MR imaging with ultrasmall superparamagnetic iron oxide particles in experimental soft-tissue infections in rats

PURPOSE: To investigate the feasibility of macrophage magnetic resonance (MR) imaging in rats by using an experimental soft-tissue infection model. MATERIALS AND METHODS: Thirteen rats with unilateral calf-muscle infection were imaged with a 4.7-T MR imager at an early chronic stage of infection (day 4 before contrast material injection, days 4-7 after injection). Eleven animals were imaged before and 3 and 24 hours after intravenous application of ultrasmall superparamagnetic iron oxide (USPIO), and eight animals were additionally imaged 48 hours and three animals 72 hours after USPIO application. Two infected rats served as controls. T1- and T2-weighted spin-echo and T2*-weighted gradient-echo sequences were applied. All animals were sacrificed, and histopathologic findings were correlated with findings on MR images. Electron microscopy was performed in two rats. For quantitative analysis, signal intensities on T2*-weighted images and T2 values on T2 maps were measured within regions of interest, and the temporal variation was analyzed by using the signed rank test. RESULTS: Visualization of USPIO-loaded macrophages was most sensitive with a T2*-weighted sequence. USPIO distribution pattern and quantitative analysis of T2 and T2* effects 3 hours after USPIO application were significantly different (P <.05) from those at 24 and 48 hours, reflecting the dynamic transit of the particle accumulation from the intravascular to the intracellular compartment by means of macrophage phagocytosis. Local signal intensity alterations could be correlated with iron-loaded macrophages at histopathologic examination. CONCLUSION: Activated macrophages in acute soft-tissue infection can be labeled with USPIOs and detected with MR imaging because of susceptibility effects.     

From here to epilepsy: the risk of seizure in patients with Alzheimer's disease

Aim. To describe the association between Alzheimer's disease and seizures by reviewing epidemiological data from available literature and to assess the putative pathophysiological links between neurodegeneration and altered cortical excitability. We also discuss specific antiepileptic treatment strategies in patients with Alzheimer's disease, as well as transient epileptic amnesia as a possible crossroads between degeneration and epilepsy. Methods. Regarding epidemiology, we searched publications in Pubmed, Medline, Scopus and Web of Science (until September 2015) using the keywords “incidence”, “prevalence” and “frequency”, as well as “Alzheimer's disease” and “seizures”. In addition, therapeutic aspects for seizures in Alzheimer's disease were searched using the key words “antiepileptic drugs”, “seizure treatment” and “Alzheimer”. Results. The prevalence and incidence rates of seizures were found to be increased 2 to 6‐fold in patients with Alzheimer's disease compared to age‐adjusted control patients. Treatment strategies have mainly been extrapolated from elderly patients without dementia, except for one single randomised trial, in which levetiracetam, lamotrigine and phenobarbital efficacy and tolerance were investigated in patients with Alzheimer's disease. Mouse models appear to show a major role of amyloid precursor protein and its cleavage products in the generation of cortical hyperexcitability. Conclusion. A link between Alzheimer's disease and epilepsy has long been described and recent cohort studies have more clearly delineated risk factors associated with the genesis of seizures, such as early onset and possibly severity of dementia. As genetic forms of Alzheimer's disease and experimental mouse models suggest, beta‐amyloid may play a prominent role in the propagation of synchronised abnormal discharges, perhaps more via an excitatory mode than a direct neurodegenerative effect.     

A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy

Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44±27 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or <20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes.     

Reproducibility and influence of hand rotation on computer-aided joint space analysis

ObjectivesComputer-aided joint space analysis (CAJSA) is a recently developed, semi-automated tool to aid in the measurement of joint space margins based on hand radiographs. The objective of this study is to verify the potential effect of hand rotation during X-ray imaging on the measurement of joint space width using CAJSA and to evaluate the reproducibility of the CAJSA technique in healthy subjects and in patients with rheumatoid arthritis.MethodsAll joint space distance (JSD) measurements were performed using CAJSA-technology at the metacarpophalangeal articulation based on conventional and digital hand radiographs.ResultsI. Hand rotation showed an effect on the reproducibility with CV ranging between 0.39% (angulation 1°) and 1.66% (angulation 19°). II. Regarding the overall reproducibility of the CAJSA method, the intra-radiograph reproducibility of JSD was calculated with CV = 0.54% for conventional images and CV = 0.38% for digital images. The inter-radiograph reproducibility error was observed with CV = 0.66% (conventional images) and CV = 0.63% (digital images). III. The study revealed a reproducibility for CAJSA measurements in RA ranging between 0.37% (JSD-MCP ring finger; van der Heijde-modification of the Sharp method Score 1) to 1.37% (JSD-MCP index finger; van der Heijde-modification of the Sharp method Score 3).ConclusionCAJSA measures JSD at the metacarpophalangeal articulation with high reproducibility in healthy subjects and in patients with differing stages of rheumatoid arthritis. Additional findings show that hand rotation during X-ray imaging has an impact on the CAJSA measurements; thus avoiding acquisition of hand radiographs with a rotation error of more than 15 degrees can be recommended.     

