Liver transplantation in glycogen storage disease type Ib: The role of SGLT2 inhibitors.

We report on liver transplantation in two patients with GSD Ib on treatment with empagliflozin. The use of this SGLT2 inhibitor resulted in a marked decrease of 1,5-anhydroglucitol which has an important role in the development of neutropenia in this condition. As intended, this caused a significant rise of neutrophil numbers. Liver transplantation alone did not produce the desired effect and our observation argues for continuing SGLT2 inhibitor treatment after transplantation.

Religious and cultural aspects of organ donation: Narrowing the gap through understanding different religious beliefs.

BACKGROUND: The supply of viable organ donations falls significantly below the demand. Discrepancies concerning the availability of transplants cannot be explained solely by the various consent models used in different countries. There is evidence that religious beliefs of patients, potential donors, and healthcare professionals also play an important role in the decision-making process. However, to date, very little research has been conducted on the consequences of specific religious beliefs on transplantation rates. The aim of this review was to outline the religious views of Christians, Muslims, Jews, Hindus, and Buddhists on organ donation. Additionally, different approaches to address this topic throughout the world are presented and can function as a helpful background for medical professionals. METHODS: The umbrella organizations of the five largest religious movements were asked for written statements concerning the subject of organ transplantation, and a literature review was performed. RESULTS: All German religious umbrella organizations have a positive view on organ donation, if certain rules are respected. Particularly, deceased donations are supported as a sign of altruism, love, and respect for another human being. Different aspects of the transplant process (e.g., consent, brain death, and respect for the dead body) are particularly stressed in some religions. CONCLUSIONS: In general, the religious groups addressed here are in favor of organ donations. Nevertheless, there are important particularities to be considered. Hopefully, understanding the different religious views on organ donations will help in reducing religious concerns about transplantation and narrowing the gap between the need and the availability of organ donations.

Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation.

Phage therapy is an experimental therapeutic approach used to target multidrug-resistant bacterial infections. A lack of reliable data with regard to its efficacy and regulatory hurdles hinders a broad application. Here we report, for the first time, a case of vancomycin-resistant Enterococcus faecium abdominal infection in a one-year-old, critically ill, and three times liver transplanted girl, which was successfully treated with intravenous injections (twice per day for 20 days) of a magistral preparation containing two Enterococcus phages. This correlated with a reduction in baseline C-reactive protein (CRP), successful weaning from mechanical ventilation and without associated clinical adverse events. Prior to clinical use, phage genome was sequenced to confirm the absence of genetic determinants conferring lysogeny, virulence or antibiotic resistance, and thus their safety. Using a phage neutralization assay, no neutralizing anti-phage antibodies in the patient's serum could be detected. Vancomycin-susceptible E. faecium isolates were identified in close relation to phage therapy and, by using whole-genome sequencing, it was demonstrated that vancomycin-susceptible E. faecium emerged from vancomycin-resistant progenitors. Covering a one year follow up, we provide further evidence for the feasibility of bacteriophage therapy that can serve as a basis for urgently needed controlled clinical trials.

[Health-related quality of life of children and adolescents with primary nocturnal enuresis who are undergoing therapy]. / Gesundheitsbezogene Lebensqualität von Kindern und Jugendlichen mit primärer Enuresis nocturna unter Therapie.

BACKGROUND: Primary nocturnal enuresis (PNE) affects a relevant proportion of children (10-15% at school entrance). While a significant impact on psychological well-being and self-esteem of children has been reported, the consequences for Health-Related Quality of Life (HRQoL) have been less addressed. The aim of this investigation is the analysis of HRQoL of PNE under therapy with an established questionnaire. METHODS: The KINDL­R questionnaire for HRQoL with 24 items in 6 dimensions was sent to all patients of the enuresis outpatient clinic (ages 7-17 years, minimum 3 months of therapy, no achieved dryness). Actual number of wet nights and eventual comorbidities were extracted from the clinical data. RESULTS: Of 57 questionnaires sent by mail, 47 were returned from patients and parents (82.5%). The patient results did not show a correlation between HRQoL and age, but there was a negative correlation of physical well-being and increasing age (r = -0.259, p < 0.05). A marked negative correlation was seen between bed-wetting frequency and HRQoL (r = -0.372, p < 0.05), especially in the dimensions "self-worthiness" (r = -0.399, p < 0.005) and "chronic-generic" (r = -0.383, p < 0.05). DISCUSSION: During enuresis treatment without achieved dryness, the patients did not show systematic limitation in HRQoL compared to reference populations. This is in contrast to limitations in HRQoL and self-esteem before therapy, but may possibly be explained by the correlation of this dimension with bed-wetting frequency in this study and the reported improvement through treatment in other studies. Both factors support the need and importance of adequate PNE therapy.

Monitoring intra-abdominal pressure after liver transplantation in children.

