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BACKGROUND: Obesity has been regarded to be protective against fracture in spite of its association with low levels of vitamin D. Vitamin D is the key regulator of bone metabolism and its deficiency contributes to higher level of parathyroid hormone (PTH), leading to the activation of bone turnover.METHODS: We studied 161 subjects of which 65 were young healthy subjects and 96 were elderly subjects. We measured creatinine, 25(OH)D, 1,25(OH)2D, PTH, albumin, and calcium plasma levels, we evaluated physical activity, and we calculated BMI. A sub-cohort of elderly subjects also underwent DXA scans.RESULTS: Overweight and obese subjects, as well as underweight ones, had lower levels of vitamin D but normal serum concentrations of 1,25(OH)2D and PTH was higher in underweight and obese subjects. Moreover, we found a nonlinear relationship between body mass index (BMI) and PTH with a significant U-shaped exponential regression. Regardless of BMI, 25(OH)D mean levels were higher in subjects who practice physical activity.CONCLUSIONS: These findings suggest that physical activity and BMI had a significant effect on the metabolism of bone and vitamin D, but the effect of BMI was different in underweight, normal weight or obese subjects. In obesity the real vitamin D deficiency could be estimate by serum 1,25(OH)2D concentrations whose lower levels contribute to the higher PTH production and consequently to bone loss and to a greater fracture risk. Refereed/Peer-reviewed

ObjectivesTo evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.MethodsDynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).ResultsAmong 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P ConclusionsA dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures, despite having greater bone mineral density (BMD) than non-diabetic subjects. This has led to the hypothesis that the presence of impaired bone quality among diabetics reduces bone strength. The Fracture Risk Assessment Score (FRAX) algorithm, introduced to facilitate the evaluation of fracture risk, underestimates the risk of fracture in diabetic patients. The purpose of this study is to confirm the relationship between the degree of metabolic compensation and the 10-year probability of a major fracture or a hip osteoporotic fracture observed in our previous study and to ascertain whether glycosylated hemoglobin (HbA1c) can improve the predictive value of FRAX in patients with T2DM. Our data derive from a retrospective clinical study conducted at the “Tor Vergata” Polyclinic in Rome on 6355 subjects over 50 years of age evaluated for osteoporosis. All available clinical records were examined. HbA1c was available for 242 of these subjects and all had had a Dual-energy X-ray Absorption (DXA) scan of the lumbar spine and femoral neck. The risk of fracture was estimated using the Italian version of the FRAX algorithm. Patients with T2DM had BMD and T-scores higher than those of non-diabetic subjects, while FRAX average values were higher in the non-diabetic group. HbA1c and FRAX are inversely correlated with each other: for each incremental percentage point of HbA1c growth, the FRAX major osteoporotic fracture probability is reduced by 0.915 points and the FRAX hip osteoporotic fracture probability by 1.438 points. The introduction of a correction factor derived from HbA1c, resulted in mean FRAX values of diabetic patients equivalent to those of non-diabetic subjects. We propose a correction factor derived from HbA1c that could enhance the predictive ability of fracture risk estimated by the FRAX algorithm in subjects with T2DM.

Background: The most common cause of hypoparathyroidism is iatrogenic in the context of surgical procedures to the neck and commonly the thyroid gland. Hypoparathyroidism is characterized by hypocalcaemia, hyperphosphatemia and low or inappropriately normal levels of parathyroid hormone (PTH) and may be associated with multiorgan complications and variable clinical presentation. Seizures may be the only presenting symptom and may result in antiepileptic therapy. Knowledge of all possible consequences of hypoparathyroidism is essential for correct patient management. Case Description: A 76-year-old woman was admitted due to loss of consciousness, seizures and hypocalcemia. She had had total thyroidectomy over 60 years ago for toxic goiter, complicated by permanent hypoparathyroidism. Her calcium levels were erratic, treated with calcium, colecalciferol and calcitriol. She developed progressive confusion, and had convulsive episode before hospitalization. Clinical investigation revealed widespread cerebral calcifications, EEG abnormalities and diffuse skeletal abnormalities. Later, during hip replacement surgery, bone histopathology showed bone marrow substitution by fibrous tissue undergoing ossification. All clinical problems occurring to the patient can be referred to hypoparathyroidism and consequent hypocalcemia not adequately corrected, including early bilateral cataracts. In the absence of consolidated hormone replacement therapy, treatment of hypoparathyroidism is represented by vitamin D and calcium supplementation. In our case, the total absence of PTH and its role on vitamin D activation did not allow optimal control of serum calcium, despite normal levels of 25-hydroxyvitamin D being observed. The achievement of target values in serum calcium was obtained only with calcitriol. Treatment with levetiracetam was thus suspended and no more seizures occurred at two year follow-up. Conclusion: Awareness that convulsions can only be caused by hypocalcemia, even in the presence of organic brain injuries, can help patients avoid using unnecessary medications and their potentially harmful side effects.

