Anti-TLR4 biological response to titanium nitride-coated dental implants: anti-inflammatory response and extracellular matrix synthesis.

Osteointegration is a key process during dental implant placement and is related to titanium surface topography. Implant coating and surface modification methods ameliorate the bone production and the osteogenic process. The current work aimed at evaluating the biological outcomes of two different surfaces of dental implants, machined and titanium nitride (TiN) coated, at an inflammation level using an in vitro model of human periodontal ligament stem cells. The TLR4/MyD88/NF-κB p65/NLRP3 pathway induced by the Porphyromonas gingivalis lipopolysaccharide was studied by means of gene- and protein-level expression. Moreover, the expression of vimentin, vinculin, and fibronectin was evaluated to investigate their effects on the cell adhesion and extracellular matrix deposition. The results of the present study suggest that TiN-coated titanium disks may modulate inflammation by the suppression of the TLR4/MyD88/NF-κB p65/NLRP3 pathway and accelerate extracellular matrix apposition.

Corrigendum: Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals.

[This corrects the article DOI: 10.3389/fcvm.2023.1223660.].

Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals.

In cancer, a patient is considered a survivor from the time of initial diagnosis until the end of life. With improvements in early diagnosis and treatment, the number of cancer survivors (CS) has grown considerably and includes: (1) Patients cured and free from cancer who may be at risk of late-onset cancer therapy-related cardiovascular toxicity (CTR-CVT); (2) Patients with long-term control of not-curable cancers in whom CTR-CVT may need to be addressed. This paper highlights the importance of the cancer care continuum, of a patient-centered approach and of a prevention-oriented policy. The ultimate goal is a personalized care of CS, achievable only through a multidisciplinary-guided survivorship care plan, one that replaces the fragmented management of current healthcare systems. Collaboration between oncologists and cardiologists is the pillar of a framework in which primary care providers and other specialists must be engaged and in which familial, social and environmental factors are also taken into account.

Incidental right atrial mass in a patient with secondary pancreatic cancer: A case report and review of literature.

BACKGROUND: The incidental detection of a right atrial mass during routine cardioncological workup is a rare condition. The correct differential diagnosis between cancer and thrombi is challenging. A biopsy may not be feasible while diagnostic techniques and tools may not be available. CASE SUMMARY: We report the case of a 59-year-old female patient with a history of breast cancer and current secondary metastatic pancreatic cancer. She developed deep vein thrombosis and pulmonary embolism and was admitted to the Outpatient Clinic of our Cardio-Oncology Unit for follow-up. Transthoracic echocardiogram incidentally found a right atrial mass. Clinical management was difficult due to the abrupt worsening of the patient's clinical condition and the progressive severe thrombocytopenia. We suspected a thrombus, according to its echocardiographic appearance, the patient's cancer history and recent venous thromboembolism. The patient was unable to adhere to low molecular weight heparin treatment. Due to worsening prognosis, palliative care was recommended. We also highlighted the distinguishing features between thrombi and tumors. We proposed a diagnostic flowchart to aid diagnostic decision making in the case of an incidental atrial mass. CONCLUSION: This case report highlights the importance of cardioncological surveillance during anticancer treatments to detect cardiac masses.

Corrigendum: Cardio-oncology in the COVID Era (Co & Co): The never-ending story.

[This corrects the article DOI: 10.3389/fcvm.2022.821193.].

The socket shield technique and its complications, implant survival rate, and clinical outcomes: a systematic review.

PURPOSE: The aim of this systematic review was to evaluate the effectiveness of the socket shield technique (SST), an innovative surgical method introduced in 2010, for reducing buccal bone plate resorption. METHODS: The review was conducted following the PRISMA guidelines. Clinical studies conducted in humans and investigating the SST were searched on PubMed (MEDLINE), Embase, Web of Knowledge, and Google Scholar in November and December 2021. The implant survival rate, percentage of complications, and clinical parameters (marginal bone loss [MBL], pink esthetic score [PES], and buccal bone plate resorption [BBPR]) were analyzed using the collected data. RESULTS: The initial search resulted in 132 articles. After article screening, the full texts of 19 studies were read and 17 articles were finally included in the review. In total, 656 implants were installed with the SST. Nine of the 656 implants experienced failure, resulting in an implant survival rate of 98.6%. The percentage of complications was about 3.81%. The analysis of clinical parameters (MBL, PES, and BBPR), showed favorable results for the SST. The mean MBL in implants placed with the SST was 0.39±0.28 mm versus 1.00±0.55 mm in those placed without the SST. PES had a better outcome in the SST group, with an average of 12.08±1.18 versus 10.77±0.74. BBPR had more favorable results in implants placed with the SST (0.32±0.10 mm) than in implants placed with the standard technique (1.05±0.18 mm). CONCLUSIONS: The SST could be considered beneficial for preserving the buccal bone plate. However, since only 7 of the included studies were long-term randomized controlled trials comparing the SST with the standard implant placement technique, the conclusions drawn from this systematic review should be interpreted with caution. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020180637.