Can Whole-body Magnetic Resonance Imaging with Diffusion-weighted Imaging Replace Tc 99m Bone Scanning and Computed Tomography for Single-step Detection of Metastases in Patients with High-risk Prostate Cancer?

Background

Technetium Tc 99m bone scintigraphy (BS) and contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis and abdomen are universally recommended for detecting prostate cancer (PCa) metastases in cancer of all stages. However, this two-step approach has limited sensitivity and specificity.

Objective

Evaluate the diagnostic accuracy of whole-body MRI (WBMRI) as a one-step screening test for PCa metastases.

Design, setting, and participants

One hundred consecutive PCa patients at high risk for metastases prospectively underwent WBMRI, CT, and BS completed with targeted x-rays (BS/TXR) in case of equivocal BS. Four independent reviewers reviewed the images.

Measurements

This study compares the diagnostic performance of WBMRI, CT, BS, and BS/TXR in detecting PCa metastases using area under the curve (AUC) receiver operator characteristics. A best valuable comparator (BVC) approach was used to adjudicate final metastatic status in the absence of pathologic evaluation.

Results and limitations

Based on the BVC, 68 patients had metastases. The sensitivity of BS/TXR and WBMRI for detecting bone metastases was 86% and 98–100%, respectively (p < 0.04), and specificity was 98% and 98–100%, respectively. The first and second WBMRI readers respectively identified bone metastases in 7 and 8 of 55 patients with negative BS/TXR. The sensitivity of CT and WBMRI for detecting enlarged lymph nodes was similar, at 77–82% for both; specificity was 95–96% and 96–98%, respectively. The sensitivity of the combination of BS/TXR plus CT and WBMRI for detecting bone metastases and/or enlarged lymph nodes was 84% and 91–94%, respectively (p = 0.03–0.10); specificities were 94–97% and 91–96%, respectively. The 95% confidence interval of the difference between the AUC of the worst WBMRI reading and the AUC of any of the BS/TXR plus CT lay within the noninferiority margin of ±10% AUC.

Conclusions

WBMRI outperforms BS/TXR in detecting bone metastases and performs as well as CT for enlarged lymph node evaluation. WBMRI can replace the current multimodality metastatic work-up for the concurrent evaluation of bones and lymph nodes in high-risk PCa patients.     

Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study

Study Type – Therapy (multi‐centre retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UUT‐UCs) are rare tumours. Because of the aggressive pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains the ‘gold‐standard’ treatment. However, conservative strategies, such as segmental ureterectomy (SU) or endourological management, have also been developed in patients with imperative indications. Some teams are now advocating the use of conservative management more commonly in cases of elective indications of UUT‐UCs. Due to the paucity of cases of UUT‐UC, only limited data are available on the oncological outcomes afforded by conservative management. We retrospectively investigated the oncological outcomes after SU and RNU in a large multi‐institutional database. Overall, 52 patients were treated with SU and 416 with RNU. There was no statistical difference between the RNU and SU groups for the 5‐year probability of cancer‐specific survival, recurrence‐free survival and metastasis‐free survival. The type of surgery was not a significant prognostic factor in univariate analysis. The results were the same in a subgroup analysis of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low stage (≤T2). Our results suggest that oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases.

OBJECTIVE

• ? To compare recurrence‐free survival (RFS), metastasis‐free survival (MFS) and cancer‐specific survival (CSS) after segmental ureterectomy (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the upper urinary tract (UUT‐UC) located in the ureter.

PATIENTS AND METHODS

• ? We performed a multi‐institutional retrospective review of patients with UUT‐UC who had undergone RNU or SU between 1995 and 2010.
• ? Type of surgery, Tumour‐Node‐Metastasis status, tumour grade, lymphovascular invasion and positive surgical margin were tested as prognostic factors for survival.

RESULTS

• ? In all, 52 patients were treated with SU and 416 with RNU. The median (range) follow‐up was 26 (10–48) months.
• ? The 5‐year probability of CSS, RFS and MFS for SU and RNU were 87.9% and 86.3%, respectively (P= 0.99); 37% and 47.9%, respectively (P= 0.48); 81.9% and 85.4%, respectively (P= 0.51).
• ? In univariable analysis, type of surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P= 0.94, 0.42 and 0.53, respectively).
• ? In multivariable analyses, pT stage and pN stage achieved independent predictor status for CSS (P= 0.005 and 0.007, respectively); the positive surgical margin and pT stage were independent prognostic factors of RFS and MFS (P= 0.001, 0.04, 0.009 and 0.001, respectively).
• ? The main limitation of the study is its retrospective design, which is due to the rarity of the disease.

