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The family of painful osteocytic tumors includes osteoblastomas and osteoid osteomas—these lesions are considered benign, but they could produce a significant painful symptomatology. Usually, people affected are between 20 s and 30 s. When symptomatic, an effective treatment is mandatory for the management of these lesions to allow for a ful quality of life. The possibilities of treatment range from chirurgical en-block resection (procedure of surgical oncology aiming to remove a tumoral mass in its entirety, completely surrounded by a continuous layer of healthy tissue) to interventional approaches that, nowadays, are considered the most affordable and sustainable in terms of effectiveness, recovery after procedure, and for bone structure sparing. The main techniques used for osteoid osteomas and osteoblastomas are radio frequency ablation (RFA) and magnetic resonance-guided focused ultrasound (MRgFUS): the most important difference between these approaches is the needleless approach of MRgFUS, which further reduces the minimal invasiveness of RFA (and the related consequences) and the absence of exposure to ionizing radiation. Despite their high efficacy, a recurrence of pathology may occur due to a failure in therapy. In light of this, describing the various possibilities of follow up protocols and the imaging aspects of recurrence or incomplete treatment is mandatory. In the scenario given in the literature, many authors have tried to asses an organized follow up protocol of these patients, but many of them did not undergo periodical magnetic resonance (MR) or computerized tomography (CT) because of the lack of symptomatology. However, even if it seems that clinical evolution is central, different papers describe the protocol useful to detect eventual relapse. The aim of our manuscript is to review the various possibilities of follow-up of these patients and to bring together the most salient aspects found during the management of these osteocytic bone lesions.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants—and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

Dear Editor, We read with interest the correspondence by Chen et al 1 about our recent article on the comparison of clinical, laboratory and artificial intelligence–radiological findings in patients with lung involvement either from macrophage activation syndrome (MAS), a secondary form of haemophagocytic lymphohistiocytosis (HLH) or severe coronavirus disease 2019 (COVID-19).2 Age is one of the most common confounding factors in any observational study since it is associated with an increased risk of comorbidities, which may influence the outcome. In our study, the matching for age was not reliable because of higher prevalence of severe COVID-19 in elderly patients, who were admitted to intensive or subintensive care units of our hospital. These results mirror what was already observed in other observational studies,3 4 in which the incidence and severity of COVID-19 are generally higher in elderly patients due to higher frequency of comorbidities, increased frailty and immunosenescence.5 Conversely, MAS complicating adult-onset Still’s disease (AOSD), as patients assessed in our study, usually affects young adults.6 Considering the scientific debate behind our study,2 about the possibility that severe COVID-19 could be considered or not part of HLH spectrum, the age of occurrence may further differentiate the clinical pictures between these diseases. Furthermore, Chen et al 1 questioned the use of Yamaguchi criteria in classifying AOSD patients .7 Although …

Sacubitril/valsartan improved the prognosis of patients with heart failure with reduced ejection fraction in the PARADIGM-HF study. Recently, the TRANSITION and PIONEER-HF studies demonstrated the safety and efficacy of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure, with treatment initiated after hemodynamic and clinical stabilization. In this case series study, we assessed the short-term effects of sacubitril/valsartan on exercise capacity, inflammation, and biomarkers in patients with acute decompensated heart failure. Patients admitted for acute decompensated heart failure to the Department of Internal Medicine of Telese Terme Hospital and Cardiovascular Department, University of Bari, from 9 March, 2017 to 9 June, 2018 were enrolled. Following hemodynamic stabilization, patients initiated sacubitril/valsartan 24/26 mg twice a day for 4 weeks, with up-titration to 49/51 mg twice a day based on tolerability after 1 week. Efficacy outcomes included the 6-min walking test, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and lymphocyte count. Safety outcomes included renal function, hyperkalemia, and symptomatic hypotension. In total, 40 patients completed the study and 27 (67.5%) patients were up-titrated. Compared with baseline, exercise capacity and relative lymphocyte count increased significantly after 4 weeks of treatment, while N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein decreased significantly. N-terminal pro-B-type natriuretic peptide and relative lymphocyte count independently predicted the 6-min walking test distance (p = 0.021). No patients experienced any relevant side effects. Early initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction after acute decompensated heart failure may be safe and effective in terms of functional capacity and biomarkers.

Background Chronic heart failure (CHF) is associated with neuroautonomic unbalance. Purpose We aimed at verifying the biomechanical and neuroautonomic adaptation to tilt test-induced volume displacement in patients with ischemic CHF. Methods Fifty-four CHF patients with a previous inferoapical/inferolateral (IA-IL) or basal/apical septal (BS-AS) myocardial infarction, free from residual ischemia, were enrolled. They underwent head-up tilt test, radionuclide ventricular function monitoring using the ambulatory ventricular function monitoring device (VEST), sympatho-vagal balance evaluation (low [LF] and high [HF] frequencies) and isoproterenol test (CD25). Results IA-IL patients had lower values of stroke volume, cardiac output and ejection fraction.The end-diastolic volume (EDV) increased in the IA-IL group (F=36.41, P LF/HF ratio not-significantly increased in IA-IL patients and decreased in BS-AS. CD25 was similar in IA-IL and BS-AS patients (IA-IL patients = 4.6±0.94 μg and BS-AS patients = 5.0±1.06 μg, P=0.79). The severity of ventricular dysfunction rather than its site correlated with the unbalance in biomechanical and neuroautonomic response. Conclusions Ischemic CHF patients showed altered biomechanical adaptation to volume displacement and compensatory sympathetic overdrive. Caution should be used with drugs interfering with the sympathetic response due to increased risk of syncope in response to volume displacement. Acknowledgement/Funding None

