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Ferritin self-assembly has been widely exploited for the synthesis of a variety of nanoparticles for drug-delivery and diagnostic applications. However, despite the crucial role of ferritin self-assembly mechanism for probes encapsulation, little is known about the principles behind the oligomerization mechanism. In the present work, the novel "humanized" chimeric Archaeal ferritin HumAfFt, displaying the transferrin receptor-1 (TfR1) recognition motif typical of human H homopolymer and the unique salt-triggered oligomerization properties of Archaeoglobus fulgidus ferritin (AfFt), was site-selectively labeled with N -(1-pyrenyl)maleimide on a topologically selected cysteine residue inside the protein cavity, next to the dimer interface. Pyrene characteristic fluorescence features were exploited to investigate the transition from a dimeric to a cage-like 24-meric state and to visualize the protein in vitro by two photon fluorescence microscopy. Indeed, pyrene fluorescence changes upon ferritin self-assembly allowed to establish, for the first time, the kinetic and thermodynamic details of the archaeal ferritins oligomerization mechanism. In particular, the magnesium induced oligomerization proved to be faster than the monovalent cation-triggered process, highly cooperative, complete at low MgCl 2 concentrations, and reversed by treatment with EDTA. Moreover, pyrene intense excimer fluorescence was successfully visualized in vitro by two photon fluorescence microscopy as pyrene-labeled HumAfFt was actively uptaken into HeLa cells by human transferrin receptor TfR1 recognition, thus representing a unique nano-device building block for two photon fluorescence cell imaging., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Context: British Thyroid Association (BTA), American Thyroid Association (ATA), and American Association of Clinical Endocrinologists (AACE/ACE/AME) recommend for thyroid nodules an ultrasound (US)-based stratification of risk of malignancy. Aim of our study was to assess the diagnostic accuracy of US classification systems and their reliability for indication to fine-needle aspiration (FNA)., Design: Prospective study on 987 thyroid nodules consecutively referred for FNA. US images were independently reviewed by four experts for assignment of malignancy risk. Cytologically benign nodules had confirmation with a second FNA, whereas Bethesda class IV, V, and VI nodules were operated upon. Class III nodules had surgery or follow-up on the basis of clinical, immunocytochemical, and US features., Results: BTA: Malignancy rate was 2.8% in benign, 10.0% in indeterminate, 51.3% in suspicion, and 80.9% in malignant US class. Sensitivity was 0.74, specificity was 0.92, and accuracy was 0.89. ATA: Malignancy rate was 0.0% in benign, 2.2% in very low suspicion, 3.0% in low suspicion, 5.8% in intermediate, and 55.0% in high suspicion US class. Sensitivity was 0.81, specificity was 0.87, and accuracy was 0.86. AACE/ACE/AME: Malignancy rate was 1.1% in low-risk, 4.4% in intermediate-risk, and 54.9% in high-risk US class. Sensitivity was 0.82, specificity was 0.87, and accuracy was 0.86. K correlation coefficient was 78.9%, 76.9%, and 82.0% for BTA, ATA, and AACE/ACE/AME classifications., Conclusions: Classification systems had elevated predictive value of malignancy in high-risk classes. ATA and AACE/ACE/AME systems were effective for ruling out indication to FNA in low-US-risk nodules. A similar diagnostic accuracy and a substantial interobserver agreement was provided by the three- and the five-category classifications.

Purpose: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules., Materials and Methods: Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated., Results: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p < 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

Multiple sclerosis (MS) is characterized by primary inflammation, demyelination, and progressive neurodegeneration. A biochemical MS feature is neuronal mitochondrial dysfunction, compensated by anaerobic metabolism increase, likely aggravating progression of neurodegeneration. Here, we characterized a pragmatic serum profile of compounds related to mitochondrial energy metabolism of potential clinical use. Blood samples of 518 well characterized (disability, disease course) MS patients and 167 healthy controls were analyzed for serum purines, pyrimidines, creatinine, and lactate. Nine of the 15 compounds assayed, hypoxanthine, xanthine, uric acid, inosine, uracil, β-pseudouridine, uridine, creatinine, and lactate, differed significantly between MS patients and controls (p < 0.0001). Using these nine compounds, a unifying Biomarker Score was calculated. Controls and MS patients had mean Biomarker Scores of 0.4 ± 0.7 and 4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Score was higher in patients with progressive (6.0 ± 1.8 than with relapsing remitting disease course (3.6 ± 1.5, p < 0.00001). High association between the Biomarker Score and increase in disability (EDSS) was also observed. Additionally, in 50 patients who underwent magnetic resonance imaging (MRI), increase in the Biomarker Score correlated to neuroanatomical alterations. These results, obtained in a large cohort of MS patients evaluated for serum metabolic compounds connected to energy metabolism, demonstrated that the Biomarker Score might represent a pragmatic, resource saving, easy to obtain, laboratory tool useful to monitor MS patients and predict at an early stage who will switch from an RR to a progressive disease course. For the first time, it was also clearly shown a link between mitochondrial dysfunction and MRI lesions characteristic of MS.

Objective: The aim of this study was to evaluate if our molecular algorithm, based on tumor circulating transcripts, may predict relapse risk in cutaneous malignant melanoma (CMM)., Results: The multi-marker panel was able to differentiate patients with CMM from HC with high diagnostic sensitivity and specificity, especially for MITF-m and TGFB2 (91-100%) whose levels decreased during follow-up of recurrence-free patients, and remained stable in the case of relapse. PAX3d higher than 2.76 copies/µL emerged as a promising biomarker [specificity = 75-93% and negative predictive value = 75-98%] to stratify subjects at high risk of CMM recurrence independently of age, gender and AJCC staging [OD = 9.5(3.2-28.0), p < 0.001]. The survival analysis confirmed PAX3d performance in relapse prediction with significant differences in recurrence risk 12 months after the basal time-point ( p = 0.008)., Materials and Methods: Peripheral blood was collected from 111 CMM patients and from 87 healthy controls (HC) randomly selected. Each specimen was examined by qRT-PCR analysis for the expression of 3 tumor-related transcripts (PAX3d, MITF-m and TGFB2) at diagnosis, and at the following 6 and 12 months during clinical monitoring., Conclusions: We demonstrated the usefulness of our molecular algorithm to indirectly detect circulating melanoma cells in blood, along with PAX3d capability to assess patients' progression and relapse prediction., Competing Interests: CONFLICTS OF INTEREST This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No author has any conflicts of interest to disclose.

Botulinum toxin is considered as first-line therapy for cervical dystonia, but few papers have addressed these issues in the long term. Aim of this study was to investigate the long-term efficacy and safety of abobotulinumtoxin A (A/Abo) in patients with primary cervical dystonia. Consecutive patients who received at least six injections with A/Abo were included. Safety was assessed on patients' self-reports. Efficacy was assessed by recording the total duration of benefit, duration of maximum efficacy, disease severity measured by means of the Tsui score, and pain intensity evaluated by means of the visual analog scale (VAS). Thirty-nine patients with PCD were included. The mean dose injected was 701.5 ± 280.6 U. The mean duration of the clinical improvement was 93.0 ± 30.7 days, while the mean duration of the maximum clinical improvement was 77.1 ± 27.1 days. The mean VAS before and 4 weeks after injection was 4.4 ± 1.8 and 1.8 ± 1.6, respectively. The mean Tsui score before and 4 weeks after treatment was 5.7 ± 1.8 and 3.5 ± 1.5, respectively. Doses of A/Abo and duration of the maximum clinical improvement significantly increased over time, while the Tsui score and VAS displayed a tendency to decrease along time. Side effects occurred in 19.6% of all the treatments but were severe in only four injections. The results of our study confirm the effectiveness and safety profile of A/Abo for the long-term treatment of primary cervical dystonia.

Background: Intrauterine growth curves are considered an essential instrument in prenatal medicine for an appropriate auxological classification of fetuses and they have a great importance in clinical practice. Nowadays, in Italy a national curve published in 1975, is the most used. It Is based on birth weights of 8458 newborns from physiological pregnancies. The aim of the present study was to develop a modern fetal growth curve based on accurately selection of 35 240 physiological singleton Italian pregnancies with sure gestational age confirmed by ultrasound., Methods: This is a retrospective analysis of 35,240 pregnancies from "A. Gemelli" University Hospital in Rome and "S. Anna" University Hospital in Turin from January 2001 to December 2006. Non-resident pregnant women or coming from other countries, women with diabetes, hypertensive disorders of pregnancy, multiple pregnancies, fetuses with major malformations and/or chromosomal disorders and stillborn fetuses were excluded., Results: An increasing trend of median neonatal weight, in comparison with the previous Italian National Curve drawn up in 1975, was found., Conclusions: Combining data from two centers, a new fetal growth curve, in which the 10th and the 90th percentiles are clinically reliable, was performed, in order to have a better tool to evaluate the Italian fetal population. A trend towards an increase of birth weight was observed if compared to previous growth curve drawn up more than 30 years ago.

