SARS-CoV-2 was already circulating in Italy, in early December 2019.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified in China, in December 2019 determines COronaVIrus Disease 19 (COVID-19). Whether or not the virus was present in Italy earlier the first autochthonous COVID-19 case was diagnosed is still uncertain. We aimed to identify anti-SARS-CoV-2 antibodies in sera collected from 4th November 2019 to 9th March 2020, in order to assess the possible spread of the virus in Italy earlier than the first official national diagnosis. PATIENTS AND METHODS: Anti-SARS-CoV-2 antibodies were evaluated in retrospective serum samples from 234 patients with liver diseases (Hep-patients) and from 56 blood donors (BDs). We used two rapid serologic tests which were confirmed by a validated chemoluminescence assay. RESULTS: Via rapid tests, we found 10/234 (4.3%) IgG-positive and 1/234 (0.4%) IgM-positive cases in the Hep-patient group. Two/56 (3.6%) IgG-positive and 2/56 (3.6%) IgM-positive cases were detected in BD group. Chemoluminescence confirmed IgG-positivity in 3 Hep-patients and 1 BD and IgM-positivity in 1 Hep-patient. RNAemia was not detected in any of the subjects, rendering the risk of transfusion transmission negligible. CONCLUSIONS: Our results suggest an early circulation of SARS-CoV-2 in Italy, before the first COVID-19 cases were described in China. Rapid tests have multiple benefits; however, a confirmation assay is required to avoid false positive results.

Interferon-free therapy in hepatitis C virus mixed cryoglobulinaemia: a prospective, controlled, clinical and quality of life analysis.

BACKGROUND: Cryoglobulinaemic vasculitis (CV) is a lymphoproliferative disorder related to hepatitis C virus (HCV) infection; anti-viral therapy is the first therapeutic option. CV can be incapacitating, compromising the patients' quality of life (QoL). In a controlled study, interferon-based therapy was associated with a lower virological response in vasculitic patients than in patients without vasculitis. Limited, uncontrolled data on direct-acting anti-virals are available. AIM: To evaluate safety, clinical efficacy, virological response and the impact of interferon-free treatment on QoL in HCV patients with and without mixed cryoglobulinaemia (MC). METHODS: We prospectively studied HCV patients with cryoglobulinaemia (with vasculitis-CV- and without vasculitis-MC-) and without cryoglobulinaemia (controls), treated with direct-acting anti-virals. Hepato-virological parameters, CV clinical response and impact on QoL were assessed. RESULTS: One hundred and eighty-two HCV patients were recruited (85 with CV, 54 with MC and 43 controls). A sustained virological response at 12 weeks (SVR12) was achieved in 166 (91.2%) patients (77/85 CV, 48/54 MC, 41/43 controls). In CV SVR patients, cryocrit levels progressively decreased and clinical response progressively improved, reaching 96.7%, 24 weeks after treatment. QoL, baseline physical and mental component summaries were lower in the CV group compared to the other groups (P < 0.05). Scores improved in all groups, and significantly in CV patients after SVR. CONCLUSIONS: No significant differences in SVR rates were recorded between cryoglobulinaemic patients and controls and a high clinical and immunological efficacy was confirmed in CV, supporting the role of interferon-free therapy as the first therapeutic option. Interestingly, CV patients had worse baseline QoL than other HCV-positive groups and interferon-free therapy was effective in significantly increasing QoL, suggesting the important role of direct-acting anti-viral-based therapy in improving CV's individual and social burden.

The therapeutic activity of sulphate-bicarbonate-calcium-magnesiac mineral water in the functional disorders of the biliary tract.

