Pediatric Liver Transplant Recipients Who Undergo Transfer to the Adult Healthcare Service Have Good Long-Term Outcomes.

Liver transplantation has transformed survival for children with liver disease necessitating the transfer of a growing number of patients to the adult healthcare service. The impact of transfer on outcomes remains unclear. The aim of this single-center study of 137 consecutive pediatric liver transplant recipients was to examine the effect of transfer on patient and graft survival. The median time from transplant to transfer was 10.4 years and the median age of the patients at transfer was 18.6 years. After transfer, there were 5 re-transplants and 12 deaths in 14 patients. The estimated posttransfer 10-year patient and graft survival was 89.9% and 86.2%, respectively. Overall, 4 patients demonstrated graft loss as a consequence of chronic rejection. Graft loss was associated with older age at first transplant (p = 0.008). When compared to young adult patients transplanted in the adult center, the transferred patients did not have inferior graft survival from the point of transfer (HR 0.28; 95% CI 0.10-0.77, p = 0.014). This suggests that transfer did not impact significantly on graft longevity. In conclusion, pediatric liver transplant recipients who undergo transfer to the adult service have good long-term outcomes.

Review article: advances in the management of patients with cirrhosis and portal hypertension-related renal dysfunction.

BACKGROUND: In cirrhosis, portal hypertension is associated with a spectrum of renal dysfunction that has significant implications for morbidity and mortality. AIM: To discuss recent progress in the patho-physiological mechanisms and therapeutic options for portal hypertension-related renal dysfunction. METHODS: A literature search using Pubmed was performed. RESULTS: Portal hypertension-related renal dysfunction occurs in the setting of marked neuro-humoral and circulatory derangement. A systemic inflammatory response is a pathogenetic factor in advanced disease. Such physiological changes render the individual vulnerable to further deterioration of renal function. Patients are primed to develop acute kidney injury when exposed to additional 'hits', such as sepsis. Recent progress has been made regarding our understanding of the aetiopathogenesis. However, treatment options once hepatorenal syndrome develops are limited, and prognosis remains poor. Various strategies to prevent acute kidney injury are suggested. CONCLUSION: Prevention of acute kidney injury in high risk patients with cirrhosis and portal hypertension-related renal dysfunction should be a clinical priority.

Review article: liver transplantation for the pulmonary disorders of portal hypertension.

BACKGROUND: Liver transplantation is potentially a life-saving therapeutic intervention for patients with portopulmonary hypertension and hepatopulmonary syndrome. However, due to limited data, listing criteria for patients with these conditions have not been clearly established. Indeed, this has led some to speculate that transplantation may not be appropriate in cases of moderate-to-severe portopulmonary hypertension and severe hepatopulmonary syndrome. AIM: To critically discuss the utility of LT for the treatment of hepatopulmonary syndrome and portopulmonary hypertension. METHODS: A literature search was conducted in 2012 on PubMed, Ovid Embase, Ovid Medline and Scopus using the following search terms: hepatopulmonary syndrome, portopulmonary hypertension, pulmonary arterial hypertension, liver transplantation. Relevant manuscripts were included in the review. RESULTS: Liver transplantation has established itself as an effective treatment for selected patients with hepatopulmonary syndrome and portopulmonary hypertension. A multidisciplinary team approach incorporating focused strategies (both pre- and post-operatively) aimed at improving oxygenation in patients with hepatopulmonary syndrome has led to a dramatic improvement in patient outcomes. Additionally, careful patient selection and the use of targeted pulmonary vascular therapies are successfully being used to treat portopulmonary hypertension and 'bridge' patients to successful liver transplantation. CONCLUSIONS: Liver transplantation is an effective therapy for patients with hepatopulmonary syndrome and portopulmonary hypertension. However, rigorous screening and early identification of these conditions allied with aggressive pre-operative optimisation of physiology and diligent post-operative care are imperative to ensuring a good outcome.

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury.

