De novo Uroplakin IIIa heterozygous mutations cause human renal adysplasia leading to severe kidney failure

Human renal adysplasia usually occurs sporadically, and bilateral disease is the most common cause of childhood end-stage renal failure, a condition that is lethal without intervention using dialysis or transplantation. De novo heterozygous mutations in Uroplakin IIIa (UPIIIa) are reported in four of 17 children with kidney failure caused by renal adysplasia in the absence of an overt urinary tract obstruction. One girl and one boy in unrelated kindreds had a missense mutation at a CpG dinucleotide in the cytoplasmic domain of UPIIIa (Pro273Leu), both of whom had severe vesicoureteric reflux, and the girl had persistent cloaca; two other patients had de novo mutations in the 3' UTR (963 T-->G; 1003 T-->C), and they had renal adysplasia in the absence of any other anomaly. The mutations were absent in all sets of parents and in siblings, none of whom had radiologic evidence of renal adysplasia, and mutations were absent in two panels of 192 ethnically matched control chromosomes. UPIIIa was expressed in nascent urothelia in ureter and renal pelvis of human embryos, and it is suggested that perturbed urothelial differentiation may generate human kidney malformations, perhaps by altering differentiation of adjacent smooth muscle cells such that the metanephros is exposed to a functional obstruction of urine flow. With advances in renal replacement therapy, children with renal failure, who would otherwise have died, are surviving to adulthood. Therefore, although the mechanisms of action of the UPIIIa mutations have yet to be determined, these findings have important implications regarding genetic counseling of affected individuals who reach reproductive age.     

Association of macroscopic gut inflammation with disease activity, functional status and quality of life in ankylosing spondylitis

The aim of this cross-sectional study was to evaluate the frequency of intestinal inflammation and its association with disease activity, functional status and quality of life in patients with ankylosing spondylitis (AS). A total of 25 patients with AS had undergone ileocolonoscopy and concomitant histological study. Clinical and demographical parameters, BASDAI, BASFI, and SF-36 scores were compared between patients with and without macroscopic gut inflammation (MGI). Colonoscopic study revealed MGI in 9 patients and macroscopically normal gut mucosa in 16 patients. On histological examination, of 25 patients 20 had gut inflammation, mostly in ileum. BASDAI score was higher (P < 0.05), SF-36 pain and physical scores, and chest expansion measurement were lower (P = 0.00, P = 0.01, P = 0.01), duration of morning stiffness was longer (P = 0.01) in patients with MGI. Serum C-reactive protein, erytrocyte sedimentation rate levels were similar between groups (P > 0.05). There is high prevalence of histological gut inflammation in AS patients. More active disease should suggest gut inflammation in AS patients.     

Similar clinical outcomes following collagen or polyurethane meniscal scaffold implantation: a systematic review

Purpose

The purpose of this systematic review is to evaluate the current literature in an effort to assess specific clinical outcomes following meniscal scaffold implantation using the two available scaffolds: Collagen Meniscal Implant (CMI) and the Actifit polyurethane meniscal scaffold.

Methods

A systematic review was performed by searching PubMed, Embase, and Cochrane Library to find studies evaluating clinical outcomes of patients undergoing meniscal scaffold implantation. Search terms used were “meniscus”, “meniscal”, “scaffold”, and “implant”. Studies were evaluated based on scaffold type, treatment failure rates, patient-reported outcome scores, concomitant procedures, and radiological findings. Radiological findings were recorded using the Genovese scale to assess morphology and signal intensity and the Yulish score to assess articular cartilage.

Results

Nineteen studies (1 level I, 1 level II, 17 level IV evidence) were identified that met inclusion criteria, including a total of 658 patients (347 Actifit, 311 CMI). The overall average follow-up was 45 months. Treatment failure occurred in 9.9% of patients receiving the Actifit scaffold at a mean follow-up of 40 months and 6.7% of patients receiving CMI at a mean follow-up of 44 months (n.s.). However, the rate of failure ranged from 0 to 31.8% amongst the included studies with a variable definition of failure. Additionally, overlapping patients and presence of concomitant surgeries such as anterior cruciate ligament reconstruction (ACLR) and high tibial osteotomy (HTO) may have a significant influence on these results. Outcomes for the Visual Analog Scale (VAS) for pain, Lysholm knee score, and Tegner activity score improved from preoperatively to latest follow-up in both groups, while the Knee Injury and Osteoarthritis Outcome Score and International Knee Documentation Committee scores improved from preoperatively to latest follow-up for Actifit scaffold patients. Overall, patients receiving CMI scaffolds had higher grades for Genovese morphology and signal intensity when compared to Actifit scaffold patients.

Conclusion

Patients undergoing meniscal scaffold implantation with either CMI or Actifit scaffold can both be expected to experience improvement in clinical outcomes when used in association with concomitant procedures such as ACLR and HTO.

Level of evidence

IV, systematic review.

     

Ring Chromosome 13 and Ambiguous Genitalia

Ambiguous genitalia, known to be associated with sex chromosome disorders, may also be seen with autosomal chromosome anomalies. Herein, we report a case with ambiguous genitalia and ring chromosome 13. Ring chromosome 13 is a rare genetic anomaly in which the loss of genetic material determines the clinical spectrum.     

Automatic determination of timing intervals for upper limit of vulnerability using ICD electrograms

Background: Implantable cardioverter defibrillator (ICD) implant testing based on the upper limit of vulnerability, or vulnerability testing, permits assessment of defibrillation safety margins without inducing ventricular fibrillation (VF) in most patients. Vulnerability testing requires that T-wave shocks be timed at the most vulnerable intervals of the cardiac cycle, defined as intervals at which the strongest shock induces VF. Our goal was to develop and test an automated method to select these timing intervals using ICD intracardiac electrograms (EGMs).
Methods: At ICD implant in 22 patients, we determined the range of the most vulnerable intervals by scanning the T wave with shocks. Simultaneously, EGMs were recorded for 351 pacing sequences used for measurement of timing intervals or T-wave shocks. EGMs were analyzed off-line using a novel automated method to identify a stable point near the maximum slope of the T wave in the far-field (shock) EGM. Fiducial timing points based both on the EGM and on the electrocardiogram (ECG) were used to predict the most vulnerable intervals. We compared the predicted most vulnerable to the measured most vulnerable intervals determined by T-shock scans.
Results: Automatically determined timing points from EGMs and operator-determined timing points from the surface ECG had comparable accuracy in identifying the measured most vulnerable intervals (91% EGM vs 86% ECG, P = NS).
Conclusions: An automated method based on ICD EGMs identifies the most vulnerable intervals with accuracy comparable to the operator-performed, clinical method based on the surface ECG. This EGM method can be implemented efficiently in an ICD to automate vulnerability testing.