Pre-treatment of tomato plants with micromolar concentrations of omeprazole (OP), a benzimidazole proton pump inhibitor in mammalian systems, improves plant growth in terms of fresh weight of shoot and roots by 49 and 55% and dry weight by 54 and 105% under salt stress conditions (200 mM NaCl), respectively. Assessment of gas exchange, ion distribution, and gene expression profile in different organs strongly indicates that OP interferes with key components of the stress adaptation machinery, including hormonal control of root development (improving length and branching), protection of the photosynthetic system (improving quantum yield of photosystem II) and regulation of ion homeostasis (improving the K + :Na + ratio in leaves and roots). To our knowledge OP is one of the few known molecules that at micromolar concentrations manifests a dual function as growth enhancer and salt stress protectant. Therefore, OP can be used as new inducer of stress tolerance to better understand molecular and physiological stress adaptation paths in plants and to design new products to improve crop performance under suboptimal growth conditions. Highlight: Omeprazole enhances growth of tomato and increases tolerance to salinity stress through alterations of gene expression and ion uptake and transport.

Objectives: The objective of this study was to investigate the prognostic role of quantitative reduction of congestion during hospitalization assessed by Bioelectrical Impedance Vector Analysis (BIVA) serial evaluations in patients admitted for acute heart failure (AHF)., Background: AHF is a frequent reason for patients to be admitted. Exacerbation of chronic heart failure is linked with a progressive worsening of the disease with increased incidence of death. Fluid overload is the main mechanism underlying acute decompensation in these patients. BIVA is a validated technique able to quantify fluid overload., Methods: a prospective, multicentre, observational study in AHF and no AHF patients in three Emergency Departments centres in Italy. Clinical data and BIVA evaluations were performed at admission (t0) and discharge (tdis). A follow-up phone call was carried out at 90 days., Results: Three hundred and thirty-six patients were enrolled (221 AHF and 115 no AHF patients). We found that clinical signs showed the most powerful prognostic relevance. In particular the presence of rales and lower limb oedema at tdis were linked with events relapse at 90 days. At t0, congestion detected by BIVA was observed only in the AHF group, and significantly decreased at tdis. An increase of resistance variation (dR/H) >11 Ω/m during hospitalization was associated with survival. BIVA showed significant results in predicting total events, both at t0 (area under the curve (AUC) 0.56, p<0.04) and at tdis (AUC 0.57, p<0.03). When combined with clinical signs, BIVA showed a very good predictive value for cardiovascular events at 90 days (AUC 0.97, p<0.0001)., Conclusions: In AHF patients, an accurate physical examination evaluating the presence of rales and lower limbs oedema remains the cornerstone in the management of patients with AHF. A congestion reduction, obtained as a consequence of therapies and detected through BIVA analysis, with an increase of dR/H >11 Ω/m during hospitalization seems to be associated with increased 90 day survival in patients admitted for AHF.

Purpose To evaluate the diagnostic accuracy of shear-wave elastography (SWE) in identifying different degrees of fibrosis in a cohort of consecutive children and adolescents with nonalcoholic steatohepatitis (NASH). Materials and Methods Consecutive pediatric patients scheduled to undergo liver biopsy were studied with an ultrasonography-based SWE system. Elastography was performed in 68 of 69 patients with biopsy-proved NASH (37 boys and 31 girls; mean age, 12.6 years ± 2.48; age range, 8-17 years). The correlations among laboratory findings, liver stiffness, and fibrosis score were analyzed, and the area under the receiver operating characteristic curve (AUC) was used to assess the presence of any fibrosis (score ≥F1) or significant fibrosis (score ≥F2). Findings from histologic examination were used as the standard of reference. Results SWE showed a very high correlation with liver fibrosis (P < .001) at univariate and multivariate analyses. The AUCs for the association of any and significant fibrosis were 0.92 (95% confidence interval [CI]: 0.86, 0.98) and 0.97 (95% CI: 0.95, 0.99), respectively. The intraclass correlation coefficient for absolute agreement was 0.95 (95% CI: 0.90, 0.97). Conclusion SWE is an accurate and reproducible noninvasive technique that efficiently depicts the presence of significant liver fibrosis and, less accurately, mild liver fibrosis in pediatric patients with nonalcoholic fatty liver disease. Larger clinical prospective studies are warranted to confirm SWE accuracy and establish threshold values for fibrosis grading in comparison or in combination with other noninvasive methods. © RSNA, 2016.

Background: Spinal anesthesia (SA) in the lateral decubitus position is often used to perform total hip arthroplasty (THA). Hypobaric local anesthetic ensures enhanced and prolonged sensory and motor block in the involved side. The aim of this study was to compare the intraoperative anesthetic efficacy of hypobaric with isobaric levobupivacaine solutions for THA., Methods: Forty patients scheduled to elective THA were allocated into two groups: isobaric levobupivacaine group (IL group) and hypobaric levobupivacaine group (HL group). All the patients were placed with the operative side uppermost on the surgical table and spinal anesthesia was performed with 4 mL (12.5 mg) of selected solution. The evolution of sensory and block on nondependent (operative) and dependent sides were checked., Results: Regarding the nondependent side the onset times for maximal sensory block level in the in HL group was 17.8±1.1 minutes vs. 24.2±4.1 minutes in IL group. In HL group the onset time for motor block was 9.2±3.5 minutes vs. 15.6±5.4 minutes in IL group. The sensory regression time to L2 was significantly prolonged in HL group (192±30.3 minutes vs. 111±13.4 min). After surgery in HL group the residual motor block degree was 2.4±0.9 vs. 0.2±0.4 in IL group., Conclusions: In patients undergoing THA under spinal anesthesia 12.5 mg of hypobaric levobupivacaine, compared with the same dose of isobaric levobupivacaine, allow shorter onset time for sensory block and delayed regression of sensory and motor block in the nondependent side.

Purpose: Fatigue is common in end-stage renal disease patients receiving hemodialysis, reduces significantly their quality of life and is associated with all-cause and cardiac-related mortality. Unfortunately, little is known about the course of fatigue in patients on chronic hemodialysis., Methods: The Vitality Subscale of the SF-36 (SF-36 VS), Short-Form Health Survey, was administered to 45 patients in January (T1), June (T2) and November (T3) 2015., Results: The score of the SF-36 VS did not differ significantly among T1, T2 and T3. Similarly, the 1-year course of the SF-36 Vitality Subscale score did not differ significantly among T1, T2 and T3 after stratification of patients for sex, age, BMI, IADL and Charlson. Between T1 and T2, 21 out of 45 patients (46.6%) changed their fatigue status: 8 fatigued patients became not-fatigued and 13 not-fatigued patients became fatigued. Between T2 and T3, 12 out of 45 (26.6%) patients changed their fatigue status: 5 fatigued patients became not-fatigued and 7 not-fatigued patients became fatigued. Between T1 and T3, 19 out of 45 patients (42.2%) changed their fatigue status: 6 fatigued patients became not-fatigued and 13 not-fatigued became fatigued., Conclusion: The present study is the first to identify variations in fatigue status among patients on chronic hemodialysis during 1-year course. These findings suggest to frequently assess the presence and severity of fatigue in patients on chronic hemodialysis.

Aim: To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis., Methods: Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylated-uncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire., Results: Thirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein (β = 0.220, R 2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls., Conclusion: SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures., Competing Interests: Conflict-of-interest statement: The Authors have no conflicts of interest to declare.