CONCLUSIONS

• ? Short‐term oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases and should be considered an option.
• ? In every other case, RNU still represents the ‘gold standard’ for the treatment of UUT‐UC.

     

Chondrocytes or adult stem cells for cartilage repair: the indisputable role of growth factors

Articular cartilage is easily injured but difficult to repair and cell therapies are proposed as tools to regenerate the defects in the tissue. Both differentiated chondrocytes and adult mesenchymal stem cells (MSCs) are regarded as cells potentially able to restore a functional cartilage. However, it is a complex process from the cell level to the tissue end product, during which growth factors play important roles from cell proliferation, extracellular matrix synthesis, maintenance of the phenotype to induction of MSCs towards chondrogenesis. Members of the TGF-β superfamily, are especially important in fulfilling these roles. Depending on the cell type chosen to restore cartilage, the effect of growth factors will vary. In this review, the roles of these factors in the maintenance of the chondrocyte phenotype are discussed and compared with those of factors involved in the repair of cartilage defects, using chondrocytes or adult mesenchymal stem cells.     

Prognostic Value of BRAF V600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes

Purpose

BRAF ^V600 mutations are frequent in melanomas, and BRAF^V600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ??2?mm according to BRAF ^V600 mutations and other previously reported prognostic criteria.

Methods

This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF ^V600 mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60?% melanoma cells.

Results

BRAF mutations (p.V600E and p.V600K in 83 and 14?% of cases, respectively) were detected in 40?% of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3?%, with a median OS of 1.4 and 2.8?years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P?=?0.005, hazard ratio 2.2, 95?% confidence interval 1.3?C3.9) and BRAF status (P?=?0.005, hazard ratio 1.9, 95?% confidence interval 1.2?C3.1).

Conclusions

BRAF ^V600 status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.     

Recurrence of Dislocation Following Total Hip Arthroplasty Revision Using Dual Mobility Cups Was Rare in 180 Hips Followed Over 7?Years

Background

Dual mobility (DM) cups of mobile polyethylene were introduced to prevent total hip arthroplasty (THA) dislocation, but no large series with this design to treat recurrent instability have been reported.

Purpose

Our retrospective investigation ascertained the efficiency of DM cups in correction of recurrent dislocation and assessed any adverse effects.

Methods

One hundred eighty THAs with recurrent instability were revised to DM cups in 180 patients (mean age, 67.4 ± 11.7 years; range, 19 to 92 years). Thirty-one patients (17.2%) underwent at least one earlier THA revision, and 15 (10.3%) incurred non-union of the greater trochanter. Of the initial group in 2009, 145 patients had completed evaluations which included assessment of the Harris Hip Score and a radiographic assessment at a mean follow-up of 7.7 ± 2.2 years (range, 4 to 14 years). The rate of survival was calculated considering any reason for revision as failure.

Results

At follow-up, Harris hip score was 83.9 ± 16.1 (range, 21 to 100). Dislocation of the large articulation occurred in seven hips (4.8%), and only two recurred (1.4%) (one requiring additional revision). In addition, two intra-prosthetic dislocations of the small articulation (1.4%) were observed and needed revision surgery. The large number of earlier surgeries and non-union of the greater trochanter were related to recurrent instability. Two cups (1.4%) showed signs of definite loosening; six (4.1%) presented signs of possible loosening. Twenty-nine hips manifested femoral or acetabular osteolysis (20%), but only three were severe. Eight-year survival rate considering revision for any reason was 92.6% (95% CI, 85.5–96.4%).

Conclusions

This series indicates that DM cups are a viable option to treat recurrent THA instability. Their design provides a low risk of recurrent instability without increasing mechanical complications.     

Traumatic hip dislocation in childhood

Traumatic dislocation of the hip in childhood is uncommon and can be a consequence of minor trauma. The authors report a series of 35 dislocations in skeletally immature patients. Most were isolated posterior dislocations without acetabular lesions. In 75% of cases, reduction of the dislocation was easy. Nine children required surgery to remove interposed joint capsule and/or osteochondral fragments to achieve anatomic reduction. Outcomes were generally good, except in one patient in whom a displaced fracture of the femoral physis was followed by total head avascular necrosis. One case of partial necrosis had a satisfactory outcome. Epiphyseal necrosis, though uncommon, appeared to be inconsistent to prevent and hard to predict. Bone scan seems to be more effective than MRI for the detection of necrosis.