Effects of environmental parameters and their interactions on the spreading of SARS-CoV-2 in North Italy under different social restrictions. A new approach based on multivariate analysis.

In 2020 North Italy suffered the SARS-CoV-2-related pandemic with a high number of deaths and hospitalization. The effect of atmospheric parameters on the amount of hospital admissions (temperature, solar radiation, particulate matter, relative humidity and wind speed) is studied through about 8 months (May-December). Two periods are considered depending on different conditions: a) low incidence of COVID-19 and very few regulations concerning personal mobility and protection ("free/summer period"); b) increasing incidence of disease, social restrictions and use of personal protections ("confined/autumn period"). The "hospitalized people in medical area wards/100000 residents" was used as a reliable measure of COVID-19 spreading and load on the sanitary system. We developed a chemometric approach (multiple linear regression analysis) using the daily incidence of hospitalizations as a function of the single independent variables and of their products (interactions). Eight administrative domains were considered (altogether 26 million inhabitants) to account for relatively homogeneous territorial and social conditions. The obtained models very significantly match the daily variation of hospitalizations, during the two periods. Under the confined/autumn period, the effect of non-pharmacologic measures (social distances, personal protection, etc.) possibly attenuates the virus diffusion despite environmental factors. On the contrary, in the free/summer conditions the effects of atmospheric parameters are very significant through all the areas. Particulate matter matches the growth of hospitalizations in areas with low chronic particulate pollution. Fewer hospitalizations strongly correspond to higher temperature and solar radiation. Relative humidity plays the same role, but with a lesser extent. The interaction between solar radiation and high temperature is also highly significant and represents surprising evidence. The solar radiation alone and combined with high temperature exert an anti-SARS-CoV-2 effect, via both the direct inactivation of virions and the stimulation of vitamin D synthesis, improving immune system function.

The function of specialized pro-resolving endogenous lipid mediators, vitamins, and other micronutrients in the control of the inflammatory processes: Possible role in patients with SARS-CoV-2 related infection.

Inflammation is an essential protective response against harmful stimuli, such as invading pathogens, damaged cells, or irritants. Physiological inflammation eliminates pathogens and promotes tissue repair and healing. Effective immune response in humans depends on a tightly regulated balance among inflammatory and anti-inflammatory mechanisms involving both innate and adaptive arms of the immune system. Excessive inflammation can become pathological and induce detrimental effects. If this process is not self-limited, an inappropriate remodeling of the tissues and organs can occur and lead to the onset of chronic degenerative diseases. A wide spectrum of infectious and non-infectious agents may activate the inflammation, via the release of mediators and cytokines by distinct subtypes of lymphocytes and macrophages. Several molecular mechanisms regulate the onset, progression, and resolution of inflammation. All these steps, even the termination of this process, are active and not passive events. In particular, a complex interplay exists between mediators (belonging to the group of Eicosanoids), which induce the beginning of inflammation, such as Prostaglandins (PGE2), Leukotrienes (LT), and thromboxane A2 (TXA2), and molecules which display a key role in counteracting this process and in promoting its proper resolution. The latter group of mediators includes: ω-6 arachidonic acid (AA)-derived metabolites, such as Lipoxins (LXs), ω -3 eicosapentaenoic acid (EPA)-derived mediators, such as E-series Resolvins (RvEs), and ω -3 docosahexaenoic (DHA)-derived mediators, such as D-series Resolvins (RvDs), Protectins (PDs) and Maresins (MaRs). Overall, these mediators are defined as specialized pro-resolving mediators (SPMs). Reduced synthesis of these molecules may lead to uncontrolled inflammation with possible harmful effects. ω-3 fatty acids are widely used in clinical practice as rather inexpensive, safe, readily available supplemental therapy. Taking advantage of this evidence, several researchers are suggesting that SPMs may have beneficial effects in the complementary treatment of patients with severe forms of SARS-CoV-2 related infection, to counteract the "cytokine storm" observed in these individuals. Well-designed and sized trials in patients suffering from COVID-19 with different degrees of severity are needed to investigate the real impact in the clinical practice of this promising therapeutic approach.

SARS-CoV-2 vaccines: What we know, what we can do to improve them and what we could learn from other well-known viruses.

In recent weeks, the rate of SARS-CoV-2 infections has been progressively increasing all over the globe, even in countries where vaccination programs have been strongly implemented. In these regions in 2021, a reduction in the number of hospitalizations and deaths compared to 2020 was observed. This decrease is certainly associated with the introduction of vaccination measures. The process of the development of effective vaccines represents an important challenge. Overall, the breakthrough infections occurring in vaccinated subjects are in most cases less severe than those observed in unvaccinated individuals. This review examines the factors affecting the immunogenicity of vaccines against SARS-CoV-2 and the possible role of nutrients in modulating the response of distinct immune cells to the vaccination.