Donation after cardiac death (DCD) liver transplantation is associated with an increased frequency of hepato-biliary complications. The implications for renal function have not been explored previously. The aims of this single-center study of 88 consecutive DCD liver transplant recipients were (1) to compare renal outcomes with propensity-risk-matched donation after brain death (DBD) patients and (2) in the DCD patients specifically to examine the risk factors for acute kidney injury (AKI; peak creatinine ≥2 times baseline) and chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m(2) ). During the immediate postoperative period DCD liver transplantation was associated with an increased incidence of AKI (DCD, 53.4%; DBD 31.8%, p = 0.004). In DCD patients AKI was a risk factor for CKD (p = 0.035) and mortality (p = 0.017). The cumulative incidence of CKD by 3 years post-transplant was 53.7% and 42.1% for DCD and DBD patients, respectively (p = 0.774). Importantly, increasing peak perioperative aspartate aminotransferase, a surrogate marker of hepatic ischemia reperfusion injury, was the only consistent predictor of renal dysfunction after DCD transplantation (AKI, p < 0.001; CKD, p = 0.032). In conclusion, DCD liver transplantation is associated with an increased frequency of AKI. The findings suggest that hepatic ischemia reperfusion injury may play a critical role in the pathogenesis of post-transplant renal dysfunction.

Chronic kidney disease after liver transplantation for acute liver failure is not associated with perioperative renal dysfunction.

Renal dysfunction of acute liver failure (ALF) may have distinct pathophysiological mechanisms to hepatorenal syndrome of cirrhosis. Yet, the impact of perioperative renal function on posttransplant renal outcomes in ALF patients specifically has not been established. The aims of this study were (1) to describe the incidence and risk factors for chronic renal dysfunction following liver transplantation for ALF and (2) to compare renal outcomes with age-sex-matched patients transplanted for chronic liver disease. This was a single-center study of 101 patients transplanted for ALF. Fifty-three-and-a-half percent had pretransplant acute kidney injury and 64.9% required perioperative renal replacement therapy. After transplantation the 5-year cumulative incidence of chronic kidney disease (eGFR <60 mL/min/1.73 m²) was 41.5%. There was no association between perioperative acute kidney injury (p = 0.288) or renal replacement therapy (p = 0.134) and chronic kidney disease. Instead, the independent predictors of chronic kidney disease were older age (p = 0.019), female gender (p = 0.049), hypertension (p = 0.031), cyclosporine (p = 0.027) and nonacetaminophen-induced ALF (p = 0.039). Despite marked differences in the perioperative clinical condition and survival of patients transplanted for ALF and chronic liver disease, renal outcomes were the same. In conclusion, in patients transplanted for ALF the severity of perioperative renal injury does not predict posttransplant chronic renal dysfunction.

Do Mediterranean crickets Gryllus bimaculatus De Geer (Orthoptera: Gryllidae) come from the Mediterranean? Largescale phylogeography and regional gene flow.

We investigate the degree of between-population genetic differentiation in the Mediterranean field cricket Gryllus bimaculatus, as well as the possible causes of such differentiation. Using cytochrome b mtDNA sequences, we estimate genetic variation in G. bimaculatus from seven South African and two Mediterranean populations. Within-population genetic variation in Europe (two haplotypes, one unique to a single individual) suggest low effective population size and strong bottlenecks with associated founder effects, probably due to cold winter environments in Europe that limit reproduction to a short part of the summer. The likely cause for this is the daily maxima in winter temperatures that fall below the critical level of 16 degrees C (enabling normal calling and courtship behaviour) in Mediterranean Europe, whereas the equivalent temperatures in southern Africa are above this limit and enable reproduction over a large part of the year. European genetic variants were either shared with Africa or closely related to African haplotypes. For survival, European populations are probably dependent on immigration from other areas, including Africa. South African populations have low but measurable gene flow with Europe and show significant between-population genetic differentiation (30 haplotypes). Isolation-by-distance is not sufficient to explain the degree of between-population genetic differences observed, and a large degree of dispersal is also required in order to account for the observed patterns. Differences in morphology and calling behaviour among these populations are underlied by these genetic differences.

