Prevalence of Posttransplantation Lymphoproliferative Disease in Pediatric Liver Transplant Recipients

Objective

The objective of this study was to identify the incidence of posttransplantation lymphoproliferative disease (PTLD) among children within 1 year after liver transplantation.

Methods

This retrospective review analyzed information in medical charts of pediatric (younger than 18 years of age) recipients of liver transplants between September 2000 and December 2007.

Results

Seventy-one patients underwent a liver transplantation and 7 (9.85%) developed PTLD. Among this group, 6 children were girls and 1 was a boy. The median age at transplantation was 35.14 months. Indications that led the children to have their transplantation were 1 case of hemangioendothelioma, 1 case of autoimmune hepatic cirrhosis, 1 case of alpha-1-antitrypsin deficiency, and 4 cases of biliary atresia. The most frequent symptoms were splenomegaly, diarrhea, and fever. The median time from the first symptoms to the initial treatment was 9.7 days. The standard treatment was withdrawal of immunosuppression and close observation of tacrolimus levels and liver function tests associated with antiviral drugs and chemotherapy. Four among 7 children died; 3 children recovered. All 3 children who recovered has presented at the transplantation center within 5 days of initiation of symptoms (P = .033896).

Conclusion

Despite its rarity, when it occurs, PTLD shows a high mortality rate. Therefore, it is necessary to have interdisciplinary work between the medical team that performs the transplantation and those promoting the primary care to diagnose the disease early and treat it effectively.     

Retrograde Versus Antegrade Nerve Sparing During Robot-assisted Radical Prostatectomy: Which Is Better for Achieving Early Functional Recovery?

Background

Although the retrograde approach to nerve sparing (NS) aimed at maximizing NS during robot-assisted radical prostatectomy (RARP) has been described, its significant benefits compared to the antegrade approach have not yet been investigated.

Objective

To evaluate the impact of NS approaches on perioperative, pathologic, and functional outcomes.

Design, setting, and participants

Five hundred one potent (Sexual Health Inventory for Men [SHIM] score >21) men underwent bilateral full NS and were followed up for a minimum of 1 yr. After propensity score matching, 344 patients were selected and were then categorized into two groups.

Surgical procedure

RARP with antegrade NS (n = 172) or RARP with retrograde NS (n = 172).

Outcome measurements and statistical analysis

Functional outcomes were assessed using validated questionnaires. Multivariable logistic regression models were applied.

Results and limitations

Positive margin rates were similar (11.1% vs 6.9%; p = 0.192), and no correlation with the NS approach was found on regression analysis. At 3, 6, and 9 mo, the potency rate was significantly higher in the retrograde approach (65% vs 80.8% and 72.1% vs 90.1% and 85.3% vs 92.9%, respectively). The multivariable model indicated that the NS approach was an independent predictor for potency recovery at 3, 6, and 9 mo, along with age, gland size, and hyperlipidemia. After adjusting for these predictors, the hazard ratio (HR) for the retrograde relative to the antegrade approach was 2.462 (95% confidence interval [CI], 1.482–4.089; p = 0.001) at 3, 4.024 (95% CI, 2.171–7.457; p < 0.001) at 6, and 2.145 (95% CI, 1.019–4.514; p = 0.044) at 9 mo. Regarding continence, the recovery rates at each time point and the mean time to regaining it were similar, and the method of NS had no effect on multivariable analysis. The absence of randomization is a major limitation of this study.

Conclusions

In patients with normal erectile function who underwent bilateral full NS, a retrograde NS approach facilitated early recovery of potency compared to that with an antegrade NS approach without compromising cancer control.     

Interferon-alpha and -beta differentially regulate osteoclastogenesis: role of differential induction of chemokine CXCL11 expression

In humans, type I interferon (IFN) is a family of 17 cytokines, among which the alpha subtypes and the beta subtype are differentially expressed. It has been suggested that IFN-beta activates a specific signaling cascade in addition to those activated by all type I IFNs. Nevertheless, no true biological relevance for a differential activity of alpha and beta IFN subtypes has been identified so far. Because type I IFNs are critical for the regulation of osteoclastogenesis in mice, we have compared the effect of IFN-alpha2 and IFN-beta on the differentiation of human monocytes into osteoclasts. Primary monocytes undergoing osteoclastic differentiation are highly and equally sensitive to both alpha2 and beta IFNs as determined by measuring the induction levels of several IFN-stimulated genes. However, IFN-beta was 100-fold more potent than the alpha2 subtype at inhibiting osteoclastogenesis. Expression profiling of the genes differentially regulated by IFN-alpha2 and IFN-beta in this cellular system revealed the chemokine CXCL11 as the only IFN-induced gene differentially up-regulated by IFN-beta. We show that recombinant CXCL11 by itself inhibits osteoclastic differentiation. These results indicate that autocrine-acting CXCL11 mediates, at least in part, the regulations of osteoclastogenesis by type I IFNs.     