SARS-CoV-2: lessons from both the history of medicine and from the biological behavior of other well-known viruses.

SARS-CoV-2 is the etiological agent of the current pandemic worldwide and its associated disease COVID-19. In this review, we have analyzed SARS-CoV-2 characteristics and those ones of other well-known RNA viruses viz. HIV, HCV and Influenza viruses, collecting their historical data, clinical manifestations and pathogenetic mechanisms. The aim of the work is obtaining useful insights and lessons for a better understanding of SARS-CoV-2. These pathogens present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne, whereas HIV and HCV are bloodborne. However, these viruses exhibit some potential similar clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2.

[High flow oxygen therapy with nasal cannula: use and applications in respiratory failure in internal medicine.] / Ossigenoterapia ad alti flussi con cannule nasali: razionale di utilizzo e applicazioni nell'insufficienza respiratoria in medicina interna.

High-flow nasal cannula (HFNC) are an oxygen therapy device developed in the last years for the treatment of patients with acute or acute on chronic hypoxemic respiratory failure with different etiology and severity (including covid-19 pneumonia). HFNC combine the possibility of delivering high flows of gases, actively humidified and heated, with the use of a comfortable nasal interface, resulting generally well tolerated by most patients. In light of these characteristics, together with the simplicity of use and versatility, they have spread not only in intensive and semi-intensive care units but also in general medical ward in which they can play an important role in the treatment of elderly, frail patients with comorbidity where other more aggressive and invasive methods of ventilations are not indicated or not practicable.

Evaluation and treatment of hyperglycemia in critically ill patients.

The hyperglycemic reaction to stress is part of adaptive metabolic response to critical illness, especially hypoxia, hemorrhage and sepsis. It involves neuro-endocrine and immune pathways leading to the development of insulin resistance and hepatic glucose production by gluconeogenesis and glycogenolysis. Over the last years the concept of stress related hyperglycemia has been replaced by the concept of dysglycemia and its three domains: hyperglycemia, hypoglycemia and glycemic variability. Each of the three domains is independently associated with increased risk of mortality in patients admitted in intensive care unit and non critically ill patients, both medical and surgical. The strongest association with mortality is demonstrated for hypoglycemia, with additive negative effects for hyperglycemia and glycemic variability. The influence of pre-existing diabetes mellitus on the relation of the three domains of dysglycemia with mortality is not clear, suggesting that patients affected by diabetes mellitus may tolerate a larger glucose variability. Advances in continuous glucose monitoring systems and insulin therapy algorithms may reduce the development of glycemic variability and hypoglycemia, but the benefits in clinical practice have not yet been established in clinical trials.

[The development of a bedside cart for the management of acute respiratory failure with non-invasive ventilation in Internal Medicine wards]. / Lo sviluppo di un carrello "bedside" per la gestione dell'insufficienza respiratoria acuta con ventilazione non invasiva nei reparti di Medicina Interna.

In order to improve the organization of a General Medical ward without a real critical care area and to optimize treatment of patients with acute respiratory failure, we developed a cart for non-invasive ventilation to be used at the patient bedside. In the rear panel, we set two i.v. drip poles used for i.v. therapy and to hold two Venturi-like flow generators for continuous positive airway pressure. On the top, two ventilators are present, a smaller one (domiciliary) and a bigger one (intensive care unit ventilator). In the front panel, there are 4 drawers called "blood - drugs", "oxygenation", "CPAP", "ventilation", in which all the devices for ventilation, oxygenation, aerosol and medical therapy are easily and quickly available. The management of acute respiratory failure is simpler, easier and safer with this cart: each necessary device is immediately available, and this avoids wasting time. This bedside non-invasive ventilation cart, as far as the cardiac emergency cart, can be useful in general medical wards lacking a critical care area in order to improve interventions in patients with acute respiratory failure.

[Benign multicystic peritoneal mesothelioma. A case report]. / Mesotelioma multicistico peritoneale benigno.

Benign multicystic peritoneal mesothelioma is a rare malignancy with unknown etiology, first described in 1980, which have been reported to date about 150 cases in the literature. Although the term "benign", used mainly to distinguish it from the classic malignant mesothelioma, a more aggressive cancer, is considered "borderline" in terms of aggression: it tends to local recurrence but cases of lymph node metastases or in other locations at a distance are not described. The symptoms are often vague and nonspecific (abdominal pain, enlarged abdomen and ascites). The common diagnostic imaging techniques (CT, MRI) may appear similar to ovarian or peritoneal cancer by more aggressive mesenchymal neoplasms. Histological examination, accurately with the aid of immunohistochemical techniques, is therefore essential for diagnosis. Treatment is surgical and consists of peritonectomy. After surgery, the prognosis is generally good. In 50% of cases may have local recurrences; so rigorous follow-up is indicated.

