Impaired bone matrix glycoprotein pattern is associated with increased cardio-metabolic risk profile in patients with type 2 diabetes mellitus.

PURPOSE: Osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC) are matrix glycoproteins which mediate bone mineralization; moreover, their effects on glucose/insulin homeostasis have recently been demonstrated. Higher circulating OPN and OPG levels have been associated with the presence of insulin resistance, atherosclerosis and coronary heart disease. No data are available on contextual changes of these markers in type 2 diabetes mellitus (T2DM). Therefore, aims of this study were to evaluate serum OPN, OPG and OC levels in T2DM patients and their clinical correlates. METHODS: We recruited 83 consecutive T2DM patients referring to our diabetes outpatient clinics at Sapienza, University of Rome, and 71 non-diabetic sex and age-comparable subjects as a control group. Study population underwent metabolic characterization and carotid ultrasound for intima-media thickness measurement. Plasma OPN, OPG and OC were measured by MILLIPLEX Multiplex Assays Luminex. RESULTS: T2DM patients had significantly higher circulating OPN and OPG levels than controls (14.3 ± 13.6 vs 10.6 ± 13.7 ng/ml p < 0.001, 0.70 ± 0.60 vs 0.54 ± 4.1 ng/ml, p = 0.02) while OC levels were similar in the two cohorts (6.35 ± 5.8 vs 7.80 ± 7.0 ng/ml, p = n.s). OPN and OPG positively correlated with greater systolic blood pressure (SBP) values, HOMA-IR and HOMA-ß, and with the presence of dyslipidemia and carotid atherosclerosis. The association between greater OPN and OPG levels and SBP was independent from possible confounders (both p = 0.01). CONCLUSIONS: Circulating OPN and OPG levels are increased in T2DM patients and identify a particularly unfavourable metabolic profile, mostly expressed by higher SBP. Bone peptides may represent novel markers of vascular stress and accelerated atherosclerosis in diabetes, constituting a possible tool for cardiovascular risk stratification in diabetes.

Measuring and benchmarking the quality of two different organizational ways in delivering infant vaccination.

The aim of this study was the quality of service evaluation of two different organizational ways in delivering infant vaccination according to a Regional Vaccination Plan. Eleven vaccination centres were selected in two Local Health Units (ASLs) belonging to the Regional Health Service of the Lazio Region, Italy. The services offering paediatric vaccinations for children under three years of age, delivered without an appointment (VACP) or with the need for an appointment (VACL), were investigated. The quality aspects under evaluation were communicational efficiency, organisational efficiency and comfort. Subjective data were collected from different stakeholders and involve the elicitation of best and worst feasible performance conditions for the ASLs when delivering VACP/VACL services. Objective data consists in the observation of current performances of the selected vaccination centres. Quality scorecards were obtained from the combination of all data. Benchmarking between VACP and VACL, i.e., two different organisational ways in delivering infant vaccination, can be performed as a result of the probabilistic meaning of the evaluated scores. An expert of vaccination services, i.e., a virtual combination of patients, doctors and nurses, claims the quality of service delivery of the ASLs under investigation with probability 78.03% and 69.67% for VACP and VACL, respectively. In other words, for short, the quality scores of the ASLs were 78.03% for VACP and 69.67% for VACL. Furthermore our results show how to practically improve the current service delivery. The QuaVaTAR approach can result in improvements of the quality of the ASLs for the two different ways of delivering paediatric vaccinations in a simple and intuitive way.

A meta-analysis of the effectiveness of mud-bath therapy on knee osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) results from loss of cartilage in-tegrity in association with changes to the structure of the entire joint. Treatment of OA is based on different pharmaceutical and no phar-maceutical approaches and the latter include the use of spa-therapy. The biological effects of mud-bath therapy are mainly secondary to heat stimulation and to physic-chemical properties of mineral waters and mud-packs. Mud-bath therapy likely exerts its effects modulating several cytokines and other molecules involved in inflammation and cartilage degradation. Our aim was to perform an updated meta-analysis of the effectiveness of the mud-bath therapy on knee osteoarthritis and briefly to discuss the mechanisms of action of this treatment. MATERIALS AND METHODS: A MEDLINE on PubMed for articles on knee OA and spa therapy published from 1995 through up to April 2019 was performed. Then, we checked the Cochrane Central Register of Controlled Trials to find additional references included up to April 2019. Articles were included if in accordance with the eligibility cri-teria. Sample size and effect sizes were processed with the MedCalc software package. RESULTS: Twenty one studies met the inclusion criteria and were included in meta-analysis. We examined WOMAC Index and VAS pain. We found significant improvements in function scores and painful symptoms after mud-bath therapy in patients with knee joint osteoarthritis. CONCLUSIONS: Spa therapy is a non-drug treatment modalities, non invasive, complication-free, and cost-effective alternative modality for the conservative treatment of knee osteoarthritis. It cannot substitute for conventional therapy but can integrated or alternated to it. Treatment with mud-bath therapy may relieve pain, stiffness and improve functio-nal status in patients with knee OA.