Edoxaban: front-line treatment for brachiocephalic vein thrombosis in primitive mediastinal seminoma: A case report and literature review.

RATIONALE: Venous thromboembolism is a feared frequent complication of cancer with a 2-way relationship. Low molecular weight heparin is the mainstay of treatment. The use of direct oral anticoagulants is supported by established evidence for the treatment of deep vein thrombosis also in active cancer and they are prioritized over low molecular weight heparin for cancer-associated thrombosis according to current guidelines. However, upper limb deep vein thrombosis is poorly studied with scant data on the use of direct oral anticoagulants in noncatheter-related deep vein thrombosis. We report the case of a patient with noncatheter-related deep vein thrombosis and a rare tumor site effectively and safely treated with a direct oral anticoagulant, edoxaban, after lack of efficacy with low molecular weight heparin. PATIENT CONCERNS: A 35-year-old man with primitive mediastinal seminoma presented at our Cardio-Oncology Unit for prechemotherapy assessment. DIAGNOSIS: Persistent brachiocephalic deep vein thrombosis, despite full-dose enoxaparin, was detected at ultrasonography. INTERVENTION: We decided to switch the anticoagulant treatment from enoxaparin to edoxaban. OUTCOME: The 3-month ultrasonography showed almost total regression of the deep vein thrombosis without any adverse effects and a good patient compliance. LESSONS: We conducted a literature review on upper limb deep vein thrombosis, since its management is challenging due to inconsistency of evidence. This report highlights the benefits of direct oral anticoagulants compared to low molecular weight heparins in cancer-associated thrombosis therapy in terms of efficacy, safety and ease of use.

Cancer-Associated Thrombosis: Not All Low-Molecular-Weight Heparins Are the Same, Focus on Tinzaparin, A Narrative Review.

Cancer-associated thrombosis (CAT) is the second main cause of cancer death with high related mortality and morbidity, leading to anticancer agent delays and interruptions. The recommended therapy, low-molecular-weight heparin (LMWH), however, is burdensome for patients and costly for society, as treatment should last until cancer is no longer active, even indefinitely. Tinzaparin is a manageable, efficient, safe, and cost-effective option. Compared to the other LMWHs, advantages are single-daily dose and safety in the elderly and those with renal impairment (RI). The purpose of this review is to critically discuss recent data on its efficacy and safety in CAT.

Corrigendum: Cardio-Oncology in the COVID Era (Co & Co): The Never Ending Story.

[This corrects the article DOI: 10.3389/fcvm.2022.821193.].

Corrigendum: Portrait of Italian Cardio-Oncology: Results of a Nationwide Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Survey.

[This corrects the article DOI: 10.3389/fcvm.2021.677544.].

A Narrative Review: Gingival Stem Cells as a Limitless Reservoir for Regenerative Medicine.

The gingival tissue can be collected in an easy way and represent an accessible source to isolate gingival-derived mesenchymal stem cells (GMSCs). GMSCs are a subpopulation of dental-derived mesenchymal stem cells that show the mesenchymal stem cells (MSCs) features, such as differentiation abilities and immunomodulatory properties. Dental-derived stem cells are also expandable in vitro with genomic stability and the possibility to maintain the stemness properties over a prolonged period of passages. Moreover, several preclinical studies have documented that the extracellular vesicles (EVs) released from GMSCs possess similar biological functions and therapeutic effects. The EVs may represent a promising tool in the cell-free regenerative therapy approach. The present review paper summarized the GMSCs, their multi-lineage differentiation capacities, immunomodulatory features, and the potential use in the treatment of several diseases in order to stimulate tissue regeneration. GMSCs should be considered a good stem cell source for potential applications in tissue engineering and regenerative dentistry.

[A strange case of wide QRS tachycardia during paclitaxel chemotherapy]. / Uno strano caso di tachicardia a QRS largo in corso di chemioterapia con paclitaxel.

We report the case of a 50-year-old female patient with breast cancer who, during preoperative workup, presented repeated wide QRS complex tachycardias, recorded by Holter ECG. She was immediately referred to a hub center for electrophysiological study where she was diagnosed with right ventricular outflow tract ventricular tachycardia and underwent catheter ablation. The chemotherapy with paclitaxel that the patient was receiving combined with psychological stress may have triggered the arrhythmias.

Echocardiography Monitoring during Anthracycline Administration in Hodgkin and Non-Hodgkin's Lymphoma: The Tei Index Evaluation.