The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure.

BACKGROUND: Although renal dysfunction is a common complication of acute liver failure (ALF) with significant prognostic implications, the pathophysiological mechanisms remain unclear. The current hypothesis suggests that the renal dysfunction may mirror the hepatorenal syndrome of cirrhosis. However, ALF has distinct clinical characteristics and the circulatory derangement may be more comparable with sepsis. OBJECTIVES: To examine the relationship between the systemic inflammatory response syndrome (SIRS) and renal dysfunction in ALF, and to identify additional risk factors for renal dysfunction. METHODS: A single-centre retrospective study of 308 patients with ALF was carried out. Renal dysfunction was defined according to the RIFLE criteria for acute kidney injury. RESULTS: 67% of patients developed renal dysfunction. On univariate analysis, renal dysfunction patients were more likely to be hypothermic (p = 0.010), had a faster heart rate (p<0.001), a higher white cell count (p = 0.001) and a lower PaCO(2) (p = 0.033). 78% of renal dysfunction patients and 53% of non-renal dysfunction patients had SIRS (p<0.001). On multivariate analysis, the risk factors for renal dysfunction were age (p = 0.024), fulfilled Kings College Hospital prognostic criteria (p<0.001), hypotension (p<0.001), paracetamol-induced ALF (p<0.001), infection (p = 0.077) and SIRS (p = 0.017). SIRS remained an independent predictor of renal dysfunction in the subgroup of patients with non-paracetamol-induced ALF (n = 91, p = 0.001). In contrast, in patients with paracetamol-induced ALF (n = 217), no relationship between SIRS and renal dysfunction was demonstrated (p = 0.373). CONCLUSION: SIRS is strongly associated with the development of renal dysfunction in patients with non-paracetamol-induced ALF. It is proposed that the systemic inflammatory cascade plays a key role in its pathogenesis.

Phonotactic response of female crickets on the Kramer treadmill: methodology, sensory and behavioural implications.

Since population-level variation in female mating preferences can shape intraspecific communication systems within the context of sexual selection it is essential to quantify these preferences and their sources of variation. We calculated individual female response functions for four male calling song traits in the field cricket Gryllus bimaculatus, by performing untethered phonotaxis measurements on a spherical locomotor compensator (Kramer treadmill). Firstly, we quantify the population-level sources of phonotactic variation and correct for factors that adversely affect this measurement. Secondly, we develop methodology for the characterisation of individual female phonotactic response functions suitable for population-level analyses and demonstrate the applicability of our method with respect to recent literature on Orthopteran acoustic communication. Phonotaxis towards a preferred stimulus on different occasions is highly repeatable, with lower repeatabilities away from the most preferred signal traits. For certain male signal traits, female preference and selectivity are highly repeatable. Although phonotactic response magnitude deteriorated with age, preference functions of females remained the same during their lifetimes. Finally, the limitations of measuring phonotaxis using a spherical locomotor compensator are described and discussed with respect to the estimation of the selectivity of female response.

Review article: recent advances in the management of bleeding gastric varices.

Gastric variceal bleeding can be challenging to the clinician. Tissue adhesives can control acute bleeding in over 80%, with rebleeding rates of 20-30%, and should be first-line therapy where available. Endoscopic ultrasound can assist in better eradication of varices. The potential risks of damage to equipment and embolic phenomena can be minimized with careful attention to technique. Variceal band ligation is an alternative to tissue adhesives for the management of acute bleeding, but not for secondary prevention due to a higher rate of rebleeding. Endoscopic therapy with human thrombin appears promising, with initial haemostasis rates typically over 90%. The lack of controlled studies for thrombin prevents universal recommendation outside of clinical trials. Balloon occluded retrograde transvenous obliteration is a recent technique for patients with gastrorenal shunts, although its use is limited to clinical trials. Transjugular intrahepatic portosystemic stent shunt is an option for refractory bleeding and secondary prophylaxis, with uncontrolled studies demonstrating initial haemostasis obtained in over 90%, and rebleeding rates of 15-30%. Non-cardioselective beta-blockers are an alternative to transjugular intrahepatic portosystemic stent shunt for secondary prophylaxis, although the evidence is limited. Shunt surgery should be considered in well-compensated patients. Splenectomy or embolization is an option in patients with segmental portal hypertension.