Aim The aim of this study is to evaluate the relationship between OPG and the degree of glycaemic control in a population of elderly subjects. Methods and results Data presented included 172 elderly subjects, of whom 107 were hospitalized for a hip fracture and 65 were non fractured outpatients. All participants received a multidimensional geriatric evaluation and underwent blood sampling. HbA1c, OPG, CTX and OC were measured and DXA scans were performed. Carotid intima-media thickness (IMT) was measured in all outpatients. Diabetic patients had more comorbidities, higher mean values of lumbar spine and femoral neck BMD and T-score, lower circulating levels of OC and CTX, and higher circulating levels of OPG compared to non-diabetic subjects. OPG was directly correlated with HbA1c. This association was most evident in non-fractured elderly subjects. Moreover, diabetic patients with IMT>1.5 mm had greater mean values of OPG than non-diabetic subjects with high IMT and than elderly subjects with IMT Conclusions Diabetic patients have reduced circulating levels of OC and CTX, and elevated serum levels of OPG, suggesting a state of low bone turnover. Reduced bone turnover causes an increase of BMD and could lead to a poor bone quality. OPG and HbA1c were directly correlated and OPG mean values were higher in diabetic patients with poor glucose control. Diabetic osteopathy could be considered a late complication of T2DM, directly related with the degree of glucose control and the duration of the disease.

Vascular aging in obesity and type 2 diabetes (T2D) is associated with progressive vascular calcification, an independent predictor of morbidity and mortality. Pathways for vascular calcification modulate bone matrix deposition, thus regulating calcium deposits. We investigated the association between biomarkers of vascular calcification and vasodilator function in obesity or T2D, and whether antidiabetic therapies favorably impact those markers. Circulating levels of proteins involved in vascular calcification, such as osteopontin (OPN), osteoprotegerin (OPG), regulated on activation, normal T cell expressed and secreted (RANTES), and fetuin-A were measured in lean subjects, individuals with metabolically healthy obesity (MHO), and patients with metabolically unhealthy obesity (MUO) or T2D. Vasodilator function was assessed by infusion of ACh and sodium nitroprusside (SNP). Circulating levels of OPN were higher in the MUO/T2D group than in lean subjects ( P < 0.05); OPG and RANTES were higher in MUO/T2D group than in the other groups (both P < 0.001); fetuin-A was not different between groups ( P > 0.05); vasodilator responses to either ACh or SNP were impaired in both MUO/T2D and MHO compared with lean subjects (all P < 0.001). In patients with T2D who were enrolled in the intervention trial, antidiabetic treatment with glyburide, metformin, or pioglitazone resulted in a significant reduction of circulating OPG ( P = 0.001), without changes in the other biomarkers and vasodilator responses (all P > 0.05). In conclusion, obese patients with MUO/T2D have elevated circulating OPN, OPG, and RANTES; in these patients, antidiabetic treatment reduces only circulating OPG. Further study is needed to better understand the mechanisms of vascular calcifications in obesity and diabetes.