Anthracyclines are widely employed in lymphoma's chemotherapy and has been shown to induce heart failure. Echocardiographic parameters of left ventricular (LV) systolic function are usually used to monitor the cardiac side effects during and after anthracyclines treatment. The measurement of theTei index could anticipate the onset of LV dysfunction. The aim of this study was to evaluate the performance of the delta Tei index for the early detection of cardiac toxicity in a prospective population of anthracycline-treated lymphoma patients. Our preliminary data suggest that the Tei index may predict the risk for cardiotoxicity in this subset of patients earlier than LV ejection fraction alteration.

Cardio-Oncology in the COVID Era (Co & Co): The Never Ending Story.

The pathophysiology of some non-communicable diseases (NCDs) such as hypertension, cardiovascular disease (CVD), diabetes, and cancer includes an alteration of the endothelial function. COVID-19 is a pulmonary and vascular disease with a negative impact on patients whose damaged endothelium is particularly vulnerable. The peculiar SARS-CoV-2-induced "endothelitis" triggers an intriguing immune-thrombosis that affects both the venous and arterial vascular beds. An increased liability for infection and an increased likelihood of a worse outcome have been observed during the pandemic in patients with active cancer and in cancer survivors. "Overlapping commonalities" between COVID-19 and Cardio-Oncology have been described that include shared phenotypes of cardiovascular toxicities such as left ventricular dysfunction, ischemic syndromes, conduction disturbances, myocarditis, pericarditis and right ventricular failure; shared pathophysiologic mechanisms such as inflammation, release of cytokines, the renin-angiotensin-aldosterone-pathway, coagulation abnormalities, microthrombosis and endothelial dysfunction. For these features and for the catalyst role of NCDs (mainly CVD and cancer), we should refer to COVID-19 as a "syndemic." Another challenging issue is the persistence of the symptoms, the so-called "long COVID" whose pathogenesis is still uncertain: it may be due to persistent multi-organ viral attacks or to an abnormal immune response. An intensive vaccination campaign is the most successful pharmacological weapon against SARS-CoV-2, but the increasing number of variants has reduced the efficacy of the vaccines in controlling SARS-CoV-2 infections. After a year of vaccinations we have also learned more about efficacy and side-effects of COVID-19 vaccines. An important byproduct of the COVID-19 pandemic has been the rapid expansion of telemedicine platforms across different care settings; this new modality of monitoring cancer patients may be useful even in a post pandemic era. In this paper we analyze the problems that the cardio-oncologists are facing in a pandemic scenario modified by the extensive vaccination campaign and add actionable recommendations derived from the ongoing studies and from the syndemic nature of the infection.

Enhanced Extracellular Matrix Deposition on Titanium Implant Surfaces: Cellular and Molecular Evidences.

The surface structure of the titanium dental implants can modulate the activity of mesenchymal stem cells in order to promote the upregulation of osteoblastic related genes and the release of extracellular matrix (ECM) components. The present work was focused on the in vitro evaluation of the interaction of human periodontal ligament stem cells (hPDLSCs) and two different implant titanium surfaces topography (CTRL and TEST). This study was aimed at analyzing the cytotoxicity of the dental implant surfaces, the cellular adhesion capacity, and the improvement in the release of ECM molecules in an in vitro model. These parameters were carried out by means of the microscopic evaluation, viability assays, immunofluorescence, Western blot and RT-PCR investigations. The knowledge of the cell/implant interaction is essential for implant healing in order to obtain a more performing surfaces that promote the ECM release and provide the starting point to initiate the osseointegration process.

[ANMCO Position paper: Cardio-oncology in the COVID-19 era]. / Position paper ANMCO: Cardio-oncologia in era COVID-19.

The COVID-19 pandemic and its impact on patients with cancer and cardiovascular disease have confirmed the particular vulnerability of this population. Indeed, not only a higher risk of contracting the infection has been reported, but also an increased occurrence of a more severe course and unfavorable outcome. Beyond the direct consequences of COVID-19, the pandemic has an enormous impact on global health systems. Screening programs and non-urgent tests have been postponed; clinical trials have suffered a setback. Similarly, in the area of cardiology care, a significant decline in ST-elevation myocardial infarction accesses and an increase in cases of late presenting heart attacks with increased mortality and complication rates have been reported. Health care systems must therefore get ready to tackle the "rebound effect" that will likely show a relative increase in the short and medium term incidence of diseases such as heart failure, myocardial infarction, arrhythmias and cardio- and cerebrovascular complications. Scientific societies are taking action to provide general guidance and recommendations aimed at mitigating the unfavorable outcomes of this pandemic emergency. Cardio-oncology, as an emerging discipline, is more flexible in modulating care pathways and represents a beacon of innovation in the development of multi-specialty patient management. In the era of the COVID-19 pandemic, cardio-oncology has rapidly modified its clinical care pathways and implemented flexible monitoring protocols that include targeted use of cardiac imaging, increased use of biomarkers, and telemedicine systems. The goal of these strategic adjustments is to minimize the risk of infection for providers and patients while maintaining standards of care for the treatment of oncologic and cardiovascular diseases. The aim of this position paper is to evaluate the impact of the COVID-19 pandemic on the management of cardio-oncologic patients with the-state-of-the-art knowledge about SARS-CoV-2 and COVID-19 in order to optimize medical strategies during and after the pandemic.