BACKGROUND AND AIM: Functional disorders of the biliary tract involve gallbladder and sphincter of Oddi and cause pain and/or digestive troubles. In this context, in addition to pharmacological treatments, an important role is played by the use of sodium-sulphate and sulphate-bicarbonate mineral waters that, because of their composition into ions macro and trace elements, can stimulate the release or modulate the activity of some neurohumoral regulators of the digestive process. We want to do a study on the effects of hydropinotherapy with a sulphate-bicarbonate-calcium-magnesium mineral water in patients suffering from pain and other symptoms caused by biliary dyskinesias, biliary sand (without gallstones), or following a cholecystectomy (post-cholecystectomy syndromes). MATERIALS AND METHODS: We enrolled 43 patients suffering from those affections; all the patients did two cycles in one year of hydropinotherapy with Acqua Santa at Italy's Chianciano Spa; 20 of these patients did a third cycle of hydropinotherapy in the second year of the study. At the end of the second and of the third cycle we compared the frequency of eleven main symptoms in both groups and we also performed an longitudinal-observational study on the frequency of those symptoms before the beginning of the first cycle of the therapy and at the end of the second and of the third cycle. Statistical analyses were based on the use of Pearson's χ2 test. RESULTS: The frequency of the symptoms observed at the end of second and third cicle of hydropinotherapy was significantly lower than that considered before starting therapy. The differences were statistically significant. CONCLUSIONS: The results of our research regarding the hydropinotherapy by sulphate-bicarbonate-calcium-magnesium mineral water show a significant improvement of symptoms in patients suffering from disturbances of biliary tract.

[The possible uses of balneotherapy in treating chronic venous insufficiency of lower limbs]. / Possibilità della balneoterapia termale nell'insufficienza venosa cronica degli arti inferiori.

The Chronic Venous Insufficiency (CVI) of inferior limbs is a widespread disease, with an increasing incidence as a consequence of longer life expectance, life-style, obesity, smoking, use of drugs as oestrogens and progestins and working conditions. Medical therapy is still lacking for evidence of efficacy, and compression therapy is useful only in preventing a worsening of this condition. Surgical treatment is the only radical therapy effective for the advanced phases of the disease. In this context spa balneotherapy can be considered as a possible chance to improve some subjective and objective symptoms of CVI of inferior limbs, and to prevent worsening of this condition. The authors performed a review of the relevant scientific literature concerning the treatment of CVI of inferior limbs with mineral water balneotherapy, in order to evaluate its effects on objective and subjective symptoms and its effectiveness to prevent further worsening. We searched the PubMed/Medline, Cochrane Library, Embase, Web of Science databases for articles published between 1990 and 2011 on this topic. To this end, the authors selected few clinical-controlled and case-controlled studies; patients affected from CVI of inferior limbs were treated with balneotherapy at health spas with sulphureous, sulphate, salsojodic or salsobromojodic mineral waters. Baths in mineral waters were often associated with idromassotherapy and vascular pathway. Effects of spa balneotherapy are related to some aspecific properties, like hydrostatic pressure, osmotic pressure and water temperature, partly related with specific chemico-physical properties of the adopted mineral water. The controlled clinical studies on spa therapy showed significant improvement of subjective (such as itch, paresthesias, pain, heaviness) and objective symptoms (namely edema and skin discromias). These studies suggest that spa balneotherapy may give a good chance of secondary prevention and effective therapy of CVI of inferior limbs, but also that it needs of other clinical controlled trials.

Changes, functional disorders, and diseases in the gastrointestinal tract of elderly / Cambios, dolencias funcionales y enfermedades en el sistema gastrointestinal en personas mayores

This article describes changes in the basic digestive functions (motility, secretion, intraluminal digestion, absorption) that occur during aging. Elderly individuals frequently have oropharyngeal muscle dysmotility and altered swallowing of food. Reductions in esophageal peristalsis and lower esophageal sphincter (LES) pressures are also more common in the aged and may cause gastroesophageal reflux. Gastric motility and emptying and small bowel motility are generally normal in elderly subjects, although delayed motility and gastric emptying have been reported in some cases. The propulsive motility of the colon is also decreased, and this alteration is associated with neurological and endocrine-paracrine changes in the colonic wall. Decreased gastric secretions (acid, pepsin) and impairment of the mucous-bicarbonate barrier are frequently described in the elderly and may lead to gastric ulcer. Exocrine pancreatic secretion is often decreased, as is the bile salt content of bile. These changes represent the underlying mechanisms of symptomatic gastrointestinal dysfunctions in the elderly, such as dysphagia, gastroesophageal reflux disease, primary dyspepsia, irritable bowel syndrome, primary constipation, maldigestion, and reduced absorption of nutrients. Therapeutic management of these conditions is also described. The authors also review the gastrointestinal diseases that are more common in the elderly, such as atrophic gastritis, gastric ulcer, colon diverticulosis, malignant tumors, gallstones, chronic hepatitis, liver cirrhosis, Hepato Cellular Carcinoma (HCC), and chronic pancreatitis (AU)