Alessia Valentini,1 Massimo Federici,1 Maria Assunta Cianfarani,1 Umberto Tarantino,2 Aldo Bertoli1 1Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy; 2Department of Orthopaedics and Traumatology, University of Rome “Tor Vergata”, Rome, Italy Introduction: Frailty is a condition characterized by reduced resistance to low-level stress events, resulting from the progressive decline of multiple physiological systems observed with aging. Many factors can contribute to the pathogenesis of frailty, and nutritional status appears to play a key role. The objective of the study was to investigate the relationship between nutritional status, evaluated using Mini Nutritional Assessment (MNA), and frailty among older people. Patients and methods: An observational study was carried out at the University Hospital “Tor Vergata” in Rome among patients aged 65years or older, with or without hip fracture. The study sample included 62 patients hospitalized for a hip fracture and 50 outpatients without fracture. All subjects underwent blood sampling for laboratory assays and received a multidimensional geriatric evaluation comprising Activity of Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Mini–Mental State Examination (MMSE), Geriatric Depression Scale (GDS), and MNA. Comorbidity was assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Muscle strength was measured by handgrip dynamometry, and frailty score was calculated using the Survey of Health, Ageing and Retirement in Europe-Frailty Index (SHARE-FI). Results: Approximately 38% of the study population was frail, with the prevalence of frailty being greater among hospitalized older patients. Among frail subjects, 65% were at risk of malnutrition (RMN) and 10% were malnourished. The prevalence and RMN progressively diminished in the pre-frail group and not frail group. Nutritional status was closely associated with the degree of frailty, and in a logistic regression, MNA was the best variable predicting both pre-frailty and frailty. Discussion and conclusion: Malnutrition contributes to the development of frailty. MNA can generate vital information to help identify a substantial part of both frail and pre-frail patients at low cost and care. Keywords: frailty, malnutrition, Mini Nutritional Assessment, older peopleCorrigendum for this paper has been published&nbsp

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures, despite having greater bone mineral density (BMD) than non-diabetic subjects. This has led to the hypothesis that the presence of impaired bone quality among diabetics reduces bone strength. The Fracture Risk Assessment Score (FRAX) algorithm, introduced to facilitate the evaluation of fracture risk, underestimates the risk of fracture in diabetic patients. The purpose of this study is to confirm the relationship between the degree of metabolic compensation and the 10-year probability of a major fracture or a hip osteoporotic fracture observed in our previous study and to ascertain whether glycosylated hemoglobin (HbAOur data derive from a retrospective clinical study conducted at the "Tor Vergata" Polyclinic in Rome on 6355 subjects over 50 years of age evaluated for osteoporosis. All available clinical records were examined. HbAPatients with T2DM had BMD and T-scores higher than those of non-diabetic subjects, while FRAX average values were higher in the non-diabetic group. HbAWe propose a correction factor derived from HbA

Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials & methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/131/20), grazoprevir/elbasvir ± ribavirin (N = 34), glecaprevir/pibrentasvir (N = 20). Notably, 18.1% of NS5A-failing patients did not show any resistance-associated-substitutions (RAS), while 81.9% showed at least one NS5A-RAS, with multiclass-resistance in 35.5%. NS5A-RAS were observed more frequently in glecaprevir/pibrentasvir failures (GT1a 83.3%: Y93H + Q30H/D or +H58D; GT3a: 83.3% Y93H + A30K/G or +L31I) compared to sofosbuvir/velpatasvir (GT1a 16.6%: Y93H + Q30H, p = 0.08; GT3a 20.0%: Y93H/N + A30K/T, p = 0.03). To date, 105 failures have started a retreatment: sofosbuvir/velpatasvir ± ribavirin (N = 30), sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (N = 67), glecaprevir/pibrentasvir (N = 4), grazoprevir/elbasvir ± sofosbuvir + ribavirin (N = 3), 3D + sofosbuvir + ribavirin (N = 1). The majority of patients were cirrhotic (51.9%) and relapsers (87.5%). The prevalence of NS5A-RASs before retreatment was 80.9%, with multiclass-resistance 29.5%. Among patients completing post-retreatment follow-up, a sustained-viral-response at week 12 (SVR12) was observed in 26/33 (78.8%). SVR4 was documented in 49/56 (87.5%). SVR12 was 76.0% with sofosbuvir/velpatasvir ± ribavirin (N = 25). Differently, SVR12 was 100% with glecaprevir/pibrentasvir for 8/12/16 weeks (N = 3), grazoprevir/elbasvir ± sofosbuvir + ribavirin for 12/24 weeks (N = 3) or 3D + sofosbuvir + ribavirin for 24 weeks (N = 1), despite the presence of NS5A-RASs. Until now, 67 patients started sofosbuvir/velpatasvir/voxilaprevir ± ribavirin recommended-retreatment for 12 weeks. 54/67 (80.6%) showed at least one baseline NS5A-RAS, 23/67 (34.3%) multiple-NS5A-RASs, and 22/67 (32.8%) multiclass-resistance. Of 25 patients with available outcome, 96.0% had SVR4. Only 1 GT1b infected patient was non-responder, without RASs before retreatment. Conclusions: In this real-life setting, NS5A-RASs were frequently detected at failure, and multiclass-resistance was around 30%. Overall, SVR after resistance-test-guided retreatment was >95%, with the exception of the sofosbuvir/velpatasvir retreatment. Our results show how HCV resistance-test at failure may be useful to optimize retreatment strategies.

