Objectives The aim of this study was to investigate the diagnostic performance of99m Tc-hexamethypropylene amine oxime labeled autologous white blood cell (99m Tc-HMPAO-WBC) scintigraphy in patients ...with suspected infections associated with cardiovascular implantable electronic devices (CIEDs). Background Early, definite recognition of CIED-related infections combined with accurate localization and quantification of disease burden is a prerequisite for optimal treatment strategies. Methods All 63 consecutive patients underwent clinical examination, blood chemistry, microbiology, and echography of the cardiac region/venous pathway of the device. Final diagnosis of infection was established in 32 of 63 patients and in 23 of 32 by microbiology. Results Sensitivity of99m Tc-HMPAO-WBC single-photon emission computed tomography/computed tomography (SPECT/CT) was 94% for both detection and localization of CIED-associated infection. SPECT/CT imaging had a definite added diagnostic value over both planar and stand-alone SPECT. Pocket infection was often associated with lead(s) involvement; the intracardiac portion of the lead(s) more frequently exhibited99m Tc-HMPAO-WBC accumulation and presented the highest rate of complications, infectious endocarditis, and septic embolism. Two false negative cases and no false positive results were observed. None of the patients with negative99m Tc-HMPAO-WBC scintigraphy developed CIED-related infection during follow-up of 12 months. Echography of the cardiac region/venous pathway of the device had 90% specificity, but low sensitivity (81% when intracardiac leads infection only was considered). The Duke criteria had 31% sensitivity for the definite category (100% specificity) and 81% for the definite and possible categories (77% specificity). Conclusions99m Tc-HMPAO-WBC scintigraphy enabled the confirmation of the presence of CIED-associated infection, definition of the extent of device involvement, and detection of associated complications. Moreover,99m Tc-HMPAO-WBC scintigraphy reliably excluded device-associated infection during a febrile episode and sepsis, with 95% negative predictive value.
OBJECTIVE (a) To establish whether the cognitive decline of the early phase of relapsing-remitting multiple sclerosis depends on the progression of the burden of disease, or on the loss of brain ...parenchyma, or is influenced by both; (b) to monitor the loss of brain parenchyma in the early phase of the disease; and (c) to examine its possible relation with the progression of physical disability. METHODS For 2 years 53 patients with clinically definite relapsing-remitting multiple sclerosis with disease duration 1–5 years and expanded disability status scale⩽5.0 at baseline were monitored. The neuropsychological performances, the psychological functioning, the neurological impairment, and the disability have been assessed at baseline and after 2 years. Patients also underwent PD/T2 and T1 weighted brain MRI. T2 and T1 lesion volumes were measured by a semiautomatic technique. Quantification of brain parenchymal volumes was obtained using a highly reproducible computerised interactive program. The relation between cognitive impairment and MRI findings has been investigated by partial correlation and stepwise multiple regression analyses excluding the effects of age, education, anxiety, depression, and total days of steroid use. RESULTS In the 2 years of the study the mean change for T2 and T1 lesion volumes and brain parenchymal volumes were +1.7 ml (95% confidence interval (95% CI) 1.3–2.2, p=0.005, (29.8%); +0.2 ml, 95% CI 0.15–0.26, p=0.004, (25%); and –32.3 ml, 95% CI 24.2–42.3, p<0.0001, (2.7%), respectively. Overall, 14 patients (26.4%) were judged to be cognitively impaired at baseline and 28 (52.8%) at the end of the follow up. Of the 18 neuropsychological tests and subtests employed in the study, patients with multiple sclerosis failed 5.8 (SD 2.3) tests at the baseline and 8.4 (SD 2.9) (p<0.0001) tests at the end of the study. When the cognitive changes were examined in individual patients, five (9.4%) of them were considered cognitively improved, 33 (62.3%) remained stable, and 15 (28.3%) worsened over 2 years. T2 and T1 volume changes in improved, stable, and worsened patients did not show any significant difference, whereas brain parenchymal volume decrease in cognitively worsened patients was significantly greater (−66 ml (5.4%), 95% CI 37–108.9, p=0.0031). The cognitive impairment was independently predicted over 2 years only by the change of brain parenchymal volumes (R=0.51, p=0.0003). Ten patients (18.9%), who worsened by one or more points in the EDSS during the follow up period had significant decreases in brain parenchymal volumes (−99 ml (8%), 95% CI 47.6–182.3, p=0.005). At the end of the study the loss of brain parenchyma correlated significantly with change in EDSS (r= 0.59, p<0.0001). CONCLUSIONS In the early phase of relapsing-remitting multiple sclerosis the cognitive deterioration relies more on the development of brain parenchymal volume atrophy than on the extent of burden of disease in the brain. The loss of brain parenchymal volume underlies the progressive accumulation of physical disability from the initial phase of the disease, which becomes more demonstrable only if studied with longer observation periods. Probably, the main pathological substrate of brain atrophy in the early stage of the disease is early axonal loss, which causes the progression of neurological deficits and the development of cognitive impairment. These data support the debated opinion that disease modifying therapy should be initiated as early as possible.