Este artículo describe los cambios en las funciones digestivas básicas (motilidad, secreción, digestión intraluminal, absorción) que ocurren en el envejecimiento. Los individuos ancianos a menudo presentan una dismotilidad de la musculatura orofaríngea y una alteración de la deglución de los alimentos. Las reducciones en el peristaltismo esofágico y de las presiones del esfínter esofágico inferior (EEI) también son más frecuentes en las personas mayores y pueden causar un reflujo gastroesofágico. La motilidad y el vaciamiento gástricos así como la motilidad intestinal son, por lo general, normales en los individuos ancianos, si bien se han notificado en algunos casos una motilidad y vaciamiento gástricos retardados. La motilidad propulsora del colon también está disminuida y esta alteración se asocia con cambios neurológicos y endocrinos-paracrinos de la pared colónica. En el anciano se describen frecuentemente disminución de las secreciones gástricas (ácido, pepsina) y alteración de la barrera mucosa-bicarbonato, lo cual puede favorecer la úlcera gástrica. A menudo la secreción pancreática exocrina está disminuida, así como el contenido en sales biliares de la bilis. Estos cambios representan mecanismos subyacentes de las disfunciones gastrointestinales sintomáticas del anciano tales como disfagia, enfermedad por reflujo gastroesofágico, dispepsia primaria, síndrome del intestino irritable, estreñimiento primario, maladigestión y disminución de la absorción de nutrientes. También se describe el manejo terapéutico de estos trastornos. Los autores también revisan las enfermedades gastrointestinales que son más frecuentes en el anciano, tales como las gastritis atrófica, la úlcera gástrica, la diverticulosis colónica, los tumores malignos, los cálculos biliares, la hepatitis crónica, la cirrosis hepática, el carcinoma hepatocelular (CHC) y la pancreatitis crónica (AU)

Changes, functional disorders, and diseases in the gastrointestinal tract of elderly.

This article describes changes in the basic digestive functions (motility, secretion, intraluminal digestion, absorption) that occur during aging. Elderly individuals frequently have oropharyngeal muscle dysmotility and altered swallowing of food. Reductions in esophageal peristalsis and lower esophageal sphincter (LES) pressures are also more common in the aged and may cause gastroesophageal reflux. Gastric motility and emptying and small bowel motility are generally normal in elderly subjects, although delayed motility and gastric emptying have been reported in some cases. The propulsive motility of the colon is also decreased, and this alteration is associated with neurological and endocrine-paracrine changes in the colonic wall. Decreased gastric secretions (acid, pepsin) and impairment of the mucous-bicarbonate barrier are frequently described in the elderly and may lead to gastric ulcer. Exocrine pancreatic secretion is often decreased, as is the bile salt content of bile. These changes represent the underlying mechanisms of symptomatic gastrointestinal dysfunctions in the elderly, such as dysphagia, gastroesophageal reflux disease, primary dyspepsia, irritable bowel syndrome, primary constipation, maldigestion, and reduced absorption of nutrients. Therapeutic management of these conditions is also described. The authors also review the gastrointestinal diseases that are more common in the elderly, such as atrophic gastritis, gastric ulcer, colon diverticulosis, malignant tumors, gallstones, chronic hepatitis, liver cirrhosis, Hepato Cellular Carcinoma (HCC), and chronic pancreatitis.

[SPA treatments of diseases pertaining to internal medicine]. / I mezzi di cura termale nella terapia di malattie di competenza internistica.

