Adjunctive use of oral MAF is associated with no disease progression or mortality in hospitalized patients with COVID-19 pneumonia: The single-arm COral-MAF1 prospective trial.

Based on a growing body of evidence that a dysregulated innate immune response mediated by monocytes/macrophages plays a key role in the pathogenesis of COVID-19, a clinical trial was conducted to investigate the therapeutic potential and safety of oral macrophage activating factor (MAF) plus standard of care (SoC) in the treatment of hospitalized patients with COVID-19 pneumonia. Ninety-seven hospitalized patients with confirmed COVID-19 pneumonia were treated with oral MAF and a vitamin D3 supplement, in combination with SoC, in a single-arm, open label, multicentre, phase II clinical trial. The primary outcome measure was a reduction in an intensive care unit transfer rate below 13% after MAF administration. At the end of the study, an additional propensity score matching (PSM) analysis was performed to compare the MAF group with a control group treated with SoC alone. Out of 97 patients treated with MAF, none needed care in the ICU and/or intubation with mechanical ventilation or died during hospitalization. Oxygen therapy was discontinued after a median of nine days of MAF treatment. The median length of viral shedding and hospital stay was 14 days and 18 days, respectively. After PSM, statistically significant differences were found in all of the in-hospital outcomes between the two groups. No mild to serious adverse events were recorded during the study. Notwithstanding the limitations of a single-arm study, which prevented definitive conclusions, a 21-day course of MAF treatment plus SoC was found to be safe and promising in the treatment of hospitalized adult patients with COVID-19 pneumonia. Further research will be needed to confirm these preliminary findings.

The Role of Lung Ultrasound in SARS-CoV-19 Pneumonia Management.

Purpose: We aimed to assess the role of lung ultrasound (LUS) in the diagnosis and prognosis of SARS-CoV-2 pneumonia, by comparing it with High Resolution Computed Tomography (HRCT). Patients and methods: All consecutive patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in COVID Centers were enrolled. LUS and HRCT were carried out on all patients by expert operators within 48−72 h of admission. A four-level scoring system computed in 12 regions of the chest was used to categorize the ultrasound imaging, from 0 (absence of visible alterations with ultrasound) to 3 (large consolidation and cobbled pleural line). Likewise, a semi-quantitative scoring system was used for HRCT to estimate pulmonary involvement, from 0 (no involvement) to 5 (>75% involvement for each lobe). The total CT score was the sum of the individual lobar scores and ranged from 0 to 25. LUS scans were evaluated according to a dedicated scoring system. CT scans were assessed for typical findings of COVID-19 pneumonia (bilateral, multi-lobar lung infiltration, posterior peripheral ground glass opacities). Oxygen requirement and mortality were also recorded. Results: Ninety-nine patients were included in the study (male 68.7%, median age 71). 40.4% of patients required a Venturi mask and 25.3% required non-invasive ventilation (C-PAP/Bi-level). The overall mortality rate was 21.2% (median hospitalization 30 days). The median ultrasound thoracic score was 28 (IQR 20−36). For the CT evaluation, the mean score was 12.63 (SD 5.72), with most of the patients having LUS scores of 2 (59.6%). The bivariate correlation analysis displayed statistically significant and high positive correlations between both the CT and composite LUS scores and ventilation, lactates, COVID-19 phenotype, tachycardia, dyspnea, and mortality. Moreover, the most relevant and clinically important inverse proportionality in terms of P/F, i.e., a decrease in P/F levels, was indicative of higher LUS/CT scores. Inverse proportionality P/F levels and LUS and TC scores were evaluated by univariate analysis, with a P/F−TC score correlation coefficient of −0.762, p < 0.001, and a P/F−LUS score correlation coefficient of −0.689, p < 0.001. Conclusions: LUS and HRCT show a synergistic role in the diagnosis and disease severity evaluation of COVID-19.

Achilles Tendon Rupture and Dysmetabolic Diseases: A Multicentric, Epidemiologic Study.

