Use of a Dermal Regeneration Template in a two-stage reconstruction after extensive skin surgery for Bowen's disease of the anterior neck - Case report.

INTRODUCTION: Dermal Regeneration Templates may be used in the reconstruction of large skin defects after cutaneous malignancy excisions. Bowen's disease (BD; squamous cell carcinoma in situ) is a common and persistent condition that can be related to chronic sun damage, and consequently, is usually located on the head and neck area or on the lower limbs. Literature does not provide clear guidelines on the treatment of BD, limiting itself to describing a wide range of different methods that can be used, including surgery, laser therapy or topical options. However, large lesions tend to scar in the post-operative setting and hence are difficult to treat surgically. PRESENTATION OF CASE: In this paper the authors present a case of a male in his 60s, ASA III score, who presented with a history of histopathologically-confirmed squamocellular carcinoma in the neck and supraclavicular region. Due to recurrent carcinomas the patient was treated with an extensive skin excision and a successful reconstruction using a Dermal Regeneration Template. The work has been reported in line with the SCARE criteria. DISCUSSION: The main surgical problem caused by BD is reaching complete oncological resection and, consequently, the need for extensive skin excisions. CONCLUSION: The use of the skin substitute resulted in a satisfactory functional and aesthetic result, with total clearance and no recurrence observed after 16 months.

Jupiter Science Enabled by ESA's Jupiter Icy Moons Explorer.

ESA's Jupiter Icy Moons Explorer (JUICE) will provide a detailed investigation of the Jovian system in the 2030s, combining a suite of state-of-the-art instruments with an orbital tour tailored to maximise observing opportunities. We review the Jupiter science enabled by the JUICE mission, building on the legacy of discoveries from the Galileo, Cassini, and Juno missions, alongside ground- and space-based observatories. We focus on remote sensing of the climate, meteorology, and chemistry of the atmosphere and auroras from the cloud-forming weather layer, through the upper troposphere, into the stratosphere and ionosphere. The Jupiter orbital tour provides a wealth of opportunities for atmospheric and auroral science: global perspectives with its near-equatorial and inclined phases, sampling all phase angles from dayside to nightside, and investigating phenomena evolving on timescales from minutes to months. The remote sensing payload spans far-UV spectroscopy (50-210 nm), visible imaging (340-1080 nm), visible/near-infrared spectroscopy (0.49-5.56 µm), and sub-millimetre sounding (near 530-625 GHz and 1067-1275 GHz). This is coupled to radio, stellar, and solar occultation opportunities to explore the atmosphere at high vertical resolution; and radio and plasma wave measurements of electric discharges in the Jovian atmosphere and auroras. Cross-disciplinary scientific investigations enable JUICE to explore coupling processes in giant planet atmospheres, to show how the atmosphere is connected to (i) the deep circulation and composition of the hydrogen-dominated interior; and (ii) to the currents and charged particle environments of the external magnetosphere. JUICE will provide a comprehensive characterisation of the atmosphere and auroras of this archetypal giant planet.

Cocoa Consumption Decreases Oxidative Stress, Proinflammatory Mediators and Lipid Peroxidation in Healthy Subjects: A Randomized Placebo-Controlled Dose-Response Clinical Trial.

INTRODUCTION: Cocoa flavonoids have been described to reduce the cardiovascular risk. Nevertheless, the involved mechanisms should be clarified and the dose-effect relation has never been evaluated. AIM: To investigate the dose-dependent effects of cocoa flavonoids on markers of endothelial and platelet activation and oxidative stress. METHODS: According to a randomized, double-blind, controlled, cross-over design, 20 healthy nonsmokers were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. RESULTS: Compared with flavonoid-free cocoa control, cocoa reduced sICAM-1 mean values [from 1190.2 to 1123.0; 906.3; 741.7 and 625.6 pg/mL (p = 0.0198 and p = 0.0016, for 500 and 800 mg respectively], sCD40L mean values [from 218.8 to 210.2; 165.5; 134.5 and 128.4 pg/mL (p = 0.023 and p = 0.013, for 500 and 800 mg respectively] and 8-isoprostanes F2 mean values [from 4703.9 to 4670.7; 2000.1; 2098.4 and 2052.3 pg/mL (p = 0.025; p = 0.034 and p = 0.029, for 200, 500 and 800 mg respectively)]. CONCLUSIONS: In our study we observed that short-term cocoa consumption improved proinflammatory mediators, lipid peroxidation and oxidative stress with a significant effect for higher dosages of flavonoids. Our findings suggest cocoa might be a valid tool for dietary intervention in prevention of atherosclerosis.