Aims: Charcot neuroarthropathy (CN) is a disabling complication, culminating in bone destruction and involving joints and articular cartilage with high inflammatory environment. Its real pathogenesis is as yet unknown. In autoinflammatory diseases, such as rheumatoid arthritis, characterized by inflammation and joint involvement, autoantibodies against oxidative post-translationally modified (oxPTM) collagen type I (CI) and type II (CII) were detected. Therefore, the aim of our study was to assess the potential involvement of autoimmunity in charcot neuroarthropathy, investigating the presence of autoantibodies oxPTM-CI and oxPTM-CII, in participants with charcot neuroarthropathy., Methods: In this case-control study, we enrolled 124 participants with type 2 diabetes mellitus (47 with charcot neuroarthropathy, 37 with diabetic peripheral neuropathy without charcot neuroarthropathy, and 40 with uncomplicated diabetes), and 32 healthy controls. The CI and CII were modified with ribose and other oxidant species, and the modifications were evaluated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding of sera from the participants was analyzed with enzyme-linked immunosorbent assay., Results: Age, body mass index, waist and hip circumferences, and lipid profile were similar across the 4 groups, as well as glycated hemoglobin and duration of diabetes among people with diabetes. An increased binding to both native and all oxidation-modified forms of CII was found in participants with CN and diabetic neuropathy. Conversely, for CI, an aspecific increased reactivity was noted., Conclusions: Our results detected the presence of autoantibodies against oxidative post-translational modified collagen, particularly type 2 collagen, in participants with charcot neuroarthropathy and diabetic neuropathy, suggesting the possible involvement of autoimmunity. Further studies are required to understand the role of autoimmunity in the pathogenesis of charcot neuroarthropathy., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: There is uncertainty about the optimal method for measuring the decompressive craniectomy (DC) surface area and how large the DC should be., Methods: A radiological technique for measuring the surface area of removed bone flaps in a series of 73 DCs was developed. Preoperative and early postoperative computed tomography scans of each patient were evaluated. Midline shift (MLS) was considered the key factor for successful DC and was assigned to either normal (0-4 mm) or pathological (≥5 mm) ranges. The association between postoperative MLS and patient survival at 12 months was assessed., Results: Measurements of all removed bone flaps yielded a mean surface area of 7759 mm 2 . The surface area of the removed bone flap did not influence survival (surviving 7643 mm 2 vs. deceased 7372 mm 2 ). The only factor associated with survival was reduced postoperative MLS (P < 0.034). Risk of death was 14.4 (3.0-70.1)-fold greater in patients with postoperative shift ≥5 mm (P < 0.001)., Conclusion: The ideal surface area for "large" square bone flaps should result in an MLS of <5 mm. Enlargement of the craniectomy edges should be considered for patients in whom MLS ≥5 mm persists according to early postoperative computed tomography scans., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of the present study was to determine the characteristics associated with functional impairment in chronic hemodialysis, and to evaluate if functional impairment represents a risk factor for reduced survival in chronic hemodialysis., Methods: All 132 chronic hemodialysis referring to the Hemodialysis Service of the Catholic University, Rome, Italy between November 2007 and May 2015 were included. All patients underwent comprehensive geriatric assessment; functional ability was estimated using two questionnaires exploring independency in bathing, dressing, toileting, transferring, continence, feeding (ADLs), and independency in using the telephone, shopping, food preparation, housekeeping, laundering, traveling, taking medications, and handling finances (IADLs). Functional impairment was diagnosed in presence of dependence in one or more ADLs/IADLs. Mood was assessed using the 30-item Geriatric Depression Scale. Logistic regression was used to evaluate factors associated with functional impairment. The association between functional impairment and survival was assessed by Cox regression., Results: ADLs impairment was present in 34 (26 %) participants, while IADLs impairment was detected in 64 (48 %) subjects. After a follow up of 90 months, 55 (42 %) patients died. In logistic regression, depressive symptoms were associated with ADLs and IADLs impairment (OR 1.12; 95 % CI = 1.02-1.23; OR 1.16; 95 % CI = 1.02-1.33; respectively). In Cox regression, ADLs impairment was associated with mortality (HR 2.47; 95 % CI-1.07-5.67) while IADLs impairment was not associated with reduced survival (HR .80; 95 % CI-.36-1.76)., Conclusions: Functional impairment is associated with depressive symptoms; also, impairment in the ADLs represents a risk factor of reduced survival in chronic hemodialysis. These associations and their potential implication should be assessed in dedicated studies.

Background Context: Back pain at a young age is considered to be predictive of chronicity. Several studies have investigated the relationship between the use of a schoolbag and back pain, although some aspects are still unclear., Purpose: The aim of this study was to evaluate back pain due to schoolbag use in terms of (1) prevalence and intensity, (2) differences between male and female pupils, and (3) predisposing factors., Study Design: This is a cross-sectional study., Patient Sample: The sample was composed of 5,318 healthy pupils aged 6 to 19 years (classified according to three age groups: children, younger adolescents, and older adolescents)., Outcome Measures: Schoolbag-related pain was assessed by means of an ad hoc questionnaire. The intensity of pain was assessed using the Wong scale., Methods: Subjects underwent a face-to-face interview using an ad hoc questionnaire. The intensity of pain was assessed using the Wong scale. On the basis of the prevalence and intensity of back pain, we divided our population into two groups: (1) no or mild pain group and (2) moderate or severe pain group. The "schoolbag load" (ratio between schoolbag and pupil weight multiplied by 100) was calculated for each subject., Results: More than 60% of the subjects reported pain. Although the schoolbag load decreased from children to young and older adolescents, schoolbag-related pain significantly increased (p<.001). Girls reported significantly more frequent and more severe pain than boys. The logistic model confirmed that adolescent girls are the group at greatest risk of suffering from intense pain. The schoolbag load had a weak impact on back pain, whereas the schoolbag carrying time was a strong predictor., Conclusions: Adolescent girls have the highest risk of experiencing severe back pain, regardless of schoolbag load. This suggests that other factors (anatomical, physiological, or environmental) might play an important role in pain perception. These aspects should be investigated to plan appropriate preventive and rehabilitative strategies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The usefulness, the methods and the criteria of intra-operative monitoring of the parathyroid hormone (ioPTH) during parathyroidectomy (PTX) for renal secondary hyperparathyroidism (rSHPT) in patients on chronic hemodialysis remain still matter of debate. The present study aimed to evaluate the ability of a low cost central-laboratory second generation PTH assay to predict an incomplete resection of parathyroid glands (PTG)., Methods: The ioPTH decay was determined In 42 consecutive patients undergoing PTX (15 subtotal and 27 total without auto-transplant of PTG) for rSHPT. The ioPTH monitoring included five samples: pre-intubation, post-manipulation of PTG and at 10, 20 and 30min post-PTG excision. The patients with PTH exceeding the normal value (65pg/ml) at the first postoperative week, 6 and 12months were classified as persistent rSHPT., Results: The concentrations of ioPTH declined significantly over time in patients who received total or subtotal PTX; however, no difference was found between the two types of PTX. Irrespective of the type of PTX and the number of PTG removed, combining the absolute and percentage of ioPTH decay at 30min after PTG excision, we found high sensitivity (100%), specificity (92%), negative predictive value (100%) and accuracy (93%) in predicting the persistence of rSHPT., Conclusions: The monitoring of the ioPTH decline by a low cost central-laboratory second generation assay is extremely accurate in predicting the persistence of disease in patients on maintenance hemodialysis undergoing surgery for rSHPT., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Laser ablation may be useful in debulking of benign thyroid nodules., Methods: In order to retrospectively evaluate the effectiveness and safety of laser ablation, 45 patients with benign solid thyroid nodules, with a fluid component ≤20%, were included in our series between October 2009 and January 2011. All reported pressure and/or cosmetic complaints. Nd:YAG laser at 1064 nm was used, with a fix-power (3W), changing the application time. All patients were evaluated at baseline, 6 months, and 12 months and any complications were recorded., Results: Mean nodule volume reduction decreased from 24.2 mL ± 19.4 to 4.5 ± 5.2 at 12 months (p < .001). Mean nodule volume reduction was 84% ± 13. Cosmetic signs were completely resolved in 87%, reduced in 9%, unchanged in 2%, and pressure symptoms were resolved in 88%. One patient experienced transient dysphonia., Conclusion: Ultrasound-guided laser ablation is an effective tool for treatment of symptomatic benign thyroid nodules in patients not eligible for surgery., (© 2014 Wiley Periodicals, Inc.)

Objectives: To compare the CACS and CAD severity assessed by MDCT in neuropathic type-2 diabetic patients with and without Charcot-neuroarthropathy (CN)., Methods: Thirty-four CN asymptomatic-patients and 36 asymptomatic-patients with diabetic-neuropathy (DN) without CN underwent MDCT to assess CACS and severity of CAD. Patients were classified as positive for significant CAD in presence of at least one stenosis >50 % on MDCT-coronary-angiography (MDCT-CA). Groups were matched for age, sex and traditional CAD risk-factors. The coronary-angiography (CA) was performed in all patients with at least a significant stenosis detected by MDCT-CA, both as reference and eventually as treatment., Results: CN patients showed higher rates of significant CAD in comparison with DN subjects [p < 0.001], while non-significant differences were observed in CACS (p = 0.980). No significant differences were also observed in CACS distribution in all subjects for stenosis ≥/<50 % (p = 0.814), as well as in both groups (p = 0.661 and 0.559, respectively). The MDCT-CA showed an overall diagnostic-accuracy for significant CAD of 87%., Conclusions: These preliminary data suggest that CN-patients have a higher prevalence of severe CAD in comparison with DN-patients, while coronary plaques do not exhibit an increased amount of calcium. MDCT may be helpful to assess the CV risk in such asymptomatic type-2-diabetic patients with autonomic-neuropathy., Key Points: Type 2-diabetic-patients with CN result having more severe coronary artery plaque-burden. MDCT-CA may stratify the CV risk in type 2-diabetic-patients with CN. Adequate diagnostic is mandatory for optimal management of type 2-diabetic-patients with CN.