Little is known on the relationship between obesity and hydration levels in children. This study assessed whether and by which mechanisms hydration status differs between obese and non-obese ...children.
Hydration levels of 86 obese and 89 normal weight children (age: 7-11 years) were compared. Hydration was measured as the average free water reserve (FWR=urine output/24 h minus the obligatory urine output total 24 h excreted solutes/97th percentile of urine osmolality of children with adequate water intake, that is, 830 mOsm/kg) over 2 days. Three days of weighed dietary and fluid intakes were recorded. Non-parametric tests were used to compare variables that were skewed and to assess which variables correlated with hydration. Variables mediating the different hydration levels of obese and normal weight children were assessed by co-variance analysis.
Obese children were less hydrated than normal weight peers FWR=median (IQR): 0.80 (-0.80-2.80) hg/day vs 2.10 (0.10-4.45) hg/day, P<0.02; 32% of obese children vs 20% of non-obese peers had negative FWR, P<0.001. Body mass index (BMI) z-score (z-BMI) and water intake from fluids correlated with FWR (ρ=-0.18 and 0.45, respectively, both P<0.05). Water intake from fluids completely explained the different hydration between obese and normal weight children FWR adjusted for water from fluids and z-BMI=2.44 (0.44) hg vs 2.10 (0.50) hg, P=NS; B coefficient of co-variation between FWR (hg/day) and water intake from fluids (hg/day)=0.47, P<0.001.
Obese children were less hydrated than normal weight ones because, taking into account their z-BMI, they drank less. Future prospective studies are needed to explore possible causal relationships between hydration and obesity.
Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). ...There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second 'Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.
We aimed to assess in obese youths the relationships between interleukin-6 (IL-6), fat meal-induced endotoxemia and glucose homeostasis. Twenty obese children/adolescents (9-17 years old, 11 boys) ...underwent a standard oral glucose tolerance test and, 7-14 days later, a 5-h fat meal test (fat=69% of energy, saturated/monounsaturated/polyunsaturated fatty acids=31.5%/35%/33.5%), with serial measures of IL-6 and two markers of lipopolysaccharide (LPS) exposure and translocation, LPS-binding protein (LBP) and soluble CD14 (sCD14). IL-6 correlated not only with basal (homeostatic model assessment-insulin resistance) but also with post-prandial (Matsuda index) insulin sensitivity (r=0.61 (0.24-0.82), P=0.005, r=-0.53 (0.12-0.78), P=0.03, respectively). IL-6 did not change after the meal whereas LBP and sCD14 decreased significantly, indicating LPS translocation. Neither basal sCD14 and LBP nor their incremental concentrations correlated with IL-6 or glucose homeostasis. In our sample, IL-6 was associated with insulin sensitivity but not with LPS exposure, suggesting that meals with a balanced content of saturated/monounsaturated/polyunsaturated fatty acids may not be associated with LPS-induced inflammation and metabolic impairment.
Summary
Background
The aetiology of intrahepatic cholestasis of pregnancy is unknown, but more than 10 different MDR3 gene mutations have recently been identified.
Aim
To evaluate the genetic ...contribution of the MDR3 gene in the pathogenesis of intrahepatic cholestasis of pregnancy in Italian subjects.
Methods
We performed a multicentre prospective case–control study, enrolling 80 women with intrahepatic cholestasis of pregnancy at the third trimester of pregnancy and 80 pregnant women without intrahepatic cholestasis of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes using standard procedures. The polymerase chain reaction was used to amplify exon 14 of the MDR3 gene and the polymerase chain reaction products were sequenced using a Big Dye Terminator Cycle Sequencing kit.
Results
Three novel non‐synonymous heterozygous mutations in exon 14 were found (4%; E528D, R549H, G536R) among the 80 intrahepatic cholestasis of pregnancy patients, whereas the pregnant controls were all negative for exon 14 polymorphisms. The three patients involved had normal GGT and bilirubin, but high levels of both ALT and serum bile acids. One had cholesterol bile stones. The outcome of pregnancy was normal for two (with vaginal delivery), while foetal distress was recorded in the third.