An integrative review exploring the physical and psychological harm inherent in using restraint in mental health inpatient settings

In Western society, policy and legislation seeks to minimize restrictive interventions, including physical restraint; yet research suggests the use of such practices continues to raise concerns. Whilst international agreement has sought to define physical restraint, diversity in the way in which countries use restraint remains disparate. Research to date has reported on statistics regarding restraint, how and why it is used, and staff and service user perspectives about its use. However, there is limited evidence directly exploring the physical and psychological harm restraint may cause to people being cared for within mental health inpatient settings. This study reports on an integrative review of the literature exploring available evidence regarding the physical and psychological impact of restraint. The review included both experimental and nonexperimental research papers, using Cooper's (1998) five‐stage approach to synthesize the findings. Eight themes emerged: Trauma/retraumatization; Distress; Fear; Feeling ignored; Control; Power; Calm; and Dehumanizing conditions. In conclusion, whilst further research is required regarding the physical and psychological implications of physical restraint in mental health settings, mental health nurses are in a prime position to use their skills and knowledge to address the issues identified to eradicate the use of restraint and better meet the needs of those experiencing mental illness.     

Urinary bladder inflammation induces changes in urothelial nerve growth factor and TRPV1 channels

Background and Purpose

The urinary bladder urothelium expresses various receptors and in response to chemical and mechanical stimuli releases mediators, thereby modulating bladder sensory pathways. Transient receptor potential vanilloid 1 (TRPV1) ion channels and nerve growth factor (NGF) in those cells are implicated in this modulatory effect and play a role in sensitizing pain-related afferent pathways during inflammation. In this study, we investigated the interaction between NGF and TRPV1 channels in urothelial cells.

Experimental Approach

Urothelial cells from female Sprague-Dawley rat bladders were cultured to quantify membrane expression of TRPV1 channels and capsaicin-induced ATP release in the presence of NGF alone or with TrKA or PI3K inhibitors. Pain scores from rats with cyclophosphamide (CYP)-induced bladder inflammation were assessed after treatment with a TrkA antagonist. Bladders (from control and CYP rats) were collected and analysed for NGF content and TRPV1 channel expression.

Key Results

Cultured cells responded to NGF with increased TRPV1 channel expression in the cell membrane and increased release of ATP. Both responses were blocked by either a TrkA antagonist or a PI3K inhibitor. Treatment in vivo with the TrkA antagonist alleviated pain symptoms and reduced CYP-induced NGF overexpression in the mucosa. Furthermore, in urothelial cells from animals with bladder inflammation, expression of TRPV1 channels in the membrane was significantly increased.

Conclusions and Implications

During bladder inflammation, increased production of NGF in urothelial cells induced increased expression and activity of TRPV1 channels in the cell membrane. This effect was primarily mediated by the PI3K pathway.     

Non-vitamin K antagonist oral anticoagulation versus left atrial appendage occlusion for primary and secondary stroke prevention after cardioembolic stroke

IntroductionThis study aimed to evaluate the performance of non-vitamin K antagonist oral anticoagulation (NOAC) in patients with previous stroke and non-valvular atrial fibrillation (AF) compared with left atrial appendage occlusion (LAAO) in primary and secondary stroke prevention settings.MethodsThis was a prospective, single-center, non-randomized cohort study of 302 consecutive patients with non-valvular AF and at high risk for stroke. Two treatment strategies were compared: LAAO (n=91) and long-term treatment with NOAC (n=149). The primary outcome was the composite endpoint of death, stroke and major bleeding. Propensity score and cause-of-death analyses were performed to compare outcomes.ResultsIn a mean follow-up of 13 months, there were 30 deaths (LAAO 8.8% vs. NOAC 14.8%), five strokes (LAAO 1.1% vs. NOAC 2.7%) and six major bleeds (LAAO 1.1% vs. NOAC 3.4%). There was a non-significant trend for a lower incidence of the primary endpoint in the LAAO group (11.0% vs. 20.9%; HR 0.42, 95% CI 0.17-1.05, p=0.064). Considering only secondary prevention LAAO patients (34.1% of the LAAO group), there was also a non-significant lower incidence of the primary endpoint (LAAO 6.5% vs. 20.9%; HR 0.30, 95% CI 0.07-1.39, p=0.12). While about a fifth of LAAO patients stopped antiplatelet treatment six months after device implantation due to recurrent minor bleeding, no adverse cardiovascular event or major bleeding occurred in this subset of patients.ConclusionIn this registry-based study, LAAO was a reasonable alternative to NOAC for the prevention of a composite endpoint of all-cause mortality, stroke and major bleeding in patients at high risk for stroke.     

Stress distribution of different implant connections associated with multiple implant-supported prostheses

Abstract

In some clinical situations, the clinician may encounter previously installed implants that should be associated with other implants for a proper rehabilitation. The aim of this study was to evaluate the biomechanical behaviour of a multiple prosthesis joined by different implant connections using photoelasticity. Photoelastic models with a screwed fixed prosthesis supported by implants with different connection systems (Morse taper, external hexagon, internal hexagon, and Flexcone), and different combinations among them, were fabricated. Each assembly was placed in a circular polariscope, and axial and oblique (45°) loads of 100 N were applied on the occlusal surface of the crowns. The fringe patterns were photographed and the analysis was performed by counting the number of high-intensity fringes and also according to the stress distribution region where they appeared. Among implants of the same connection, the external connections obtained a greater number of high intensity fringes when compared to the internal connections. From the biomechanical point of view, the association between different types of connections obtained positive results.