Magnetic Resonance Imaging Evaluation of Bone Metastases Treated with Radiotherapy in Palliative Intent: A Multicenter Prospective Study on Clinical and Instrumental Evaluation Assessment Concordance (MARTE Study).

Metastasis to bone is a common occurrence among epithelial tumors, with a high incidence rate in the Western world. As a result, bone lesions are a significant burden on the healthcare system, with a high morbidity index. These injuries are often symptomatic and can lead to functional limitations, which in turn cause reduced mobility in patients. Additionally, they can lead to secondary complications such as pathological fractures, spinal cord compression, hypercalcemia, or bone marrow suppression. The treatment of bone metastases requires collaboration between multiple healthcare professionals, including oncologists, orthopedists, neurosurgeons, physiatrists, and radiotherapists. The primary objective of this study is to evaluate the correlation between two methods used to assess local control. Specifically, the study aims to determine if a reduction in the volume of bone lesions corresponds to better symptomatic control in the clinical management of patients, and vice versa. To achieve this objective, the study evaluates morphological criteria by comparing pre- and post-radiotherapy treatment imaging using MRI and RECIST 1.1 criteria. MRI without contrast is the preferred diagnostic imaging method, due to its excellent tolerance by patients, the absence of exposure to ionizing radiation, and the avoidance of paramagnetic contrast media side effects. This imaging modality allows for accurate assessment of bone lesions. One of the secondary objectives of this study is to identify potentially useful parameters that can distinguish patients into two classes: "good" and "poor" responders to treatment, as reported by previous studies in the literature. These parameters can be evaluated from the imaging examinations by analyzing morphological changes and radiomic features on different sequences, such as T1, STIR (short tau inversion recovery), and DWI-MRI (diffusion-weighted).

Secondary Complications in COVID-19 Patients: A Case Series.

INTRODUCTION: Coronavirus SARS-CoV-2, the causative agent of COVID-19, primarily causes a respiratory tract infection that is not limited to respiratory distress syndrome, but it is also implicated in other body systems. Systemic complications were reported due to an exaggerated inflammatory response, which involves severe alveolar damage in the lungs and exacerbates the hypercoagulation that leads to venous thrombosis, ischemic attack, vascular dysfunction and infarction of visceral abdominal organs. Some complications are related to anticoagulant drugs that are administrated to stabilize hypercoagulability, but increase the risk of bleeding, hematoma and hemorrhage. The aim of this study is to report the diagnostic role of CT in the early diagnosis and management of patients with severe COVID-19 complications through the most interesting cases in our experience. MATERIAL AND METHODS: The retrospective analysis of patients studied for COVID-19 in our institution and hospitals, which are part of the university training network, was performed. CASES: Pneumomediastinum, cortical kidney necrosis, splenic infarction, cerebral ischemic stroke, thrombosis of the lower limb and hematomas are the most major complications that are reviewed in this study. CONCLUSIONS: Since the onset of the COVID-19 pandemic, the CT imaging modality with its high sensitivity and specificity remains the preferred imaging choice to diagnose early the different complications associated with COVID-19, such as thrombosis, ischemic stroke, infarction and pneumomediastinum, and their management, which significantly improved the outcomes.

Alert Germ Infections: Chest X-ray and CT Findings in Hospitalized Patients Affected by Multidrug-Resistant Acinetobacter baumannii Pneumonia.

Acinetobacter baumannii (Ab) is an opportunistic Gram-negative pathogen intrinsically resistant to many antimicrobials. The aim of this retrospective study was to describe the imaging features on chest X-ray (CXR) and computed tomography (CT) scans in hospitalized patients with multidrug-resistant (MDR) Ab pneumonia. CXR and CT findings were graded on a three-point scale: 1 represents normal attenuation, 2 represents ground-glass attenuation, and 3 represents consolidation. For each lung zone, with a total of six lung zones in each patient, the extent of disease was graded using a five-point scale: 0, no involvement; 1, involving 25% of the zone; 2, 25−50%; 3, 50−75%; and 4, involving >75% of the zone. Points from all zones were added for a final total cumulative score ranging from 0 to 72. Among 94 patients who tested positive for MDR Ab and underwent CXR (males 52.9%, females 47.1%; mean age 64.2 years; range 1−90 years), 68 patients underwent both CXR and chest CT examinations. The percentage of patients with a positive CT score was significantly higher than that obtained on CXR (67.65% > 35.94%, p-value = 0.00258). CT score (21.88 ± 15.77) was significantly (p-value = 0.0014) higher than CXR score (15.06 ± 18.29). CXR and CT revealed prevalent bilateral abnormal findings mainly located in the inferior and middle zones of the lungs. They primarily consisted of peripheral ground-glass opacities and consolidations which predominated on CXR and CT, respectively.

