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.     

Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity

Null mutations in the PCSK1 gene, encoding the proprotein convertase 1/3 (PC1/3), cause recessive monogenic early onset obesity. Frequent coding variants that modestly impair PC1/3 function mildly increase the risk for common obesity. The aim of this study was to determine the contribution of rare functional PCSK1 mutations to obesity. PCSK1 exons were sequenced in 845 nonconsanguineous extremely obese Europeans. Eight novel nonsynonymous PCSK1 mutations were identified, all heterozygous. Seven mutations had a deleterious effect on either the maturation or the enzymatic activity of PC1/3 in cell lines. Of interest, five of these novel mutations, one of the previously described frequent variants (N221D), and the mutation found in an obese mouse model (N222D), affect residues at or near the structural calcium binding site Ca-1. The prevalence of the newly identified mutations was assessed in 6,233 obese and 6,274 lean European adults and children, which showed that carriers of any of these mutations causing partial PCSK1 deficiency had an 8.7-fold higher risk to be obese than wild-type carriers. These results provide the first evidence of an increased risk of obesity in heterozygous carriers of mutations in the PCSK1 gene. Furthermore, mutations causing partial PCSK1 deficiency are present in 0.83% of extreme obesity phenotypes.     

Range of motion in femoroacetabular impingement

Recent epidemiological studies have demonstrated that radiographic features specific to femoroacetabular impingement appear far more frequently in healthy and asymptomatic cohorts than previously anticipated. It remains unclear how incidental findings should be interpreted clinically. In addition, several authors have suggested that a decreased range of motion is part of the clinical presentation of femoroacetabular impingement. The purpose of the present study was to describe and analyze differences in range of motion between femoroacetabular impingement patients, asymptomatic individuals with incidental radiographic findings and healthy controls, using a validated electromagnetic tracking system. Furthermore, it was evaluated which motions were clinically relevant and could be used to differentiate between these three groups. We found all evaluated motions to differ significantly between patients and controls. The anterior impingement test showed a significant difference between patients and asymptomatic cases. In conclusion, functional evaluation of the range of motion appeared in this study as a useful tool in the diagnostic work-up of femoracetabular impingement.     

Expression of minichromosome maintenance MCM6 protein in meningiomas is strongly correlated with histologic grade and clinical outcome

The 2007 World Health Organization histologic grading of meningiomas is associated with recurrence and clinical outcome. However, distinction of grade I from grade II (atypical) meningiomas can be challenging. In the World Health Organization classification, there are 4 parameters on the basis of which grade II status can be determined: mitotic rate, cytoarchitectural features, brain invasion, and/or histologic subtype. Furthermore, this classification fails to detect grade I recurrent meningiomas, for which other prognostic criteria would be needed. The aim of this study was to evaluate the respective value of several markers involved in cell cycle as effective tools to predict recurrence. This retrospective study was based on a series of 59 meningiomas (grade I: 32 of 59, grade II: 27 of 59, all harboring ≥4 mitoses/1.6 mm), analyzed with the following immunohistochemical markers: MCM6, Ki-67, PHH3, cyclin D1, and p53. We found a significant correlation between histologic grade and mean labeling index for MCM6 (grade I: 21.8% vs. grade II: 65.8%; P<0.001), Ki-67 (3.2% vs. 16.9%; P<0.001), PHH3 (0.7‰ vs. 2.8‰; P<0.001), cyclin D1 (50.4% vs. 70.0%; P=0.005), and p53 (17.3% vs. 32.4%; P=0.017). Histologic grading and mitotic index were correlated with progression-free survival (P=0.010 and P=0.020, respectively). A nearly linear correlation was found between progression-free survival and staining for MCM6 (P<0.001), Ki-67 (P=0.003), and PHH3 (P=0.037) but not for cyclin D1 (P=0.400) and p53 (P=0.758). The interobserver agreement coefficients for MCM6, Ki-67, PHH3, cyclin D1, and p53 were, respectively, 0.97 (95% confidence interval, 0.95-0.98), 0.93 (0.89-0.96), 0.81 (0.70-0.88), 0.90 (0.83-0.94), and 0.84 (0.73-0.90). In conclusion, because of its strong level of expression and sharp difference in labeling index between indolent and recurrent tumors, MCM6 is the most efficient marker to identify tumors with a high risk of recurrence.     

