine bleeding in a patient on maintenance hormonal therapy for breast cancer should raise concern for endometrial abnormalities including rare uterine metastasis from the breast. Hormonal receptor profile changes in metastatic lesions favoring human epidermal growth factor receptor 2 (HER2) overexpression may be involved in the pathogenesis of metastasis to the uterus.

Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies.

Metaplastic breast cancer (MBC) is a rare subtype of invasive breast cancer that tends to have an aggressive clinical presentation as well as a variety of distinct histologic designations. Few systemic treatment options are available for MBC, as it has consistently shown a suboptimal response to standard chemotherapy regimens. These characteristics result in a worse overall prognosis for patients with MBC compared to those with standard invasive breast cancer. Due to its rarity, data focusing on MBC is limited. This review will discuss the clinical presentation, breast imaging findings, histologic and molecular characteristics of MBC as well as potential future research directions.

Proximal screws placement in intertrochanteric fractures treated with external fixation: comparison of two different techniques.

BACKGROUND: To compare two different techniques of proximal pin placement for the treatment of intertrochanteric fractures in elderly patients utilizing the Orthofix Pertrochanteric Fixator. METHODS: Seventy elderly high-risk patients with an average age of 81 years were treated surgically for intertrochanteric fracture, resulting from a low energy trauma. Patients were randomly divided in two groups regarding to the proximal pin placement technique. In Group A the proximal pins were inserted in a convergent way, while in Group B were inserted in parallel. RESULTS: All fractures healed uneventfully after a mean time of 98 days. The fixator was well accepted and no patient had significant difficulties while sitting or lying. The mean VAS score was 5.4 in group A and 5.7 in group B. At 12 months after surgery, in group A the average Harris Hip Score and the Palmer and Parker mobility score was 67 and 5.8, respectively. In group B, the average Harris Hip Score and the Palmer and Parker mobility score was 62 and 5.6, respectively. No statistically significant difference was found regarding the functional outcome. The mean radiographic exposure during pin insertion in Group A and Group B was 15 and 6 seconds, respectively. The difference between the two groups, regarding the radiographic exposure, was found to be significant. CONCLUSION: Proximal screw placement in a parallel way is simple, with significant less radiation exposure and shorter intraoperative duration. In addition, fixation stability is equal compared to convergent pin placement.