Unlabelled: Human chitotriosidase (Chit) increases during the osteoclast differentiation and their activity. We demonstrated that serum Chit was significantly higher in osteoporotic subjects than in healthy control ones and revealed a negative correlation between Chit and bone mineral density (BMD). This is the first study showing a correlation between Chit and severe postmenopausal osteoporosis., Introduction: Mammalian chitinases exert important biological roles in the monocyte lineage and chronic inflammatory diseases. In particular, Chit seems to promote bone resorption in vitro. No in vivo studies have been performed to confirm this finding. We aim to evaluate Chit activity in postmenopausal women affected by severe osteoporosis., Methods: In this cross-sectional study, 91 postmenopausal women affected by osteoporosis and 61 with either osteopenia or normal BMD were screened. All subjects were assessed by dual-energy X-ray absorptiometry (DXA) and X-ray vertebral morphometry. Osteoporotic subjects were considered eligible if they were affected by at least one vertebral osteoporotic fracture (group A = 57 subjects). Osteopenic or healthy subjects were free from osteoporotic fractures (group B = 51 subjects). Enzymatic Chit and serum β-CrossLaps (CTX) were measured in the whole population., Results: Group A showed higher serum levels of beta-CTX compared to group B (0.40 ± 0.26 ng/mL vs 0.29 ± 0.2 ng/mL, p = 0.022). Chit was significantly higher in group A than in group B (1042 ± 613 nmol/mL/h vs 472 ± 313 nmol/mL/h, p < 0.001, respectively) even after adjustment for age (p < 0.001). Spearman correlation test revealed a negative correlation between Chit and BMD at each site (lumbar spine: r = -0.38, p = 0.001, femoral neck: r = -0.35, p = 0.001, total femur: r = -0.39, p < 0.001). Furthermore, a positive correlation between Chit and PTH was observed (r = 0.26, p = 0.013). No significant correlation was found between Chit and beta-CTX (r = 0.12, p = 0.229). After a multivariate analysis, a positive correlation between severe osteoporosis and Chit (p < 0.001), beta-CTX (p = 0.013), and age (p < 0.001) was observed., Conclusion: This is the first clinical study showing a correlation between Chit and severe postmenopausal osteoporosis. Larger and prospective studies are needed to evaluate if Chit may be a promising clinical biomarker and/or therapeutic monitor in subjects with osteoporosis.

Background: This study aims to evaluate, in patients on chronic hemodialysis (PHD), the levels of endotoxin through a chemiluminescent bioassay based on the oxidative burst reaction of activated neutrophils to complement coated LPS-IgM immune complexes and define the variables possibly correlated., Methods: In 61 PHD, we measured serum endotoxin activity (EA) with the Endotoxin Activity Assay (EAA™) and we defined the possible association with demographic, clinical and laboratory variables., Results: Mean serum EA was 0.43 ± 0.26 UI. EA was low (<0.40) in 29 patients (47.5%), intermediate (0.40-0.60) in 14 (23%) and high (>0.60) in 18 (29.5%). A significant exponential relationship was detected between EA and serum interleukin-6 (IL-6) levels (r = 0.871). At the multiple regression analysis, intermediate-high EA was directly associated only with serum IL-6 levels. In a second model of multiple regression analysis without the variable serum IL-6 levels, intermediate-high EA was directly associated with constipation and serum troponin levels and inversely associated with serum albumin and the monthly number of sevelamer tablets., Conclusions: A high percentage of PHD has intermediate or high EA. Intermediate-high EA is significantly associated with serum IL-6 levels., (© 2016 S. Karger AG, Basel.)

Aim: Data on the outcome of chronic kidney disease (CKD) patients who are hospitalized and start unplanned urgent haemodialysis (HD) are lacking. This prospective, longitudinal, observational study aimed to define the hospital mortality rate and associated factors in CKD patients who start unplanned urgent HD., Methods: Between January 2003 and December 2009, all patients with CKD who were hospitalized, diagnosed with ESRD and started unplanned urgent haemodialysis at Haemodialysis Service of the Catholic University of Rome, Italy were recruited. Exclusion criteria were: acute renal failure, prior history of dialysis, multiple organ failure, coma, and dementia. Hospital mortality rate was the primary outcome., Results: Three and hundred sixteen patients were studied: 99 died after 19.5 ± 27.3 days and 217 survived until discharge. Of these, 154 were prescribed chronic HD and 63 restored renal function. Patients who died were significantly older and had a higher Charlson Comorbidity Index score. The mortality rates were 51.1% in patients with 81-90 years, 37.8% with 71-80 years, 34.1% with 61-70 years and 13.9% with age ≤60 years. Logistic regression analysis showed that age only was an independent risk factor for all-cause mortality., Conclusions: In CKD patients who need hospitalization and start unplanned urgent haemodialysis the mortality is very high and significantly related to age., (© 2015 Asian Pacific Society of Nephrology.)

Objectives: A systematic review was conducted to assess the effectiveness of MRI in evaluating upper airway structures in children affected by obstructive sleep apnoea syndrome (OSAS)., Methods: A literature search was performed in the Cochrane Central Register of Controlled Trials, Web of Science, Scopus and PubMed databases from their inception to 31/03/2016, including available randomized controlled trials and controlled clinical trials published in English assessing the use of MRI integrated with traditional polysomnography (PSG) among children up to 15 years of age affected by OSAS. The primary outcome to be evaluated was the efficacy of MRI in analyzing the upper airway total volume among healthy children compared with children affected by OSAS. Secondary outcomes were to compare the efficacy of MRI in analyzing the upper airway cross-sectional area in the areas adjacent to the adenoids and tonsils, adenoid and tonsil volume, and soft-tissue and maxillofacial bone parameters in the same sample. Results were expressed using a random-effects model and mean differences (MD) with 95% confidence intervals (CI)., Results: The search yielded 1005 titles in total; the selection process narrowed to 3 titles, which were all assessed as indicating an unclear level of risk of bias. The meta-analysis found evidence of MRI effectiveness in evaluating differences in the upper airway total volume between paediatric patients affected by OSAS and paediatric patients not affected by OSAS (MD -0.56 cm(3); 95% CI: -1.05 to -0.07)., Conclusions: Although MRI could be considered effective in evaluating upper airway structures in children affected by OSAS, based on the present evidence, PSG is still the golden standard and further studies are required to verify MRI reliability.

