Tumor enlargement in adrenal incidentaloma is related to glaucoma: a new prognostic feature?

PURPOSE: The uncertainty on the management of small adrenal incidentalomas (AIs) still represents a challenge in real clinical practice. Considering the lack of knowledge on risk factors implicated in tumour enlargement, the aim of this study was to identify risk factors for morphological changes during follow-up of adrenal incidentalomas (AIs). METHODS: We retrospectively evaluated demographic, clinical, radiological and biochemical parameters of 153 AIs (2007-2021). Patients with histological diagnosis of metastases or pheochromocytoma were excluded. To detect risk factors for tumor enlargement, diseases associated with AIs were included if their prevalence was higher than 2%. Patients were divided into two groups (A: radiological stability; B: tumor enlargement defined as > 5 mm/year in the main diameter). RESULTS: Group A: 89.5% and group B: 10.5%, mean follow-up 38.6 ± 6.9 months (range 6-240). Tumor enlargement when occurred was within 36 months of follow-up. In group B high body weight (p < 0.03), dehydroepiandrosterone sulfate (DHEAS) (p < 0.05) and direct renin concentration (DRC) (p < 0.04) were higher than group A, while aldosterone levels were lower; moreover, considering comorbidities, glaucoma and dysglycemia (p < 0.01 for both) had higher prevalence in group B. Glaucoma and dysglycemia were independent predictors of enlargement. Patients affected by glaucoma, atrial fibrillation, dysglycemia had a lower dimensional change-free survival than non-affected. CONCLUSIONS: Glaucoma might be a novel risk factor for AI enlargement. If subtle undetectable cortisol hypersecretion has a role is a topic for further research.

Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

PURPOSE: Registered trials and real-world evidence (RWE) studies provided evidence on the efficacy of once-weekly (OW) semaglutide on hyperglycaemia and cardiovascular risk factors as add-on or de-novo treatment in type 2 diabetes (T2D). METHODS: In a retrospective analysis of electronic data files from 258 T2D patients, this RWE study aimed to explore the impact of OW semaglutide on biochemical and anthropometric outcomes after 6 and 12 months in patients receiving at least one prescription of OW semaglutide between September 2019 and May 2021. RESULTS: During the study period, 154 and 56 consecutive patients completed the 6 and 12 months of OW semaglutide treatment. HbA1c levels decreased by -1.02±0.1% after 6 months and -1.1±0.1% after 12 months of OW semaglutide (p<0.0001 for both). At these time-points, HbA1c values were <7% in 61% and 57% of cases. HbA1c reduction was greater in patients with higher baseline HbA1c levels and it occurred irrespective of gender, age, insulin therapy and complications. The residual number of cases with HbA1c ≥9% by the study end was low (5.3% vs 18.9% at baseline). Weight loss occurred in 73.5% and 78.1% of cases and, compared to baseline, it was ≥5% in 21.2- 25.4% and ≥10% in 6.8-18.2% after 6 and 12 months, respectively. Significant predictors of HbA1c reduction after 6 months of OW semaglutide treatment were baseline HbA1c (p<0.0001), bodyweight reduction (p<0.0001) and disease duration (p<0.001), while baseline HbA1c was the only predictor of HbA1c response after 12 months (p<0.0001). Reported adverse events were consistent with the known safety profile of semaglutide. CONCLUSIONS: Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

Thyroid function in the subacute phase of traumatic brain injury: a potential predictor of post-traumatic neurological and functional outcomes.

