Role of combined DWIBS/3D-CE-T1w whole-body MRI in tumor staging: Comparison with PET-CT

Objectives

To assess the diagnostic performance of whole-body magnetic resonance imaging (WB-MRI) by diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) in malignant tumor detection and the potential diagnostic advantages in generating fused DWIBS/3D-contrast enhanced T1w (3D-CE-T1w) images.

Methods

45 cancer patients underwent 18F-FDG PET-CT and WB-MRI for staging purpose. Fused DWIBS/3D-CE T1w images were generated off-line. 3D-CE-T1w, DWIBS images alone and fused with 3D-CE T1w were compared by two readers groups for detection of primary diseases and local/distant metastases. Diagnostic performance between the three WB-MRI data sets was assessed using receiver operating characteristic (ROC) curve analysis. Imaging exams and histopathological results were used as standard of references.

Results

Areas under the ROC curves of DWIBS vs. 3D-CE-T1w vs. both sequences in fused fashion were 0.97, 0.978, and 1.00, respectively. The diagnostic performance in tumor detection of fused DWIBS/3D-CE-T1w images were statistically superior to DWIBS (p < 0.001) and 3D-CE-T1w (p ≤ 0.002); while the difference between DWIBS and 3D-CE-T1w did not show statistical significance difference. Detection rates of malignancy did not differ between WB-MRI with DWIBS and 18F-FDG PET-CT.

Conclusion

WB-MRI with DWIBS is to be considered as alternative tool to conventional whole-body methods for tumor staging and during follow-up in cancer patients.     

Studies with low micromolar levels of ascorbic and dehydroascorbic acid fail to unravel a preferential route for vitamin C uptake and accumulation in U937 cells

Mammalian cells accumulate vitamin C either as ascorbic acid (AA), via Na+-AA co-transport, or dehydroascorbic acid (DHA, the oxidation product of AA), via facilitative hexose transport. As the latter, unlike the former, is a high-capacity transport mechanism, cultured cells normally accumulate greater levels of vitamin C when exposed to increasing concentrations of DHA as compared with AA. We report herein similar results using the U937 cell clone used in our laboratory only under conditions in which DHA and AA are used at concentrations greater than 50-60?μm. Below 60?μm, i.e. at levels in which AA is normally found in most biological fluids, AA and DHA are in fact taken up with identical rates and kinetics. Consequently, extracellular oxidation of AA switches the mode of uptake with hardly any effect on the net amount of vitamin C accumulated. As a final note, under these conditions, neither AA nor DHA causes detectable toxicity or any change in the redox status of the cells, as assessed by the reduced glutathione/reduced pyridine nucleotide pool. These findings therefore imply that some cell types do not have a preferential route for vitamin C accumulation, and that the uptake mechanism is uniquely dependent on the extracellular availability of AA v. DHA.     

Efficacy and tolerability of different brands of intravenous immunoglobulin in the maintenance treatment of chronic immune‐mediated neuropathies

High‐dose intravenous immunoglobulin (IVIg) is effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Not all brands of IVIg are however licensed for these neuropathies. We reviewed six patients with CIDP and seven with MMN treated with maintenance therapy with IVIg from 2009 to 2013. In all patients, we measured the Medical Research Council (MRC) and Overall Neuropathy Limitation Scale (ONLS) scores before each infusion, registered the monthly dose and brand of IVIg, and recorded adverse events. Patients were treated for 25–60 months (mean 49 months) alternating different brands of IVIg including IgVena, Gammagard, Kiovig, and Flebogamma. Minor and transient side effects were equally observed with each brand. No difference in the MRC or ONLS scores was observed in relation to the brand of IVIg used. Chronic maintenance treatment with IVIg in patients with MMN and CIDP was not associated with a different tolerability or efficacy despite the use of different brands of IVIg.     