Introduction and Objectives: In recent years, Botulinum Toxin has been shown to be efficacious and safe in the treatment of sialorrhea, but scanty data are available on its long term use. The aim of this study was to investigate adverse events, discriminate differences in safety, and evaluate the efficacy of long-term use of both abobotulinumtoxinA and rimabotulinumtoxinB ultrasound-guided injections for sialorrhea in a retrospective trial. Moreover we review the literature on this topic., Patients and Methods: Consecutive patients with severe sialorrhea and receiving at least two ultrasound-guided intrasalivary glands abobotulinumtoxinA 250 U or rimabotulinumtoxinB 2500 U injections were included. Clinical and demographic data were collected. Safety and tolerability were assessed on the basis of patients' self-reports. Efficacy was assessed by recording the duration of benefit and by the Drooling Severity Scale and Drooling Frequency Scale 4 weeks after intervention. A review of literature was performed using 'Botulinum Toxin' and/or 'drooling' and/or 'sialorrhea' and/or 'hypersalivation' as keywords., Results: Sixty-five patients (32 Amyotrophic Lateral Sclerosis and 33 Parkinson's Disease) were treated in a total of 317 sessions (181 rimabotulinumtoxinB and 136 abobotulinumtoxinA). Both serotypes induced a clear-cut benefit in 89% of injections. Mean benefit duration was 87 days (range 30-240), similar for abobotulinumtoxinA and rimabotulinumtoxinB but significantly shorter in Amyotrophic Lateral Sclerosis group compared to Parkinson's Disease (p < 0.001). Older age was positively correlated to benefit duration (p = 0.003). Botulinum Toxin-related and injection-related side effects complicated respectively 8,2% and 1,5% of treatments. The only Botulinum Toxin-related adverse event was a change of saliva thickness, mostly rated mild to moderate and more frequent in Amyotrophic Lateral Sclerosis patients (p = NS)., Conclusions: Both 250 U abobotulinumtoxinA and 2500 U rimabotulinumtoxinB administered by ultrasound-guided intrasalivary gland injection are safe and effective in treating sialorrhea, even in long-term follow-up. Older age is significantly associated with longer benefit duration. Parkinson's Disease patients showed a more favorable safety-efficacy ratio than did Amyotrophic Lateral Sclerosis patients, due to lower adverse events (p = NS) and longer benefit duration (p < 0.001)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity., Patients: Clinical records of 1534 consecutive laser-treated nodules in 1531 patients from eight Italian thyroid referral centers were assessed. Inclusion criteria were as follows: solid or mixed nodules with fluid component up to 40%; benign cytological findings; and normal thyroid function., Methods: LAT was performed with a fixed-power protocol, whereas the number of applicators and illumination times were different according to target size. From one to three illuminations with pullback technique and with a total energy delivery based on the nodule volume were performed during the same session. Patients were evaluated during LAT, within 30 days, and 12 months after the procedure., Results: Total number of treatments was 1837; 1280 (83%) of nodules had a single LAT session. Mean nodule volume decreased from 27 ± 24 mL at baseline to 8 ± 8 mL 12 months after treatment (P < .001). Mean nodule volume reduction was 72% ± 11% (range 48%-96%). This figure was significantly greater in mixed nodules (79% ± 7%; range 70%-92%) because they were drained immediately before laser illumination. Symptoms improved from 49% to 10% of cases (P < .001) and evidence of cosmetic signs from 86% to 8% of cases (P < .001). Seventeen complications (0.9%) were registered. Eight patients (0.5%) experienced transitory voice changes that completely resolved at the ear-nose-throat examination within 2-84 days. Nine minor complications (0.5%) were reported. No changes in thyroid function or autoimmunity were observed., Conclusions: Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low.

Background: Melanoma is highly curable in early stages but holds devastating consequences in advanced phases with a median survival of 6-10 months. Lungs are a common metastasis target, but despite this, limited data are available on the molecular status of pulmonary lesions., Materials and Methods: 25 patients with surgically resected melanoma lung metastases were screened for BRAF, NRAS, CKIT and EGFR alterations. The results were correlated with time to lung metastasis (TLM), relapse-free survival after metastasectomy (RFS) and overall survival (OS)., Results: BRAF or NRAS were mutated in 52% and 20% of cases while CKIT was unaffected. Chromosome 7 polysomy was detected in 47% of cases with 17.5% showing EGFR amplification and concomitant BRAF mutation. NRAS mutated patients developed LM within 5 yrs from primary melanoma with larger lesions compared with BRAF (mean diameter 3.3 ± 2.2cm vs 1.9 ± 1.1cm, p = 0.2). NRAS was also associated with a shorter median RFS and OS after metastasectomy. Moreover, Cox regression analysis revealed that NRAS mutation was the only predictive factor of shorter survival from primary melanoma (p = 0.039, OR = 5.5 (1.1-27.6))., Conclusions: Molecular characterization identifies advanced melanoma subgroups with distinct prognosis and therapeutic options. The presence of NRAS mutation was associated to a worse disease evolution.

A better knowledge of the fatigue could be of the greatest importance for the high-grade glioma (HGG) patients, who are a unique and vulnerable population. The aim of this study was to evaluate the occurrence and the predictors of the fatigue in HGG patients, using a specific fatigue scale. The study was designed as a cross-sectional study. The study population included sixty-seven consecutive outpatients with HGG. We used these measures: Brief Fatigue Inventory, Karnofsky Performance Scale, Functional Independence Measure, Brief Psychiatric Rating Scale and Psychological Distress Inventory and SF-36, EORTC QLQ-30 and EORTC QLQ-BN20 for quality of life (QoL). Sixteen out of sixty-seven (23.9 %) patients were affected by Anaplastic Astrocytoma and 51/67 (76.1 %) by Glioblastoma Multiforme. About one-third (36.2 %) of patients had a clinically relevant fatigue (Brief Fatigue Inventory ≥3). In regression analysis, physical and mental aspects of QoL were statistically significant related with fatigue (p < 0.01 and p < 0.02, respectively). Our data underlined the relevant occurrence of fatigue in HGG patients and support the development of further studies exploring a tailored rehabilitation program.

Background Aims: Subcutaneous fat represents a valuable reservoir of adipose-derived stem cells (ASCs) in the stromal vascular fraction (SVF), widely exploited in regenerative medicine applications, being easily harvested through lipoaspiration. The lack of standardized procedures for autologous fat grafting guided research efforts aimed at identifying possible differences related to the harvesting site, which may affect cell isolation yield, cell growth properties and clinical outcomes. Subcutaneous fat features a complex architecture: the superficial fascia separates superficial adipose tissue (SAT) from deep layer tissue (DAT). We aimed to unravel the differences between SAT and DAT, considering morphological structure, SVF composition, and ASC properties., Methods: SAT and DAT were collected from female donors and comparatively analyzed to evaluate cellular yield and viability, morphology, immunophenotype and molecular profile. ASCs were isolated in primary culture and used for in vitro differentiation assays. SAT and DAT from cadaver donors were also analyzed through histology and immunohistochemistry to assess morphology and cell localization within the hypoderm., Results: Liposuctioned SAT contained a higher stromal tissue compound, along with a higher proportion of CD105-positive cells, compared with DAT from the same harvesting site. Also, cells isolated from SAT displayed increased multipotency and stemness features. All differences were mainly evidenced in specimens harvested from the abdominal region. According to our results, SAT features overall increased stem properties., Conclusions: Given that subcutaneous adipose tissue is currently exploited as the gold standard source for high-yield isolation of adult stem cells, these results may provide precious hints toward the definition of standardized protocols for microharvesting., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Unlabelled: No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium., Introduction: Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint., Methods: The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months., Results: After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group (p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months (p < 0.001), respectively. No cases of hypercalcemia or hypercalciuria were detected during the study., Conclusion: The results of this study indicate that alendronate/cholecalciferol increases BMD in postmenopausal women with NPHPT. Alendronate/cholecalciferol or vitamin D alone does not affect serum or urinary calcium.

Context: Little is known about activated immune-inflammatory pathways and interleukin-6 (IL-6) in the development of fatigue and/or depression in patients with end-stage renal disease on chronic hemodialysis (HD)., Objectives: To evaluate the possible correlation between fatigue and serum levels of IL-6 in patients on chronic HD., Methods: One hundred HD patients were assessed for the presence of fatigue using the SF-36 Vitality subscale and were administered the Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), the Mini-Mental State Examination (MMSE), the activities of daily living (ADL), and the instrumental activities of daily living (IADL). We also calculated the time of recovery after hemodialysis (TIRD) and the number/severity of comorbidities using the Charlson Comorbidity Index (CCI). Laboratory parameters were measured as well as serum IL-6., Results: Forty-three patients constituted the fatigued group and 57 the nonfatigued group. Age, CCI, BDI, HARS, and TIRD were significantly higher in fatigued patients than in the nonfatigued patients. Conversely, the scores of ADL, IADL, and MMSE were significantly lower in fatigued than in nonfatigued patients. Serum IL-6 levels (pg/mL) were higher in the fatigued group (5.1 ± 3.4) than in the nonfatigued group (1.6 ± 1.5; P < 0.001); serum albumin and creatinine levels were significantly lower. Twenty-six patients (26%) had no symptoms of depression (BDI score <10), and 74 patients (74%) had symptoms of depression (BDI score >9). Patients with a BDI score >9 were older; had a higher CCI; a lower MMSE; a higher TIRD; lower serum albumin, creatinine, and urea levels; and higher serum IL-6 levels. The correlation analyses showed that the score of the SF-36 Vitality subscale was associated with age, dialytic age, TIRD, ADL, IADL, CCI, BDI, HARS, MMSE, serum urea, creatinine, albumin, and IL-6 levels. On multivariate general linear model analyses, with fatigue as the dependent variable and gender as a second factor, BDI and serum IL-6 levels were independently associated with the score of the SF-36 Vitality subscale. A canonical correlation analysis was performed including in the model fatigue, BDI, and biomarkers; the correlation was 0.679 (R(2) = 0.462). Fatigue, BDI, and IL-6 among biomarkers showed the strongest association with the underlying construct (standardized canonical coefficients = -0.989, 0.015, and 0.852, respectively), thus explaining a correlation of IL-6 with both depression and fatigue., Conclusion: Fatigue was significantly associated with symptoms of depression and serum IL-6 levels in patients receiving chronic HD., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: A new rapid, automatic, and sensitive screening test useful to detect cryoglobulins in serum samples is proposed., Design and Methods: The increase of turbidity during the cryoglobulin aggregation was monitored spectrophotometrically in sera from 400 patients with clinical evidence of cryoglobulinemia related disorders and 100 controls. Results were correlated to those obtained by the traditional method., Results: Kinetics of the aggregation curves were described by their maximum turbidity increase, lag time, and slope. Despite a partial correspondence between the traditional and the rapid test, patients with symptomatic cryoglobulinemia showed turbidity values significantly higher than the determined cutoff. Moreover, a functional classification of cryoglobulins is proposed., Conclusions: Due to its high reproducibility, operator independence, low cost, and results obtained within 2 hours, the rapid test can be used as a "real time" monitoring of cryoglobulinemia related diseases and for the evaluation of plasmapheresis efficacy.