Introduction: Achilles tendon ruptures are common. Metabolic disorders, such as diabetes mellitus, hypercholesterolemia, thyroid disorders, and obesity, impair tendons health, leading to Achilles tendinopathy and likely predisposing patients to Achilles tendon ruptures. Materials and methods: Patients who visited the Orthopedic Outpatient Clinics and the Accident and Emergency Departments of five different hospitals in Italy were recruited. Through telephone interviews, we administered a questionnaire to all the patients who had undergone surgical ATR repair, evaluating their past medical history, sport- and work-related activities, drug use, and post-operative rehabilitation outcomes. Results: "Return to work activities/sport" was negatively predicted by the presence of a metabolic disorder (ß = -0.451; OR = 0.637) and 'open' surgery technique (ß = -0.389; OR = 0.678). "Medical complications" were significantly predicted by metabolic disorders (ß = 0.600 (0.198); OR = 1.822) and was negatively related to 'mini-invasive' surgery (i.e., not 'open' nor 'percutaneous') (ß = -0.621; OR = 0.537). "Immediate weightbearing" and "immediate walking without assistance" were negatively predicted by 'open' technique (ß = -0.691; OR = 0.501 and ß = -0.359 (0.174; OR = 0.698)). Conclusions: Metabolic conditions can strongly affect post-operative outcomes following surgical repair of acute Achilles tendon tears.

Insertional Calcific Tendinopathy of the Achilles Tendon and Dysmetabolic Diseases: An Epidemiological Survey.

OBJECTIVE: This study reports the incidence of insertional calcific tendinopathy (ICT) of the Achilles tendon in the general population and the percentage of symptomatic patients. The secondary aim is to ascertain whether ICT is associated with diabetes mellitus, thyroid disorders, obesity, and hypercholesterolemia. We hypothesized that metabolic diseases increase the risk of ICT of the Achilles tendon. DESIGN: Prospective observational study (level III study). SETTING: Orthopedic Outpatients Clinic and Emergency Department of Tor Vergata University Hospital, Rome, Italy. PARTICIPANTS: Four hundred thirty-three subjects who met the inclusion criteria. INTERVENTION METHODS: We collected the plain radiographs of the foot and ankle of patients who attended the hospital. Personal data were recorded [age, sex, and body mass index (BMI)], and comorbidities investigated (diabetes mellitus, hypothyroidism, hyperthyroidism, obesity, and hypercholesterolemia). Multivariate regression analyses were performed to study the predictors of the occurrence of Achilles ICT. RESULTS: A total of 101 patients (23.3%) showed radiographic evidence of ICT, and 3% (13 patients) were symptomatic. Age [odds ratio (OR) 1.05], diabetes (OR 2.95), hypercholesterolemia (OR 2.27), and hypothyroidism (OR 3.32) were significantly associated with the presence of ICT of the Achilles tendon. Independent predictors of ICT were age, diabetes, hypercholesterolemia, and hypothyroidism. A BMI >30 was associated with a higher incidence of calcifications, and patients with 2 or more comorbidities had more than 10 times higher risk to develop ICT. CONCLUSION: Insertional calcific tendinopathy of the Achilles tendon is common, but few patients are symptomatic. The incidence of ICT increases with age and is significantly higher in patients with diabetes mellitus and hypothyroidism.

Dalbavancin treatment for spondylodiscitis: multi-center clinical experience and literature review.

Dalbavancin is a novel lipoglycopeptide antibiotic, characterized by a broad spectrum of activity against Gram-positive cocci. However, its efficacy in spondylodiscitis treatment is not fully established. All adult patients diagnosed with spondylodiscitis and treated with dalbavancin were included across four Italian medical centers from January 2018 to April 2021. We collected clinical and laboratory data, and presented follow-up findings along with a thorough literature review. 13 patients (mean age= 65 years) were included in this study. Dalbavancin was administered as first line treatment in six (46%) of the patients. Reasons for using Dalbavancin included treatment simplification (62%) and clinical failure of previous antibiotics (23%). In general, Dalbavancin was well tolerated with minimal adverse events, and clinical success was achieved in 11/13 (85%) of the patients during hospitalization with additional antibiotics required in the remaining two cases. Five months after discharge, no mortality was observed, however, 42% of patients required additional antibiotics for signs of infection on follow-up imaging. Our study suggests that Dalbavancin could be an effective and safe option in treating spondylodiscitis, however, the scarcity of studies on the topic is concerning. Thus, further studies with large samples and long-term follow-up are warranted to compare the efficacy of Dalbavancin with other available treatment options.