Ultrastructural and quantitative study of clitoral cavernous tissue from living subjects

IntroductionThere has never been an investigation about the in vivo clitoral structure.AimTo study the “in vivo” age-related structural changes of the clitoris in healthy women and in those affected by metabolic disorders.MethodsForty-three women subgrouping in (i) five teenagers, aged 14–18; (ii) eight young premenopausal women, aged 23–32; (iii) 10 premenopausal women, aged 38–47; (iv) nine diabetic premenopausal women, aged 27–43; and (v) 11 naturally postmenopausal women aged 51–55. Each woman underwent microbiopsy of the clitoral body by means of an 18G needle, length 100 mm, using a semiautomatic gun during total anesthesia for a benign gynecological pathology. The tissue removed was processed for electron microscopy. A morphometric procedure was used on electron micrographs.Main Outcome MeasureMicro ultrastructure observation of clitoral tissue.ResultsThe cavernous tissue from the teenagers and young women showed large amounts of smooth muscle cells (SMCs). The intercellular connective tissue showed scanty, small isometric collagen fibers and amorphous extracellular matrix. In the premenopausal diabetic women, ultrastructural abnormalities of SMCs were observed, consisting of increase of glycogen deposits, infolding cell borders, and cytoplasmic vacuoles. Moreover, the intercellular connective tissue was increased by densely packed collagen fibers. Finally, in the healthy, natural postmenopausal women, the SMCs were moderately reduced in number. We observed age-related structural changes of the vascular spaces and of the vascular lacunae. The SMC mean thickness was reduced with age; vascular abnormalities appeared to be correlated with the presence of metabolic diseases, such as diabetes.ConclusionOur “in vivo” study could help to understand some aspects of the physiology of the clitoris and its role in sexual response. Apart from data obtained by studying healthy women and women affected by diabetes, other investigations are needed to study subgroups of otherwise healthy sexually dysfunctional women. Caruso S, Cianci A, Malandrino C, Cavallari L, Gambadoro O, Arena G, Pispisa L, Agnello C, Romano M, and Cavallari V. Ultrastructural and quantitative study of clitoral cavernous tissue from living subjects.     

Circulating mir-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk

miRNAs play a central role in the complex signaling network of cancer cells with the tumor microenvironment. Little is known on the origin of circulating miRNAs and their relationship with the tumor microenvironment in lung cancer. Here, we focused on the cellular source and relative contribution of different cell types to circulating miRNAs composing our risk classifier of lung cancer using in vitro/in vivo models and clinical samples. A cell-type specific expression pattern and topography of several miRNAs such as mir-145 in fibroblasts, mir-126 in endothelial cells, mir-133a in skeletal muscle cells was observed in normal and lung cancer tissues. Granulocytes and platelets are the major contributors of miRNAs release in blood. miRNAs modulation observed in plasma of lung cancer subjects was consistent with de-regulation of the same miRNAs observed during immunosuppressive conversion of immune cells. In particular, activated neutrophils showed a miRNA profile mirroring that observed in plasma of lung cancer subjects. Interestingly mir-320a secreted by neutrophils of high-risk heavy-smokers promoted an M2-like protumorigenic phenotype through downregulation of STAT4 when shuttled into macrophages. These findings suggest a multifactorial and nonepithelial cell-autonomous origin of circulating miRNAs associated with risk of lung cancer and that circulating miRNAs may act in paracrine signaling with causative role in lung carcinogenesis and immunosuppression.     

Does fatigue in Parkinson’s disease correlate with autonomic nervous system dysfunction?

Background

Despite its negative impact on quality of life, fatigue in Parkinson’s disease (PD) remains an under-recognized issue and the underlying pathology is undetermined.

Objective

To contribute at understanding the pathogenesis of fatigue in a naturalistic cohort of cognitively intact PD patients.

Methods

In a Caucasian population of PD patients (n?=?27), we evaluated to what extent fatigue (quantified as PFS-16 score) is associated with PD duration and with autonomic dysfunction, studied by both MIBG scintigraphy and autonomic nervous system testing. The latter included the head-up tilt test, Valsalva maneuver, deep breathing, and handgrip tests.

Results

PFS-16 score correlated with disease duration (R?=?0.57, p?=?0.002). Fatigue showed a clear correlation with deep breathing test (R?=???0.53, p?=?0.004) but not with the MIBG H/M ratios.

Conclusions

Our data are consistent with a multifactorial pathogenesis of fatigue and with effects of dopamine depletion in PD-related fatigue; on the other hand, our findings do not support a role for sympathetic denervation in PD-related fatigue.

     

Type I spinal muscular atrophy patients treated with nusinersen: 4-year follow-up of motor,respiratory and bulbar function

Background

We report the 4-year follow-up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number.

Methods

The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE-II).

Results

Forty-eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE-II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2–4 years, 5–11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE-2 increased significantly in patients younger than 2 years at treatment. In a mixed-model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not.

Conclusions

Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time.