Background: Little is known about the correlation between fatigue and survival in patients on chronic hemodialysis and whether fatigue is an independent predictor of outcome above and beyond the effects of depression. The aim of the present study was to determine if fatigue is a predictor of mortality in patients on chronic hemodialysis (CHP) and if this occurs independently of the symptoms of depression., Methods: CHP referring to the Hemodialysis Service of the Università Cattolica of Rome, Italy between November 2007 and January 2015 were studied. Demographic, clinical, and laboratory data were recorded for each patient at the moment of the inclusion in the study. Fatigue levels were assessed in patients using the Vitality Scale of SF-36 (SF-36 VS), functional ability by the activities of daily living (ADL) and instrumental activities of daily living (IADL), depressive symptoms through the Geriatric Depression Scale (GDS), cognitive function using the Mini Mental State Examination (MMSE), and comorbidity through the Charlson Comorbidity Index (CCI). Patients were grouped into four groups (quartiles): Quartile 1 (Q1), >65; Q2, ≥50 to <65; Q3, ≥35 to <50; Q4, <35., Results: We studied 126 patients: 11 were transplanted and 53 died. Patients who later died were older and had a worse cognitive performance, higher CCI and GDS scores, lower ADL, IADL and SF-36 VS scores, lower serum creatinine and albumin levels. Kaplan-Meier survival was significantly lower in Q4 than in Q1 (p = 0.0001). According to Cox regression analysis, higher fatigue (Q4) was associated with a higher risk of mortality (HR, 95% CI: 5.29, 2.2-12.73)., Conclusion: Fatigue is associated with an increased risk of mortality in CHP, with the relationship independent of symptoms of depression. Fatigue should be assessed routinely and may be a potential target of interventions that aim to reduce mortality in CHP., (© 2015 S. Karger AG, Basel.)

Background: The aim of the present trial on ultrasound (US)-guided laser ablation therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy, side effects, and predictability of outcomes in different centers operating with the same procedure., Patients: Two hundred consecutive patients were randomly assigned to a single LAT session (group 1, 101 cases) or to follow-up (group 2, 99 cases) at four thyroid referral centers. Entry criteria were: solid thyroid nodule with volume of 6-17 mL, repeat benign cytological findings, normal thyroid function, no autoimmunity, and no thyroid gland treatment., Methods: Group 1: LAT was performed in a single session with two optical fibers, a 1064 nm Nd-YAG laser source, and an output power of 3 W. Volume and local symptom changes were evaluated 1, 6, 12, 24, and 36 months after LAT. Side effects and tolerability of treatment were registered. Group 2: Follow-up with no treatment., Results: One patient was lost to follow-up in each group. Group 1: Volume decrease after LAT was -49 ± 22%, -59 ± 22%, -60 ± 24%, and -57 ± 25% at 6, 12, 24, and 36 months, respectively (P < .001 vs baseline). LAT resulted in a nodule reduction of >50% in 67.3% of cases (P < .001). Local symptoms decreased from 38 to 8% of cases (P = .002) and cosmetic signs from 72 to 16% of cases (P = .001). Baseline size, presence of goiter (P = .55), or US findings (fluid component ≤ 20% [P = .84], halo [P = .46], vascularization [P = .98], and calcifications [P = .06]) were not predictive factors of a volume decrease > 50%. The procedure was well tolerated in most (92%) cases. No changes in thyroid function or autoimmunity were observed. In group 2, nodule volume increased at 36 months (25 ± 42%; P = .04). The efficacy and tolerability of the procedure were similar in different centers., Conclusions: A single LAT treatment of solid nodules results in significant and persistent volume reduction and local symptom improvement, in the absence of thyroid function changes.

Background: With patients referred to emergency departments (EDs) for acute dyspnea, emergency physicians should consider all possible diagnoses and assess patients' risk stratification. Copeptin has been shown to have prognostic power for subsequent events, such as death and rehospitalization in patients admitted for dyspnea. The aim of this study was to investigate prognostic role of copeptin variations during hospitalization in patients admitted for dyspnea., Methods: We conducted a prospective, multicentric, observational study in acute dyspneic patients in three ED centers in Italy. Clinical data and copeptin assessments were performed at admission, and at discharge. A 90-day follow-up was performed., Results: A total of 336 patients were enrolled, and on the basis of final diagnosis distinguished into two groups: acute heart failure and no acute heart failure. Compared to a control group, in all studied population copeptin values at admission resulted in a significantly (p<0.001) higher median (maximum-minimum): 31 (0-905) versus 8 (0-13) pmol/L. Median copeptin value at admission was 42 (0-905) pmol/L in acute heart failure patients and 20 (0-887) pmol/L in no acute heart failure, respectively (p<0.001). In all studied patients and in each group copeptin at admission and discharge showed significant predictive value for 90-day events (p<0.001). Furthermore, in all patients population and in both groups Δ copeptin values from admission to discharge also showed significant predictive value for 90-day events (p<0.001)., Conclusions: In patients admitted for acute dyspnea, admission, discharge and Δ copeptin variations have significant prognostic value from subsequent 90-day death and rehospitalization.

The aim of this study was to investigate the severity of coronary artery disease (CAD) and the plaque composition in neuropathic type 2 diabetic subjects with and without Charcot neuroarthropathy (CN) undergoing multidetector computed tomography coronary angiography (MDCT-CA). The study was a single-center, observational, with unmatched case-control design. We selected 17 CN patients and 18 patients with diabetic neuropathy (DN) without CN. In all the patients, multidetector computed tomography was performed to assess the coronary artery calcium score (CACS) and degree of coronary artery stenosis. Patients were classified as positive in the presence of significant CAD if there was at least one stenosis >50 % on MDCT-CA. The invasive coronary angiography was performed in case of significant stenosis detected with MDCT-CA, both as reference to standard and eventually as treatment. Groups were matched for age, sex, and traditional CAD risk factors. As compared to DN individuals, CN exhibited higher rates of significant coronary stenoses (p = 0.027; OR 7.7 [1.3-43.5]). However, no significant differences were observed in the CACS, which reflects plaque burden, in the two groups (p = 0.759). No significant differences were observed comparing CACS distribution in all subjects for stenosis higher/equal or lower than 50 % (p = 0.320). Finally, no significant differences were observed comparing CACS distribution in CN and DN subjects for coronary stenoses higher/equal or lower than 50 %. Our results suggest that CN patients have a higher prevalence of severe coronary plaques compared to DN patients. Nevertheless, coronary plaques in CN patients did not exhibit an increased degree of calcification.

Objectives: Cardiovascular changes during laparoscopic surgery have been described in several studies. Pneumoperitoneum effects on cardiac performance instead have not been much investigated and are less known. The carbon dioxide insufflation necessary in order to perform laparoscopic procedures represents a higher force against which the myocardial fibers must shorten during ventricular contraction. Hypothesis of this study is that the intra-abdominal pressure at 12 mmHg could acutely affect the left ventricular wall stress and work. Aim of the study was to evaluate the impact of relationship pneumoperitoneum on the echocardiographic measures of left ventricular contractile function., Patients and Methods: We studied 20 healthy, ASA I women, undergoing laparoscopic hysterectomy. Transthoracic echocardiography was performed preoperatively, after induction of anaesthesia, 15' after pneumoperitoneum, 15' after Trendelenburg positioning and 15' after the end of surgery. Left ventricular end-systolic wall stress, stroke work, left ventricular ejection time and mean velocity of fiber shortening were registered., Results: Carbon dioxide insufflation caused a consistent increase in left ventricular end-systolic wall stress and left ventricular ejection time, while the mean velocity of fiber shortening decreased. The Trendelenburg position did not produce any other signficant effects. These changes were transient with a return to preinsufflation values at the last measurement. Pneumoperitoneum adversely affects left ventricular performance during laparoscopy, leading to an increase of left ventricular end-systolic wall stress and reducing the mean velocity of circumferential fiber shortening. These cardiac consequences appear to be reversible since all the echocardiographic parameters normalized at the end of surgery., Conclusions: Our results suggest that there is an adaptation of the cardiac systolic contractile status to the pressure overload during laparoscopy.