Immune-mediated inflammatory diseases after anti-SARS-CoV-2 vaccines: new diagnoses and disease flares.

OBJECTIVE: New-onset immune-mediated inflammatory diseases (IMIDs) and flares of pre-existing IMIDs have been reported following anti- SARS-CoV2 vaccination. Our study aimed at describing a retrospective cohort of patients developing new-onset IMIDs or flares of known IMIDs within 30 days after any anti-SARS-CoV2 vaccine dose. METHODS: We evaluated clinical records of all inpatients and outpatients referring to our institution between February 2021 and February 2022 with any clinical manifestations. We then selected those having received any anti-SARS-CoV2 vaccine dose within the prior 30 days and classified them as having or not a previous IMID according to predefined criteria. We recorded new-onset IMIDs or flares of known IMIDs and investigated any relationship with demographic, clinical and serological variables. RESULTS: 153 patients that received any anti-SARS-CoV2 vaccine dose within the previous 30 days were included of which 45 (29%) already had a diagnosis of IMID while 108 (71%) had no previously diagnosed IMID. 33 (30%) of the 108 patients, were diagnosed with a new-onset IMID. Pericarditis, polymyalgia rheumatica and vasculitis were the most frequent conditions. Among the 45 patients that already had an IMID, disease flare was the reason for referral in 69% of patients. Patients with an IMID flare had a lower number of comorbidities and tended to be younger compared with those who developed other conditions after anti-SARS-CoV2 vaccination. CONCLUSION: We provided a retrospective overview of a cohort of patients who developed new-onset IMIDs or flares of known IMIDs within 30 days after any dose of anti-SARS-CoV2 vaccine. While vaccination campaigns proceed, postvaccination surveillance programmes are ongoing and hopefully will soon clarify whether a causal relationship between vaccines and new-onset/flares of IMIDs exists.

Electrocardiographic Abnormalities in Hospitalized Patients with COVID-19 and the Associations with Clinical Outcome.

The cardiovascular (CV) system can often be affected during SARS-CoV-2 infection and several acute manifestations, such as myocardial infarction, pericarditis, myocarditis and arrhythmias have been described. We provide a retrospective overview of electrocardiographic (ECG) features and their relationship with clinical outcomes in a cohort of patients admitted to our COVID-19 Unit between November 2020 and May 2021. Resting standard 12-lead ECGs were performed in all patients at admission and in those recovering from SARS-CoV-2 infection also at discharge. Clinical and serological records alongside ECG measurements were retrospectively evaluated and statistical analysis was performed to identify relationships between variables. A total of 123 patients (44% females) with a mean age of 73.9 years were enrolled. Ninety-five (77%) patients recovered from SARS-CoV-2 infection and were discharged while 28 (23%) died in hospital. Almost 90% of patients displayed at least one CV risk factor and 41 (33%) patients had at least one previous CV event. We observed that heart rate, corrected QT interval dispersion (QTcd) and inverted T waves are independently associated with in-hospital death and inverted T waves show the strongest association. This association remained significant even after correcting for the number of CV risk factors at baseline and for the type of CV risk factor at baseline. Our study demonstrated that some ECG abnormalities at admission are independently associated with in-hospital death regardless of pre-existing CV risk factors. These findings may be of particular relevance in clinical settings with limited access to advanced techniques, such as cardiac magnetic resonance and could help improve the outcomes of patients with cardiac involvement related to SARS-CoV-2 infection.

Differences in Diagnosis and Management of Hypertensive Urgencies and Emergencies According to Italian Doctors from Different Departments Who Deal With Acute Increase in Blood Pressure-Data from Gear (Gestione Dell'emergenza e Urgenza in ARea Critica) Study.

Background: Diagnosis and treatment of hypertension emergency (HE) and urgency (HU) may vary according to the physicians involved and the setting of the treatment. The aim of this study was to investigate differences in management of HE and HU according to the work setting of the physicians. Methods: The young investigators of the Italian Society of Hypertension developed a 23-item questionnaire spread by email invitation to the members of Italian Scientific societies involved in the field of emergency medicine and hypertension. Results: Six-hundred and sixty-five questionnaires were collected. No differences emerged for the correct definitions of HE and HU or for the investigation of possible drugs that may be responsible for an acute increase in BP. The techniques used to assess BP values (p < 0.004) and the sizes of cuffs available were different according to the setting. Cardiologists more frequently defined epistaxis (55.2% p = 0.012) and conjunctival hemorrhages (70.7%, p < 0.0001) as possible presentation of HE, and rarely considered dyspnea (67.2% p = 0.014) or chest pain (72.4%, p = 0.001). Intensive care (IC) unit doctors were more familiar with lung ultrasound (50% p = 0.004). With regard to therapy, cardiologists reported the lowest prescription of i.v. labetalol (39.6%, p = 0.003) and the highest of s.l. nifedipine (43.1% p < 0.001). After discharge, almost all categories of physicians required home BP assessment or referral to a general practitioner, whereas hypertensive center evaluation or ambulatory BP monitoring were less frequently suggested. Conclusion: Management and treatment of HE and HU may be different according to the doctor's specialty. Educational initiatives should be done to standardize treatment protocols and to improve medical knowledge.