PURPOSE: That thyroid hormones exert pleiotropic effects and have a contributory role in triggering seizures in patients with traumatic brain injury (TBI) can be hypothesized. We aimed at investigating thyroid function tests as prognostic factors of the development of seizures and of functional outcome in TBI. METHODS: This retrospective study enrolled 243 adult patients with a diagnosis of mild-to-severe TBI, consecutively admitted to our rehabilitation unit for a 6-month neurorehabilitation program. Data on occurrence of seizures, brain imaging, injury characteristics, associated neurosurgical procedures, neurologic and functional assessments, and death during hospitalization were collected at baseline, during the workup and on discharge. Thyroid function tests (serum TSH, fT4, and fT3 levels) were performed upon admission to neurorehabilitation. RESULTS: Serum fT3 levels were positively associated with an increased risk of late post-traumatic seizures (LPTS) in post-TBI patients independent of age, sex and TBI severity (OR = 1.85, CI 95% 1.22-2.61, p < 0.01). Measured at admission, fT3 values higher than 2.76 pg/mL discriminated patients with late post-traumatic seizures from those without, with a sensitivity of 74.2% and a specificity of 60.9%. Independently from the presence of post-traumatic epilepsy and TBI severity, increasing TSH levels and decreasing fT3 levels were associated with worse neurological and functional outcome, as well as with higher risk of mortality within 6 months from the TBI event. CONCLUSIONS: Serum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

Gestational Diabetes Mellitus: Clinical Characteristics and Perinatal Outcomes in a Multiethnic Population of North Italy.

AIM: To evaluate clinical characteristics and perinatal outcomes in a heterogeneous population of Caucasians born in Italy and High Migration Pressure Countries (HMPC) women with GDM living in Piedmont, North Italy. METHODS: We retrospectively analyzed data from 586 women referring to our unit (2015-2020). Epidemiological (age and country of origin) and clinical-metabolic features (height, weight, family history of DM, parity, previous history of GDM, OGTT results, and GDM treatment) were collected. The database of certificates of care at delivery was consulted in relation to neonatal/maternal complications (rates of caesarean sections, APGAR score, fetal malformations, and neonatal anthropometry). RESULTS: 43.2% of women came from HMPC; they were younger (p < 0.0001) and required insulin treatment more frequently than Caucasian women born in Italy (χ 2 = 17.8, p=0.007). Higher fasting and 120-minute OGTT levels and gestational BMI increased the risk of insulin treatment (OGTT T0: OR = 1.04, CI 95% 1.016-1.060, p=0.005; OGTT T120: OR = 1.01, CI 95% 1.002-1.020, p=0.02; BMI: OR = 1.089, CI 95% 1.051-1.129, p < 0.0001). Moreover, two or more diagnostic OGTT glucose levels doubled the risk of insulin therapy (OR = 2.03, IC 95% 1.145-3.612, p=0.016). We did not find any association between ethnicities and neonatal/maternal complications. CONCLUSIONS: In our multiethnic GDM population, the need for intensive care and insulin treatment is high in HPMC women although the frequency of adverse peripartum and newborn outcomes does not vary among ethnic groups. The need for insulin therapy should be related to different genetic backgrounds, dietary habits, and Nutrition Transition phenomena. Thus, nutritional intervention and insulin treatment need to be tailored.

Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome.

PURPOSE: Angiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predicts non-alcoholic fatty liver disease (NAFLD) and altered metabolic homeostasis in the general population as well as in persons with common and genetic obesity, including the Prader-Willi syndrome (PWS). However, its metabolic correlate in paediatric patients with respect to PWS is unknown. METHODS: This cross-sectional study investigated circulating ANGPTL8 and adipocytokines levels in 28 PWS and 28 age-, sex- and BMI-matched children and adolescents (age, 7.0-17.8y) in relation to NAFLD and metabolic homeostasis assessed by OGTT, paediatric metabolic index (PMI) and fatty liver index (FLI), liver ultrasonography (US), as well as dual-energy X-ray absorptiometry (DEXA) for analysis of fat (FM) and fat-free mass (FFM). RESULTS: At the set level of significance, PWS children showed lower values of FFM (p < 0.01) but healthier insulin profiles (p < 0.01) and PMI values (p < 0.05) than matched controls. By US, the prevalence of NAFLD was similar between groups but less severe in PWS than controls. Analysis of ANGPTL8 levels showed no difference between groups, yet only in PWS ANGPTL8 levels were associated with ALT levels, FLI values and NAFLD. In stepwise multivariable regression analysis on merged data, ANGPTL8 levels were independently predicted by BMI SDS, leptin levels and NAFLD. CONCLUSION: ANGPTL8 levels are similar in PWS and controls and, overall, they are directly associated with the presence and severity of NAFLD in patients with PWS.