Background: Few data are available on diagnostic and prognostic role of quantitative fluid retention evaluated by bioelectrical impedance vector analysis (BIVA) in acute heart failure (AHF) patients at the moment of emergency department presentation., Methods and Results: Point vectors and hydration index (HI) by BIVA were obtained in 381 patients referring to an emergency department. For evaluating cardiovascular events, a 30-day follow-up was performed. Patients were divided into AHF (n=270; 70.8%) and no-AHF groups, (n=111; 29.2%). Compared with the no-AHF cohort, the HI value resulted significantly higher in the AHF group (81.2% ± 6.7 vs. 72.9 ± 3.6%, p<0.001). HI showed a significant diagnostic power for AHF (cut-off 73.4%, area under curve (AUC) 0.87, sensitivity 90%, specificity 54%) and also showed a significant prognostic value both by univariate (odds ratio 1.03 (1-1.07), p =0.025) and multivariate analysis (odds ratio 1.96 (1.05-3.66) p= 0.034) for cardiac events at 30 days. Although in the overall population BIVA did not increase diagnostic accuracy provided by brain natriuretic peptide (BNP), for AHF patients in BNP 'grey values' (100-400 pg/ml) HI showed a significant additive improvement for diagnosis (net reclassification improvement (NRI) 77%) and prognosis (NRI 45%)., Conclusions: While in the overall population BIVA did not increase diagnostic accuracy provided by BNP, in AHF patients a quantitative evaluation of fluid congestion obtained by BIVA at the time of emergency department arrival provides significant additive diagnostic and 30-day prognostic value to BNP, particularly in the BNP 'grey-zone'. This could lead to a better management of these patients with possible improvement in reducing subsequent cardiovascular events.

Purpose: We aimed to estimate dietary intakes of trace elements, minerals, and vitamins in hemodialysis patients (HDP) of three centers in one metropolitan and two urban areas of Italy., Methods: Daily dietary intake was assessed using a 3-day diet diary in 128 HDP., Results: Mean daily intakes of trace elements were as follows: zinc, 7.6 ± 5.4 mg; copper, 14.3 ± 11.8 mg; selenium, 28.3 ± 18.1 μg; and iron, 7.2 ± 4.1 mg (7.8 ± 2.6 mg in women, 6.9 ± 2.4 mg in men). The distribution of patients by daily intakes of trace elements showed most were under the recommended values, with the exception of copper intake, which was much higher. Mean daily intakes of minerals were as follows: magnesium, 174.4 ± 94.3 mg; phosphorus, 842.6 ± 576.8 mg; calcium, 371.8 ± 363.7 mg; potassium, 1,616.2 ± 897.3 mg; and sodium, 1,350 ± 1,281 mg. Mean daily intakes of vitamins were as follows: vitamin A, 486.1 ± 544.6 μg; vitamin B1, 0.86 ± 0.7 mg; vitamin B2, 1.1 ± 0.7 mg; vitamin B3, 13.3 ± 8.1 mg; vitamin C, 47.8 ± 50.3 mg; and vitamin E, 9.5 ± 3.6 mg. The distribution of patients by daily intakes of vitamins showed most were under the recommended values. Daily intakes of trace elements and vitamins were similar among the three centers and did not differ between dialysis and non-dialysis days., Conclusions: Many HDP have daily dietary intakes of trace elements and vitamins below the recommended values, whereas the intake of copper is much higher.

Background: Previous studies have documented the negative influence of pneumoperitoneum on cardiac and renal function during laparoscopy. In this respect, regard there is a lack of data regarding the use of an appropriate management of fluid therapy to decrease these side effects. The aim of this study was to investigate the cardiac and renal responses to the administration of different amounts of crystalloid solution, alone or in association with dopamine during laparoscopy., Methods: Sixty ASA I patients undergoing laparoscopic surgery for endometriosis were randomly assigned to three groups. Group A was given saline solution at 5 mL/kg/h; group B received saline solution at 5 mL/kg/h and dopamine 3 mg/kg/min, and group C received saline solution at 10 mL/kg/h. Patients received A, B or C perioperatively. Renal function was evaluated by assessing total intraoperative diuresis and estimated glomerular filtration rate. Vasopressin plasmatic levels before and after surgery were measured. Transthoracic echocardiography was performed to estimate left ventricular filling pressure by using Tissue Doppler Imaging and registering the E/Ea ratio every hour after pneumoperitoneum., Results: Total intraoperative diuresis was impaired in group A and significantly increased in group C (P<0.001). In group A estimated glomerular filtration rate significantly decreased after the end of surgery (P<0.003) and vasopressin significantly increased (P<0.001). The E/Ea ratio was significantly increased in group C (P<0.001). The infusion of saline solutions with the addition of dopamine slightly affected this parameter., Conclusion: A low rate of saline infusion could lead to an impaired renal function during laparoscopic surgery. This could be prevented by increasing the amount of saline solutions infused per hour or by adding a dopamine infusion.

Introduction: We evaluated the gene expression levels of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha in skeletal muscle samples of patients with gastric cancer and controls., Methods: We studied 38 cancer patients and 12 controls who underwent surgery for gastric adenocarcinoma and benign abdominal diseases, respectively. A biopsy specimen was obtained from the rectus abdominis muscle from all participants. The relative gene expression of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha was determined by quantitative real-time polymerase chain reaction analysis., Results: Atrogin-1 and MuRF1 mRNA expression was similar between cancer patients and controls and was unaffected by the disease stage or the severity of body weight loss. Transcript levels of myostatin and follistatin did not differ between cases and controls and were similar across disease stages and categories of weight loss. Finally, no differences were detected in activin A and inhibin alpha gene expression between cancer patients and controls., Conclusions: In skeletal muscle, the gene expression of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha is not affected by the presence of cancer. The expression of atrophy-related genes is unaffected by the disease stage and the degree of weight loss., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Thromboxane (TX) A2 is a pro-thrombotic prostanoid synthesized by activated platelets, biotransformed into 11-dehydro-TXB2, measurable in urines. Eleven-dehydro-TXB2 excretion is increased in high risk cardiovascular diseases; however, this cardiovascular biomarker awaits validation in large trials. The need of large urine volume (8 - 10 mL) and the unknown stability of 11-dehydro-TXB2 in urine after collection might limit its implementation., Methods: We scaled the original method for urine extraction and 11-dehydro-TXB2 measurement down to 1 mL, and assessed its stability at 4 degrees C or 25 degrees C up to 6 days after collection. The sensitivity of the 1 mL procedure was also tested in aspirin-treated patients with low 11-dehydro-TXB2 excretion, Results: The 1 mL adapted method was highly correlated with the original assay (rho = 0.98, p < 0.001, n = 33). Both methods showed similar recoveries in samples spiked with exogenous 11-dehydro-TXB2. Urinary 11-dehydro-TXB2 values in samples immediately frozen were comparable and highly correlated to values in samples at 4 degrees C (day 6: rho = 0.99, p > 0.001, n = 8) or 25 degrees C (day 6: rho = 0.98, p < 0.001, n = 23) up to 6 days in controls and patients., Conclusions: Eleven-dehydro-TXB2 can be measured in small urine volumes and is relatively stable for a few days after collection, even at 25 degrees C. These data allow the validation of this non-invasive cardiovascular biomarker in large studies.