Endothelin-1 contributes to maintenance of systemic but not portal haemodynamics in patients with early cirrhosis: a randomised controlled trial.

BACKGROUND AND AIMS: Increased endothelin (ET)-1 activity may contribute to the complications of cirrhosis and portal hypertension. The aim of this study was to assess the systemic and portal haemodynamic effects of selective ET-A and ET-B receptor antagonism in patients with cirrhosis. METHODS: Sixteen patients with cirrhosis and portal hypertension (aged 52 (1) years, Pugh score 6.2 (0.3)) underwent 24 studies with infusions of: (A) selective ET-A antagonist, BQ-123 (n = 8), at 1000 and 3000 nmol/min; (B) selective ET-B antagonist, BQ-788 (n = 8), at 100 and 300 nmol/min; or (C) matched saline placebo (n = 8) in a double blind randomised manner. Haemodynamic measurements were performed through pulmonary artery, hepatic venous, and femoral artery catheters. RESULTS: Baseline patient characteristics were well matched. Compared with placebo, BQ-123 decreased mean arterial pressure (MAP -15 (11) mm Hg (-18%); p<0.02) and pulmonary vascular resistance index (PVRI -81 (54) dyn x s x m2/cm5 (-64%); p<0.05), with no effect on hepatic venous pressure gradient (HVPG), cardiac index (CI), or systemic vascular resistance index (SVRI). Compared with placebo, BQ-788 increased MAP (+11 (3) mm Hg (+12%); p<0.03) and SVRI (+1101 (709) dyn x s x m2/cm5 (+50%); p<0.05), reduced CI (-1.0 (0.4) l/min/m2 (-29%); p = 0.05) with no effect on HVPG or PVRI. CONCLUSIONS: ET-1 contributes to maintenance of systemic and pulmonary haemodynamics without acutely affecting HVPG in patients with early cirrhosis. In this group of patients, the use of selective ET-A and ET-B antagonists for the management of variceal haemorrhage is likely to be limited.

Inducible nitric oxide synthase activity contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites.

BACKGROUND: Overexpression of inducible nitric oxide synthase (iNOS) and increased nitric oxide generation may be associated with the hyperdynamic circulation of patients with cirrhosis. We have, for the first time, used the highly selective iNOS inhibitor, 1400W, to determine whether iNOS activity contributes to the regulation of vascular tone in patients with cirrhosis and ascites. METHODS: Bilateral forearm blood flow was measured using strain gauge plethysmography in eight patients with cirrhosis and ascites, and eight matched healthy volunteers during intrabrachial infusion of 1400W (0.1-1 micromol/min), N(G)-monomethyl-L-arginine (L-NMMA, a non-selective NOS inhibitor; 2-8 micromol), and norepinephrine (a control vasoconstrictor; 60-480 pmol/min). RESULTS: In patients with cirrhosis, 1400W, L-NMMA, and norepinephrine caused dose dependent reductions in forearm blood flow: peak reductions of 11 (5)%, 37 (4)%, and 48 (5)%, respectively (p < 0.05 for all). In contrast, 1400W had no effect on blood flow (+4 (8)%; NS) in healthy controls despite similar reductions in blood flow with L-NMMA and norepinephrine (39 (5)% and 49 (5)%, respectively; p < 0.05 for both). CONCLUSIONS: We have, for the first time, demonstrated that 1400W causes peripheral vasoconstriction in patients with cirrhosis but not healthy matched controls. This suggests that iNOS contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites, and may contribute towards the hyperdynamic circulation associated with this condition.

Treatment outcomes for adolescent ectodermal dysplasia patients treated with dental implants.