Authors resume the therapeutic employment of mineral waters, muds and baths in internistic syndromes or diseases. Mineral waters are used in the therapy of functional dyspepsia, gastro-oesophageal reflux, chronic primary stipsis, irritable bowel, biliary dyskinesias, mainly hypokinetic gallbladder and Oddi's sphincter, spasm, postcolecystectomy syndrome. The therapeutic effects of mineral waters are determined by their anion and cation content, the presence of undissociated salts and also by the presence of oligoelements. Additionally, the effects of a mineral waters are connected with physical constants: osmotic pressure and temperature. Many researches showed activity of the mineral waters on intestinal autonomic nerves and plexus (CIA), motility, exocrine, endocrine and paracrine digestive secretions and therapeutic properties belonging to evidence based medicine. Mud and bath therapy are effective in treatment of osteoarthritis. During and after mud-therapy effects on diencephalic-pituitary-adrenal axis were displayed, producing increase of endogenous opioids and cortisol. Clinical controlled trials showed significant improvement of symptoms as pain and stiffness. Inhalant therapy by sulphureous and salsojodic mineral waters improve symptoms as cough and escreate and functional indices as FEV1 in chronic obstructive pulmonary disease. The oligomineral waters are very useful in the treatment and secondary prevention of urolithiasis and of relapses of urinary stones after spontaneous expulsion, surgical treatment, stones removal by percutaneous or uretheroendoscopic treatment and lithotrypsia. Patients must drink at least 2L every day, substantially for ever. Chloruratesodic and bicarbonate mineral waters show improvement in disorders of lipidic and urate metabolism.

Sulphate-bicarbonate mineral waters in the treatment of biliary and digestive tract diseases.

The authors point out the therapeutic properties of sulphate-bicarbonate mineral waters. After summarizing the general mechanism of action of mineral waters, the main indications of such waters in thermal treatment are examined including: biliary sand, biliary dyskinesia, functional dyspepsia, irritable colon, chronic primitive constipation. The dysfunctions of biliary and digestive tracts are growing, mainly in the affluent world, because of the increase for stress, dietary habits, modern life style. Now they affect from 2,4% of general population to 7% of men and 20% of women, according to different studies. Mineral waters can improve symptoms and care some physiopathological underlying mechanisms. Authors stress the efficacy of sulphate-bicarbonate mineral waters in the therapy of biliary dyskinesias, namely gallbladder hypokinesia and Oddi's sphincter spasm, caused by their content in SO4 = anion and Mg++ cation and related effects on paracrine-endocrine gastrointestinal system. In addition, they report the effects of sulphate-bicarbonate mineral waters in the lithogenic bile (sand bile), because of their diluting and washing activity. Among the sulphate-bicarbonate mineral waters, the Authors outline the well-documented therapeutic activity of Acqua Santa and Fucoli of Chianciano Terme. Acqua Santa has stimulating effect on cholecystis's motility, as proved by controlled clinical trials. Finally, the therapeutic use of sulphate-bicarbonate mineral water is discussed in functional dyspepsia, chronic primitive constipation and irritable bowel syndrome.

[Spa therapy in osteoarthritis: experience in Cervia]. / La terapia termale nell'osteoartrosi: esperienza di Cervia.

AIMS: Mud-bath treatment has a relevant therapeutic activity in reducing symptoms and disabilities in rheumatic diseases, as studies on inflammation process and clinical symptomatology have shown. Objective of this study is to evaluate the efficacy of mud therapy by natural limans of Cervia on clinical parameters in patients with lumbar spine osteoarthrosis (OA). MATERIALS AND METHODS: 30 patients (20 females and 10 males) suffering from lumbar OA, diagnosed by clinical symptoms and X-Ray findings (osteophytosis, morphological changes of vertrebral somes, tightness of intervertebral spaces, alterated lumbar physiologic lordosis) were studied. All patients were examined first when recruited (T0) and after two weeks of therapy (T1). Interviews were submitted in order to estimate functional restrictions and pain. Statistical analysis was performed via t test for paired data. RESULTS: On the basis of the statistical analysis a very significant difference was demonstrated between the average values of the tests before and after the treatment. These results confirm the improvement of the symptoms concerning the pain, the articular functionality and the quality of life. CONCLUSIONS: The results of the study demonstrate the efficacy of the mud-bath treatment with natural limans of Cervia on the patients affected by lumbar spine osteoarthrosis (OA).