IAH after LTX can impair perfusion and threaten graft viability. This study aimed to assess the feasibility of longitudinal IAP measurements as an IAH screening method in children after LTX. A cohort of 23 children with a mean age (range) 3.1 (3 months-14 years) who underwent LTX between May 2017 and February 2018 were evaluated retrospectively. Longitudinal IAP measurements were compared to bedside Doppler US monitoring data. In total, 425 IAP measurements and 257 US examinations were performed. The mean ± SD (range) time expenditure for IAP measurement was 1.9 ± 0.4 (0.5-3.2) minutes. The mean post-operative IAP was 7.9 ± 3.6 (1-25) mm Hg. IAH (IAP ≥ 10 mm Hg) was noted in 102 (24%) of 257 measurements. Agitation had a significant impact on IAP (estimate: 9.3 mm Hg, CI: 6.72-11.97, P < .01). In patients with TAC, IAP was increased (6.7 ± 2.1 vs 8.7 ± 3.1 mm Hg, P = .02) while peak portal venous velocities decreased (38 ± 27 vs 26 ± 22 cm/s, P = .03) after patch reduction. An abdominal compartment syndrome with severely impaired vascular flow was noted in one patient. Episodes of elevated IAP were noted in a large proportion of patients, underscoring the need for IAP monitoring in pediatric liver transplant recipients. The safety and low time expenditure associated with IAP measurement could be included easily into standard nursing procedures for these patients.

Partial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation.

AIM: To investigate the relation of two different mutations to the outcome of partial external biliary diversion (PEBD) in severe bile salt export pump (BSEP) deficiency. METHODS: Mutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney (HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatography-tandem mass spectrometry. Wild-type and mutant BSEP transport of [3H]-labeled taurocholate (TC) and taurochenodeoxycholate (TCDC) was assessed by vesicular transport assays. RESULTS: A girl (at 2 mo) presented with pruritus, jaundice and elevated serum bile salts (BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919del and the nonsense mutation p.R1235X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy (age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives (< 5%). The patients' native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919del and p.G1032R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild-type BSEP transporter per minute, respectively. CONCLUSION: In summary, our findings suggest that residual function of BSEP as well as substrate specificity influence the therapeutic effectiveness of PEBD in progressive familial intrahepatic cholestasis type 2 (PFIC-2).

Differentiation of subgroups of monosymptomatic enuresis according to prepulse inhibition of the startle reflex.

AIM: Monosymptomatic enuresis (ME) is a common disorder in children with serious social and psychological consequences. Treatment is usually initiated with desamino-arginine vasopressin (dDAVP) and/or alarm therapy as first-line treatment and imipramine as second-line. All treatments have proven efficacy, but are not successful with all patients. Therefore, a differentiation into subgroups according to treatment efficacy would be beneficial. METHODS: A group of patients resistant to first-line treatment was treated with imipramine and compared with matched controls successfully treated with dDAVP and/or alarm therapy. Prepulse inhibition (PPI) to acoustic startle reflexes was measured in all patients. RESULTS: In a group of 23 nonresponders, the median PPI was 72% (range 43-94%) compared with the matched dDAVP/alarm - responders with a median PPI of 26% (range 0-61%) (p < 0.0001). The response rate to imipramine was 87%. CONCLUSION: The presented data provide evidence that PPI allows to identify two subgroups of ME. The results offer further insight into (at least) two different pathomechanisms involved in ME: (i) a maturational delay of reflex inhibition with reduced PPI and (ii) a normal PPI, possibly with abnormal sleep patterns, that can be influenced by imipramine.

Implications for the usage of the left lateral liver graft for infants ≤10 kg, irrespective of a large-for-size situation--are monosegmental grafts redundant?

Organ donor shortage for infant liver transplant recipients has lead to an increase in splitting and living donation. For cases in which even transplantation of the left lateral graft (Couinaud's segments II + III) results in a "large for size situation" with an estimated graft body weight ratio (GBWR) of >4%, monosegmental liver transplantation was developed. This, however, bears complications because of greater parenchymal surface and suboptimal vascular flow. We exclusively use the left lateral graft from living donors or split grafts. Temporary abdominal closure is attempted in cases of increased pressure. We report of 41 pediatric transplants in 38 children ≤10 kg. Within this group, there were 23 cases with a GBWR of ≥4, and 15 cases with a GBWR <4. There was no statistical difference in vascular or biliary complications. Despite a more frequent rate of temporary abdominal closure, we did not find a higher rate of intra-abdominal infections. Overall, patient and graft survival was excellent in both groups (one death, three re-transplants). We noticed, however, that the ventro-dorsal diameter of the graft appears to be more relevant to potential graft necrosis than the actual graft size. In conclusion, the usage of monosegmental grafts seems unnecessary if transplantation of left lateral grafts is performed by an experienced multidisciplinary team, and temporary abdominal closure is favored in cases of increased abdominal pressure.