Autograft and pulmonary allograft performance in the second post-operative decade after the Ross procedure: insights from the Rotterdam Prospective Cohort Study

Aims The objective of the present study was to report our ongoing prospective cohort of autograft recipients with up to 21 years of follow-up. Methods and results All consecutive patients (n = 161), operated between 1988 and 2010, were analysed. Mixed-effects models were used to assess changes in echocardiographic measurements (n = 1023) over time in both the autograft and the pulmonary allograft. The mean patient age was 20.9 years (range 0.05-52.7)-66.5% were male. Early mortality was 2.5% (n = 4), and eight additional patients died during a mean follow-up of 11.6 ± 5.7 years (range 0-21.5). Patient survival was 90% [95% confidence interval (CI), 78-95] up to 18 years. During the follow-up, 57 patients required a re-intervention related to the Ross operation. Freedom from autograft reoperation and allograft re-intervention was 51% (95% CI 38-63) and 82% (95% CI 71-89) after 18 years, respectively. No major changes were observed over time in autograft gradient, and allograft gradient and regurgitation. An initial increase of sinotubular junction and aortic anulus diameter was observed in the first 5 years after surgery. The only factor associated with an increased autograft reoperation rate was pre-operative pure aortic regurgitation (AR) (hazard ratio 1.88; 95% CI 1.04-3.39; P= 0.037). Conclusion We observed good late survival in patients undergoing autograft procedure without reinforcement techniques. However, over half of the autografts failed prior to the end of the second decade. The reoperation rate and the results of echocardiographic measurements over time underline the importance of careful monitoring especially in the second decade after the initial autograft operation and in particular in patients with pre-operative AR.     

Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation

Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. Conclusion: This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy.     

PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?

Purpose

To evaluate the effect of vardenafil on renal function after renal ischemia–reperfusion (IR) injury (IRI) in a rat model.

Materials and methods

Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3–6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated.

Results

Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI.

Conclusions

Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.     

Enamel Matrix Derivative in Intrabony Defects: Prognostic Parameters of Clinical and Radiographic Treatment Outcomes

Background: The purpose of this retrospective case series study is to identify possible preoperative parameters that could predict postoperative probing depth (PD), clinical attachment level (CAL) gain, or radiographic defect resolution in intrabony defects treated with enamel matrix derivative (EMD). Methods: Sixty‐one chronic periodontitis patients, each contributing a 2‐ or 3‐wall intrabony defect treated with EMD, were included. Clinical parameters recorded included the following: PD; CAL; gingival margin position; supracrestal soft tissue (SST); surgical distances of cemento‐enamel junction (CEJ) to bone crest (CEJ‐BC), CEJ to base of the defect (CEJ‐BD), and BC to BD (BC‐BD); and depth of 2‐ and 3‐wall components. Radiographic parameters recorded included the following: CEJ‐BC, CEJ‐BD, BC‐BD distances, and radiographic defect angle. Postoperative assessments were performed at 12 months. Results: The probability of postoperative PD >4 mm increased 1.6‐fold (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.2 to 2.3) with each 1‐mm baseline PD increase. Baseline PD and surgical CEJ‐BD were statistically significant predictors of CAL gain; the greater the baseline PD (OR = 0.5; 95% CI = 0.3 to 0.8) and bone loss (OR = 0.6; 95% CI = 0.3 to 0.9), the less likely that postoperative CAL gain was ≤3 mm. Smoking and SST were significantly associated with defect resolution; failure to achieve ≥65% defect resolution was six‐fold greater for smokers (OR = 6.5; 95% CI = 1.7 to 24.5) and almost double (OR = 1.7; 95% CI = 1.1 to 2.8) for each millimeter of SST increase. Conclusion: In EMD‐treated intrabony defects, baseline PD predicts both CAL gain and postoperative PD. Smoking and SST are predictors of defect resolution.     

Levodopa‐induced dyskinesias in tyrosine hydroxylase deficiency

The objective of this study was to characterize levodopa (l‐ dopa)–induced dyskinesias in patients with tyrosine hydroxylase deficiency. Clinical observation was carried out on 6 patients who were diagnosed with tyrosine hydroxylase deficiency and were treated with escalating doses of l‐ dopa. All 6 patients showed l ‐dopa‐induced dyskinesias of variable intensity early in the course of treatment and regardless of the age of initiation. l ‐Dopa–induced dyskinesias were precipitated by increases in the dose of l ‐dopa and also by febrile illnesses and stress. They caused dysfunction and distress in 2 patients. The dyskinesias were improved by decreasing the l ‐dopa dose or by slowing its titration upward. Increasing the dose frequency was helpful in 2 patients, and introducing amantadine was helpful in another 2 patients. l ‐Dopa–induced dyskinesias are a common phenomenon in tyrosine hydroxylase deficiency. The current observations show that l‐ dopa–induced dyskinesias are frequent in a dopamine‐deficient state in the absence of nigrostriatal degeneration. Although l ‐dopa–induced dyskinesias in tyrosine hydroxylase deficiency are phenomenologically similar to those that occur in Parkinson's disease, they are different in a number of other respects, suggesting intrinsic differences in the pathophysiologic basis of l‐ dopa–induced dyskinesias in the 2 conditions. © 2013 Movement Disorder Society     

ESCAP CovCAP survey of heads of academic departments to assess the perceived initial (April/May 2020) impact of the COVID-19 pandemic on child and adolescent psychiatry services

In April 2020, the European Society for Child and Adolescent Psychiatry (ESCAP) Research Academy and the ESCAP Board launched the first of three scheduled surveys to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on child and adolescent psychiatry (CAP) services in Europe and to assess the abilities of CAP centers to meet the new challenges brought on by the crisis. The survey was a self-report questionnaire, using a multistage process, which was sent to 168 heads of academic CAP services in 24 European countries. Eighty-two responses (56 complete) from 20 countries, representing the subjective judgement of heads of CAP centers, were received between mid-April and mid-May 2020. Most respondents judged the impact of the crisis on the mental health of their patients as medium (52%) or strong (33%). A large majority of CAP services reported no COVID-19 positive cases among their inpatients and most respondents declared no or limited sick leaves in their team due to COVID-19. Outpatient, daycare, and inpatient units experienced closures or reductions in the number of treated patients throughout Europe. In addition, a lower referral rate was observed in most countries. Respondents considered that they were well equipped to handle COVID-19 patients despite a lack of protective equipment. Telemedicine was adopted by almost every team despite its sparse use prior to the crisis. Overall, these first results were surprisingly homogeneous, showing a substantially reduced patient load and a moderate effect of the COVID-19 crisis on psychopathology. The effect on the organization of CAP services appears profound. COVID-19 crisis has accelerated the adoption of new technologies, including telepsychiatry.