Correction: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

Reduction of High Cholesterol Levels by a Preferably Fixed-Combination Strategy as the First Step in the Treatment of Hypertensive Patients with Hypercholesterolemia and High/Very High Cardiovascular Risk: A Consensus Document by the Italian Society of Hypertension.

The primary and secondary prevention strategies of atherosclerotic cardiovascular disease (ASCVD) largely rely on the management of arterial hypertension and hypercholesterolemia, two major risk factors possibly linked in pathophysiological terms by the renin-angiotensin system activation and that often coexist in the same patient synergistically increasing cardiovascular risk. The classic pharmacologic armamentarium to reduce hypercholesterolemia has been based in the last two decades on statins, ezetimibe, and bile acid sequestrants. More recently numerous novel, additive resources targeting different pathways in LDL cholesterol metabolism have emerged. They include drugs targeting the proprotein convertase subtilisin/kexin type 9 (PCSK9) (inhibitory antibodies; small-interfering RNAs), the angiopoietin-like protein 3 (inhibitory antibodies), and the ATP-citrate lyase (the inhibitory oral prodrug, bempedoic acid), with PCSK9 inhibitors and bempedoic acid already approved for clinical use. With the potential of at least halving LDL cholesterol levels faster and more effectively with the addition of ezetimibe than with high-intensity statin alone, and even more with the addition of the novel available drugs, this document endorsed by the Italian Society of Hypertension proposes a novel paradigm for the treatment of the hypertensive patient with hypercholesterolemia at high and very high ASCVD risk. Our proposal is based on the use as a first-line of a preferably fixed combination of lipid-lowering drugs, under the motto "Our goal: achieve control. No setback: combine and check".

Adherence to the Mediterranean diet and the impact on clinical features in primary Sjögren's syndrome.

OBJECTIVES: The relationship between dietary patterns, including the Mediterranean diet, and rheumatic and musculoskeletal diseases (RMDs) has been increasingly assessed but data on patients with established primary Sjögren's syndrome (pSS) is lacking. The aim of the study was to explore the adherence to the Mediterranean diet and its relationship with metabolic and inflammatory features in a cohort of patients with pSS. METHODS: Demographic, clinical and serological data, including anthropometric parameters and cardiovascular (CV) disease risk factors/events among others were collected from 91 pSS patients. Adherence to the Mediterranean diet over the previous 12 months was assessed with the 14-item PREvencion con DIeta MEDiterranea (PREDIMED) tool and the 28-item Mediterranean Lifestyle (MEDLIFE) index. RESULTS: According to the PREDIMED score 29 (31%) patients had a good adherence to the Mediterranean Diet, 57 (61%) a medium adherence and only 7 (8%) a poor adherence. No difference could be identified across groups with regard to demographic data, disease activity, CV risk factors or other parameters. With regard to the MEDLIFE, the total of blocks 1 and 2, that are related to Mediterranean foods and dietary habits, did not correlate with the total of block 3 (related to other healthy habits such as physical activity), meaning that the patients adhering the most to the Mediterranean Diet not necessarily had an overall healthy lifestyle. The PREDIMED score was inversely correlated with disease activity, as measured by ESSDAI (Spearman's rho=-0.27, p=0.009) and ClinESSDAI (Spearman's rho=-0.26, p=0.01). Fish consumption was associated with lower prevalence of hypertension. CONCLUSIONS: Adherence to the Mediterranean diet, with particular attention to fish consumption, may be beneficial on various domains in pSS, such as the CV system and the inflammatory environment, and as such should be recommended to patients with this disease.

Pericarditis after SARS-CoV-2 Infection: Another Pebble in the Mosaic of Long COVID?