[Efficacy of mud-bath therapy with Mineral Water from the Sillene spring at Italy's Chianciano Spa for osteoarthritis of the knee: a clinical statistical study]. / Effcacia della fangobalneoterapia con Acqua Minerale Sillene (Terme di Chianciano, Italia) nell'osteoartrosi del ginocchio: uno studio clinico-statistico.

AIMS: Many previous researches showed clinical benefits, effects on inflammatory mediators and pain, immune system, hormones and on the diencephalic-pituitary-adrenal axis. Our study evalues the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy's Chianciano Spa in patients with osteoarthritis of the knee. MATERIALS AND METHODS: In study we compared: physical examination of the knee joint, visual analogue scale (VAS) assessment of pain, and Lequesne Algo-functional Index. Tests were performed in 61 patients divided into 2 groups. The group A underwent three full cycles of mud-bath therapy over 1 year's time, the group B did not. An observational longitudinal study was also conducted on the patients of group A, before and after completion of the treatment protocol. Statistical analyses were based on use of Pearson's chi² test, Student's t tests for paired and unpaired data. RESULTS: The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B (differences were highly significant); the mean value of VAS and the overall Lequesne indexes mean score reported in group A was significantly lower than that reported in group B. The same we observed comparing the clinical conditions of group A patients before and after mud-bath therapy. No adverse effects were observed in any of the patients in group A. CONCLUSIONS: The mud-bath therapy at Chianciano Spa significantly improves the clinical conditions of patients with knee osteoarthritis and significantly reduces the frequency and severity of symptoms and the disability they cause.

Gout and related morbid conditions: pharmacological and SPA therapy.

Gouty arthritis is estimated to be the most frequent manifestation of inflammatory arthritis in men aged over 40. Hyperuricemia occurs because of both exogenous and genetic factors, which are particularly influential in some populations such as Taiwan aborigines. Current understanding of the disease etiopathogenesis, its clinical manifestations and the stages of its progression are presented here. The criteria for a correct diagnosis of the disease are also reported, pointing out how to distinguish gout from clinical events of different origin but with a very similar symptomatology. A distinction is made between the agents used to relieve the acute attack (colchicine, nonsteroidal anti-inflammatory drugs, corticosteroids) and those used with the purpose of correcting hyperuricemia and preventing recurrences and complications (allopurinol, uricosurics). Mecha-nisms of action, administration routes, doses, side effects and contraindications of every drug are described. Besides pharmacological therapy, the importance and the efficacy of spa therapy is underlined. Finally, perspectives opened by gene therapy are mentioned.

[Spa therapy in urolithiasis]. / Cure termali nella calcolosi urinaria.

In the present paper we remind epidemiology, etiopathogenesis and physiopathology of urolythiasis, emphasizing the role of lythogenic and antilythogenic urinary costituents. Mineral waters used in prevention and therapy of urolythiasis are described, namely oligomineral waters and, in uric lythiasis, bicarbonate mineral waters. We stress the activity of oligomineral waters, regarding their very low concentration of solute, presence of oligoelements, and antilythogenic components. At the end, we outline the role of spa therapy in the correction of metabolic disorders, which are etiologic and pathogenetic factors of urolythiasis.

[Spa and climate therapy in chronic obstructive pulmonary diseases]. / Possibilità crenoterapiche e climatoterapiche nelle malattie ostruttive polmonari croniche.

The authors remind the main epidemiological and clinical findings of Chronic Obstructive Pulmonary Disease (COPD); the prevalence and incidence of COPD is increasing and COPD is now the IV cause of death in the world. Moreover, it is cause of increasing pharmaceutic and hospital charges. COPD has multifactorial etiology, linked to genetic and exogenous factors, as tobacco smoke, air pollution, microbial infections and cold. The GOLD guide lines of the medical therapy of the COPD are showed. The spa therapy of COPD is based on the inhalation use of mineral water, mainly sulphurous and salsojodic. Sulphurous mineral waters have vasodilating activity on vessels of bronchial mucose, improving its trophic state, and increase the production of secretory IgA and muco-ciliary clearance; they have fluidificant activity on bronchial secretion. Clinical trials showed improvement of cough, sputum and functional indexes as FEV1 and CV. Salsojodic mineral waters increase the fluidity of the bronchial mucus, muco-ciliary clearance and the trophism of the bronchial mucose. The authors remind the properties of sulphate and bicarbonate mineral waters in the spa therapy of COPD. Finally authors refer about some effects of spa therapy and climatic-environmental situations on COPD morbidity.