Clinical picture and the treatment of TBI-induced hypopituitarism.

Traumatic brain injury (TBI) is an important public health problem with an increasing incidence in the last years. Relatively few cases are fatal; most individuals will survive and, in the long-term, the sequalae of TBI will include neuroendocrine dysfunctions with a much higher frequency than previously suspected. Patients who develop hypopituitarism after TBI present manifestations due to the number of deficient hormones, severity of hormonal deficiency, and the duration of hypopituitarism without diagnosis and treatment. The clinical spectrum of hypopituitarism is very large and many signs and symptoms of TBI survivors such as fatigue, concentration difficulties, depressive symptoms are nonspecific and overlap with symptoms of post-traumatic stress disorder and variably severe hypopituitarism related to brain damage remaining undiagnosed. This can explain why the diagnosis of hypopituitarism is often missed or delayed after this condition with potentially serious and hazardous consequences for the affected patients. Moreover, clinical experience cumulatively suggests that TBI-associated hypopituitarism is associated with poor recovery and worse outcome, since post-traumatic hypopituitarism is independently associated with cognitive impairment, poor quality of life, abnormal body composition, and adverse metabolic profile. In the present review, the current data related to clinical consequences of pituitary dysfunction after TBI in adult patients and therapeutic approaches are reported.

Correction to: Transsphenoidal surgery for pituitary adenomas: early results from a single center.

Unfortunately in the original publication, the affiliation of the author Paolo Marzullo was incorrect. The author inadvertently missed out to include his second affiliation.

Use of administrative health databases to estimate incidence and prevalence of acromegaly in Piedmont Region, Italy.

PURPOSE: Recent studies from national registries have described changing patterns in epidemiology of acromegaly. Our retrospective study used administrative databases to estimate prevalence and incidence of acromegaly in the Piedmont Region, Italy. METHODS: This study was conducted in Piedmont between 2012 and 2016 on administrative health databases for inpatients and outpatients of any age. Enrollees were included if claims suggestive of acromegaly were identified in at least two of the following databases: Drug Claims Registry, Hospital Information System, Co-payment Exemption Registry and Outpatient Specialist Service Information System. RESULTS: 369 individuals (M = 146, F = 223) met our criteria. Overall incidence was 5.3 per million person years (95% CI 4.2-6.7), and prevalence was 83 cases per million inhabitants (95% CI 75-92). Mean age was 50.9 years. Both incidence and prevalence were slightly higher among women (rate ratio 1.08, prevalence ratio 1.43). Age-specific incidence was similar between sexes up to 39 years and diverged thereafter, with an increasing trend recorded among men. Prevalence was higher in women aged 40-79 years, and increased continuously up to 79 years in both sexes. CONCLUSIONS: This is the first population-based study conducted in Italy to estimate incidence and prevalence of acromegaly and results show a higher prevalence than previously reported. Although our algorithm requires proper validation, it constitutes a promising tool to describe the epidemiology of acromegaly.

Transsphenoidal surgery for pituitary adenomas: early results from a single center.