COVID-19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence.

BACKGROUND: Homocysteine assessment has been proposed as a potential predictive biomarker for the severity of COVID-19 infection. The purpose of this review was to analyze the correlation between the prevalence of MTHFR C677 T gene polymorphism and COVID-19 incidence and mortality worldwide. METHODS: Data regarding MTHFR C677 T gene mutation were obtained from the interrogation of the Genome Aggregation Database (genomAD), which is publicly available from the web"https://gnomad.broadinstitute.org." COVID-19 cases, including prevalence and mortality, were obtained from"https://www.worldometers.info/coronavirus" 27 August 2020. RESULTS: There is a clear trend toward the worldwide prevalence of MTHFR 677 T and COVID-19 incidence and mortality. The prevalence of MTHFR 677 T allele in the Latino population, and the incidence and mortality for COVID-19 was higher for this ethnic group than that reported for most other populations globally. Statistical analysis showed a relatively strong correlation between C677 T and death from coronavirus. CONCLUSIONS: Genetic polymorphism of MTHFR C677 T may modulate the incidence and severity of COVID-19 pandemic infection.

Ultrasound of Small Bowel Obstruction: A Pictorial Review.

Small bowel obstruction (SBO) is a common condition requiring urgent attention that may involve surgical treatment. Imaging is essential for the diagnosis and characterization of SBO because the clinical presentation and results of laboratory tests may be nonspecific. Ultrasound is an excellent initial imaging modality for assisting physicians in the rapid and accurate diagnosis of a variety of pathologies to expedite management. In the case of SBO diagnosis, ultrasound has an overall sensitivity of 92% (95% CI: 89-95%) and specificity of 93% (95% CI: 85-97%); the aim of this review is to examine the criteria for the diagnosis of SBO by ultrasound, which can be divided into diagnostic and staging criteria. The diagnostic criteria include the presence of dilated loops and abnormal peristalsis, while the staging criteria are represented by parietal and valvulae conniventes alterations and by the presence of free extraluminal fluid. Ultrasound has reasonably high accuracy compared to computed tomography (CT) scanning and may substantially decrease the time to diagnosis; moreover, ultrasound is also widely used in the monitoring and follow-up of patients undergoing conservative treatment, allowing the assessment of loop distension and the resumption of peristalsis.

Mortality in peripheral arterial disease: a comparison of patients managed by vascular specialists and general practitioners.

BACKGROUND: Peripheral arterial disease (PAD) is undertreated by general practitioners (GPs). However, the impact of the suboptimal clinical management is unknown. OBJECTIVE: To assess the mortality rate of PAD patients in relation to the type of physician who provides their care (GP or vascular specialist). DESIGN: Prospective study. SETTING: Primary care practice and academic vascular laboratory. PARTICIPANTS: GP patients (n = 60) were those of the Peripheral Arteriopathy and Cardiovascular Events study (PACE). Patients managed by specialists (n = 82) were consecutive subjects with established PAD who were referred to our vascular laboratory during the enrollment period of the PACE study. MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: After 32 months of follow-up, specialist management was associated with a lower rate of all-cause mortality (RR = 0.04; 95% CI 0.01-0.34; p = .003) and cardiovascular mortality (RR = 0.07; 95% CI 0.01-0.65; p = .020), after adjustment for patients' characteristics. Specialists were more likely to use antiplatelet agents (93% vs 73%, p < .001), statins (62% vs 25%, p < .001) and beta blockers (28% vs 3%, p < .001). Survival differences between specialists and GPs disappeared once the use of pharmacotherapies was added to the proportional hazard model. The fully adjusted model showed that the use of statins was significantly associated with a reduced risk of all-cause mortality (RR = 0.02; 95% CI 0.01-0.73, p = .034) and cardiovascular mortality (RR = 0.02; 95% CI 0.01-0.71, p = .033). CONCLUSIONS: Specialist management of patients with symptomatic PAD resulted in better survival than generalist management. This effect appears to be mainly caused by the more frequent use of effective medicines by specialists.

[Intermittent claudication in Italy. The Peripheral Arteriopathy and Cardiovascular Events (PACE) study]. / La claudicatio intermittens in Italia. lo studio Peripheral Arteriopathy and Cardiovascular Events (PACE).