With the emerging success of the COVID-19 vaccination programs, the incidence of acute COVID-19 will decrease. However, given the high number of people who contracted SARS-CoV-2 infection and recovered, we will be faced with a significant number of patients with persistent symptoms even months after their COVID-19 infection. In this setting, long COVID and its cardiovascular manifestations, including pericarditis, need to become a top priority for healthcare systems as a new chronic disease process. Concerning the relationship between COVID-19 and pericardial diseases, pericarditis appears to be common in the acute infection but rare in the postacute period, while small pericardial effusions may be relatively common in the postacute period of COVID-19. Here, we reported a series of 7 patients developing pericarditis after a median of 20 days from clinical and virological recovery from SARS-CoV-2 infection. We excluded specific identifiable causes of pericarditis, hence we speculate that these cases can be contextualized within the clinical spectrum of long COVID. All our patients were treated with a combination of colchicine and either ASA or NSAIDs, but four of them did not achieve a clinical response. When switched to glucocorticoids, these four patients recovered with no recurrence during drug tapering. Based on this observation and on the latency of pericarditis occurrence (a median of 20 days after a negative nasopharyngeal swab), could be suggested that post-COVID pericarditis may be linked to ongoing inflammation sustained by the persistence of viral nucleic acid without virus replication in the pericardium. Therefore, glucocorticoids may be a suitable treatment option in patients not responding or intolerant to conventional therapy and who require to counteract the pericardial inflammatory component rather than direct an acute viral injury to the pericardial tissue.

Correction: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

Acute and Long Term Effects of a Nutraceutical Combination on Lipid Profile, Glucose Metabolism and Vascular Function in Patients with Dyslipidaemia with and Without Cigarette Smoking.

INTRODUCTION: Lifestyle changes present a fundamental role in cardiovascular prevention. Nutraceuticals also supplementing diet could help in controlling the cardiometabolic risk. AIM: (1) to evaluate acute effects of a combination of nutraceuticals (cNUT) on vascular function, BP, metabolism in dyslipidaemic patients before and after smoking; (2) to evaluate 12 weeks effects of the cNUT on lipid profile, insulin resistance and vascular function in patients with hypercholesterolemia not on statins. METHODS: After 14 d run-in period, 33 patients assumed a cNUT [patented formula containing: berberine (531.25 mg), red yeast rice powder (220 mg, 3.3 mg monacolin K) and leaf extract of Morus alba (200 mg) (LopiGLIK®, Akademy Pharma)]. To evaluate acute effects, cNUT or cNUT + smoking (in smoking subjects) on the morning of the first day of the study and then 26 patients prolonged 12 weeks effects. RESULTS: In non smokers, cNUT improved FMD (p = 0.041 for treatment). In smokers, FMD decreased after smoking, this was counteracted by intake of cNUT. In smokers, DBP increased after smoking a cigarette (p = 0.042 for treatment), counteracted by the cNUT intake. In non smokers, thermogenesis was increased after cNUT administration (p < 0.0001 for treatment). After 12 weeks of cNUT, FMD significantly increased (p < 0.05) and SBP (p = 0.04), total cholesterol and LDL cholesterol (p = 0.03) decreased. CONCLUSIONS: Our study suggests benefits of cNUT on cardiovascular prevention in hypercolesterolemic patients, non statin treated, that goes beyond the cholesterol and insulin resistance reduction protecting the subject from negative effects induced by smoking too.

Blood Pressure Profiles and Cognitive Function from Adulthood to Old Age: Chasing a Golden Middle Way?

With the demographic shift toward advanced ages, it is imperative to understand the biological mechanisms behind common, disabling age-related diseases such as cognitive impairment in its mild form to overt dementia. Hypertension, a major cardiovascular risk factor, is epidemiologically linked to vascular and Alzheimer-type dementia, with possible mechanisms being atherosclerotic macro- and microvascular damage leading to neuronal cell death, as well as proinflammatory events responsible for neurodegeneration. Nevertheless, there is currently a knowledge gap as to which population to target, what the diagnostics test, and how to manage early pathogenic events in order to prevent such a dramatic and disabling condition. While clinical trials data support the benefit of active BP control with antihypertensive medications on the risk of future cognitive impairment, hypotension appears to be related to accelerated cognitive decline in both the fit and the cognitively frail elderly. Dedicated, technologically advanced studies assessing the relation of BP with dementia are needed to clarify the pathophysiological mechanisms in the association before a tailored preventive, diagnostic, and therapeutic approach to one of the most widespread modern medical challenges becomes a reality.

Preexisting Oral Anticoagulant Therapy Ameliorates Prognosis in Hospitalized COVID-19 Patients.