Anterior suspension combined with posterior reconstruction during robot-assisted laparoscopic prostatectomy improves early return of urinary continence: a prospective randomized multicentre trial

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Urinary incontinence is one of the major drawbacks of radical prostatectomy, regardless of the procedure used (i.e. open, laparoscopic or robotic‐assisted). Several technical modifications have been described to improve postoperative continence, highlighting the role of puboprostatic ligaments and posterior reconstruction of the rhabdomyosphincter. The results obtained are inconsistent when applied to robotic surgery. The present multicentre randomized study shows that anterior suspension combined with posterior reconstruction is a safe and easy‐to‐perform technique for improving early continence after robotic‐assisted laparoscopic prostatectomy.

OBJECTIVE

• ? To assess the impact on urinary continence of anterior retropubic suspension with posterior reconstruction during robot‐assisted laparoscopic prostatectomy (RALP).

PATIENTS AND METHODS

• ? In total, 72 patients who were due to undergo prostatectomy between July 2009 and July 2010 were prospectively randomized into two groups: group A underwent a standard RALP procedure and group B had anterior suspension and posterior reconstruction during RALP.
• ? The primary outcome measure was urinary continence, assessed using the University of California Los Angeles Prostate Cancer Index questionnaire at 15 days, and at 1, 3 and 6 months, after surgery. Other data recorded were operation duration, blood loss, length of hospital stay, duration of bladder catheterization, complications and positive margin rate.

RESULTS

• ? The continence rates at 15 days, and at 1, 3 and 6 months, after surgery were 3.6%, 7.1%, 15.4% and 57.9%, respectively, in group A, and 5.9%, 26.5%, 45.2% and 65.4%, respectively, in group B. The continence rates differed statistically between groups at 1 and 3 months (P = 0.047 and P = 0.016, respectively).
• ? There was no significant difference between groups regarding complications (P = 0.8) or positive margin rate (P = 0.46).

CONCLUSION

• ? Anterior suspension associated with posterior reconstruction during RALP improved the early return of continence, without increasing complications.

     

Axillary Recurrence After a Tumor-Positive Sentinel Lymph Node Biopsy Without Axillary Treatment: A Review of the Literature

Background

Sentinel lymph node biopsy (SLNB) has become standard of care as a staging procedure in patients with invasive breast cancer. A positive SLNB allows completion axillary lymph node dissection (cALND) to be performed. The axillary recurrence rate (ARR) after cALND in patients with positive SLNB is low. Recently, several studies have reported a similar low ARR when cALND is not performed. This review aims to determine the ARR when cALND is omitted in SLNB-positive patients.

Methods

A literature search was performed in the PubMed database with the search terms ??breast cancer,?? ??sentinel lymph node biopsy,?? ??axillary?? and ??recurrence.?? Articles with data regarding follow-up of patients with SLNB-positive breast cancer were identified. To be eligible, patients should not have received cALND and ARR should be reported.

Results

Thirty articles were analyzed. This resulted in 7,151 patients with SLNB-positive breast cancer in whom a cALND was omitted (median follow-up of 45?months, range 1?C142?months). Overall, 41 patients developed an axillary recurrence. 27 studies described 3,468 patients with micrometastases in the SLNB, of whom 10 (0.3?%) developed an axillary recurrence. ARR varied between 0 and 3.7?%. Sixteen studies described 3,268 patients with macrometastases, 24 (0.7?%) axillary recurrences were seen. ARR varied between 0 and 7.1?%. Details regarding type of surgery and adjuvant treatment were lacking in the majority of studies.

Conclusions

ARR appears to be low in SLNB-positive patients even when a cALND is not performed. Withholding cALND may be safe in breast cancer selected patients such as those with isolated tumor cells or micrometastatic disease.     

Patellofemoral arthroplasty influences tibiofemoral kinematics: the effect of patellar thickness

Purpose

Although controversy still remains, isolated patellofemoral arthroplasty recently gained in popularity as a treatment option for patellofemoral osteoarthritis. It has compared to total knee arthroplasty the advantage of preserving the tibiofemoral articulation, which in theory would allow the preservation of natural tibiofemoral kinematics. Today, however, no data exist to support this assumption. This study was therefore performed in order to investigate the effect of isolated patellofemoral arthroplasty on the native three-dimensional tibiofemoral kinematic behaviour and whether a change in patellar thickness would have an influence.