Aldo Bertoli,1 Alessia Valentini,1 Maria Assunta Cianfarani,1 Elena Gasbarra,2 Umberto Tarantino,2 Massimo Federici1 1Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy; 2Department of Orthopaedics and Traumatology, University of Rome “Tor Vergata”, Rome, Italy Introduction: Frailty is associated with a functional decline of multiple physiological systems, of which they may be a cause or consequence. The objective of the study was to evaluate the prevalence of thyroid hormone modifications in elderly frail subjects and its relationship with frailty.Study population and methods: An observational study was carried out at the University Hospital “Tor Vergata” in Rome among ambulatory and hospitalized patients. The study population consisted of 112 elderly subjects: 62 were hospitalized following hip fracture and 50 control subjects were outpatients. Participating patients received a multidimensional geriatric evaluation. The Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI) was used to assess the degree of frailty. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured to evaluate thyroid status.Results: FT3, but not FT4, was significantly correlated with Frailty score, both in patients with hip fracture and in patients from the control group. In the entire study population, FT3 under normal limits is effective in discriminating frail/prefrail subjects from nonfrail subjects.Discussion: The reduction in serum concentrations of FT3 is a clear manifestation of stress associated with fractures. Numerous preexisting factors, such as the fracture patients’ nutritional status, sarcopenia, disability and comorbidities, which characterize the condition of frailty and influence its pathogenesis, are strongly correlated with FT3 values, suggesting the existence of latent nonthyroidal illness syndrome (NTIS).Conclusion: We conclude that measuring FT3 can be a useful laboratory parameter in clinical assessment, which can play an important role in identifying vulnerable elderly subjects and in quantifying the condition of frailty. Keywords: FT3, frailty, NTIS, hip fracture, aging

Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. Methods In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. Results After PI-failure, 121 patients (cirrhotic = 86.8%) were retreated following three different strategies: A) with ‘GRT-guided’ regimens (N = 18); B) with ‘AASLD/EASL recommended, not GRT-guided’ regimens (N = 72); C) with ‘not recommended, not GRT-guided’ regimens (N = 31). Overall SVR rate was 91%, but all 18 patients treated with ‘GRT-guided’ regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving ‘AASLD/EASL recommended, not GRT-guided’ regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a ‘not recommended, not GRT-guided regimen’ (p

Valentini A, Federici M, Cianfarani MA, Tarantino U, Bertoli A. Clin Interv Aging. 2018;13:1237–1244. Page 1238, Patients and methods, the first two paragraphs are incorrect, the text should read as shown below.Read the original article&nbsp

Thyroid Associated Ophthalmopathy (TAO) is a complex pathology to treat and a considerable threat for Graves' Disease (GD) patients. Thus, there is great interest to find tools able to predict the onset and prognosis of TAO. Chronic inflamed tissues are characterized by tissue damage and recruitment of cells from the bloodstream, events that can lead to self-antigen exposure and induce autoimmune phenomena. In this study, we determined whether the occurrence of antibody anti-extracellular matrix (ECM) molecules [Collagen CI, CIII, CIV, CV, laminin (LM) and fibronectin, (FN)], anti-smooth muscle (ASM), anti-nuclear antigen (ANA), anti-ribonucleoprotein (RNP) and anti-thyroid-stimulating hormone (TSH) receptor (TRAbs) were associated with TAO in GD patients. We analyzed serum of 50 patients affected by GD, 24 of whom were affected by TAO, and 40 healthy donors (HD). The occurrence of TRAbs or ANA, anti-SM and anti-RNP antibodies did not allow to discriminate TAO+ from TAO- GD patients. Among the 24 TAO+ and 26 TAO- patients, 15/24 and 17/26 displayed TRAbs, respectively. None of the GD patients displayed anti-RNP antibodies, while 20/24 TAO+ and 17/26 TAO- patients were found to be positive for ANA and 3/24 TAO+ and 4/26 TAO- patients showed anti-SM antibodies. Conversely, when compared with HD control sera, GD sera showed antibodies to all individual ECM molecules. Remarkably, anti-CHI autoantibodies of the IgG isotype were significantly associated with GD TAO+ patients (p=0.045). Indeed, 6 out of 24 GD TAO+ patients scored positive for anti-CIII IgGs as compared to only 1 out of 26 TAO-. Our results suggest the potential involvement of anti-ECM antibodies in GD and a contribution of anti-CIII IgGs in TAO pathogenesis of GD patients. Copyright © by BIOLIFE, s.a.s.