UNLABELLED: To evaluate dental implant survival in patients with ectodermal dysplasia (ED). To assess patterns of hypodontia in this patient group. METHOD: . A retrospective analysis of the use of dental implants in ED patients treated at the Royal Children's Hospital, Melbourne. RESULTS: Sixty-one implants were placed into 14 patients (nine male and five female). The mean age of patients receiving maxillary implants was 18 years 6 months (range 17 years 9 months-20 years 0 months) and mandibular implants was 17 years 5 months (range 12 years 2 months-21 years 11 months). The mean follow-up period was 3 years 4 months (range 1 year 18 months-5 years 1 month). Forty-three implants were placed in the anterior mandible, three in the posterior mandible and the remaining 15 in the anterior maxilla. Of the 61 implants placed, 54 [88.5%] successfully integrated and were able to be restored. Three of the 15 implants placed into the anterior maxilla [20%] failed, while four of the 46 in the anterior mandible failed [8.7%]. Five of the 14 patients [35.7%] had at least one implant fail prior to abutment connection. At the 12-month review appointments, 41 of the integrated 54 implants [76%] were reviewed and classed as successful, giving an overall success at follow up of 67.2%. Thirteen implants [21.3%] were unable to be reviewed owing to geographical reasons. Teeth most likely to be present in the maxilla were the central incisors [71%], first molars [54%] and canines [43%], whereas in the mandible they were the canines [53%] and the first premolars and first molars [40%]. CONCLUSIONS: Dental implants can be placed, restored and loaded in ED patients. Maxillary teeth most likely to be present are the central incisors, canines and first molars, whereas in the mandible the canines, first premolars and molars are most likely to be present. Prior to cessation of growth, implant placement in the symphyseal region of the anterior mandible may be performed with caution. Despite the limited numbers and with due consideration to jaw development, the results support the continual use of endosseous dental implants in this group of patients for optimal clinical outcomes.

The Palmer notation system and its use with personal computer applications.

The arguments for and against the Palmer dental notation system are briefly discussed, including the perceived difficulty of reproducing this on personal computers. Some technical solutions to the problems encountered in everyday Windows-based programs are outlined, with suggestions as to possible future applications.

Steroid cover for dental patients on long-term steroid medication: proposed clinical guidelines based upon a critical review of the literature.

Based to a great extent upon mainly anecdotal case reports and theory, there is a general acceptance that patients on long-term systemic steroid medication should receive supplementary glucocorticoids or "steroid cover" when undergoing certain types of stressful treatment including dentistry. The theoretical basis to this practice is that exogenous steroids suppress adrenal function to an extent that insufficient levels of cortisol can be produced in response to stress, posing the risk of acute adrenal crisis with hypotension and collapse. The purpose of this paper is to review relevant literature and propose clinical guidelines for dental practitioners. Of numerous reported cases of adrenal crisis following procedural interventions, few stand up to critical evaluation. Other reviewers have reached similar conclusions. A number of studies confirm the low likelihood of significant adrenal insufficiency even following major surgical procedures. Various authors have suggested modified guidelines for management of patients on steroid medications. Patients on long-term steroid medication do not require supplementary "steroid cover" for routine dentistry, including minor surgical procedures, under local anaesthesia. Patients undergoing general anaesthesia for surgical procedures may require supplementary steroids dependent upon the dose of steroid and duration of treatment.

Latex allergy in dentistry. Review and report of case presenting as a serious reaction to latex dental dam.

Latex allergy may have severe consequences including development of anaphylaxis. This report describes a patient who underwent a reaction to latex dental dam manifesting as erythema, facial swelling and mild airway compromise. Restorative procedures under latex dental dam were performed under local anaesthesia on two occasions resulting in reactions of increasing severity. Following the first event the cause of the reaction was undetermined, but attributed to a possible allergy to local anaesthetic, and managed with corticosteroids and antihistamines. On a subsequent occasion the swelling was more severe, associated with difficulty in swallowing and mild airway compromise, and was managed as previously with adrenaline also being required. Latex allergy was subsequently confirmed.