Universal Access to Advanced Imaging and Healthcare Protection: UHC and Diagnostic Imaging.

Universal Health Coverage (UHC) is a set of principles adopted by the World Health Organization (WHO) aimed to guarantee access to primary care for the entire world population through a range of essential health services without neglecting the diagnostic aspect. Italy is one of the signatory states, which means that diagnostic services should be appropriated and exigible throughout the national territory equally. Our research analyzed and identified the main criticalities in terms of age, territorial distribution, and technological and health appropriateness of installed Computed Tomography (CT) needed to meet the principles of UHC. Data analyzed in our study were published by Assobiomedica at the end of 2016 and by COCIR, which included and investigated the installed fleet of diagnostic equipment in the Italian sanitary system and in various European countries. The 6th point of the Alma Ata Declaration defines the concept of "primary health care", which includes the importance of the diagnostic phase in the Italian health care system to provide Essential Levels of Assistance (LEA). It is clear from our studies that the technology at the national level is not adequate to satisfy the UHC principles or the European criteria, with negative effects on the diagnostic standards and on advanced screenings. This study conducted on the installed CTs in Italy at the end of 2016 confirms the persistence of progressive aging that has been recorded for several years in the health facilities of the country and suggests incentive policies for the replacement of obsolete equipment, which represent a form of investment rather than a cost, due to the nature of the expenditure itself, one-off and amortizable over time.

Evolution of CT Findings and Lung Residue in Patients with COVID-19 Pneumonia: Quantitative Analysis of the Disease with a Computer Automatic Tool.

PURPOSE: the purpose of this study was to assess the evolution of computed tomography (CT) findings and lung residue in patients with COVID-19 pneumonia, via quantified evaluation of the disease, using a computer aided tool. MATERIALS AND METHODS: we retrospectively evaluated 341 CT examinations of 140 patients (68 years of median age) infected with COVID-19 (confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR)), who were hospitalized, and who received clinical and CT examinations. All CTs were evaluated by two expert radiologists, in consensus, at the same reading session, using a computer-aided tool for quantification of the pulmonary disease. The parameters obtained using the computer tool included the healthy residual parenchyma, ground glass opacity, consolidation, and total lung volume. RESULTS: statistically significant differences (p value ≤ 0.05) were found among quantified volumes of healthy residual parenchyma, ground glass opacity (GGO), consolidation, and total lung volume, considering different clinical conditions (stable, improved, and worsened). Statistically significant differences were found among quantified volumes for healthy residual parenchyma, GGO, and consolidation (p value ≤ 0.05) between dead patients and discharged patients. CT was not performed on cadavers; the death was an outcome, which was retrospectively included to differentiate findings of patients who survived vs. patients who died during hospitalization. Among discharged patients, complete disease resolutions on CT scans were observed in 62/129 patients with lung disease involvement ≤5%; lung disease involvement from 5% to 15% was found in 40/129 patients, while 27/129 patients had lung disease involvement between 16 and 30%. Moreover, 8-21 days (after hospital admission) was an "advanced period" with the most severe lung disease involvement. After the extent of involvement started to decrease-particularly after 21 days-the absorption was more obvious. CONCLUSIONS: a complete disease resolution on chest CT scans was observed in 48.1% of discharged patients using a computer-aided tool to quantify the GGO and consolidation volumes; after 16 days of hospital admission, the abnormalities identified by chest CT began to improve; in particular, the absorption was more obvious after 21 days.

Pharmacokinetics of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Extreme Obesity.

PURPOSE: Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for oral anticoagulation therapy; however, data and clinical experiences supporting the use of DOACs in patients with a body mass index ≥40 kg/m2 or weight >120 kg remain limited. The aim of this study was to evaluate the pharmacokinetic properties of DOACs in patients with AF and extreme obesity. METHODS: We enrolled all consecutive patients with AF and extreme obesity undergoing treatment with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th hours from the last dose intake in patients receiving apixaban and dabigatran and at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban. The DOACs' peak and trough plasma levels obtained from our study population were compared with those sourced from pharmacokinetic studies among patients without obesity, defined as a normal reference range in the literature. If at least 1 peak or trough plasma level was found ​​below or above the normal reference ranges, the patients were classified as having out-of-range DOAC plasma levels. Study population was then divided into in-range and out-of-range groups. Baseline characteristics, including DOAC treatment, were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed to identify baseline variables associated with DOACs' plasma concentration out of the expected range. FINDINGS: A total of 58 patients (mean [SD] age, 70.93 [8.73] years; 40% female) with extreme obesity (mean [SD] body mass index. 44.43 [3.54] kg/m2) and AF while undergoing DOAC treatment were included in the present study. In 9 patients (15.5 %), the DOAC plasma concentrations were out of the expected ranges (out-of-range group);, indicating a greater likelihood of edoxaban 30 mg treatment (33% vs 2%; P < 0.01) and inappropriate DOAC underdosing (56% vs 4%; P < 0.005) compared with the in-range group. According to the multivariate logistic analysis (P = 0.0011), the inappropriate DOAC underdosing (hazard ratio = 29.37; P = 0.0002) was an independent predictor of DOAC plasma levels out of the expected ranges. IMPLICATIONS: Patients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma concentrations in the expected range. The inappropriate DOAC underdosing seems to be the only independent clinical factor associated with a plasma concentration of the drug out of the expected range.