The principal sites of gastrin production in man are localized at the level of the gastric antrum; both the oral glucose load and the protein meal stimulate the gastrin secretion. The aim of this study was to verify the gastrin response in patients with gastric resections presented with various stimuli. In the operated patients, the behavior of serum gastrin after a protein meal was different with respect to that observed in control subjects. After glucose, on the contrary, a very similar result was seen when compared to controls. The increase in serum gastrin of patients with Billroth II provides a further confirmation of an extragastric origin of gastrin.

Randomized clinical trials have demonstrated that the increased intake of omega-3 polyunsaturated fatty acids significantly reduces the risk of ischemic cardiovascular disease, but no investigations have been performed in hereditary cardiomyopathies with diffusely damaged myocardium. In the present study, delta-sarcoglycan-null cardiomyopathic hamsters were fed from weaning to death with an alpha-linolenic acid (ALA)-enriched versus standard diet. Results demonstrated a great accumulation of ALA and eicosapentaenoic acid and an increased eicosapentaenoic/arachidonic acid ratio in cardiomyopathic hamster hearts, correlating with the preservation of myocardial structure and function. In fact, ALA administration preserved plasmalemma and mitochondrial membrane integrity, thus maintaining proper cell/extracellular matrix contacts and signaling, as well as a normal gene expression profile (myosin heavy chain isoforms, atrial natriuretic peptide, transforming growth factor-beta1) and a limited extension of fibrotic areas within ALA-fed cardiomyopathic hearts. Consequently, hemodynamic indexes were safeguarded, and more than 60% of ALA-fed animals were still alive (mean survival time, 293+/-141.8 days) when all those fed with standard diet were deceased (mean survival time, 175.9+/-56 days). Therefore, the clinically evident beneficial effects of omega-3 polyunsaturated fatty acids are mainly related to preservation of myocardium structure and function and the attenuation of myocardial fibrosis.

Interventions that focus on changing lifestyles through the combined use of dietary management, weight reduction, and increased physical activity are essential for managing type 2 diabetes mellitus (T2DM). The objective of the present study was to examine mildly obese T2DM patients [ n=10; mean age (+/-SD), 51.29+/-6.80 years; body mass index (BMI), 30.26+/-6.19 kg/m(2); and glycosylated haemoglobin (HbA(1c)), 8.16+/-1.16%)] and to compare them with normoglycaemic persons ( n=10; age, 53.00+/-9.48 years; BMI, 27.63+/-3.33 kg/m(2), and HbA(1c), 5.85+/-0.56%) in terms of energy expenditure while performing physical activities of various intensities (i. e. light, moderate, and heavy). The resting metabolic rate for T2DM patients was significantly higher than that for healthy controls (2200+/-354 kcal/day vs. 1628+/-176 kcal/day, respectively; p