OBJECTIVE: To evaluate early results of transsphenoidal surgery for pituitary adenomas. DESIGN: Retrospective evaluation of 90 consecutive patients undergoing endoscopic pituitary adenoma surgery (2007-2016) at "Maggiore della Carità" Hospital in Novara, Italy. Age at diagnosis, sex, symptoms at presentation, hormonal and radiological data, complications of surgery, and short-term follow-up information were collected. RESULTS: The majority of patients were male (M/F: 1.5/1, mean age at diagnosis 62.1 ± 1.5 years mean ± SEM). Most patients (91.1%) presented with a macroadenoma (27.4 mm ± 1.1 mm mean ± SEM), while 77.8% were non-functioning pituitary adenomas. Clinical presentations related to mass effect were visual impairment (74.0%) and/or hypopituitarism (55.1%). The main surgery complication was insipidus diabetes (12.2%), followed by cerebral hemorrhage (4.4%), cerebrospinal fluid (CSF) leaks (4.4%), syndrome of inappropriate antidiuresis (SIAD) (2.2%), and epistaxis (2.2%); only one patient died because of stroke. Risk of complications was not associated with tumor size (OR = 0.588, 95% CI 0.967-1.081, p = 0.443). Visual function improved in 70.6% of patients, while recovery of normal pituitary function occurred in 48.1%. Early neuroimaging studies demonstrated no residual tumor in 27.6% of patients. Invasion of cavernous sinus (OR = 3.293, 95% CI 0.897-16.738, p = 0.05) and maximum tumor diameter (OR = 6.857, 95% CI 1.039-1.309, p < 0.01) were associated with an unfavorable surgical outcome. CONCLUSIONS: Transsphenoidal endoscopic surgery for pituitary adenomas is safe and is frequently followed by improvement in visual symptoms, whereas recovery of pituitary function is less common. In our patients, complete surgical removal of adenomas is comparable to that of other series, but further investigations will be necessary to clarify the long-term risk of tumor recurrence.

Serum uric acid potentially links metabolic health to measures of fuel use in lean and obese individuals.

BACKGROUND AND AIMS: Uric acid (UA) is a byproduct of the high-energy purine metabolism and is conventionally regarded as a marker of cardio-metabolic impairment. Its potential relationship with energy homeostasis is unknown to date. METHODS AND RESULTS: In a cross-sectional study on 121 otherwise healthy obese and 99 sex- and-age-matched lean subjects, UA levels were analyzed in relation to metabolic health, inflammatory markers, respiratory quotient (RQ) and resting energy expenditure (REE) as assessed by indirect calorimetry, fat mass (%FM) and fat-free mass (FFM) as determined by bioimpedance analysis. As expected, obese and lean subjects differed in BMI, glucolipid homeostasis, leptin and insulin levels, inflammatory markers, %FM and FFM (p < 0.001 for all). Likewise, UA levels (p < 0.001) and rates of hyperuricaemia (40.5% vs 3.0%, p < 0.0001) were also higher in obese than lean controls. Further, indirect calorimetry confirmed that obesity increased REE and decreased RQ significantly (p < 0.001). Beyond the expected metabolic correlates, in individual and merged groups UA levels were associated negatively with RQ and positively with REE (p < 0.0001 for both). In multivariable regression analysis, significant independent predictors of UA were BMI and sex. When BMI was replaced by measures of body composition, %FM and FFM emerged as significant predictors of serum UA (p < 0.0001). CONCLUSIONS: A potential link relates serum UA to measures of resting energy expenditure and their determinants.

Non-surgical ablative therapies for inoperable benign insulinoma.