Subclinical vascular alterations in young adults with type 1 diabetes detected by arterial tonometry.

BACKGROUND: Diabetes mellitus is characterized by a very high prevalence of atherosclerotic disease. Aims of this study were to determine arterial compliance parameters in type 1 diabetes (T1D) patients as an expression of early pre-clinical endothelial dysfunction and to evaluate the impact of glucose exposure parameters such as the duration of diabetes and glycosylated haemoglobin (HbA(1c)) on the risk of developing alterations in vascular compliance. METHODS: 23 patients with uncomplicated type 1 diabetes (mean age: 32.78 +/- 9.06 years, mean disease duration: 10.78 +/- 7.51 years, mean HbA(1c) levels: 7.7 +/- 1.9) and 26 age- and sex-matched healthy subjects (mean age: 32.3 +/- 8.51 years) were recruited. In these subjects, we evaluated arterial compliance by calibrated tonometry (HDI/Pulsewave() CR-2000). Parameters included the following: large artery elasticity (C1), small artery elasticity (C2), systemic vascular resistance (SVR) and total vascular impedance (TVI). RESULTS: Patients with longer duration of T1D (>10 years) showed significant alterations in C2 (4.97 +/- 2.7 mL/mmHg x 100) and in SVR (1464.67 +/- 169.16 dina x s x cm(-5)) when compared with both healthy individuals (C2: 8.28 +/- 2.67 mL/mmHg x 100, p = 0.001; SVR: 1180.58 +/- 151.55 dina x s x cm(-5), p = 0.01) and patients with recent-onset disease (

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.

[The historical-scientific foundations of thalassotherapy: state of the art]. / Le basi storico-scientifiche della talassoterapia: stato dell'arte.

Throughout the ages the interest in the use of sea water in medicine has fluctuated from century to century and from nation to nation. In this paper, the historical development of sea medicine from the ancient Egyptians until the 20th century is given. The medical world has viewed it with different opinions, from very enthusiastic to extremely critical, and from beneficial to harmful. In the last decades, thalassotherapy is receiving renewed attention from many medical specialties and health tourists. The aim of this review is that of offer an update on the real therapeutic possibility of the thalassotherapy. However, the exact therapeutic potential of thalassotherapy still remains largely unknown. Better and more profound scientific evidence for its efficacy is therefore warranted, in particular for its effects on the musculoskeletal system and skin. The main researches belong to the activity of thalassotherapy and the clinic outcomes, namely in osteoarthritis patients, were referred.

[Fine tuning of the many regulations of quality system: the role of the quality in the thermal medicine]. / Messa a punto delle varie normative che regolano il Sistema "Qualità": il ruolo della Qualità nel sistema termale.

In the last decades, quality has imposed itself as a competitive need for firms, and also as a new normative parameter to guarantee the production process and the final product which the costumer buys. In the case of health services, the importance of quality is even greater because of the special value of this service, and the special relationship between the supplier and the costumer/patient. This relationship is often mediated by the State which has to provide the health services and the financial support for them. Thus, also in the case of Thermal Medicine, quality and its certification play a key role for the evaluation of the efficiency of the health service, and tend always more to be part of the health service accreditation process. In this article, we review the development of the idea of quality of service from the ancient Egyptian until the 20th century and we briefly recall the main European and Italian norms. We also examine the norms for the accreditation of the thermal health structures, and we review the main indicators of quality in Thermal Medicine, and the role of scientific research. Finally, we indicate that the cost of the lack of quality can be so prohibitive that the firms which do not follow the new standards, are put out of the market.

Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile.