To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, by considering pre-existent resistance (pRes).pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated.Three hundred and nine patients were analysed; 5.8% of them showed resistance to both NRTIs and NNRTIs, while 12.6% showed resistance to only one of these drug classes. By 72 weeks, the probability of VR was 11.3%. A higher probability of VR was found in the following groups: (i) patients with NRTI + NNRTI pRes compared with those harbouring NRTI or NNRTI pRes and with those without reverse transcriptase inhibitor pRes (39.2% versus 11.5% versus 9.4%, P 0.0001); (ii) patients with a virus with full/intermediate resistance to both tenofovir/emtricitabine and rilpivirine compared with those having a virus with full/intermediate resistance to tenofovir/emtricitabine or rilpivirine and those having a virus fully susceptible to TDF/FTC/RPV (36.4% versus 17.8% versus 9.7%, P 0.001); and (iii) patients with pre-therapy viraemia500 000 copies/mL compared with those with lower viraemia levels (500 000: 16.0%; 100 000-500 000: 9.3%;100 000 copies/mL: 4.8%, P = 0.009). pRes and pre-therapy viraemia500 000 copies/mL were independent predictors of VR by multivariable Cox regression.TDF/FTC/RPV as a treatment simplification strategy shows a very high rate of VS maintenance. The presence of pRes to both NRTIs and NNRTIs and a pre-therapy viraemia500 000 copies/mL are associated with an increased risk of VR, highlighting the need for an accurate selection of patients before simplification.

1880 www.thelancet.com Vol 380 November 24, 2012 In November, 2010, a 75-year-old woman presented to us with persistent diarrhoea, anorexia, and weight loss. She did not respond to empiric antibiotics or loperamide. She had a history of hypertension, and was being treated with perindopril, autoimmune hypo thyroidism treated with thyroxine, and widespread arthrosis. On physical examination, she was in a stable condition, with dry mucous membranes and skin. Stool tests suggested watery diarrhoea. The faecal volume exceeded 1 L per day, and persisted despite fasting. Stool para sitological examination and culture were negative. Upper gastrointestinal endoscopy and colonoscopy were done immediately and were normal so a biopsy sample was not taken. Laboratory tests showed mild normo chromic, microcytic, anaemia (haemoglobin 110 g/L), hyponatraemia, and persistent hypokalaemia. C-reactive protein was 47 mg/L, total protein 50 g/L, and albumin was 27 g/L. Serum protein electrophoresis showed an irregular gamma profi le. Serum iron and ferritin were normal, and transferrin was low 1·03 g/L, (normal range 2–3·6). Total cholesterol and HDL choles terol concen trations were low (2·28 mmol/L and 0·44 mmol/L). Tryglicerides were normal. An HIV test was negative. Serological investigation for coeliac disease was negative, and total IgA was normal. Tumour markers were negative. Normal values of gastrin, chromogranin, and 5-hydroxyindoleacetic acid excluded the possibility of endocrine syndrome. Vasoactive intestinal polypeptide and somatostatin assays were not available. A total body CT scan was normal. After admission our patient was put on a fast and total parenteral nutrition was initiated. Within a few days, she had progressive reduction of consciousness leading to a comatose state. No focal signs or symptoms preceded or followed the loss of consciousness. An MRI of the brain showed a diff usion-weighted imaging abnormality in the thalamus bilaterally, which was consistent with Wernicke syndrome triggered by the infusion of glucose. Clinical resolution of the coma and radiological remission of bilateral thalamus abnormalities after treatment with Persistent watery diarrhoea and coma in an elderly woman

R. Salpini1, M. Surdo1, N. Warner2, M.F. Cortese1, C. Mirabelli 1,3, D. Colledge2, S. Soppe2, P. Saccomandi1, M. Pollicita1, R. Longo4, S. Romano4, G. Cappiello4, A. Spano4, P. Trimoulet5, H. Fleury5, J. Vecchiet6, N. Iapadre7, A. Barlattani8, A. Bertoli 1, T. Mari9, C. Pasquazzi10, G. Missale11, C. Sarrecchia12, E. Orecchini13, A. Michienzi13, M. Andreoni12, S. Francioso14, M. Angelico14, F. Ceccherini-Silberstein1, S. Locarnini2, C.F. Perno1, V. Svicher1 1 Department of Experimental Medicine, University of Rome “Tor Vergata” Rome, Italy 2 Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia 3 Institut Pasteur, Unite de Biologie des virus enteriques, 25 rue du Dr Roux, 75015 Paris, France 4 S. Pertini Hospital”, Rome, Italy 5 Hopital Pellegrin Tripode, Bordeaux, France 6 SS Annunziata” Hospital, Chieti, Italy 7 S Salvatore” Hospital, L’Aquila, Italy 8 “S Giacomo” Hospital, Rome, Italy 9 “Regina Margherita” Hospital, Rome, Italy 10 “S Andrea” Hospital, Rome, Italy 11 Hospital of Parma, Parma, Italy 12 Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy 13 Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome, Italy 14 Tor Vergata University Hospital, Hepatology Unit, Rome, Italy