PURPOSE: Benign insulinoma is the most common functioning neuroendocrine tumor of the pancreas. The gold-standard therapeutic approach for insulinoma is surgery, which allows for tumor removal, histology and immunochemical analyses. If surgery is not feasible, minimally invasive ablative procedures performed by interventional radiology can lead to partial or complete remission of hormone hypersecretion and tumor control in insulinoma patients. METHODS: We performed a review of existing literature on non-chemotherapeutic/radioactive ablative techniques employed for the treatment of benign, otherwise inoperable, pancreatic insulinoma. For this purpose, feasibility, effectiveness and safety of ablative treatments for pancreatic insulinoma were reviewed from literature data published from 1982 to date. RESULTS: A total of 44 insulinoma cases treated with non-surgical ablative techniques were desumed, and divided as follows: 7 cases of tumor embolization, 26 ethanol ablations, 7 radiofrequency ablations, 2 high intensity focused ultrasound ablation, 1 irreversible electroporation and 1 percutaneous microwave ablation. Most cases involved single insulinoma, predominantly located in the pancreas head and body. In the majority of patients, ablation was chosen instead of surgery due to severe comorbidities. After an average follow-up of 16 months, the overall success rate of non-surgical ablative treatments of insulinoma was 84%, the recurrence/persistence rate was 16%, and transient adverse events were noted in 23% of cases. Adverse events were usually self-limiting and medically manageable. CONCLUSIONS: Non-surgical ablation is a feasible, safe and repeatable procedure in patients with pancreatic insulinoma, who are not candidate to surgery or refuse it. Partial or complete control of symptoms and tumor growth is experienced by the majority of patients.

Imaging assessment of portal venous system: pictorial essay of normal anatomy, anatomic variants and congenital anomalies.

The purpose of this pictorial essay is to describe anatomic variants and congenital anomalies of portal venous system and related liver parenchymal alterations. The imaging findings of some of these entities have been previously described in other articles, however this work encompasses all congenital anomalies of portal venous system with attention to their features on various imaging modalities; in particular we illustrated with detailed pictures all the main portal vein variants, congenital extra- and intra-hepatic porto-systemic venous shunts and portal vein aneurysm. Variants of portal branches and intrahepatic portosystemic shunts are quite uncommon, however, when present, they should be recognized before performing surgery or interventional procedures. Congenital absence of the portal vein is an important finding as the complete loss of portal perfusion predisposes the liver to focal or diffuse hyperplastic or dysplastic changes. Portal vein aneurysm is a rare clinical entity that can affect intra- and extra-hepatic portal branches; although usually asymptomatic, thrombosis can occur. Awareness of congenital variants of portal venous system among radiologists should allow a more confident diagnosis and permit an accurate planning of surgical procedures and percutaneous interventions; identification of portal system anomalies also suggest an accurate evaluation of associated hepatic parenchymal anomalies such as nodular regenerative hyperplasia, focal nodular hyperplasia (FNH), and adenomas with high risk of malignant transformation.

Preoperative staging of colorectal cancer using virtual colonoscopy: correlation with surgical results.

OBJECTIVE: The aim of this study was to evaluate the clinical usefulness of computed tomography colonography (CTC) in the preoperative staging in patients with abdominal pain for occlusive colorectal cancer (CRC) and to compare the results of CTC with the surgical ones. PATIENTS AND METHODS: 127 patients with abdominal pain, iron deficiency anemia and occlusive CRC underwent a CTC examination in prone position without intravenous contrast agent and in prone position after administration of intravenous contrast medium. All the patients underwent surgery after CTC. Two radiologists with different experience analyzed the images first independently and then by consensus. They evaluated the location of the lesion, the depth of the invasion of the colon-rectal wall (T stage), lymph node involvement (N stage) and the presence or absence of distant metastasis (M stage). CTC findings were correlated with surgical outcomes. RESULTS: The overall accuracy values for tumour localization according to consensus reading of CTC examinations in comparison to surgical results were 100% (K = 1, p = 0.0001). The overall accuracy values of agreement for T staging of reader 1, reader 2 and consensus reading of CTC examinations in comparison to surgical results were respectively 95.5% (K = 0.876, p = 0.0035), 93.3% (K = 0.858, p = 0.0037) and 97.7% (K = 0.926, p = 0.0014) for ≤ T2; 91.3% (K = 0.839, p = 0.0027), 88.3% (K = 0.817, p = 0.0031), and 92.9% (K = 0.894, p = 0.0025) for T3; 89.6% (K = 0.825, p = 0.0037), 86.2% (K = 0.837, p = 0.0032) and 89.6% (K = 0.821, p = 0.0023) for T4. The overall accuracy values for N staging for reader 1, reader 2 and consensus reading was 90.2% (K = 0.865, p = 0.0029). The overall accuracy values for M staging of reader 1, reader 2 and consensus reading was 92% (K = 0.875, p = 0.0019). CONCLUSIONS: CTC with is a very useful tool for accurate pre-treatment staging and localization of occlusive CRC.