ANMCO POSITION PAPER: cardio-oncology in the COVID era (CO and CO).

The COVID-19 pandemic and its impact on patients with cancer and cardiovascular disease have confirmed the particular vulnerability of these populations. Indeed, not only a higher risk of contracting the infection has been reported but also an increased occurrence of a more severe course and unfavourable outcome. Beyond the direct consequences of COVID-19 infection, the pandemic has an enormous impact on global health systems. Screening programmes and non-urgent tests have been postponed; clinical trials have suffered a setback. Similarly, in the area of cardiology care, a significant decline in STEMI accesses and an increase in cases of late presenting heart attacks with increased mortality and complication rates have been reported. Health care systems must therefore get ready to tackle the 'rebound effect' that will likely show a relative increase in the short- and medium-term incidence of diseases such as heart failure, myocardial infarction, arrhythmias, and cardio- and cerebrovascular complications. Scientific societies are taking action to provide general guidance and recommendations aimed at mitigating the unfavourable outcomes of this pandemic emergency. Cardio-oncology, as an emerging discipline, is more flexible in modulating care pathways and represents a beacon of innovation in the development of multi-specialty patient management. In the era of the COVID-19 pandemic, cardio-oncology has rapidly modified its clinical care pathways and implemented flexible monitoring protocols that include targeted use of cardiac imaging, increased use of biomarkers, and telemedicine systems. The goal of these strategic adjustments is to minimize the risk of infection for providers and patients while maintaining standards of care for the treatment of oncologic and cardiovascular diseases. The aim of this document is to evaluate the impact of the pandemic on the management of cardio-oncologic patients with the-state-of-the-art knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19) in order to optimize medical strategies during and after the pandemic.

Portrait of Italian Cardio-Oncology: Results of a Nationwide Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Survey.

Aims: Cardio-oncology has achieved a pivotal role in science, but real world data on its clinical impact are still limited. Methods: A questionnaire was sent out to all cardio-oncology services across Italy (n = 120). The questionnaire was made up of 28 questions divided into four blocks: (A) general information on hospitals and service, (B) the inner organization of cardio-oncology and its relationships with out-of-hospital cardiologists and general practitioners, (C) educational needs and referral guidelines, and (D) activities/specific workload. Results: Ninety-six out of 120 (80%) completed the questionnaire; 9.4% were cancer centers while 90.6% were general hospitals. A cardio-oncology team was present in 56% of the cancer centers and in 20% only of general hospitals, and a cardio-oncology pathway was active in 55% of cancer centers and in just 14% of the general hospitals. Relationships with out-of-hospital cardiologists and general practitioners were lacking. The guidelines of reference were ESC and ANMCO/AIOM. Patients receiving anthracycline chemotherapy underwent scheduled monitoring by means of echocardiography in 58% of cases. Routine use of cardiac damage biomarkers was overall low, ranging from 22 to 33% while the use of global longitudinal strain reached 44%. Conclusions: Italian cardio-oncology showed a growing influence on clinical practice but still has room for improvement. Cardio-oncology teams are still scarce, and the application of dedicated paths is poor. The need for specific training has been highlighted.

Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.

Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche "Mario Negri", conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m2) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease.

Improving Provision of Care for Long-term Survivors of Lymphoma.

The progressive improvement of lymphoma therapies has led to a significant prolongation of patient survival and life expectancy. However, lymphoma survivors are at high risk of experiencing a range of early and late adverse effects associated with the extent of treatment exposure. Among these, second malignancies and cardiopulmonary diseases can be fatal, and neurocognitive dysfunction, endocrinopathy, muscle atrophy, and persistent fatigue can affect patients' quality of life for decades after treatment. Early recognition and reduction of risk factors and proper monitoring and treatment of these complications require well-defined follow-up criteria, close coordination among specialists of different disciplines, and a tailored model of survivorship care. We have summarized the major aspects of therapy-related effects in lymphoma patients, reviewed the current recommendations for follow-up protocols, and described a new hospital-based model of survivorship care provision from a recent multicenter Italian experience.