OBJECTIVE: Osteopontin (OPN) is a sialoprotein implicated in different immunity and metabolic pathways. Capable of activating dendritic cells and inducing Th1-Th17-mediated tissue damage, OPN plays a significant role in the development/progression of several autoimmune diseases; interestingly, it was also shown that OPN participates in the acute pancreatic islets response to experimentally induced diabetes in non-obese diabetic (NOD) mice. Furthermore, OPN promotes adipose tissue dysfunction, systemic inflammation and insulin resistance. Our aims of this study were to evaluate circulating OPN levels in adult patients with type 1 diabetes mellitus (T1DM) compared to non-diabetic control participants and to unravel clinical and biochemical correlates of OPN concentration. DESIGN: Case-control study. METHODS: We enrolled 54 consecutive T1DM patients referred to our diabetes outpatient clinic at Sapienza University of Rome and 52 healthy sex and age-comparable controls. The study population underwent clinical evaluation, blood sampling for biochemistry and complete screening for diabetes complications. Serum OPN levels were measured by MILLIPLEX Multiplex Assays Luminex. RESULTS: T1DM patients had significantly higher serum OPN levels than controls (17.2±12.9 vs 10.5±11.6 mg/ml, P=0.009). OPN levels correlated with T1DM, higher blood pressure, BMI, creatinine, γ-GT, ALP and lower HDL; the association between high OPN levels and T1DM was independent from all confounders. No correlation was shown between OPN and HbA1c, C-peptide, insulin requirement, co-medications and diabetes duration. CONCLUSIONS: This study demonstrates for the first time in a case-control study that adults with T1DM have increased serum OPN levels, and that higher OPN concentrations are associated with an unfavorable metabolic profile in these patients.

Inhibition in the Limulus lateral eye in situ.

Inhibition in the Limulus lateral eye in situ is qualitatively similar to that in the excised eye. In both preparations ommatidia mutually inhibit one another, and the magnitude of the inhibitory effects are linear functions of the response rate of individual ommatidia. The strength of inhibition exerted between single ommatidia is also about the same for both preparations; however, stronger effects can converge on a single ommatidium in situ. At high levels of illumination of the retina in situ the inhibitory effects are often strong enough to produce sustained oscillations in the discharge of optic nerve fibers. The weaker inhibitory influences at low levels of illumination do not produce oscillations but decrease the variance of the optic nerve discharge. Thresholds for the inhibitory effects appear to be determined by both presynaptic and postsynaptic cellular processes. Our results are consistent with the idea that a single ommatidium can be inhibited by more of its neighbors in an eye in situ than in an excised eye. Leaving intact the blood supply to the eye appears to preserve the functional integrity of the retinal pathways which mediate inhibition.

[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.

Prevention and treatment of nephrolithiasis: a review on the role of spa therapy.

The prevalence and incidence of nephrolithiasis is reported to be increasing across the world. It is a disease of increased urinary concentration of stone-forming salts. The physicochemical mechanism of stone formation includes precipitation, homogenous/heterogeneous nucleation, growth, aggregation and concretion of various modulators in urine. Necessary condition to develop stones is urinary supersaturation, due to reduced urinary volume or to an excesses solutes. Fluid intake is the main determinant of urine volume. Urine dilution can significantly decrease both the crystallization rate of the urinary salts and the aggregation of the crystals. A correct fluid intake can act on different effects: urinary tract washing, urinary volume increasing and dilution of solutes. In addition mineral waters have other particular features: greater diuretic effect, more important urinary dilution with solutes and microbial concentration reduction, urinary pH changes, superior washout effect due to mechanical effects and ureteral contractions. Adequate water intake is the most important conservative strategy in urolithiasis prevention; particularly hydropinotherapy with oligomineral water should be considered as an important instrument to prevent stones in subjects predisposed to the disease (family members of people suffering from kidney stones), to reduce relapses, and can help to eliminate residual fragments also after extracorporeal shock wave lithotripsy. It is recommended a management with increased mineral water intake to promote urine volume of at least 2.5L each day to prevent stone formation. Obviously water intake shall be varied in relation to the presence of contraindications or any diseases.

[Ethics in clinical practice and in health care]. / L'etica nella pratica clinica e nell'assistenza sanitaria.