The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation. Our case series involved 27 patients [mean age 70 ± 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65–74 years, Sex category): 6 ± 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 ± 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin. The mean left ventricular ejection fraction was 48 ± 9 %, the left atrial diameter was 46.5 ± 7 mm, and the estimated glomerular filtration rate was 45 ± 21 mL/min/1.73 m2. The mean duration of treatment was 15 ± 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose. Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications.

Background Prognostic stratification of elderly patients with chronic obstructive pulmonary disease (COPD) is difficult due to the wide inter-individual variability in the course of the disease. No marker can exactly stratify the evolution and natural history of COPD patients. Studies have shown that leukocyte count is associated with increased risk of mortality in COPD patients. The aim of this study was to evaluate the possible role of relative lymphocyte count as a risk marker for mortality in elderly patients with COPD. Methods and results This is a3-year prospective study. A total of 218patients, mean age 75.2±7 years, with moderate to severe COPD and free from conditions affecting lymphocyte count were enrolled. The population was divided into two groups according to the relative lymphocyte count, with a cut-off of 20%. Eighty-five patients (39%) had a relative lymphocyte count ≤20%. Three-year mortality rates from any cause in patients with relative lymphocyte count ≤ or > 20% were 68 and 51%, respectively (p = 0.0012). Survival curve analysis showed higher mortality in patients with relative lymphocyte count ≤20% (p = 0.0005). After adjustment for age and sex, the hazard ratio for mortality risk according to lymphocyte count was 1.79 (95% confidence interval [CI]: 1.26–2.57, p = 0.0013), even in the analysis limited to the 171 patients without congestive heart failure (1.63; 95% CI: 1.03–2.58, p = 0.038). Conclusions Low relative lymphocyte count was associated with higher mortality in elderly patients with severe COPD. Electronic supplementary material The online version of this article (10.1186/s12890-018-0685-6) contains supplementary material, which is available to authorized users.

To evaluated the safety of direct oral anticoagulants as compared to warfarin in a subgroup of patients with atrial fibrillation (AF) who should undergo antithrombotic therapy such as patients with CHADS2 score ≥ 3. We evaluated the incidence of major bleeding in patients with AF and CHADS2 score ≥ 3 in the RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE studies. Also we evaluated the incidence of major bleeding in patients at higher hemorrhagic risk (HAS-BLED ≥ 3). Data was derived from eleven studies whose results came from the pivotal trials. Our aim was to propose a critical debate on the collected data. There were some striking differences between the 4 considered studies: a high percentage of bleeding in the subpopulation at high risk of stroke or systemic embolism or at high risk of bleeding. Some studies reported a higher frequency of bleeding in the warfarin arm. The excess in the bleeding rate in the warfarin group was likely to be associated with Asian ethnicity as Asian patients often have higher warfarin sensitivity. Asian patients may require lower initiation and maintenance doses of warfarin. Careful evaluation of patients in need for anticoagulation is essential for the prescription of these drugs and the extension of global use.

The aim of this study was to evaluate the effect of exercise training on cardiac function in heart failure (HF) patients recently suffering from acute decompensation. Radionuclide ambulatory ventricular function monitoring (VEST) was used to detect variations in cardiac hemodynamics during training period.This was a monocentric, randomized, controlled trial. We enrolled 72 HF patients [left ventricle ejection fraction (LVEF)40%] within two weeks after acute cardiogenic pulmonary edema: 40 in the elderly group, 32 in the middle-aged group. Trained patients underwent a specific four-weeks exercise program (closed-chain resistive activities and abdominal exercises) which was supervised by a therapist in agreement with patients' characteristics. Catecholamines at rest, echocardiography, right-heart catheterization, and bicycle ergometer were performed. VEST was performed at the end of the 4weeks-training in all patients in order to assess patients' cardiac hemodynamics [LVEF, cardiac output (CO), stroke volume].Exercise training significantly improved exercise duration, peak oxygen consumption, and ventilatory threshold both in elderly and middle-aged patients (p0.0001) after the 4-week controlled training. Despite age (F=35.086, p0.0001; F=16.967, p0.0001; F=42.574, p=0.03, respectively), training reliably influence previous cardiopulmonary parameters (F=29.402, F=16.421, F=26.80, p0.0001, respectively). Norepinephrine and epinephrine were significantly reduced in both trained groups. Peak LVEF (37.3±4.7% vs 34±6.2%, p=0.002), peak stroke volume (43.3±3.9% vs 37.5±4.3%, p=0.001), and peak CO (63.4±6.1% vs 48.2±4.7%, p0.0001) increased in middle-aged patients after 4-week training.Exercise training improves cardiac performance indexes and pulmonary function in both middle-aged and elderly HF patients early after an acute episode of cardiac decompensation.