Profiling cancer gene mutations in longitudinal epithelial ovarian cancer biopsies by targeted next-generation sequencing: a retrospective study.

BACKGROUND: The majority of patients with stage III-IV epithelial ovarian cancer (EOC) relapse after initially responding to platinum-based chemotherapy, and develop resistance. The genomic features involved in drug resistance are unknown. To unravel some of these features, we investigated the mutational profile of genes involved in pathways related to drug sensitivity in a cohort of matched tumors obtained at first surgery (Ft-S) and second surgery (Sd-S). PATIENTS AND METHODS: Matched biopsies (33) taken at Ft-S and Sd-S were selected from the 'Pandora' tumor tissue collection. DNA libraries for 65 genes were generated using the TruSeq Custom Amplicon kit and sequenced on MiSeq (Illumina). Data were analyzed using a high-performance cluster computing platform (Cloud4CARE project) and independently validated. RESULTS: A total of 2270 somatic mutations were identified (89.85% base substitutions 8.19% indels, and 1.92% unknown). Homologous recombination (HR) genes and TP53 were mutated in the majority of Ft-S, while ATM, ATR, TOP2A and TOP2B were mutated in the entire dataset. Only 2% of mutations were conserved between matched Ft-S and Sd-S. Mutations detected at second surgery clustered patients in two groups characterized by different mutational profiles in genes associated with HR, PI3K, miRNA biogenesis and signal transduction. CONCLUSIONS: There was a low level of concordance between Ft-S and Sd-S in terms of mutations in genes involved in key processes of tumor growth and drug resistance. This result suggests the importance of future longitudinal analyses to improve the clinical management of relapsed EOC.

Complete clinical remission of psoriasis 6 months after renal transplantation.

BACKGROUND: Psoriasis, one of the most common immune-mediated inflammatory diseases of the skin is mediated by activated effector T cells. CASE REPORT: We report a case of a 56-year-old white man with a 22-year history of severe psoriasis vulgaris with plaque and joint involvement, who experienced a complete clinical remission after renal transplantation. The patient had been on hemodialysis for 6 years because of chronic renal failure caused by an undetermined chronic nephropathy. Psoriasis, which worsened over the years, was symmetrically distributed as erythematous scaly plaques that had increased until they covered about 50% of the body surface, involving mainly the abdomen, legs, back, and arms. The patient also complained of severe itching an responsive to drugs. He had been treated with topical and systemic corticosteroids and phototherapy several times without benefit. After renal transplantation he underwent immunosuppressive therapy with corticosteroids, mycophenolate mofetil (MMF), and tacrolimus (Advagraf, beginning starting dose 1 mg/kg/day, C0 10 ng/mL). RESULTS: From the early days post-surgery the patient reported a fast improvement in the itching with progressive reduction of the skin lesions. After 4 months follow-up the psoriasis had completely regressed, presumably due to the immunosuppressive regimen. CONCLUSION: This finding suggests that systemic immunosuppressive drugs may be useful for psoriasis an responsive to conventional therapy.

Altered endocannabinoid signalling after a high-fat diet in Apoe(-/-) mice: relevance to adipose tissue inflammation, hepatic steatosis and insulin resistance.