Conclusions
These three novel mutations add further information on the involvement of the MDR3 gene in intrahepatic cholestasis of pregnancy. As in other studies, we found only heterozygous mutations that could cause an impaired transport protein function, not its absence (which is responsible for more severe liver disease). Different genetic backgrounds might justify the presence of novel MDR3 gene mutations.
Purpose
The differential prevalence of eating disorders in males and females can be explained by the impact of gender-role orientations. Inside the Italian socio-cultural context, gender ...socialization can be influenced by stereotypical gender beliefs, and this may contribute to the psychological distress of individuals who identify with discrepant gender roles from their biological sex. Our study explored, within the Italian context, the potential moderating effect of masculinity and femininity on the relationships between gender and attitudes about body and eating.
Methods
Nine hundred and twenty Italian male and female adolescents (M = 427, F = 493; age 14–21 years) completed the Eating Disorder Inventory-2 (EDI-2) and the Bem Sex-Role Inventory (BSRI).
Results
A moderating effect of gender role on the relationship between gender and bulimia, and drive of thinness emerged. Girls with higher levels of masculinity scored higher on bulimia than did their counterparts with lower levels, and boys with higher levels of femininity scored higher on bulimia and on drive for thinness than did their counterparts with lower levels. Data did not reveal a moderating effect of gender role on the relationship between gender and body satisfaction.
Conclusions
Our data suggest that adolescents who endorsed a gender role that is socially considered discrepant from their biological sex (girls with higher levels of masculinity and boys with higher levels of femininity) are more likely to show higher level of bulimia and drive of thinness. This suggests the need for prevention and treatment programmes for eating disorders that take into account individuals’ gender-role orientation and the influence that culturally dominant gender beliefs can exert on it.
The aim of the study was to determine whether the presence of anti-Epstein-Barr virus (EBV) antibodies is associated with MRI measures of brain injury and neurodegeneration in patients with multiple ...sclerosis (MS).
135 patients with MS (86 women, 49 men) underwent brain MRI and testing for antibodies against EBV. MRI measurements included gadolinium enhancing lesion volume, T1 and T2 lesion volumes and fractions of whole brain parenchyma (BPF), white matter and grey matter (GMF). The anti-EBV panel included anti-EBV early antigen IgG, anti-EBV nuclear antigen IgG and anti-EBV viral capsid antigen (VCA) IgG levels. The relationships between antibody levels and MRI measurements were assessed in regression analysis. Repeat measurements of anti-EBV VCA IgG and MRI measures were available for a subset of 50 patients after a mean follow-up of 3.1 years.
GMF (R(2) = 0.24 for overall model, p = 0.002) and BPF (R(2) = 0.39 for overall model, p<0.001) showed negative associations with anti-EBV-VCA IgG levels. A greater decline in BPF over 3 years was significantly associated with increased 3 years prior time point anti-EBV VCA IgG levels (p<0.001).
The results suggest that the presence of anti-EBV antibodies is associated with MRI markers of GM atrophy in MS and with increased loss of brain volume over 3 years.
Skipping breakfast influences cognitive performance. The aim of our study was to investigate the relationship between the variation of hormonal and metabolic postprandial parameters induced by ...breakfast consumption or fasting and cognitive performance in obese children.
Cross-sectional study for repeated measures. Memory and attention assessment tests, hormones and nutrient oxidation were measured before and after consuming breakfast vs fasting in 10 prepubertal obese children.
Fasting induced a significant (P<0.05) increase of the Overall Index of the Continuous Performance Test II (a global index of inattention) and the Test of Memory and Learning Word Selective Reminding (a test of verbal memory), whereas no changes were found after breakfast. Fasting was associated with a reduction of insulin and an increase in glucagon, with no changes in glucose. The increase in inattention was associated with a reduction of carbohydrate oxidation (ρ=-0.66, P<0.05). We found no difference in the area under the curve of peptide YY and glucagon-like peptide-1 after breakfast or fasting, whereas Ghrelin was significantly lower. No association between postprandial hormone variation and cognitive performance was found.
Attention and visual memory performance in the morning were reduced when the children skipped breakfast. No association was found with hormones or metabolic changes, but we did find an association with a reduction of carbohydrate oxidation. Nevertheless, these preliminary findings need confirmation in larger sample size.
To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of ...HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = −0.31, P =0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone.
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