[Therapeutic effect of the association between pulmonary ventilation and aerosol--inhalation with sulphureous mineral water in the chronic bronchopneumopathies]. / Effetto terapeutico dell'associazione ventilazione polmonare e aerosol-inalazione con acqua minerale solfurea nelle broncopneumopatie cronico-ostruttive (BPCO).

AIM: Our research evaluates the efficacy of the inalation therapy by mineral sulphureous water in patients suffering from cronic bronchopneumopathy. MATERIALS AND METHODS: From August to October 2002, two groups of patients, randomly selected, suffering from cronic bronchopneumonopathy, were studied at spa center "Pompeo" in Ferentino (FR). Every patient was treated daily during a cycle of twelve days. The first group was treated by pneumonic mechanical ventilation associated to sulphureous water aerosolinalation, the second by mechanical pulmonary ventilation associated to sulphureous water aerosol-inalation medicated with flunisolide. Every patient carried out spirometry, before and after treatment, and the measurement of FEV1 was considered a good parameter to evaluate the respiratory function. RESULTS: All patients reported an improvement in symptoms as dyspnea and cough. Results obtained show a significant functional improvement of respiratory function in both groups, evaluated by FEV1. Equal efficacy treating the patients by medicated and not medicated treatments stress the therapeutic role of mineral sulphureous waters in chronic bronchopneumopathies. Our research points out the usefullness of pneumonic ventilation associated with sulphureous water aerosol-inalation in patients suffering from chronic bronchopneumopathies.

[Meta-analytical study of gastrointestinal stromal tumors (GIST)]. / Studio metanalitico dei tumori stromali gastrointestinali (GIST).

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gut wall. GIST have still today controversial aspects of their histogenesis that are reflected on the classification, clinical behaviour and prognosis. The authors analyzed 14 studies observed between 2000 and 2001; also the tumors early classified as leiomyomas, leiomyosarcomas and schwannomas were included in these studies because, on the basis of immunohistochemical analysis, their cells were c-Kit positive. The GIST occurred in 728 patients with the age range of 12 days-96 years with a male predominance (59.3%). The most common symptoms were abdominal pain (25.4%) and gastrointestinal bleeding (23.4%). CT scan was the most important diagnostic technique. Surgery was the only useful treatment; in this study completeness of resection predicted for longer survival. Overall survival was between 21.4% and 88.8%; the percentage of deaths was between 11.1% and 78.5%. Distant metastases, localised in liver and lungs, and locoregional recurrences developed in a percentage between 9% and 68%.

[MDR (multidrug resistance) in hepatocarcinoma clinical-therapeutic implications]. / MDR (multidrug resistance) nell'epatocarcinoma: implicazioni clinico-terapeutiche.

Our purpose was to summarize current knowledge on "multidrug resistance", or MDR, an intrinsic or acquired cross resistance to a variety of structurally and functionally unrelated drugs, still representing one of the major problems in the therapy of cancer and other diseases. MDR depends on various mechanisms, the best known being the activity of ABC transport proteins, mainly Pgp, MDR1 gene product,and MRPs; but also other transporters can cause resistance, for example TAP, a peptide transporter, CFTR, cystic fibrosis transmembrane regulator, ABCG2, or breast cancer resistance protein (BCRP) and LRP, lung resistance protein. MDR has been detected in nearly all types of cancer, because it affects many organs and can occur against a wide number of drugs; it is frequent even in other diseases, such as epilepsy and HIV. We focused on MDR phenomenon in HCC, one of the commonest tumors in the world, and one of the most resistant to pharmacological treatment. This characteristic might be partly determined by a link between MDR and angiogenic phenotypes. The relationship between MDR in hepatocellular carcinoma and the effectiveness of therapeutic treatments has been particularly examined. Finally, the importance to overcome the strong chemoresistance of hepatocellular carcinoma with methods alternative to drugs, namely gene therapy, which makes use of antisense oligonucleotides and anti-MDR1 ribozymes, has been pointed out.