AIMS/HYPOTHESIS: Apolipoprotein E (ApoE) deficiency is associated with reduced fat accumulation in white adipose tissue (WAT) and high liver triacylglycerol content. Elevated levels of endocannabinoids and cannabinoid receptor type 1 (CB(1)) receptors in the liver and in epididymal vs subcutaneous WAT are associated with fatty liver, visceral adipose tissue, inflammatory markers and insulin resistance. METHODS: We investigated, in Apoe (-/-) and wild-type (WT) mice, the effect of a high-fat diet (HFD) on: (1) subcutaneous and epididymal WAT accumulation, liver triacylglycerols, phospholipid-esterified fatty acids, inflammatory markers in WAT and liver, and insulin resistance; and (2) endocannabinoid levels, and the gene expression levels of the Cb ( 1 ) receptor and endocannabinoid metabolic enzymes in liver and WAT. RESULTS: After a 16 week HFD, Apoe (-/-) mice exhibited lower body weight, WAT accumulation and fasting leptin, glucose and insulin levels, and higher hepatic steatosis, than WT mice. Glucose clearance and insulin-mediated glucose disposal following the HFD were slower in WT than Apoe (-/-) mice, which exhibited higher levels of mRNA encoding inflammatory markers (tumour necrosis factor-α [TNF-α], monocyte chemoattractant protein-1 [MCP-1], cluster of differentiation 68 [CD68] and EGF-like module-containing mucin-like hormone receptor-like 1 [EMR1]) in the liver, but lower levels in epididymal WAT. HFD-induced elevation of endocannabinoid levels in the liver or epididymal WAT was higher or lower, respectively, in Apoe (-/-) mice, whereas HFD-induced decrease of subcutaneous WAT endocannabinoid and CB(1) receptor levels was significantly less marked. Alterations in endocannabinoid levels reflected changes in endocannabinoid catabolic enzymes in WAT, or the availability of phospholipid precursors in the liver. CONCLUSIONS/INTERPRETATION: Liver and adipose tissue endocannabinoid tone following an HFD is altered on Apoe deletion and strongly associated with inflammation, insulin resistance and hepatic steatosis, or lack thereof.

Erythropoietin enhances immunostimulatory properties of immature dendritic cells.

Dendritic cells (DCs) are the most potent antigen-presenting cells and play a crucial role by modulating the T cell immune response against infective agents, tumour antigens and alloantigens. The current study shows that differentiating bone marrow (BM)-derived DCs but not fully differentiated DCs are targets of erythropoietin (EPO). Indeed, DCs emerging from rat bone marrow, but not splenic DCs, express the EPO receptor (Epo-R) and respond to EPO stimulation displaying a more activated phenotype with increased CD86, CD40 and interleukin (IL)-12 expression levels and a higher allostimulatory capacity on T cells than untreated DCs. Moreover, results here presented show that EPO up-regulates Toll-like receptor (TLR)-4 in differentiating DCs rendering these cells more sensitive to stimulation by the TLR-4 ligand lipopolysaccharide (LPS). Indeed, DCs treated with EPO and then stimulated by LPS were strongly allostimulatory and expressed CCR7, CD86, CD40, IL-12 and IL-23 at higher levels than those observed in DCs stimulated with LPS alone. It is tempting to speculate that EPO could act as an additional danger signal in concert with TLR-4 engagement. Thus, EPO, beyond its erythropoietic and cytoprotective effects, turns out to be an immune modulator.

External quality assessment programmes for detection of HCV RNA, HIV RNA and HBV DNA in plasma: improved proficiency of the participants observed over a 2-year period.