Methods

Six fresh-frozen cadavers were fixed on a custom-made mechanical knee rig. Full 3D kinematics was analysed during passive flexion–extension cycles, open chain extension, with and without mechanical resistance, as well as deep knee squats, using infrared motion capture cameras and retroflective markers. Measurements were taken for the native knee and after prosthetic trochlear resurfacing with and without patellar resurfacing in three different patellar thicknesses.

Results

Compared to the natural knee, patellofemoral arthroplasty resulted in significant changes in tibiofemoral kinematics, which were most pronounced in the most loaded motor tasks. Increased internal tibial rotation was noted in the mid- and high flexion ranges, reaching at 120° of flexion a mean difference of 4.5° ± 4.3° (p < 0.0001) during squat motion, over the whole flexion range during open chain motion and in deeper flexion beyond 50° (mean at 70°, 1.9° ± 3.7°) during resisted open chain. During squats, also, a more posterior translation of the lateral femoral condyle was observed. The effect was accentuated in case of patella overstuffing, whereas kinematics was closer to normal with patellar thinning.

Conclusion

Isolated patellofemoral arthroplasty alters natural tibiofemoral kinematics, and the effects become more pronounced in case of increased patellar thickness. Therefore, it might be recommended to aim for a slight over-resection of patellar bone if sufficient bone stock is available.     

Radiosynthesis and in vivo evaluation of fluorinated huprine derivates as PET radiotracers of acetylcholinesterase

IntroductionDeveloping positron emission tomography (PET) radiotracers for non-invasive study of the cholinergic system is crucial to the understanding of neurodegenerative diseases. Although several acetylcholinesterase (AChE) PET tracers radiolabeled with carbon-11 exist, no fluorinated radiotracer is currently used in clinical imaging studies. The purpose of the present study is to describe the first fluorinated PET radiotracer for this brain enzyme.MethodsThree structural analogs of huprine, a specific AChE inhibitor presenting high affinity towards AChE in vitro, were synthesized and labeled with fluorine-18 via a mesylate/fluoro-nucleophilic aliphatic substitution: ([¹⁸ F]-FHUa, [¹⁸ F]-FHUb and [¹⁸ F]-FHUc). Initial biological evaluation included in vitro autoradiography in rat with competition with an AChE inhibitor at different concentrations, and microPET-scan on anesthetized rats. In vivo PET studies in anesthetized cat focused on [¹⁸ F]-FHUa.Results and ConclusionsAlthough radiosynthesis of these huprine analogs was straightforward, they showed poor brain penetration potential, partially reversed after pharmacological inhibition of P-glycoprotein. These results indicated that current huprine analogs are not suitable for PET mapping of brain AChE receptors, but require physicochemical modulation in order to increase brain penetration.     

Mid-term results of a new cementless hydroxyapatite coated anatomic unicompartmental knee arthroplasty

Introduction

We report the mid term results of a cement less HA coated unicompartmental knee prosthesis.

Material and methods

One hundred and fifty-nine Unicompartmental knee arthroplasties were done between 1995 and 2000 with ALPINA^® UNI, a cementless HA coated anatomic prosthesis. One hundred and twenty knees were available for the mid-term follow-up at a mean of 6.5 years.

Results

The mean IKS improved from 87.1 ± 22.1 points preoperatively to 168.2 ± 26.1 at the latest follow-up (P < 0.001). Ninety-four percent of the knees were rated good and excellent. The mean knee flexion has significantly improved from 120° preoperatively to 126° at the latest follow-up (P < 0.001). Ten knees were revised: three for degeneration of osteoarthritis in the opposite compartment of the knee, four for polyethylene insert fracture, one for severe polyethylene wear and two for tibial component loosening. When revision for any reason was defined as the end point, the 5-year Kaplan–Meier survival rate was 95.7% (95% confidence interval, 90.1–98.2%) and when revision due to implant mechanical failure (excluding degeneration of osteoarthritis in the opposite compartment of the knee) was defined as the end point, the 5-year survival rate was 96.6% (95% confidence interval, 91.2–98.7%).

Conclusion

This study confirms the reliability of HA coated unicompartimental knee replacement. With careful indications it seems to be a good alternative to osteotomy of total arthroplasty.