BACKGROUND: The epidemiology of intermittent claudication in the primary care settings has been studied almost exclusively in northern European and northern American populations. This article compares the results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study, the first survey in Italy to assess the prevalence, comorbidity and natural history of intermittent claudication, with those observed in other western countries. METHODS: From the lists of seven general practitioners, all patients aged 40-80 years (n = 4352) received a Rose questionnaire. In those reporting leg pain while leg pain while walking (n = 760), Doppler examination was performed. Intermittent claudication was defined as an ankle/branchial index of < 0.90, or reduced flow velocity. For each claudicant, three age- and sex-matched controls were randomly selected from patients negative to the questionnaire. RESULTS: The prevalence of both intermittent claudication (1.6%) and associated cardiovascular disease (34%) tended to be lower in Italy than in the United Kingdom, Netherlands, and North America. Conversely, no between country difference was observed with respect to mortality, which was very high (relative risk 4.08; 95% confidence interval 1.50-10.84, p = 0.006) in the PACE claudicants. CONCLUSIONS: In this regard it is noteworthy that these patients, who were managed almost exclusively by their general practitioner were undertreated with respect to the use of antiplatelet therapy and correction of risk factors. There is need to alert them to this topic.

Prevalence, risk factors and cardiovascular comorbidity of symptomatic peripheral arterial disease in Italy.

The epidemiology of peripheral arterial disease (PAD) has been studied almost exclusively in northern European and northern American populations. We report the first survey in Italy to describe the prevalence of symptomatic PAD and clinical correlates. From the lists of seven general practitioners, all subjects aged 40-80 years (n = 4352) received a Rose Questionnaire (RQ). In those reporting pain in the leg while walking, which did not disappear while continuing to walk (n = 760), Doppler examination was performed. PAD was defined by ankle/brachial < or = 0.90, or reduced flow velocity. The prevalence of symptomatic PAD was 1.6% (2.4% in men, 0.9% in women). For each PAD patient, three controls matched for sex and age were randomly selected. At the multivariate analysis, smoking, diabetes and hypertension were significantly associated with PAD. A coexistent cardiovascular disease was found in 34% of patients and 11% of controls (P < 0.001). Only PAD was shown to be independently associated with a previous cardiovascular event. Although symptomatic, 45% of the patients were unaware of their condition. In conclusion, prevalence and cardiovascular comorbidity of symptomatic PAD in Italy seem to be lower than in other western countries. The finding that PAD was unrecognised in about 50% of affected individuals implies that a large proportion of PAD population is not given preventive therapy, so remaining at high cardiovascular risk. Thus, there is need to alert general practitioners to this topic.

Increased inflammatory status and higher prevalence of three-vessel coronary artery disease in patients with concomitant coronary and peripheral atherosclerosis.

The aim of this study was to determine whether patients with coronary artery disease (CAD) and concomitant peripheral arterial disease (PAD) have a greater inflammatory status than those with CAD alone. To this aim, we evaluated PAD (ankle/brachial pressure index <0.9), and measured plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6) and the soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in 234 patients who underwent coronary angiography. Median levels of CRP, IL-6 and sICAM-1 were higher in the CAD without PAD (n=134) and CAD+PAD (n=40) groups than in 60 patients without either disease ("controls"). Median CRP values were higher in patients with CAD+PAD than in patients with CAD alone (4.7 mg/L [1.5; 7.6] vs 2.4 mg/L [0.9; 3.8], p < 0.01).Three-vessel CAD was diagnosed in 60% of CAD+PAD patients and in 21% (p< 0.01) of CAD only patients. After adjustment for confounding factors, only PAD was independently associated with three-vessel CAD (p<0.001). This association was maintained after adjustment for IL-6, the only inflammatory parameter significantly associated with three-vessel CAD at univariate analysis (p<0.01). In conclusion, in CAD the coexistence of PAD is associated with a greater inflammatory status and more widespread coronary atherosclerosis. These results could help to explain the high cardiovascular risk of patients with concomitant CAD and PAD and suggest that PAD be included among the variables used to identify CAD patients for further diagnostic evaluation.