Through this study we evaluated whether the HIV-1 tropism determined by genotypic analysis correlates with HIV-1 markers, such as CD4 cell count and plasma HIV-RNA. The analysis was performed on 1221 HIV-1 B-subtype infected patients with an available V3 sequence (all maraviroc naive). Of them, 532 were antiretroviral therapy (ART) naive and 689 ART experienced. Tropism determination was performed by using the geno2pheno (co-receptor) algorithm set at a false-positive rate (FPR) of 10% and 2%. Potential associations of FPR with CD4 cell count and viraemia were evaluated. Association of V3 mutations with genotypic-determined tropism was also evaluated according to different FPR ranges. About 26% of patients (either ART naive or ART experienced) were infected by X4-tropic viruses (using the classical 10% FPR cut-off). However, a significantly lower proportion of ART-naive patients had FPR ≤ 2% in comparison with ART-experienced patients (4.9% vs. 12.6%, respectively, p

Presence of drug-resistance mutations in drug-naïve hepatitis B virus (HBV) infected patients can seriously compromise response to antiviral treatment. Therefore, our study was aimed at defining the prevalence of HBV drug-resistance in a population of 140 patients, all infected with HBV-D-genotype (the most common HBV-genotype in Eastern Europe, Mediterranean countries and Middle East) and naïve to antiviral therapy. HBV reverse-transcriptase (RT) region was sequenced and analyzed for 20 mutations, confirmed by in vitro studies as associated with resistance to nucleos(t)ide HBV-RT inhibitors (rtL80I/V-rtI169T-rtV173L-rtL180M-rtA181T/V/S-rtT184A/S/G/C-rtA194T-rtS202C/G/I-rtM204V/I-rtN236T-rtM250V). Amino acid changes at other six RT positions, potentially associated with resistance, were also analyzed (rtV84M-rtV191I-rtV207L-rtV214A-rtQ215S-rtI233V). Overall, only 2/140 (1.4%) patients carried primary drug-resistance mutations [rtA181V (0.7%), and rtA194T (0.7%)], while 3/140 (2.1%) patients harbored the secondary mutations rtV173L (1.4%) and rtL180M (0.7%). Additionally, five polymorphic mutations, with a suggested role in drug resistance, were detected [rtQ215S (12.8%), rtI233V (4.3%), rtV214A (3.6%), rtV191I (0.7%), rtV207L (0.7%)]. Notably, no YMDD mutations, namely rtM204V/I, were found. Taken together, the rate of important drug resistance mutations in naïve HBV D-genotype infected patients is today very low, and suggests the potential full efficacy of new-generation antiviral drugs used in first line therapy. Whether such low rate can be extrapolated to non HBV-D subtypes, requires a detailed investigation to be performed in a different cohort of patients.

Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function.

Insulin resistance and obesity are intimately related to a chronic low grade systemic inflammation. Interleukin-6 (IL-6) may influence the pathogenesis of obesity-related diseases. The aim of this study is to investigate the effect of body's fat mass on the relationships between -174G/C IL-6 promoter gene polymorphism, IL-6 circulating level and insulin resistance. A population of 150 Caucasian women was studied, subdivided according to their body composition in non-obese (NW), Normal Weight Obese (NWO) and preobese-obese (OB). The NWO subjects were found in an intermediate position between the NW and OB subjects in terms of body weight, fat mass percentage (FM%), abdominal FAT%, hs-CRP and plasma triglyceride level. Fasting plasma IL-6 concentration was positively correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) in all subjects analyzed (P=0.0014). In NWO and OB women a significantly increased IL-6 mean value was observed compared with NW subjects. In G/G population, the IL-6 plasma level of NWO and OB was significantly higher with respect to NW. No significant differences of IL-6 concentrations were observed in the three groups carrying G/C genotype. NWO and OB women homozygous for the allele C have significantly lower value of IL-6 with respect to NW subjects. IL-6 concentration was positively correlated with FM% in G/G (R(2)=0.397, P