Clinical Outcome Prediction in COVID-19 Patients by Lymphocyte Subsets Analysis and Monocytes' iTNF-α Expression.

In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

COVID-19 vaccination in adults with congenital heart disease: Real-world data from an Italian tertiary centre.

Background: real-world data on COVID-19 vaccine safety, immunogenicity and acceptance in adults with congenital heart disease (ACHD) are lacking. Methods: ACHD patients who were offered COVID-19 vaccination from January to June 2021 were included. Data on adverse events, on patients' attitude towards vaccination and antispike IgG titre were retrospectively collected. A group of healthy individuals with similar age and sex undergoing vaccination was included for comparison. Results: 208 patients followed in a single ACHD tertiary centre (33.3 [26-45] years, 54% male) received COVID-19 vaccine, 65% vaccinated at our institution: 199 (96%) received Pfizer-BioNTech BNT162b2 vaccine, 4 (2%) Moderna-1273 and 5 (2%) AstraZeneca-ChAdOx1. Median follow-up after vaccination was 79 [57-96] days. No major adverse event was reported and the incidence of minor events was not different between ACHD patients and the control group. One patient was diagnosed with acute pericarditis. There were two deaths unrelated to the vaccine during follow-up. Three (1.5%) vaccinated patients tested positive for COVID-19. Antispike IgG titre, available in 159 (76%) patients, was 1334 [600-3401] BAU/ml, not significantly different from the control group (p=0.2). One patient with Fontan failure was seronegative. Advanced physiological stage was associated with lower antibody response, independently from previous viral exposure (p<0.0001). Fourteen percent refused COVID-19 vaccination at our institution. However, 50% of vaccinated patients declared to have been influenced by the discussion with the ACHD cardiologist and 66% of those vaccinated in situ reported that undergoing COVID-19 vaccination at the ACHD centre made them feel safer. Conclusion: COVID-19 vaccines appear safe in ACHD with satisfactory immunogenicity. However, the most vulnerable patients showed lower antibody response. ACHD team may play a key role in vaccine acceptance.

Apixaban in a Morbid Obese Patient with Atrial Fibrillation: A Clinical Experience Using the Plasmatic Drug Evaluation.

We present the case of a 45-year-old man with atrial fibrillation and morbid obesity (weight 128 kg, height 168 cm, BMI 45.4) who was switched from Warfarin 5 mg once daily to Apixaban 5 mg twice daily because he did not achieve at least 60% of the time in therapeutic range. We performed serial determinations of apixaban plasma concentration (at 2, 6, 12, 24 hrs after intake) showing drug levels within reference range, even when the patient lose weight.

Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study.

A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel. Based on CD4 T cell count before treatment, patients were divided in late (LP: CD4 <350/mmc), intermediate (IP: 350/mmc500/mmc) presenters. In all groups, cART introduction increased CD4 and CD4/CD8 T cell ratio, naïve T cell (CD4 and CD8) and CD127-expressing CD4 T cells. In parallel, cART significantly reduced effector memory T cells (CD4 and CD8) and T cell activation (CD38+CD8 and CD95+CD4 T cells). Moreover, the frequency of Naïve and Effector CD4 T cells before treatment correlated with several immune parameters key associated with the pathogenesis of HIV, thus mirroring the health of immune system. Interestingly, we identified the Naïve/Effector CD4 T cell ratio (N/EM) at w0 as a marker able to predict early immune recovery. Specifically, in LP, N/EM ratio was significantly higher in immunological responder patients (CD4>500/mmc at w24) when compared to immunological non responder (CD4 T cells <500/mmc at w24). Finally, a multivariate analysis indicates that after 24w patients with N/EM ratio higher than 1.86 at w0 recovered 96 CD4 T cells more than those with N/EM ratio lower than 0.46. Altogether, our data define an easy protocol able to define reliable immunological markers useful for the characterization of immune profile in viremic HIV patients and identify the naïve/effector CD4 T cell ratio as a new tool able to predict an early immune reconstitution potential.