Inflammatory status and endothelial function in asymptomatic and symptomatic peripheral arterial disease.

Peripheral arterial disease (PAD) is a predictor of cardiovascular risk. However, it is unknown whether PAD severity influences inflammatory status and endothelial function, which play a major role in atherosclerosis. Accordingly, we measured brachial artery flow-mediated dilation (FMD), and plasma levels of several inflammatory markers in 15 control subjects, and 19 asymptomatic and 19 symptomatic PAD patients. Each symptomatic patient was matched to an asymptomatic patient for age, sex, risk factors, presence of cardiovascular disease, and pharmacological treatments. Asymptomatic patients had similar inflammatory profiles as controls, but lower median FMD (11.7% vs 8.5%, p < 0.01). Compared with asymptomatic patients, symptomatic patients had higher median C-reactive protein (1.5 mg/l vs 6.0 mg/l, p < 0.05) and interleukine-6 (1.5 pg/ml vs 3.5 pg/ml, p < 0.05), and lower FMD (8.5% vs 5.1%, p < 0.01). In the 38 PAD patients, the ankle/brachial pressure index correlated positively with FMD (p < 0.01), and negatively with C-reactive protein (p < 0.05), soluble intercellular adhesion molecule-1 (p < 0.05) and soluble vascular cell adhesion molecule-1 (p < 0.05). Thus, in PAD, endothelial function and inflammatory status are related to the severity of the circulatory impairment. This finding may contribute to the explanation of the increasingly poor prognosis with increased PAD severity.

Vitamin C prevents endothelial dysfunction induced by acute exercise in patients with intermittent claudication.

In patients with intermittent claudication, exercise is associated with a marked increase in oxidative stress, likely responsible for systemic endothelial perturbation. In 31 claudicant patients, we assessed the effect of vitamin C administration on the acute changes induced by maximal and submaximal exercise in endothelium-dependent, flow-mediated dilation (FMD), and in plasma levels of thiobarbituric acid-reactive substances (TBARS) and soluble intercellular adhesion molecule-1 (sICAM-1). In 16 claudicants, maximal exercise reduced FMD (from 8.5+/-0.9 to 3.7+/-0.8%, P<0.01), and increased plasma levels of TBARS (from 1.93+/-0.06 to 2.22+/-0.1 nmol/ml, P<0.02) and of sICAM-1 (from 282+/-17 to 323+/-19 ng/ml, P<0.01). In eight of these patients, randomized to vitamin C, exercise-induced changes in FMD and biochemistry were abolished. This beneficial effect was not observed in the eight patients randomized to saline. In 15 patients, who walked until the onset of claudication pain (submaximal exercise), and in ten control subjects, who performed maximal exercise, no changes were observed with exercise. Thus, in claudicants, vitamin C prevents the acute, systemic impairment in endothelial function induced by maximal exercise. This finding provides a rationale for trials investigating antioxidant therapy and cardiovascular risk in patients with intermittent claudication.

Early vascular alterations in acromegaly.

Acromegaly is associated with increased cardiovascular mortality; however, little is known about the early atherosclerotic changes occurring in such patients. Endothelial function, in the form of flow-mediated dilation (FMD) of the brachial artery, and intima-media thickness (IMT) of the carotid artery were measured by B-Mode ultrasound in: 1) 18 patients with active acromegaly; 2) 12 subjects cured from acromegaly; 3) 18 subjects without acromegaly, each of them matched to an acromegalic patients for age, sex, risk factors and treatments; and 4) 10 healthy subjects. Results are expressed as median plus (25th, 75th) percentile. In active acromegalic patients, FMD was 5.7 (3.9, 7.7)%, significantly lower than in both healthy subjects (P < 0.01) and matched controls (P < 0.01). No difference between groups was observed for endothelium-independent vasodilation. Acromegalic patients had also higher IMT than healthy controls (P < 0.05), whereas no difference was observed with matched controls. In cured acromegalic patients, FMD was 9.2 (7.7, 10.5)%, significantly lower (P < 0.01) than in healthy controls but higher (P < 0.01) than in active patients. No difference in IMT was observed between active and cured patients. In conclusion, patients with acromegaly have functional and morphological vascular alteration that seems, at least in part, dependent on the GH excess itself.