Introduction: Acute heart failure (AHF) is associated with a higher risk for the occurrence of rehospitalization and death. Galectin-3 (GAL3) is elevated in AHF patients and is an indicator in predicting short-term mortality. The total body water using bioimpedance vector analysis (BIVA) is able to identify mortality within AHF patients. The aim of this study was to evaluate the short- and long-term predictive value of GAL3, BIVA, and the combination of both in AHF patients in Emergency Department (ED)., Methods: 205 ED patients with AHF were evaluated by testing for B type natriuretic peptide (BNP) and GAL3. The primary endpoint was death and rehospitalization at 30, 60, 90, and 180 days and 12 and 18 months. AHF patients were evaluated at the moment of ED arrival with clinical judgment and GAL3 and BIVA measurement., Results: GAL3 level was significantly higher in patients >71 years old, and with eGFR < 30 cc/min. The area under the curve (AUC) of GAL3 + BIVA, GAL3 and BIVA for death and rehospitalization both when considered in total and when considered serially for the follow-up period showed that the combination has a better prognostic value. Kaplan-Meier survival curve for GAL3 values >17.8 ng/mL shows significant survival difference. At multivariate Cox regression analysis GAL3 is an independent variable to predict death + rehospitalization with a value of 32.24 ng/mL at 30 days (P < 0.005)., Conclusion: In patients admitted for AHF an early assessment of GAL3 and BIVA seems to be useful in identifying patients at high risk for death and rehospitalization at short and long term. Combining the biomarker and the device could be of great utility since they monitor the severity of two pathophysiological different mechanisms: heart fibrosis and fluid overload.

Background and Aims: The knowledge of the barriers that are associated with decreased physical activity (PA) in patients on chronic hemodialysis (PCH) may be of primary importance for the nephrologists. Thus, we aimed to assess the barriers associated with the absent or reduced PA in PCH of a Mediterranean country., Methods: Patients were invited to answer the question 'How often do you exercise during your leisure time?'. Also, patients included in the study were asked to answer questions regarding barriers to physical activity lower than desired., Results: We studied 105 patients. Forty (38.1%) patients reported to never exercise, 6 (5.7%) reported to exercise less than once/week, 4 (3.8%) once/week, 23 (21.9%) two to three times/week, 12 (11.4%) four to five times/week and 20 (19%) daily. Overall, 46 (43.8%) patients never exercised or exercised less than once/week ('inactive') and 59 (56.2%) did exercise more often ('active'). At the multivariate analysis, reduced walking ability, fatigue on the non-dialysis days, and shortness of breath were independently and negatively associated with PA. The same results were found when the reduced model of the multivariate logistic backward regression was built introducing in the model also clinical and laboratory variables., Conclusion: In PCH, fatigue on the non-dialysis days, reduced walking ability, and shortness of breath are barriers independently associated to decreased PA. Knowledge about the causes and mechanisms that generate these barriers has to be acquired., (© 2014 S. Karger AG, Basel.)

Objective: The objective of this study was to assess variables associated with xerostomia in patients on chronic hemodialysis (HD)., Design and Methods: This was a cross-sectional study of 75 HD patients at an outpatient HD service. Demographic, clinical (renal disease, HD regimen/duration, Charlson comorbidity index, activities of daily living, instrumental activities of daily living [IADL], body mass index), and laboratory (hemoglobin, albumin, interleukin-6 [IL-6], and parathyroid hormone) parameters were recorded. We assessed the appetite through the Hemodialysis Study Appetite questionnaire and xerostomia through the Xerostomia Inventory (XI). A single question ("How often does your mouth feel dry?"; never = Class 1, almost never = Class 2, occasionally = Class 3, often = Class 4, very often = Class 5) was also included in the study questionnaire., Main Outcome Measure: The main outcome measure was factors correlated with XI., Results: The median XI score was 18 (min-max = 11-33). Forty patients had an XI score of 18 or less (Group 1) and between 18 and 35 (Group 2). In Group 2, age, Charlson comorbidity index score, and number of patients with poor/very poor appetite were significantly higher. At the univariate analysis, the score of the XI was significantly associated with age, appetite, IADL, Charlson comorbidity index, and serum IL-6 levels. Multiple linear regression analysis showed that the XI was independently associated with age and appetite. Thirty-one patients were in Class 1 to 2, 23 were in Class 3, and 21 were in Class 4 to 5. In Classes 4 to 5, age and the number of patients with poor/very poor appetite were higher (P = .012 and .09, respectively)., Conclusion: Xerostomia is associated with old age and poor appetite in patients on chronic HD., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Sorafenib has become the standard first-line treatment for patients with advanced HCC and acts by inducing alterations in tumor vascularity. We wanted to evaluate the feasibility of dynamic CEUS (D-CEUS) as a predictor of early tumor response to sorafenib and to correlate functional parameters with clinical efficacy end points., Methods: Twenty-eight HCC patients treated with sorafenib 400mg bid were prospectively enrolled. CEUS was performed at baseline (T0) and after 15 (T1) and 30 (T2) days of treatment. Tumor vasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software (Q-Lab, Philips). Variations between T1/T2 and T0 were calculated for five D-CEUS functional parameters (peak intensity, PI; time to PI, TP; area under the curve, AUC; slope of wash in, Pw; mean transit time, MTT) and were compared for responders and non-responders. The correlation between D-CEUS parameters, overall survival (OS), and progression-free survival (PFS) was also assessed. A p value <0.05 was considered statistically significant., Results: The percentage variation at T1 significantly correlated with response in three D-CEUS parameters (AUC, PI and Pw; p=0.002, <0.001, and 0.003, respectively). A decrease of AUC (p=0.045) and an increased/unchanged value of TP (p=0.029) and MTT (p=0.010) were associated with longer survival. Three D-CEUS parameters (AUC, TP, Pw) were significantly associated with PFS., Conclusions: D-CEUS provides a reliable and early measure of efficacy for anti-angiogenic therapies and could be an excellent tool for selecting patients who will benefit from treatment., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Erythropoiesis is affected during deep saturation dives. The mechanism should be related to a downregulation of serum Erythropoietin (s-EPO) concentration or to a toxic effect of the hyperbaric hyperoxia. We evaluated s-EPO and other haematological parameters in 6 scuba divers before, during and after a 14-days guinness saturation dive (8-10 m). Athletes were breathing air at 1.8-2 ATA, under the control of a team of physicians. Serum parameters were measured before diving (T0) and: 7 days (T1), 14 days (T2) after the beginning of the dive and 2 h (T3) and 24 h (T4) after resurfacing. Hgb, and many other haematological parameters did not change whereas Ht, s-EPO, the ratio between s-EPO predicted and that observed and reticulocytes (absolute, percent) declined progressively from T0 to T3. At T4 a significant rise in s-EPO was observed. Hgb did not vary but erythropoiesis seemed to be affected as s-EPO and reticulocyte counts showed. All these changes were statistically significant. The experiment, conducted in realistic conditions of dive length, oxygen concentration and pressure, allows us to formulate some hypotheses about the role of prolonged hyperbarism on erythropoiesis. The s-EPO rise, 24 h after resurfacing, is clearly documented and related to the "Normobaric Oxygen Paradox". This evidence suggests interesting hypotheses for new clinical applications such as modulation of s-EPO production and Hgb content triggered by appropriate O₂ administration in pre-surgical patients or in some anemic disease., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Shear stress triggers conformational stretching of von Willebrand factor (VWF), which is responsible for its self-association and binding to the platelet receptor glycoprotein (GP)Ibα. This phenomenon supports primary hemostasis under flow. Type 2B VWF natural mutants are considered to have increased affinity for platelet GPIbα., Objectives: To assess the mechanism responsible for the enhanced interaction of the p.R1306W VWF mutant with the platelet receptor., Methods: The interaction of GPIbα with wild-type (WT) and p.R1306W VWF multimers and A1-A2-A3 constructs was investigated with surface plasmon resonance spectroscopy. Analysis of the static VWF conformation in solution was performed with dynamic light scattering spectroscopy. The shear stress-induced self-association of VWF multimers was investigated with atomic force microscopy (AFM) over a 0-60 dyn cm(-2) range., Results: WT VWF did not interact with GPIbα under static conditions, whereas the mutant at ~ 2 μg mL(-1) already bound to the receptor. By contrast, the WT and p.R1306W-A1-A2-A3 constructs showed comparable affinities for GPIbα (Kd  ~ 20 nm). The hydrodynamic diameter of resting R1306W VWF multimers was significantly greater than that of the wild type (210 ± 60 nm vs. 87 ± 22 nm). At shear forces of < 14 dyn cm(-2) , the p.R1306W multimers rapidly changed conformation, entering a regime of self-aggregation, which, in contrast, was induced for WT VWF by shear forces of > 30 dyn cm(-2) . Mechanical stretching AFM experiments showed that p.R1306W multimers needed less energy per length unit (~ 10 pN) to be stretched than the WT protein., Conclusions: The increased affinity of p.R1306W VWF for GPIbα arises mostly from higher sensitivity to shear stress, which facilitates exposure of GPIbα binding sites., (© 2013 International Society on Thrombosis and Haemostasis.)