The clinical ethics is the identification, analysis and solution of moral problems that can arise during the care of a patient. Given that when dealing with ethical issues in health care some risks will be encountered (talking about ethics in general, or as a problem overlapped with others in this area, or by delegation to legislative determinations) in the text certain important aspects of the topic are examined. First of all ethics as human quality of the relationship between people for the common good, especially in health services where there are serious problems like the life and the health. It is also necessary a "humanizing relationship" between those who work in these services in order to achieve quality and efficiency in this business. It is important a proper training of health professionals, especially doctors, so that they can identify the real needs and means of intervention. It is also important that scientific research must respect fundamental ethical assumptions. In conclusion, ethics in health care is not a simple matter of "cookbook" rules, but involves the responsibility and consciousness of individual operators.

TSH levels are associated with vitamin D status and seasonality in an adult population of euthyroid adults.

A circannual periodicity in thyrotropin (TSH) secretion has been reported but the causes of these phenomenon are still undefined. Vitamin D exerts a direct influence on pituitary axes including the hypothalamus-pituitary-thyroid axis. Aims of the present study were to investigate the presence of a seasonal variability of TSH secretion and to study the association between vitamin D status and TSH levels in a population of euthyroid adults. For this purpose, we recruited 294 euthyroid adults (M/F 133/161, 48.5 ± 12.4 years). Study participants underwent clinical examination and routine biochemistry assessment. Vitamin D deficiency was diagnosed for serum 25(OH) vitamin D <25 nmol/l. Significantly higher TSH levels were found in subjects who underwent blood sampling during the Autumn-Winter compared with individuals evaluated in Spring-Summer (2.3 ± 1.3 vs. 1.8 ± 1.1 µIU/ml, p = 0.03). Vitamin D deficiency was strongly associated with higher TSH levels (p = 0.01) after adjusting for sex, age, and sample's season. Although vitamin D deficiency was also associated with metabolic syndrome and its components, the association between TSH levels and vitamin D status persisted also considering these confounders. These data reveal the occurrence of seasonal variability of serum TSH concentration in euthyroid subjects and provide evidence for the first time that an association exists between vitamin D status and serum TSH levels.

Polymyalgia rheumatica and systemic giant cell arteritis. Bioptic findings of the subclavian arteries in a case of aortic arch syndrome.

A 64 year old woman complained of aches and stiffness of the neck and the shoulders with fever and E.S.R. increase. A nonsteroid anti-inflammatory treatment was unsuccessful. A clinical examination revealed absence of both radial pulses and presence of murmurs at level of the carotids. The angiographic findings confirmed an aortic arch syndrome with severe stenosis of the subclavian and axillary arteries. The diagnostic approach, in spite of a negativity of the temporal artery biopsy, was for systemic giant cell arteries with general manifestations of polymyalgia rheumatica. The biopsies of both subclavian arteries, performed during a surgery revascularization, showed a typical giant cell arteries in acute stage. The histopathological pattern of extratemporal giant cell arteries obtained by means of a surgical biopsy is really uncommon, being the previous reports performed on necroscopic findings only. In addition this case confirms that polymyalgia rheumatica implies a systemic arteries even if the clinical and histopathological signs of temporal arteritis are lacking. Therefore the temporal artery should be only considered as a particular and inconstant localization of this vasculitis.

[Incidence and treatment of postprostatectomy urinary incontinence. Personal experience]. / Incidenza e terapia dell'incontinenza urinaria postprostatectomia. Nostra esperienza.

BACKGROUND: To evaluate frequency of postprostatectomy urinary incontinence in order to establish the last invasive and most efficacious treatment to completely restore urinary incontinence. METHODS: Between 1992 and 2000, twenty-four patients with retropubic postprostatectomy urinary incontinence were studied. The symptoms reported by all patients referred to lack of control of urine with consequent leakage upon activities exerting increased abdominal pressure (sneezing, lifting of heavy weights). These patients were submitted to urodynamic examinations and the degree of incontinence was further evaluated from the number of pads used daily (slight, 0-1; medium 2-3; severe, >3). Mean follow-up was three years, eight months. RESULTS: Of the twenty-four patients, twenty (83%) presented stress incontinence, two (8.5%) urge incontinence, and two (8.5%) a mixed type incontinence. Eighteen patients (36%) reported slight precocious incontinence which disappeared spontaneously within three-six months. Six patients (12%) reported total incontinence which had not improved within twelve months, in four of these patients, continence was achieved by means of perineal rehabilitation whilst in the remaining patients, use of pads (up to three pads/day) was necessary, due to failure of rehabilitation. CONCLUSIONS: Once the need has been established for radical anatomic prostatectomy which offers the possibility of postoperative continence, perineal rehabilitation represents the first choice treatment on account not only of the high percentage of successful results but also due to low invasiveness, whilst the use of the AMS 800 sphincter offers the only solution in those forms of severe incontinence refractory to less invasive forms of treatment.