[Continuous positive airway pressure in acute pulmonary edema. application in a general medical ward]. / Sistemi CPAP (Continuous Positive Airway Pressure) nell'edema polmonare acuto cardiogenico: loro impiego in Reparto di Medicina Interna.

BACKGROUND: The application of a Continuous Positive pressure to Patient's airway (CPAP) represents one of the most important respiratory treatments during Acute Respiratory Failure (ARF) due to Acute Cardiogenic Pulmonary Edema (ACPE). Thanks to its hemodynamic and ventilatory effects, CPAP improves clinical and gasanalytic parameters and lead to a decrease of mortality and need of intubation in these patients. CPAP can be applied with different devices: ventilators, Venturi-like flow generators and Boussignac's device. AIM: To verify and to compare effectiveness and tolerability of two different CPAP's devices (Venturi-like flow generator and Buossignac's device) in ARF due to ACPE. The study was performed in a General Medical Ward. MATERIALS AND METHODS: 20 patients with ARF due to ACPE were randomized in two group: the first group (10 patients) received CPAP with a Venturi-like flow generator, the second group (10 patients) with Boussignac's device. At the end of CPAP treatment each patient gave a score to tolerability. RESULTS: In each group we noted a significant (p<0.05) improvement in clinical and gasanalytic parameters since the first hour of treatment; these improvements were confirmed in following determinations and were not significantly different in the two group of patients. The Boussignac group showed a better tolerability. CONCLUSIONS: The two CPAP's devices resulted similar in term of effectiveness. Boussignac's device has shown a better tolerability: this characteristic, together with the simple use, should stimulate the diffusion of this device where a flow generator or a ventilator are not present (outside Intensive Care Units, for example in General Medical Wards).

[Echocardiographic evaluation of anti-tumor necrosis factor-alpha therapy with infliximab in patients without cardiac pathologies]. / Effetti del trattamento anti-Tumor Necrosis Factor-alpha con infliximab in pazienti non cardiopatici: valutazione ecocardiografica.

In the course of heart failure, plasmatic levels of Tumor Necrosis Factor-alpha (TNF-alpha) are high and are related to prognosis and mortality. Infliximab, a recombinant chimeric antibody anti-TNF-alpha, was used in heart failure with disappointing results, similar to those obtained with other biological drugs.The aim of this study was the echocardiographic evaluation of infliximab infusion in nine patients without cardiac pathologies. The findings demonstrate a reduction of sistolic function and a modification of diastolic function after infliximab infusion in patients without cardiopathy. This study confirms the protective role played by TNFalpha on the myocardium, as suggested by previous experimental studies.

HCV and HGV infection, iron overload and liver disease in multitransfused patients with thalassaemia and persistently normal or abnormal transaminase levels.

Prevalence and influence on liver disease of HCV and HGV infections, and HCV genotypes were studied in 28 HCV-Ab positive multitransfused thalassaemia patients with persistently normal ALT levels (group A) matched by sex and age with 28 patients with increased ALT levels (group B). Laboratory and virologic tests (all patients), liver biopsy (28 patients) and LIC by SQUID (30 patients) were performed. In group A, HCV-RNA was positive in 39%, genotype 2a was detected in 91%. In Group B, HCV-RNA was positive in 89%, prevalence of genotype 1b and 2a was 52% and 48% respectively; compared with group A, they had significantly increased values of gammaGT, AF, BA, TP, IgG, IgA, LIC (group B: 2,142 -/+ 1,524 microg/g liver; group A: 1,084 -/+ 610 microg/g liver). Overall prevalence of HGV-RNA was low (12.5%) and not significantly different between groups. Liver biopsies revealed no cirrhosis and severe fibrosis was found in 3 HCV viremic patients in group B. In 14 viremic patients examined both for LIC and liver histology, mild fibrosis was observed in 71%, in which iron overload was below 5 times the normal value. In conclusion, in patients with normal ALT levels, active HCV infection must be excluded by evaluation of HCV-RNA. Liver biopsy is indicated in HCV viremic patients, independent of ALT levels; in non-viremic patients, increased ALT levels may be due to iron overload and LIC measurement is indicated. Our data emphasise the crucial role of chelation therapy to maintain low LIC levels in order to prevent progression of fibrosis to cirrhosis in patients with HCV chronic hepatitis.