Non‐invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological‐pathological correlation analysis

Objectives

To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis.

Methods

Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification.

Results

A total of 40 elastography scans were carried out (median creatinine 172.5 μmol/L [interquartile range 133.8–281.8 μmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8–25.7 kPa] vs 22.3 kPa [interquartile range 19.0–26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7–18.0 kPa] vs 15.6 kPa [interquartile range 14.4–18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70–0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78–0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61–0.89), 0.85 (95% CI 0.75–0.95) and 0.65 (95% CI 0.53–0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively.

Conclusions

Shear wave elastography can be used as a non‐invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis.     

Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice

Background and purpose:

W/W^v and wild-type murine bladders were studied to determine whether the W/W^v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Experimental approach:

Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.

Key results:

Wild-type and W/W^v detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/W^v detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/W^v strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both tissue types. Wild-type and W/W^v detrusors had similar resting membrane potentials of −48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/W^v preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both preparations.

Conclusions and implications:

Bladders from W/W^v mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/W^v and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/W^v strain may not be the best model to study ICC function in the bladder.     

A profile of the online dissemination of national influenza surveillance data

Background  

Influenza surveillance systems provide important and timely information to health service providers on trends in the circulation of influenza virus and other upper respiratory tract infections. Online dissemination of surveillance data is useful for risk communication to health care professionals, the media and the general public. We reviewed national influenza surveillance websites from around the world to describe the main features of surveillance data dissemination.     

Ocular globe luxation under general anesthesia

We present a case of ocular globe luxation after general anesthesia. Upon completion of the surgery, the upper eyelid was retracted to examine for conjunctival edema, which resulted in globe luxation. The posterior aspect of the globe was visualized and a small tethering white structure ("check ligament") was observed. The upper lid was retracted, and the globe easily repositioned into the orbit. Ophthalmic sequelae would not be anticipated if the episode of globe luxation is brief. Anesthesiologists should be aware of the risk factors associated with globe luxation and know how to appropriately treat this complication.     

Association of seborrhoeic warts with skin cancer in renal transplant recipients**

Background Renal transplant recipients (RTR) have a well recognized increased risk of cutaneous malignancy. A clinical observation that RTR with skin cancer often had multiple seborrhoeic warts prompted an investigation in RTR into the relationship between seborrhoeic warts and skin cancer and an exploration into potential risk factors for seborrhoeic warts in this population, including infection with human papillomavirus (HPV). Methods This was a case control study involving 308 RTR. Clinical examinations identified seborrhoeic warts. Histological records reviewed to look for evidence of prior cutaneous malignancy. Seroprevalence of antibodies to 34 different HPV types tested using multiplex serology. Odds ratios (OR) calculated using unconditional logistic regression analysis to look for associations between skin cancer, HPV infection and seborrhoeic warts, controlling for potential confounding factors of gender, age and time since transplantation. Results Seborrhoeic warts were associated with non‐melanoma skin cancer [OR = 3.7; 95% confidence intervals (CI) ranging from 1.6–8.9; P = 0.002] when confounding factors of gender, age and time since transplantation were controlled for. There was also an association between seborrhoeic warts and viral warts (OR = 3.0, CI: 1.6–5.4; P < 0.0001), but no association between seborrhoeic warts and infection with single or multiple HPV types. Conclusions Seborrhoeic warts are associated with cutaneous malignancy, but not with any of the HPV types tested. The reasons for this association are unclear. RTR with multiple seborrhoeic warts may require more regular cutaneous examination to monitor for early signs of skin cancer.     

Psychiatric genetics researchers' views on offering return of results to individual participants

In the middle of growing consensus that genomics researchers should offer to return clinically valid, medically relevant, and medically actionable findings identified in the course of research, psychiatric genetics researchers face new challenges. As they uncover the genetic architecture of psychiatric disorders through genome‐wide association studies and integrate whole genome and whole exome sequencing to their research, there is a pressing need for examining these researchers' views regarding the return of results (RoR) and the unique challenges for offering RoR from psychiatric genetics research. Based on qualitative interviews with 39 psychiatric genetics researchers from different countries operating at the forefront of their field, we provide an insider's view of researchers' practices regarding RoR and the most contentious issues in psychiatry researchers' decision‐making around RoR, including what are the strongest ethical, scientific, and practical arguments for and against offering RoR from this research. Notably, findings suggest that psychiatric genetics researchers (85%) overwhelmingly favor offering RoR of at least some findings, but only 22% of researchers are returning results. Researchers identified a number of scientific and practical concerns about RoR, and about how to return results in a responsible way to patients diagnosed with a severe psychiatric disorder. Furthermore, findings help highlight areas for further discussion and resolution of conflicts in the practice of RoR in psychiatric genetics research. As the pace of discovery in psychiatric genetics continues to surge, resolution of these uncertainties gains greater urgency to avoid ethical pitfalls and to maximize the positive impact of RoR.