[Postprostatectomy erectile dysfunction]. / Deficit erettile postprostatectomia.

BACKGROUND: To evaluate the frequency of erectile dysfunction in patients submitted to radical prostatectomy due to prostate carcinoma and to the possibility, with appropriate treatment, of restoring adequate erections for a satisfactory sexual activity. METHODS: Between 1996 and 2000, thirty-eight patients with prostate carcinoma have been submitted to radical prostatectomy. According to TNM classification upon diagnosis, thirty-three patients (87%) were stage pT2N0M0 and five patients (13%) stage pT3N0M0. Mean age of patients was 62.4 years (range 55-76). Mean follow-up was two years and seven months. Diagnosis of erectile dysfunction was made from personal history as well as that of the patient plus partner, and from nocturnal penile tumescence evaluation with Rigiscan. RESULTS: Eighteen patients (47%) presented erectile dysfunction as a complication 16 (89%) of whom showed no nocturnal reaction at the Rigiscan test, while in the remaining two (1%), one-two nocturnal erections of less than five minutes were obtained. Of the eighteen patients, 14 (78%) showed a positive response to treatment with intracavernous drug infusion (papaverine+Phentolamine+Alprostadil), whilst only one patient benefited from treatment with oral Sildenafil. CONCLUSIONS: This study showed the high frequency (47%) of erectile dysfunction in patients submitted to radical prostatectomy as well as the need to perform radical nerve-sparing surgery (particularly in the neoplastic forms not involving the prostate capsule) which is useful not only for preserving erectile function but also on account of better response to oral Sildenafil treatment following the use of this technique.

[Immunotherapy in the management of metastatic renal carcinoma]. / Immunoterapia nel trattamento del carcinoma renale metastatico.

BACKGROUND: Renal cell carcinoma (RCC) is a relatively rare tumor representing 2-3% of all neoplasias. Approximately 30% of patients diagnosed as having RCC present metastases: mean survival ranges between 6 and 10 months, whilst 10-20% present a 2-year survival rate. Treatment of patients with metastatic RCC is a difficult challenge. Hormones and chemotherapy, either alone or associated with surgical resection of the primary lesion have been used. In our experience, IL-2 + IFN-a has been shown to be an encouraging form of treatment. METHODS: During the period between October 1997 and December 1999, 5 patients (3 males, 2 females), mean age 52.5 years, with metastatic RCC, came to our attention. TC revealed a circumscribed area the margins of which were not well defined, in a mid-renal localization, positive inter aorta caval and obturator lymph nodes, but no lung, brain or hepatic involvement. Patients were submitted to nephrectomy and lymphadenectomy followed later by immunotherapy with IFN-alpha (3 Mil twice a week) + low dose IL-2 (1 Mil/m2/12 h): treatment was given for 4 consecutive weeks and then repeated every 3 weeks for 1 year. RESULTS: At 30 months' follow-up all patients showed regression of the disease (100% of cases) and in none of the cases there was evidence of metastases. Only one patient (20%) presented side-effects (nausea, vomiting, slight rise in temperature) all of which disappeared at the end of the first week of treatment. CONCLUSIONS: These results, even if on a limited number of patients and for a limited follow-up period, show that in some patients with metastatic renal cell carcinoma, treatment with IL-2 and IFN-a following nephrectomy and lymphadenectomy should be considered the therapy of choice.

Mineral waters in treatment of metabolic changes from fatigue in sportsmen.

The authors list the principal metabolic consequences of fatigue in athletes with special reference to alterations of fluid-electrolyte balance, acid-base balance, macroelements and trace elements. They then go on to stress the role which mineral waters, especially the bicarbonate ones, can play in the compensation of these disorders thus preventing or curing the fatigue syndrome in athletes.