Objective: Altered coagulation parameters in COVID-19 patients is associated with a poor prognosis. We tested whether COVID-19 patients on chronic oral anticoagulants (cOACs) for thromboembolism prophylaxis could receive protection from developing more severe phenotypes of the disease. Approach and Results: We searched the database of the SARS-RAS study (Clinicaltrials.gov: NCT04331574), a cross-sectional observational multicenter nationwide survey in Italy designed by the Italian Society of Hypertension. The database counts 2,377 charts of Italian COVID-19 patients in 26 hospitals. We calculated the Charlson comorbidity index (CCI), which is associated with death in COVID-19 patients. In our population (n = 2,377, age 68.2 ± 0.4 years, CCI: 3.04 ± 0.04), we confirm that CCI is associated with increased mortality [OR: 1.756 (1.628-1.894)], admission to intensive care units [ICU; OR: 1.074 (1.017-1.134)], and combined hard events [CHE; OR: 1.277 (1.215-1.342)]. One hundred twenty-five patients were on cOACs (age: 79.3 ± 0.9 years, CCI: 4.35 ± 0.13); despite the higher CCI, cOACs patients presented with a lower risk of admissions to the ICU [OR 0.469 (0.250-0.880)] but not of death [OR: 1.306 (0.78-2.188)] or CHE [OR: 0.843 (0.541-1.312)]. In multivariable logistic regression, cOACs confirmed their protective effect on ICU admission and CHE. The CCI remains the most important risk factor for ICU admission, death, and CHE. Conclusions: Our data support a mechanism for the continuation of cOAC therapy after hospital admission for those patients who are on chronic treatment. Our preliminary results suggest the prophylactic use of direct cOACs in patients with elevated CCI score at the time of the COVID-19 pandemic even in absence of other risks of thromboembolism.

Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI).

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio < 100. The latter, significantly benefited by the early use of non-invasive mechanical ventilation. Our study identified PaO2/FiO2 ratio at admission and comorbidity as the main alert signs to inform clinical decisions and resource allocation in non-critically ill COVID-19 patients admitted to IMU.

Real-World Hypertension Prevalence, Awareness, Treatment, and Control in Adult Diabetic Individuals: An Italian Nationwide Epidemiological Survey.

INTRODUCTION: Hypertesion is the leading cause of morbidity and mortality, worldwide, and its prevalence has been increasing in several countries, including Italy. AIMS: To assess hypertension prevalence, awareness, treatment, and control in a real-world sample of adults with self-reported diabetes compared with nondiabetic individuals. METHODS: Following the 2018 World Hypertension Day, a nationwide, cross-sectional epidemiological survey on cardiovascular risk factors ("Abbasso la Pressione!") in 3956 Italian pharmacies enrolled 47217 self-presenting volunteers (≥ 18 years). Participants underwent standardized blood pressure (BP) measurements and answered a questionnaire on cardiovascular risk factors and lifestyle habits. Questions included if they had an established diagnosis of diabetes, hypertension or were on a BP medication. Hypertension prevalence was defined as systolic BP ≥ 140 and/or diastolic BP ≥ 90 mmHg. A double definition for hypertension control based on the recent European and US guidelines on hypertension was applied. RESULTS: Diabetic individuals (N = 5695, 12%) had higher rates of hypertension prevalence (80% vs. 54.7%, p < 0.001), awareness (85.6% vs 77.3%, p < 0.001) and treatment (85.8% vs. 76.7%, p < 0.001), but lower hypertension control rates (36.1% vs. 39.6% according to the 2018 European guidelines, p < 0.001; 25.4% vs 30.8% according to the 2017 US guidelines, p < 0.001) than nondiabetics. Diabetic participants tended to be older, sedentary, overweight/obese, dyslipidemic men, with higher 10-years cardiovascular risk than nondiabetics (p < 0.001). Uncontrolled hypertension was associated with male gender, diabetes, body mass index, unhealthy lifestyle habits, and older age. CONCLUSIONS: Elevated hypertension awareness and treatment rates in diabetic adults do not translate into adequate BP control in the real world. Concomitant unfavorable metabolic features and unhealthy lifestyle habits might contribute to this observation.

Diet in Rheumatoid Arthritis versus Systemic Lupus Erythematosus: Any Differences?

In recent years, an increasing interest in the influence of diet in rheumatic and musculoskeletal diseases (RMDs) led to the publication of several articles exploring the role of food/nutrients in both the risk of developing these conditions in normal subjects and the natural history of the disease in patients with established RMDs. Diet may be a possible facilitator of RMDs due to both the direct pro-inflammatory properties of some nutrients and the indirect action on insulin resistance, obesity and associated co-morbidities. A consistent body of research has been conducted in rheumatoid arthritis (RA), while studies in systemic lupus erythematosus (SLE) are scarce and have been conducted mainly on experimental models of the disease. This review article aims to outline similarities and differences between RA and SLE based on the existing literature.