BACKGROUND AND OBJECTIVES: Two External Quality Assessment Programmes (EQAPs) were run in 2008 and 2009 to evaluate the proficiency of blood centres in detecting, by nucleic acid amplification techniques (NAT), the possible contamination of plasma with hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV). MATERIALS AND METHODS: In the EQAP-2008, three customized panels were designed; each containing positive samples with a viral nominal concentration for the three viruses of about three times the 95% DL of the respective commercial NAT assay. In the EQAP-2009, the proficiency of the participants was evaluated with a single panel, independently on the NAT method used. RESULTS: While 84% (102/122) of the participants in the EQAP-2008 correctly identified the positive and negative samples of the panels, in the EQAP-2009 the percentage of proficient laboratories increased to 97% (118/122). Most importantly, in this 2-year experience, we observed a decrease in the number of pre-/postanalytical errors, from 14 in 2008 to two in 2009. CONCLUSIONS: The design of these two EQAPs allowed participants to assess the performance of the NAT methods applied in their routine screening of blood donations, not only with respect to analytical errors but also to human errors that, despite the high level of automation reached by NAT methods, can still occur.

An electrochemical impedance investigation of the behaviour of anodically oxidised titanium in human plasma and cognate fluids, relevant to dental applications.

In dental applications, the contact between the metal implant and the receiving living tissue is made through the oxide layer on the implant surface, which allows the osseointegration process. In dentistry, the passive film formed on titanium seems to be more stable and protective than that formed on the Ti alloys, customarily used in other medical applications. Corrosion of titanium alloys in the mouth can result from the presence of a number of corrosive species, such as the hydrogen ion (H(+)), sulfide compounds (S(2-)), dissolved oxygen (O(2)) and Cl(-) and can result in the release of Ti(4+) ions that, in turn, brings about the reduction of alkaline phosphatase activity of osteoblastic cells. The present study reports a time-dependent electrochemical corrosion study of titanium in contact with the following biologically relevant solutions: (i) SBF (simulating the inorganic part of human plasma), (ii) SBF with added ovalbumin (a protein simulating the post-implant environment) and (iii) human plasma. To the best of the authors' knowledge, this is the first report on the corrosion of Ti in human plasma. The electrochemical measurements are based on electrochemical impedance spectrometry. Impedance spectra were interpreted on the basis of the equivalent-circuit approach and estimates of the time-variation of oxide film thickness and resistance were computed. Surface Raman spectroscopy was used to characterise the structure of as-anodised and corroded TiO(2) films: the effects of phosphate and organic incorporation were highlighted. EIS and surface Raman measurements have demonstrated that the corrosion resistance of the oxide films formed on Ti is strongly affected by the presence of biomolecules in the chloride- and phosphate-based aqueous solution. In particular, ovalbumin increases corrosion performance and human plasma is found to be remarkably more aggressive in comparison to SBF. These results suggest some caution in extrapolating corrosion results obtained in simulated biological fluids to the actual behaviour in vivo.

External quality assessment for the detection of HCV RNA, HIV RNA and HBV DNA in plasma by nucleic acid amplification technology: a novel approach.

BACKGROUND AND OBJECTIVES: In this EQA study a novel approach was used to assess the performance of blood centres and blood product manufacturers in detecting the possible contamination of plasma with HCV, HIV and HBV by NAT. MATERIALS AND METHODS: A panel of 12 samples, three negative and three positive for each virus, was distributed to the EQA participants. The positive samples were prepared, using the respective WHO standards, in order to obtain a viral concentration of about three times the 95% DL of the methods most commonly used by laboratories involved in blood screening by NAT. Participants were requested to test each sample of the panel on different days, possibly by different operators using their routine NAT assay. RESULTS: Overall, the participants' performance was satisfactory. In particular, 49 of the 59 participants (83%) were able to correctly identify all samples. Regarding the remaining 10 laboratories, in three cases a deviation from the laboratory's procedure that could be attributed to an operator's mistake was observed, in two cases a possible cross-contamination occurred while in the remaining five cases the failure to detect the positive samples couldn't be ascribed to any relevant deviation in the laboratory's procedure. CONCLUSIONS: The novel design of this EQA study allowed participants to verify their day by day activity as the study was carried out in the context of their routine testing. Under these conditions, it was demonstrated that, despite the high level of automation reached by NAT assays, human errors can still occur.