Soluble CD30 correlates with clinical but not subclinical renal allograft rejection

Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for clinical renal allograft rejection, but its diagnostic characteristics regarding detection of subclinical rejection have not been assessed. We investigated sCD30 in 146 consecutive kidney allograft recipients under tacrolimus–mycophenolate‐based immunosuppression having 250 surveillance biopsies at 3 and 6 months as well as 52 indication biopsies within the first year post‐transplant. Allograft histology results were classified as (i) acute Banff score zero or interstitial infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2‐3 and (iv) isolated vascular compartment inflammation. sCD30 correlated well with the extent of clinical (P < 0.0001), but not subclinical tubulointerstitial rejection (P = 0.06). To determine diagnostic characteristics of sCD30, histological groups were assigned to two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (tubulitis t1‐3 and isolated vascular compartment inflammation). For clinical allograft inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006); however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%, specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but not subclinical renal allograft rejection limiting its clinical utility as a noninvasive rejection screening biomarker in patients with stable allograft function receiving tacrolimus–mycophenolate‐based immunosuppression.     

Up-regulation of Fas (CD95) expression in tumour cells in vivo

Both the function and regulation of Fas expression in tumours is poorly understood. Our laboratory has reported that cultured, low Fas-expressing tumours undergo massive, yet reversible, up-regulation of cell surface Fas expression when injected into mice. The present study was aimed at determining what causes this enhanced Fas expression and whether the newly expressed Fas functions as a death receptor. Newly expressed Fas is indeed capable of inducing apoptosis. Based on our observation that Fas induction is reduced when tumour cells are injected into immune-deficient mice, we propose that Fas up-regulation in vivo involves the host's immune system. Accordingly, Fas up-regulation occurs in vitro when low Fas-expressing tumour cells are cocultured with lymphoid cells. Furthermore ascitic fluid extracted from tumour-bearing mice trigger Fas up-regulation in low Fas expressing tumours. This last finding suggests that a soluble factor(s) mediates induction of Fas expression. The best candidate for this soluble factor is nitric oxide (NO) based on the following observations: the factor in the ascites is unstable; Fas expression is induced to a lesser degree after injection into inducible NO synthase (NOS)-deficient (iNOS(-/-)) mice when compared to control mice; similarly, coculture with iNOS(-/-) splenocytes induces Fas less effectively than coculture with control splenocytes; and finally, the NO donor SNAP induces considerable Fas up-regulation in tumours in vitro. Our model is that host lymphoid cells in response to a tumour increase NO synthesis, which in turn causes enhanced Fas expression in the tumour.     

Exposure to sibutramine during pregnancy

QUESTION: One of my patients who was taking sibutramine to lose weight found out that she had unexpectedly conceived. The medication was stopped as soon as she found out, about 5 weeks into the pregnancy. Is the baby at risk? Should the pregnancy be aborted? ANSWER: No data to date suggest that involuntary exposure to sibutramine during pregnancy carries major risk of congenital malformations. Nevertheless, this medication should be avoided whenever possible during pregnancy, as there is little information on its effects.     

Effects of surgery for obstructive sleep apnea on cognitive function and driving performance

Background

Obstructive sleep apnea (OSA) is associated with a significantly increased risk of motor vehicle accidents in addition to such cognitive impairments as attention and memory deficits. The aim of the study was to examine the effect of upper airway surgery for OSA on driving and cognitive function.

Methods

Adult patients who underwent surgery for OSA at a tertiary medical center in 2016–2019 were prospectively recruited. Patients were assessed before and 3–6 months after surgery with a self-report and neurocognitive battery and a driving simulation platform.

Results

The cohort included 32 patients of average age 46.9 ± 11.6 years. During the 3 years before treatment, 9 patients had been involved in road accidents and 18 were detained by police for traffic violations. After surgery, there was a significant decrease in the Epworth Sleepiness Scale (13.7 vs. 8.1, p 0.043) and a significant reduction in time to completion of the Color Trail Test (part 1: 21.4 vs 18.7 s, p = 0.049; part 2: 46.8 vs 40.5 s, p = 0.038). Improvements in divided attention and selective attention response times were noted on the advanced stages of the Useful Field of Vision Scale (p = 0.013, p = 0.054). Before surgery, patients showed a high tendency to drive over the speed limit and to cross the dividing line to the opposite lane on the simulation test. Nevertheless, all considered themselves good drivers. These tendencies decreased after treatment.

Conclusions

Surgery for OSA can significantly improve driving performance and cognitive function.

     

Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia

Summary. Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using J_H and Cμ gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing J_H bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site.
The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.